bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Intravitreal Aflibercept and Ranibizumab following Initial Treatment with Ranibizumab in Persistent Diabetic Macular Edema
Authors: Demircan Ali , Alkin Zeynep , Yesilkaya Ceren , Demir Gokhan , Kemer Burcu
Published: April 2018

Purpose. To compare the visual and anatomic outcomes in patients with persistent diabetic macular edema (DME) who switched from ranibizumab to aflibercept with those who continued with previous ranibizumab therapy. Methods. In this retrospective comparative study, medical records of consecutive patients with center-involved DME ≥ 350 μm who had at least three recent consecutive monthly ranibizumab injections followed by as-needed therapy with either aflibercept or ranibizumab were reviewed. Data were collected at presentation (preinjection), at the intermediary visit, and at the last visit (at the end of the follow-up period). Results. Forty-three eyes of 43 patients were divided into two groups: the switch group (n=20) and the ranibizumab group (n=23). Though no significant improvement was found in the mean BCVA from the intermediary visit to the last visit, there was a difference in the mean CMT in the switch group and the ranibizumab group (p<0.001 and p=0.03, resp.). The mean CMT decreased after the intermediary visit by 188.6 ± 120.5 μm in the switch group and by 60.3 ± 117.1 μm in the ranibizumab group (p=0.003). Conclusions. Both aflibercept and ranibizumab decreased CMT in patients with persistent DME who showed a poor response to ranibizumab injections. However, switching to aflibercept provided only morphologic improvement.
Bridging a Gap between Cr(VI)-Induced Oxidative Stress and Genotoxicity in Lettuce Organs after a Long-Term Exposure
Authors: Monteiro Cristina , Sario Sara , Mendes Rafael , Mariz-Ponte Nuno , Silva Sónia , Oliveira Helena , Bastos Verónica , Santos Conceição , Dias Maria Celeste
Published: April 2018

Chromium (Cr) contamination in arable soils and irrigating water remains a priority, particularly due to the challenges posed to crop production and food safety. Long-term Cr(VI) effects remain less addressed than short-term ones, particularly regarding organ-specific genotoxic profiles. Here we used the crop Lactuca sativa growing in a protected horticultural system and irrigated for 21 days with Cr(VI) (up to 200 mg/L). Besides the oxidative stress, the genotoxicity was evaluated. Shoots and roots showed distinctive oxidative stress status and genotoxic effects, in a dose-dependent manner. While 50 mg/L stimulated antioxidant activities and no major genotoxic effects were found, plants exposed to ≥150 showed an increase of oxidative disorders, together with cytostatic and DNA damage effects, and some mitotic impairment. Leaves showed less oxidative signs at 50 mg/L, while at 150/200 mg/L the antioxidant battery was stimulated. In Cr treated plants, the highest dose increased the DNA damage, reinforcing the idea that DNA breaks were related to mitotic disorders in higher doses. In conclusion, long-term exposure data show a highly responsive root, with a quadratic response meaning higher defenses at lower Cr doses, and higher oxidative and DNA damage and cytostatic effect at a higher dose.
Safety Assessment of Neoadjuvant Pertuzumab Combined with Trastuzumab in Nonmetastatic HER2-Positive Breast Cancer in Postmenopausal Elderly Women of South Asia
Authors: Hussain Nadia , Said Amira S. A. , Khan Zainab
Published: April 2018

Aim. To evaluate the safety issues and adverse effects of using TCHP regimen (docetaxel, carboplatin, trastuzumab, and pertuzumab) versus TCP regimen (docetaxel, carboplatin, and trastuzumab) in older postmenopausal women with nonmetastatic HER2-positive breast cancer. HER2 overexpressed in 20–25% of breast cancer signals an aggressive form of breast cancer and is treated with trastuzumab and pertuzumab. Methods. The patient record database was accessed to identify all postmenopausal women in the Punjab Care hospital who were above 65 years old, with stages 1–3 HER2-positive breast cancer and treated with neoadjuvant TCHP and neoadjuvant TCP from 2013 till 2016. Results. In TCH-P group and TCH group, mild fatigue (34% versus 36%) and diarrhea (48% versus 49%) were most common toxicities. Fever in TCH-P group and TCH group (12% versus 13%) was common. Anorexia affected 21% and 16% of patients receiving TCH and TCHP regimen, respectively. Febrile neutropenia was higher in TCH-P group 13% (3/23) versus 4.5% (1/22) in TCH group. Also 27.2% (6/22) of TCH-P group was hospitalized for treatment related toxicities versus 21.7% (5/23) of TCH group. Conclusion. Comparing neoadjuvant TCP and neoadjuvant TCH-P showed TCH-P regimen had an acceptable toxicity profile. Severe cardiac dysfunction was not observed. Using TCH-P regimen can be considered as relatively safe therapeutic option for elderly postmenopausal women with nonmetastatic HER2-positive breast cancer.
Preparation of Oligosaccharides by Degradation of Polysaccharides from Chinese Jujube and Its Biological Activity
Authors: Yan Xu , Wang Weiwei , Liu Mengjun , Zhao Zhihui
Published: April 2018

This study examined the degradation of polysaccharides to oligosaccharides in Chinese jujube fruits. Using a response surface model, the degradation conditions of polysaccharides under acid hydrolysis and enzymatic hydrolysis were optimized in laboratory conditions. A degradation rate of 66.9% was obtained under optimum acid hydrolysis conditions: 0.6 mol/L hydrochloric acid, 3% substrate concentration, and 1 h reaction time. A degradation rate of 41.4% was obtained under optimum enzyme hydrolysis conditions: 4.0 mL cellulose solution (10 mg/mL), 0.3 mL substrate solution (20 mg/mL), 0.7 mL citric acid buffer solution (pH 5), and 7.3 h reaction time. Using the stimulation effect for strain J-4 intestinal probiotic proliferation, the biological activity of oligosaccharides was determined. The results showed that the oligosaccharides from enzyme hydrolysis encouraged intestinal probiotic proliferation.
A New Unified Solution for Circular Tunnel Based on a Four‐Stage Constitutive Model considering the Intermediate Principal Stress
Authors: Chen Liang , Mao Xianbiao , Chen Yanlong , Li Ming , Hao Yang , Liu Ding
Published: April 2018

Based on the triaxial test, the elasto‐perfectly plastic strain‐softening damage model (EPSDM) is proposed as a new four‐stage constitutive model. Compared with traditional models, such as the elasto‐brittle‐plastic model (EBM), elasto‐strain‐softening model (ESM), elasto‐perfectly plastic model (EPM), and elasto‐peak plastic‐brittle plastic model (EPBM), this model incorporates both the plastic bearing capacity and strain‐softening characteristics of rock mass. Moreover, a new closed‐form solution of the circular tunnel is presented for the stress and displacement distribution, and a plastic shear strain increment is introduced to define the critical condition where the strain‐softening zone begins to occur. The new analysis solution obtained in this paper is a series of results rather than one specific solution; hence, it is suitable for a wide range of rock masses and engineering structures. The numerical simulation has been used to verify the correctness of the EPSDM. The parametric studies are also conducted to investigate the effects of supporting resistance, residual cohesion, dilation angle, strain‐softening coefficient, plastic shear strain increment, and yield parameter on the result. It is shown that when the supporting resistance is fully released, both the post‐peak failure radii and surface displacement could be summarized as EBM > EPBM > ESM > EPSDM > EPM; the dilation angle in the damage zone had the highest influence on the surface displacement, whereas the dilation angle in the perfectly plastic zone had the lowest influence; the strain‐softening coefficient had the most significant effect on the damage zone radii; the EPSDM is recommended as the optimum model for support design and stability evaluation of the circular tunnel excavated in the perfectly plastic strain‐softening rock mass.
Analysis of Direct and Indirect Selection and Indices in Bread Wheat (Triticum aestivumL.) Segregating Progeny
Authors: Fellahi Zine El Abidine , Hannachi Abderrahmane , Bouzerzour Hamenna
Published: April 2018

Three selection methods including direct and indirect selection along with selection index based on the phenotypic values of eleven traits of agronomic interest were assessed for their application in F4bread wheat progenies. Significant genetic variation existed among parents and crosses for the traits measured. The following were the most efficient indices for simultaneous selection of superior lines for yield and its components: base index of Williams, followed by the sum of ranks index of Smith and Hazel. The selection-based index provided the highest grain yield gains as compared to the other selection criteria, except for flag leaf area, indicating that the direct and indirect monotrait selection were not appropriate in the situation analyzed in this work. PCA identified Ain Abid × Mahon-Demias, Ain Abid × Rmada, and Ain Abid × El-Wifak as the most promising populations. At 5% selection intensity, the top 30 lines selected were distinguished, in comparison with the standard check Hidhab, by significant improvements in yield and yield components.
Clinical Outcomes of Sequential Intrastromal Corneal Ring Segments and an Extended Range of Vision Intraocular Lens Implantation in Patients with Keratoconus and Cataract
Authors: Lisa C. , Zaldivar R. , Fernández-Vega Cueto A. , Sanchez-Avila R. M. , Madrid-Costa D. , Alfonso J. F.
Published: April 2018

Purpose. To evaluate efficacy, safety, and predictability of sequential Ferrara-type intrastromal corneal ring segments (ICRS) and an extended range of vision intraocular lens (IOL) implantation in patients with keratoconus and cataract. Methods. This study comprised patients with keratoconus and cataract that had ICRS implantation followed 6 months later by extended range of vision IOL implantation. The uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and residual refractive errors, analysed using vector analysis, were recorded preoperatively, 6 months after ICRS implantation, and 6 months after IOL implantation, respectively. Results. The study enrolled 17 eyes (11 patients). The mean UDVA (logMAR scale) was 1.15 ± 0.67 preoperatively, 0.88 ± 0.69 six months after ICRS implantation (P=0.005), and 0.27 ± 0.18 six months after IOL implantation (P<0.0001). The CDVA changed from 0.26 ± 0.15 (logMAR) before surgery to 0.17 ± 0.08 six months after Ferrara-type ICRS implantation (P=0.002) and to 0.07 ± 0.06 six months after IOL implantation (P<0.0001). The spherical equivalent and the refractive cylinder declined steeply after IOL implantation (P<0.001). The magnitude of depth of focus was 2.60 ± 1.02 D. There were no statistically significant differences in visual acuity for a defocus range from +0.50 D to −0.50 D (P>0.1). Conclusion. Sequential Ferrara-type ICRS and an extended range of vision IOL implantation provided good visual and refractive outcomes, being an effective, safe, and predictable procedure for the treatment of selected cases of patients with keratoconus and cataract. In addition, this approach provides an increase of tolerance to defocus.
Evaluation of the HbA1c Reduction Cut Point for a Nonglycemic Effect on Cardiovascular Benefit of Hypoglycemic Agents in Patients with Type 2 Diabetes Based on Endpoint Events
Authors: Wu Yuchao , Tang Lizhi , Zhang Fang , Yan Zhe , Li Jing , Tong Nanwei
Published: April 2018

Background. Atherosclerotic cardiovascular disease (ASCVD) is a major cause of death among patients with diabetes but can be improved by certain hypoglycemic agents. However, adjudicating criteria on whether improvements are a glycemic or nonglycemic effect of these agents remain unclear. Methods. Hypoglycemic agents that produce a cardiovascular benefit in nondiabetic patients are considered to do so via a nonglycemic effect. We performed a subgroup analysis for primary and secondary prevention or very high risk of ASCVD in patients with type 2 diabetes (T2DM). Where glycosylated hemoglobin (HbA1c) was reduced to the same extent in a head-to-head comparison, cardiovascular benefits were judged as a nonglycemic effect. Furthermore, by analyzing the endpoints of four important randomized controlled intensive glucose control studies, UKPDS33, ADVANCE, ACCORD, and VADT, we calculated the cut point of HbA1c reduction for a nonglycemic effect on cardiovascular benefit by hypoglycemic agents in ASCVD groups of different severities. Results. For the ASCVD primary prevention group of T2DM, UKPDS33 indicated a reduction in HbA1c < 0.9%, and a cardiovascular benefit within 10 years was considered a nonglycemic effect. For ASCVD secondary prevention or in the very high-risk group, pioglitazone exerted a nonglycemic effect on cardiovascular benefit in nondiabetic patients with insulin resistance; metformin may exert a similar effect in T2DM patients in a head-to-head study. Analysis of T2DM intensive glucose control studies showed a reduction in HbA1c of <1.0%, and a cardiovascular benefit after approximately 5 years was deemed a nonglycemic effect. Conclusions. For ASCVD primary prevention in T2DM, a reduction in HbA1c < 0.9% and a cardiovascular benefit within 10 years were considered a nonglycemic effect. For ASCVD secondary prevention or in a very high-risk population, a reduction in HbA1c < 1.0% and a cardiovascular benefit within about 5 years were also considered a nonglycemic effect.
Less Expansion of Short-Pulse Laser Scars in Panretinal Photocoagulation for Diabetic Retinopathy
Authors: Higaki Masahiko , Nozaki Miho , Yoshida Munenori , Ogura Yuichiro
Published: April 2018

Purpose. To compare the expansion rates of laser photocoagulation scars between the conventional laser and short-pulse laser using fundus autofluorescence (FAF). Methods. Retrospective chart review. Conventional laser was performed on 6 eyes of 6 patients, and short-pulse laser was performed on 11 eyes of 8 patients with diabetic retinopathy. FAF images were obtained by Optos® 200Tx (Optos, Dunfermline, Scotland, UK) at 1, 3, 6, and 12 months after treatment. The average area of 20 photocoagulation scars was measured by using ImageJ software. The expansion rates were calculated from the proportion of the averaged area against the optic disc area. Regression of retinopathy and central macular thickness were also evaluated. Results. The expansion rates of the conventional laser scars compared with the size at 1 month after treatment were 1.12 ± 0.08 (3 M), 1.27 ± 0.12 (6 M), and 1.39 ± 0.11 (12 M). The expansion rates of the short-pulse laser scars were 1.04 ± 0.05 (3 M), 1.09 ± 0.04 (6 M), and 1.13 ± 0.05 (12 M). The expansion rates of the short-pulse laser were significantly lower than those of the conventional laser (p<0.01). Conclusion. FAF images were useful to evaluate the changes in the photocoagulation scar sizes. The scars with the short-pulse laser showed lower expansion rates than those of the conventional laser.
A Case of Atrioventricular Block Potentially Associated with Right Coronary Artery Lesion and Ticagrelor Therapy Mediated by the Increasing Adenosine Plasma Concentration
Authors: Li Xiaoye , Xue Ying , Wu Hongyi
Published: April 2018

Purpose. To report a case of atrioventricular block (AVB) which might be associated with the right coronary artery lesion and the novel oral antithrombotic drug ticagrelor mediated by the increasing adenosine plasma concentration (APC). Case Report. A 65-year-old man was given loading dose of ticagrelor (180 mg) before coronary angiography with total thrombotic occlusion of right coronary artery and one stent was implanted. On second day after successful percutaneous coronary intervention, ECG monitoring showed second-degree (Mobitz type I) AVB with prolonged PR interval (299 ms). Hypothesis was drawn that elevated APC levels caused by ticagrelor would be the reason for AVB after excluding combination drugs or underlying disease. APC might be an indicator of this side effect caused by the P2Y12 receptor inhibitors. On fourth day after shifting to clopidogrel, the ECG showed normal sinus rhythm and PR interval depressed to 190 ms and APC dropped from 1.62 umol/L to 0.92 umol/L. The bradycardia and AVB did not occur in the three-month follow-up. Conclusion. It was important to take the ticagrelor induced bradycardia into account particularly with the myocardial infarction of right coronary artery, treated with atrioventricular block drugs after initiating ticagrelor. Also, we should shift ticagrelor to clopidogrel if AVB occurred.
Total Penetrating Keratoplasty: Indications, Therapeutic Approach, and Long-Term Follow-Up
Authors: Krysik Katarzyna , Wroblewska-Czajka Ewa , Lyssek-Boron Anita , Wylegala Edward A. , Dobrowolski Dariusz
Published: April 2018

Purpose. Evaluation of the indications, anatomical and functional results, and complications of total penetrating keratoplasty (TPK) in disorders involving whole cornea. Materials and Methods. We analyzed outcomes of the surgical treatment of 47 eyes of 46 patients that underwent TPK. Indications were infectious keratitis, autoimmune disease, injury of the eyeball (mainly chemical burns), and other combined disorders. The surgical technique involved dissection of affected tissues with a margin of 1.0 mm. The size of the corneal graft ranged from 10.0 to 14.0 mm. We analyzed indications, outcomes, and complications of surgery. Results. Final restoration of the ocular integrity and maintenance of the globe were achieved in 27 eyes (57%). More than one surgery was necessary in a total of 29 eyes (62%). The frequency of retransplantations did not vary significantly between the groups with different causes of corneal melting/perforation (63% of eyes with infection, 66% of eyes after trauma and 70% of eyes of patients with autoimmune disorders). Surgical treatment failed in 20 eyes (43%). Evisceration was necessary in 13 eyes (28%), phthisis occurred in 7 cases (15%). Conclusion. TPK should be considered as a last line treatment in huge corneal destruction to restore integrity of the eye globe.
Troxerutin Protects Kidney Tissue against BDE‐47‐Induced Inflammatory Damage through CXCR4‐TXNIP/NLRP3 Signaling
Authors: Shan Qun , Zheng Gui-hong , Han Xin-rui , Wen Xin , Wang Shan , Li Meng-qiu , Zhuang Juan , Zhang Zi-Feng , Hu Bin , Zhang Yanqiu , Zheng Yuan-Lin
Published: April 2018

2,2 ′,4,4 ′‐Tetrabromodiphenyl ether (BDE‐47) induces oxidative stress in kidney cells, but the underlying mechanism remains poorly understood. Troxerutin, a natural flavonoid, has potential antioxidant and anti‐inflammatory efficacy. In this study, we assessed the effect of troxerutin on kidney damage caused by BDE‐47 and investigated the underlying mechanism. The results showed troxerutin reduced reactive oxygen species (ROS) level and urine albumin‐to‐creatinine ratio (ACR), decreased the activities of inflammatory factors including cyclooxygenase‐2 (COX‐2), induced nitric oxide synthase (iNOS) and nuclear factor kappa B (NF‐κB) in the kidney tissues of BDE‐47‐treated mice. Furthermore, troxerutin significantly weakened the expression of kidney NLRP3 inflammasome containing NLRP3, ASC, and caspase‐1, contributing to the decline of IL‐1β. Additionally, troxerutin inhibited the increased protein level of stromal‐derived factor‐1(SDF‐1), C‐X‐C chemokine ligand 12 receptor 4 (CXCR4), and thioredoxin interaction protein (TXNIP) caused by BDE‐47. Specifically, the immunoprecipitation assay indicated that there was a direct interaction between CXCR4 and TXNIP. CXCR4 siRNA and TXNIP siRNA also decreased the inflammatory damage, which was similar to the action of troxerutin. Our data demonstrated that troxerutin regulated the inflammatory lesions via CXCR4‐TXNIP/NLRP3 inflammasome in the kidney of mice induced by BDE‐47.
Mucosal Two-Step Pathogenesis in Gastroesophageal Reflux Disease: Repeated Weakly Acidic Stimulation and Activation of Protease-Activated Receptor-2 on Mucosal Interleukin-8 Secretion
Authors: Winkelsett Lukas , Malfertheiner Peter , Wex Thomas , Kandulski Arne
Published: April 2018

Background: Activation of protease-activated receptor-2 (PAR2) is involved in the mucosal immune pathogenesis of gastroesophageal reflux disease (GERD) that is characterized by proinflammatory cytokines such as interleukin-8 (IL-8). PAR2 activation on epithelial cells induces epithelial IL-8 secretion and initiates mucosal inflammation. Methods: A human primary esophageal epithelial cell model was established to investigate the effects of repeated stimulation with weakly acidic solutions and subsequent PAR2 activation. After creating a monolayer, cells were incubated under weakly acidic conditions for 7 h followed by 17 h at pH 7.4. This short-term exposure was repeated once. After weakly acidic stimulation, PAR2 activation was achieved by a synthetic agonist at pH 7.4. Results: After repeated weakly acidic incubation, PAR2 transcript levels were 3.6-fold upregulated (p = 0.001) and IL-8 transcripts were 2.4-fold enhanced (p = 0.034) compared to nonstimulated controls, while IL-8 protein in the cell pellet and supernatant was not increased. Only the additional PAR2 activation upon pH stimulation led to increased IL-8 secretion into the supernatant. Conclusions: We propose a 2-step mechanism in which repeated weakly acidic exposure leads to the upregulation of epithelial PAR2 expression. The subsequent activation of upregulated PAR2 contributes to the initiation of mucosal inflammation, which underlies the important role of esophageal epithelium in GERD pathogenesis.
A Web-Based Education Program for Colorectal Lesion Diagnosis with Narrow Band Imaging Classification
Authors: Aihara Hiroyuki , Kumar Nitin , Thompson Christopher C.
Published: April 2018

Background: An education system for narrow band imaging (NBI) interpretation requires sufficient exposure to key features. However, access to didactic lectures by experienced teachers is limited in the United States. Aim: To develop and assess the effectiveness of a colorectal lesion identification tutorial. Methods: In the image analysis pretest, subjects including 9 experts and 8 trainees interpreted 50 white light (WL) and 50 NBI images of colorectal lesions. Results were not reviewed with subjects. Trainees then participated in an online tutorial emphasizing NBI interpretation in colorectal lesion analysis. A post-test was administered and diagnostic yields were compared to pre-education diagnostic yields. Results: Under the NBI mode, experts showed higher diagnostic yields (sensitivity 91.5% [87.3–94.4], specificity 90.6% [85.1–94.2], and accuracy 91.1% [88.5–93.7] with substantial interobserver agreement [κ value 0.71]) compared to trainees (sensitivity 89.6% [84.8–93.0], specificity 80.6% [73.5–86.3], and accuracy 86.0% [82.6–89.2], with substantial interobserver agreement [κ value 0.69]). The online tutorial improved the diagnostic yields of trainees to the equivalent level of experts (sensitivity 94.1% [90.0–96.6], specificity 89.0% [83.0–93.2], and accuracy 92.0% [89.3–94.7], p < 0.001 with substantial interobserver agreement [κ value 0.78]). Conclusions: This short, online tutorial improved diagnostic performance and interobserver agreement.
Methods to Address Computed Tomography-Related Risk Factors in Oncology Patients: An Expert Opinion Based on Current Evidence
Authors: Del Mastro Lucia , Laghi Andrea , Ronco Claudio
Published: April 2018

Background: The present paper is intended to be a practical guide organized by statements describing methods to reduce risks related to CT examinations in cancer patients. Methods: A panel of radiologists, oncologists and nephrologists were selected based on their publication records in the field and expertise. Ten clinical questions, which were derived from clinical needs and an integration of all the committee members’ suggestions, were stated. The modified Delphi approach was used; it involved a detailed literature review and the collective judgement of experts, including electronic and face-to-face discussions. Results: Ten statements were derived from expert opinions based on the current literature, recently developed guidelines and technological advancements. Each statement is discussed in a short paragraph reporting the current key evidence. Conclusion: This paper addresses the clinical implications of performing numerous CT examinations in patients with cancer, providing clinicians with information regarding methods to reduce risk factors in this patient population.
Early Flow Disturbances of Tunnelled Haemodialysis Catheters and Topographic Landmarks in Chest X-Ray
Authors: Fahnert Jeanette , Stumpp Patrick , Kahn Thomas , Keller Frieder , Schiekofer Stephan , Petros Sirak , Halbritter Jan , Lindner Tom H. , Rasche Franz Maximilian
Published: April 2018

Background/Aims: The position of the tip of tunnelled haemodialysis (HD) catheters (THC) might influence flow characteristics during HD. In chest X-ray (CXR), carina-related landmarks may be practicable to verify the THC position, and tip-carina distance (TCD) might be useful to predict early-flow dysfunctions. Methods: In this single-centre, retrospective study, the TCD and the angle between the distal catheter and the body vertical axis (tip-body vertical-angle [TVA]) was measured in 115 THC by post-procedure CXR with 2 investigators. The parameters were proved to be feasible by interrater-reliability and correlated with the incidence of flow-dysfunction within 10 days after insertion. Results: Steep-aligned (TVA <40°, p < 0.01) and deep-ending catheters (TCD: right-sighted >1.5 cm or left-sighted >4.5 cm below the carina; p < 0.01) showed a significantly less dysfunction with a good interrater-reliability (R[TVA] = 0.8, R[TCD] = 0.9). Conclusions: Carina-related landmarks in CXR might be helpful to predict early-flow dysfunctions. However, randomized studies will be necessary to confirm this in fluoroscopic-guided placement during the insertion of THC.
Modulation of Pacemaker Potentials in Murine Small Intestinal Interstitial Cells of Cajal by Gamisoyo-San, a Traditional Chinese Herbal Medicine
Authors: Kim Doeun , Kim Jung Nam , Nam Joo Hyun , Lee Jong Rok , Kim Sang Chan , Kim Byung Joo
Published: April 2018

Background: The Gamisoyo-san (GSS) has been used for ­improving the gastrointestinal (GI) symptoms. The purpose of this study was to investigate the effects of GSS, a traditional Chinese herbal medicine, on the pacemaker potentials of mouse small intestinal interstitial cells of Cajal (ICCs). Methods: ICCs from the small intestines were dissociated and cultured. Whole-cell patch-clamp configuration was used to record pacemaker potentials and membrane currents. Results: GSS depolarized ICC pacemaker potentials in a dose-dependent manner. Pretreatment with 4-diphenylacetoxypiperidinium iodide completely inhibited GSS-induced pacemaker potential depolarizations. Intracellular GDP-β-S inhibited GSS-induced effects, and in the presence of U-73122, GSS-induced effects were inhibited. Also, GSS in the presence of a Ca2+-free solution or thapsigargin did not depolarize pacemaker potentials. However, in the presence of calphostin C, GSS slightly depolarized pacemaker potentials. Furthermore, GSS inhibited both transient receptor potential melastatin7 and Ca2+-activated Cl– channel (anoctamin1) currents. Conclusion: GSS depolarized pacemaker potentials of ICCs via G protein and muscarinic M3 receptor signaling pathways and through internal or external Ca2+-, phospholipase C-, and protein kinase C-dependent and transient receptor potential melastatin 7-, and anoctamin 1-independent pathways. The study shows that GSS may regulate GI tract motility, suggesting that GSS could be a basis for developing novel prokinetic agents for treating GI motility dysfunctions.
Langerhans-Zell-Histiozytose: Kenntnisse zur extrakutanen Manifestation sind unerlässlich
Authors: Fölster-Holst Regina
Published: April 2018

A 12-month-old healthy girl presented with a chronic diaper rash. Physical examination demonstrated crusting of the scalp, erythematous papules with surrounding petechiae on the lower abdomen, and an intraoral palatal ulcer. Further imaging demonstrated bone involvement. Histopathologic examination of involved skin and the intraoral ulcer demonstrated epithelioid histiocytes with «coffee bean-shaped» nuclei, staining positive for CD1a and langerin by immunohistochemistry, consistent with Langerhans cell histiocytosis (LCH). LCH is a disease entity of unknown etiology characterized by histiocytic proliferation that most commonly presents in young children. The cutaneous findings of LCH include a seborrheic dermatitis-like and/or red-brown papular eruption. Intraoral examination is crucial as oral mucosal and maxillofacial skeletal disease can also be seen in LCH. When a child presents with a recalcitrant seborrheic dermatitis-like eruption or chronic diaper rash, the clinician should be alerted to the possibility of LCH. Timely recognition and diagnosis of LCH is important for oncologic referral, evaluation, and treatment.
Impact of Brain Atrophy on Early Neurological Deterioration and Outcome in Severe Ischemic Stroke Treated by Intravenous Thrombolysis
Authors: Tschirret Olivier , Moreno Legast Gabriela , Mansuy Adeline , Mewton Nathan , Buisson Marielle , Hannoun Salem , Chamard Leila , Sappey-Marinier Dominique , El Khoury Carlos , Bischoff Magali , de Parisot Audrey , Derex Laurent , Nighoghossian Norbert , Berthezène Yves , Mechtouff Laura
Published: April 2018

Background: Brain atrophy has shown a protective effect on the risk of early neurological deterioration (END) related to malignant edema in patients with hemispheric infarction but could be deleterious on the outcome. Aims: We aimed to assess whether brain atrophy has an impact on the risk of END and on the outcome in severe ischemic strokes after intravenous (IV) thrombolysis. Methods: From a prospective thrombolysis registry, 137 patients who had a National Institutes of Health Stroke Scale (NIHSS) ≥15, MRI at admission, and IV thrombolysis were included. Relative cerebral volume was calculated. END was defined as a ≥2-points deterioration 72-h NIHSS and a good outcome as a modified Rankin Scale (mRS) ≤2 at 3 months. A multiple logistic regression analysis with a stepwise backward procedure was performed. Results: END and a good outcome were observed, respectively, in 20 (14.6%) and 48 (37.5%) patients. In univariate analysis, predictors of END included age (p = 0.049), diabetes (p = 0.041), and parenchymal hemorrhage (p = 0.039). In multivariate analysis, age (p = 0.018) was significantly associated with END. Brain atrophy was not associated with END even in subgroup analysis according to the baseline infarct size. In univariate analysis, age (p = 0.003), prestroke mRS (p = 0.002), hypertension (p = 0.006), baseline NIHSS (p = 0.002), END (p = 0.002), proximal occlusion (p = 0.006), and recanalization at 24 h (p < 0.001) were associated with a good outcome. Only baseline NIHSS (p = 0.006) was associated with a good outcome after adjustment. Conclusions: We did not find any impact of brain atrophy on the risk of END and the outcome at 3 months in severe ischemic strokes after IV thrombolysis.
Immunolocalization of Receptor and Chemoreceptor Modules in the Sheep Vomeronasal Organ
Authors: Ibrahim  Dalia
Published: April 2018

The vomeronasal organ (VNO) is the peripheral receptor organ of the accessory olfactory system, which is responsible for both sexual and innate behaviors. The degree of neuronal differentiation and maturation of the vomeronasal receptor cells together with the verification of the presence of the solitary chemoreceptor cells (SCCs) in the VNO of Corriedale sheep were assessed using immunofluorescence. A protein gene product 9.5 (PGP 9.5), which is a neuronal marker recognized to be expressed in most neurons of vertebrate species, an olfactory marker protein (OMP) that is precise for mature olfactory receptor cells, and lastly phospholipase C-β2 (PLC-β2), a marker in the signal transduction pathway of SCCs, were all tested. The cell bodies and dendrites of almost all receptor cells in the sensory epithelium were strongly positive for PGP 9.5 and to a lesser extent for OMP. In the nonsensory wall, all cells were negative for both PGP 9.5 and OMP; however, some positive PGP 9.5 immunoreactive fibers were identified. For PLC-β2, only 1 basally situated SCC could be identified in the sensory epithelium. A higher number was demonstrated in the nonsensory wall. Corriedale sheep possess matured, fully differentiated vomeronasal receptor cells in their sensory wall, suggesting an appropriate pheromone perception. Additionally, the VNO in sheep may participate in the usual transduction mechanisms, though it is seemingly not a chemoreceptor organ.
FoxP2 Expression in a Highly Vocal Teleost Fish with Comparisons to Tetrapods
Authors: Pengra Ian G.G. , Marchaterre Margaret A. , Bass Andrew H.
Published: April 2018

Motivated by studies of speech deficits in humans, several studies over the past two decades have investigated the potential role of a forkhead domain transcription factor, FoxP2, in the central control of acoustic signaling/vocalization among vertebrates. Comparative neuroanatomical studies that mainly include mammalian and avian species have mapped the distribution of FoxP2 expression in multiple brain regions that imply a greater functional significance beyond vocalization that might be shared broadly across vertebrate lineages. To date, reports for teleost fish have been limited in number and scope to nonvocal species. Here, we map the neuroanatomical distribution of FoxP2 mRNA expression in a highly vocal teleost, the plainfin midshipman (Porichthys notatus). We report an extensive overlap between FoxP2 expression and vocal, auditory, and steroid-signaling systems with robust expression at multiple sites in the telencephalon, the preoptic area, the diencephalon, and the midbrain. Label was far more restricted in the hindbrain though robust in one region of the reticular formation. A comparison with other teleosts and tetrapods suggests an evolutionarily conserved FoxP2 phenotype important to vocal-acoustic and, more broadly, sensorimotor function among vertebrates.
Long-Term Progression-Free Survival in a Patient with Metastatic Leiomyosarcoma of the Inguinal Region Treated with Trabectedin
Authors: Haslbauer Ferdinand
Published: April 2018

Presented here is the case of an elderly leiomyosarcoma patient with multiple comorbidities and relapses from prior lines of treatment, who experienced a long-lasting progression-free survival. After initial diagnosis, standard treatment protocols with surgery and subsequent adjuvant radiochemotherapy were administered, followed by a short course of oral pazopanib at the patient’s request, which led to a rapid relapse. Afterwards, the patient received trabectedin for 22 months, achieving disease control with good quality of life over an extended period of time. After progression from trabectedin, the patient was switched to eribulin. Future clinical trials are needed to investigate the efficacy of trabectedin maintenance treatment and to identify predictive criteria for response to trabectedin among patients with advanced sarcoma.
Efficacy of the Combination of Immunoadsorption and Rituximab for Treatment in a Case of Severe Focal and Segmental Glomerulosclerosis Recurrence after Renal Transplantation
Authors: Martin-Moreno Paloma L. , Rifon Jose , Errasti Pedro
Published: April 2018

Background/Aims: We present a case of a male patient with severe recurrence of focal and segmental glomerulosclerosis (FSGS) after transplant. Methods: Before the transplant he was treated with plasma exchange. Massive proteinuria was detected post-transplantation and plasma exchanges were performed without response. We administered 5 doses of Rituximab (375 mg/m2) and partial remission was achieved. Proteinuria relapse occurred 1 year post-transplant, so Immunoadsorption (IA) was started instead of plasma exchange with reduction of proteinuria. Later, 2 new episodes of proteinuria relapse were detected and treated by increasing the number of IA sessions and administering new cycles of Rituximab. After achieving partial remission, IA was reduced to one session every 7–10 days as maintenance therapy. Results: Despite the fact of the severe recurrence, renal function and proteinuria remain stable over 8 years after the transplantation was performed. Conclusion: Combination of maintenance IA and cycles of Rituximab is an effective treatment for aggressive forms of FSGS recurrence after renal transplantation.
Microarray Analysis of Long Noncoding RNAs in Female Diabetic Peripheral Neuropathy Patients
Authors: Luo Lin , Ji Lin-Dan , Cai Jiang-Jia , Feng Mei , Zhou Mi , Hu Su-Pei , Xu Jin , Zhou Wen-Hua
Published: April 2018

Background/Aims: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus (DM). Because of its controversial pathogenesis, DPN is still not diagnosed or managed properly in most patients. Methods: In this study, human lncRNA microarrays were used to identify the differentially expressed lncRNAs in DM and DPN patients, and some of the discovered lncRNAs were further validated in additional 78 samples by quantitative realtime PCR (qRT-PCR). Results: The microarray analysis identified 446 and 1327 differentially expressed lncRNAs in DM and DPN, respectively. The KEGG pathway analysis further revealed that the differentially expressed lncRNA-coexpressed mRNAs between DPN and DM groups were significantly enriched in the MAPK signaling pathway. The lncRNA/mRNA coexpression network indicated that BDNF and TRAF2 correlated with 6 lncRNAs. The qRT-PCR confirmed the initial microarray results. Conclusion: These findings demonstrated that the interplay between lncRNAs and mRNA may be involved in the pathogenesis of DPN, especially the neurotrophin-MAPK signaling pathway, thus providing relevant information for future studies.
Comparison of the Predictive Roles of Risk Scores of In-Hospital Major Adverse Cardiovascular Events in Patients with Non-ST Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention
Authors: Aktürk Erdal , Aşkın Lütfü , Taşolar Hakan , Türkmen Serdar , Kaya Hakan
Published: April 2018

Objective: We evaluated the relationship between various risk scores (SYNTAX score [SS], SYNTAX score-II [SS-II], thrombolysis in myocardial infarction [TIMI] risk scores, and Global Registry of Acute Coronary Events [GRACE] risk scores) and major adverse cardiovascular events (MACE) in non-ST elevation myocardial infarction (NSTEMI) patients undergoing percutaneous coronary intervention (PCI). Subjects and Methods: The study population were selected from among 589 patients who underwent coronary angiography with a diagnosis of NSTEMI. TIMI and GRACE risk scores were calculated. SS and SS-II were calculated in all patients, and points were added according to the predefined algorithm, taking into account the other 6 clinical variables being monitored (age, sex, left ventricular ejection fraction, creatinine clearance, chronic obstructive pulmonary disease, and peripheral artery disease). Patients were classified into tertile 1 (SS < 22), tertile 2 (SS 23–32), and tertile 3 (SS > 32). Results: The group with high SS-II for PCI values in the risk scores were observed from tertile 1 to tertile 3 (from 25.0 ± 7.7 to 31.6 ± 9.4, p < 0.001, respectively). The SS-II score in patients with PCI was an independent predictor of MACE, in-hospital mortality, nonfatal myocardial infarction, and stent thrombosis (OR 1.082, 95% CI 1.036–1.131, p < 0.001). The overall MACE, in-hospital mortality, and nonfatal myocardial infarction rates were significantly higher in the high SS-II for PCI group (p < 0.001). Conclusion: TIMI and GRACE risk scores were able to predict MACE. In addition to these, SS-II was also able to predict in-hospital mortality, nonfatal myocardial infarction, and stent thrombosis.
Hospitalidade e Intenção de Recompra na Economia Compartilhada: um estudo com equações estruturais em meios de hospedagem alternativos
Authors: Pinottti Rita De Cássia , Moretti Sérgio Luiz do Amaral
Published: April 2018

O consumo colaborativo, também chamado de economia compartilhada, contribui para a ruptura das formas tradicionais de transação dos serviços, principalmente no caso dos meios de hospedagem. Essa nova perspectiva pode ser colocada sob a ótica dos estudos da hospitalidade pelo foco na relação entre anfitrião e hóspede. O objetivo desta pesquisa é responder à seguinte questão: qual o impacto entre meios de hospedagem alternativos, com base na pré-experiência com o site de serviços, hospitalidade, prazer e benefícios econômicos percebidos no contexto da economia compartilhada, na intenção de recompra? A metodologia foi quantitativa, por meio de questionário, com corte transversal, baseada em amostra de usuários de meios de hospedagem alternativos. O questionário ficou hospedado no Survey Monkey. A análise foi feita pela modelagem de equações estruturais (SEM, do inglês structural equation modeling), utilizando software SmartPLS. Todas as hipóteses propostas se confirmaram como influenciadoras na intenção de recompra e, portanto, capazes de gerar impacto entre os meios de hospedagem alternativos. O instrumento provou ser capaz de medir o que propôs e os resultados alcançados puderam responder ao problema da pesquisa. Entre eles, pode-se destacar que o consumo colaborativo é motivador de novas experiências. Parece correto afirmar que as empresas que exploram o setor de locação de propriedades privadas foram capazes de inovar e gerar valor em um setor até então dominado por grupos hoteleiros e incontáveis hotéis independentes em todo mundo.
P‐Wave Amplitude and PR Changes in Patients With Inappropriate Sinus Tachycardia: Findings Supportive of a Central Mechanism
Authors: Field Michael E. , Donateo Paolo , Bottoni Nicola , Iori Matteo , Brignole Michele , Kipp Ryan T. , Kopp Douglas E. , Leal Miguel A. , Eckhardt Lee L. , Wright Jennifer M. , Walsh Kathleen E. , Page Richard L. , Hamdan Mohamed H.
Published: April 2018

Background

The mechanism of inappropriate sinus tachycardia (
IST
) remains incompletely understood.

Methods and Results

We prospectively compared 3 patient groups: 11 patients with
IST
(
IST
Group), 9 control patients administered isoproterenol (Isuprel Group), and 15 patients with cristae terminalis atrial tachycardia (AT Group). P‐wave amplitude in lead
II
and
PR
interval were measured at a lower and higher heart rate (
HR
1 and
HR
2, respectively). P‐wave amplitude increased significantly with the increase in
HR
in the
IST
Group (0.16±0.07 mV at
HR
1=97±12 beats per minute versus 0.21±0.08 mV at
HR
2=135±21 beats per minute,
P
=0.001). The average increase in P‐wave amplitude in the
IST
Group was similar to the Isuprel Group (
P
=0.26).
PR
interval significantly shortened with the increases in
HR
in the
IST
Group (146±15 ms at
HR
1 versus 128±16 ms at
HR
2,
P
<0.001). A similar decrease in the
PR
interval was noted in the Isuprel Group (
P
=0.6). In contrast, patients in the atrial tachycardia Group experienced
PR
lengthening during atrial tachycardia when compared with baseline normal sinus rhythm (153±25 ms at
HR
1=78±17 beats per minute versus 179±29 ms at
HR
2=140±28 beats per minute,
P
<0.01).

Conclusions

We have shown that
HR
increases in patients with
IST
were associated with an increase in P‐wave amplitude in lead
II
and
PR
shortening similar to what is seen in healthy controls following isoproterenol infusion. The increase in P‐wave amplitude and absence of
PR
lengthening in
IST
support an extrinsic mechanism consistent with a state of sympatho‐excitation with cephalic shift in sinus node activation and enhanced atrioventricular nodal conduction.
Smoking and Risk of Ischemic Stroke in Young Men
Authors: Markidan Janina , Cole John W. , Cronin Carolyn A. , Merino Jose G. , Phipps Michael S. , Wozniak Marcella A. , Kittner Steven J.
Published: April 2018

Background and Purpose—

There is a strong dose–response relationship between smoking and risk of ischemic stroke in young women, but there are few data examining this association in young men. We examined the dose–response relationship between the quantity of cigarettes smoked and the odds of developing an ischemic stroke in men under age 50 years.

Methods—

The Stroke Prevention in Young Men Study is a population-based case–control study of risk factors for ischemic stroke in men ages 15 to 49 years. The χ
2
test was used to test categorical comparisons. Logistic regression models were used to calculate the odds ratio for ischemic stroke occurrence comparing current and former smokers to never smokers. In the first model, we adjusted solely for age. In the second model, we adjusted for potential confounding factors, including age, race, education, hypertension, myocardial infarction, angina, diabetes mellitus, and body mass index.

Results—

The study population consisted of 615 cases and 530 controls. The odds ratio for the current smoking group compared with never smokers was 1.88. Furthermore, when the current smoking group was stratified by number of cigarettes smoked, there was a dose–response relationship for the odds ratio, ranging from 1.46 for those smoking <11 cigarettes per day to 5.66 for those smoking 40+ cigarettes per day.

Conclusions—

We found a strong dose–response relationship between the number of cigarettes smoked daily and ischemic stroke among young men. Although complete smoking cessation is the goal, even smoking fewer cigarettes may reduce the risk of ischemic stroke in young men.
From the Prodigal Son to the Last Judgement: Arian Parables of Conversion to Catholicism
Authors: Luszczynska Magdalena
Published: April 2018

Sixteenth-century Polish-Lithuania was a multicultural country that took pride in its policy of religious tolerance. Among its many denominations was an Anabaptist sect known as the Polish Brethren or Arians. The relative openness of the society to conversion allowed individuals to explore a spectrum of religious options in search of a denomination that would fulfil their personal spiritual needs. Yet, such choices could sever friendships and family ties. The story of an Arian, Balcer Wilkowski, whose son Gaspar converted to Roman Catholicism, serves as a poignant example. Through literary analysis of his writing, this paper demonstrates how Wilkowski senior deployed scriptural references, and in particular the Parable of the Prodigal Son, to express his reaction to his son’s apostasy. While obligated by his own spiritual commitments to condemn Gaspar’s conversion, as a father he continued to search for a theological justification for the hope that his son might return to the Arian fold.
The Language of Historical Religious Controversies: The Case of George Keith and the Quaker Movement in England
Authors: Roads Judith
Published: April 2018

This paper tests a proto-model of historical religious polemic discourse through a case study of a 1690s dispute between the schismatic former Quaker George Keith and Thomas Ellwood, a prominent Quaker representing the Quaker movement in England at that time. Thomas Gloning, Gerd Fritz, and others, suggest certain rhetorical strategies underlie functional and evaluative argumentation language typically employed. Findings contrast discourse elements common to the Keithian texts that do match some traditional characteristics, despite a superficial impression indicating otherwise, but show too where the model fails. An additional approach, not part of the traditional model, touches on linguistic politeness theory.