bluuebunny/crossref_metadata_2025 huggingface dataset:
A Randomized Controlled Trial of Mindfulness-Based Stress Reduction to Prevent Flare-Up in Patients with Inactive Ulcerative Colitis
Authors: Jedel S. , Hoffman A. , Merriman P. , Swanson B. , Voigt R. , Rajan K.B. , Shaikh M. , Li H. , Keshavarzian A.
Published: April 2017

Background/Aims: The primary therapeutic goals in ulcerative colitis (UC) are to maintain excellent quality of life (QOL) by treating flare-ups when they occur, and preventing flare-ups. Since stress can trigger UC flare-ups, we investigated the efficacy of mindfulness-based stress reduction (MBSR) to reduce flare-ups and improve QOL. Methods: Patients with moderately severe UC, in remission, were randomized to MBSR or time/attention control. Primary outcome was disease status. Secondary outcomes were changes in markers of inflammation and disease activity, markers of stress and psychological assessments. Results: 55 subjects were randomized. Absence of flares, time to flare and severity of flare over 1 year were similar between the two groups. However, post hoc analysis showed that MBSR decreased the proportion of participants with at least one flare-up among those with top tertile urinary cortisol and baseline perceived stress (30 vs. 70%; p < 0.001). MBSR patients who flared demonstrated significantly lower stress at the last visit compared to flared patients in the control group (p = 0.04). Furthermore, MBSR prevented a drop in the Inflammatory Bowel Disease Quality of Life Questionnaire during flare (p < 0.01). Conclusion: MBSR did not affect the rate or severity of flare-ups in UC patients in remission. However, MBSR might be effective for those with high stress reactivity (high perceived stress and urinary cortisol) during remission. MBSR appears to improve QOL in UC patients by minimizing the negative impact of flare-ups on QOL. Further studies are needed to identify a subset of patients for whom MBSR could alter disease course.
Urinary Phytoestrogen Levels and Frailty in Older American Women of the National Health and Nutrition Examination Survey (NHANES) 1999-2002: A Cross-Sectional Study
Authors: Eichholzer Monika , Richard Aline , Walser-Domjan Esther , Linseisen Jakob , Rohrmann Sabine
Published: April 2017

Background/Aims: A deficit of various hormones during the process of aging and/or a heightened inflammatory state may be causally linked to the development of frailty. Phytoestrogens as weak estrogens, antioxidants, and anti-inflammatory agents may counteract this process. Methods: In a cross-sectional study including two cycles of the National Health and Nutrition Examination Survey (NHANES, i.e. 1999-2002), logistic regression was used to analyze the association between urinary concentrations of isoflavones and lignans and frailty in 600 females aged 50 years or older (median age 66.5 years). Participants were classified as ‘frail' (meeting 3 or more of the 5 frailty criteria), ‘prefrail' (meeting 1 or 2 of the criteria), or ‘robust' (meeting none of the criteria). Four percent were frail. Results: For all of the phytoestrogens considered, the unadjusted OR were lower than 1 but generally not statistically significant aside from the association with O-desmethylangolensin (O-DMA) (OR = 0.76; 95% CI 0.61-0.92). Multivariate analysis did not attenuate this finding (OR = 0.74; 95% CI 0.61-0.90). Conclusions: This first analysis of the relationship between phytoestrogens and frailty revealed an inverse association between urinary O-DMA levels and frailty in women. However, the number of frail women was low. Although this finding may be confounded or biased, it seems worthwhile to intensify research on the potential preventive effects of O-DMA.
Human-Animal Interaction as a Context for Positive Youth Development: A Relational Developmental Systems Approach to Constructing Human-Animal Interaction Theory and Research
Authors: Mueller Megan K.
Published: April 2017

Human-animal relationships are both ubiquitous and diverse across the life span, and may be especially salient among children and adolescents. Although research into youth involvement in human-animal interaction (HAI) is growing, existing data have not adequately explored the developmental processes associated with HAI. The purpose of this article is to discuss why relational developmental systems models, which explore bidirectional influences between individuals and their contexts, constitute a useful paradigm for addressing the challenges and complexities in research pertaining to human-animal relations, particularly in the study of positive youth development. Recommendations are presented for building the field of youth HAI research through expanding the exploration of animal relationships in ways that may serve to promote trajectories of positive development across childhood and adolescence.
Cost Analysis of an Intravenous to Subcutaneous Epoetin α Conversion
Authors: Wazny Lori D. , Raymond Colette B. , Sood Amy R. , Eng Amanda , Verrelli Mauro
Published: April 2017

Background/Aims: A cost analysis of a conversion from intravenous (IV) to subcutaneous (SC) epoetin α in patients receiving chronic in-center hemodialysis (HD). Methods: This retrospective analysis compared epoetin α drug costs during a 6-month period of IV usage (July to December 2010, period 1) to a 6-month period of SC usage (July to December 2011, period 2) in four large in-center HD units. Data were collected from quarterly counts of HD patients receiving epoetin α and monthly inventory billing records. Results: 622 HD patients who received IV epoetin α (period 1) were compared to 609 HD patients who received SC epoetin α (period 2). A 12.6% decrease in dose was observed. The average weekly cost of epoetin α was USD 173.02 per patient during the IV period versus USD 151.20 per patient during the SC period. This equated to a yearly cost savings of USD 1,135 per patient with SC epoetin α. Conclusion: The switch from IV to SC epoetin α was successfully implemented in all four centers and realized significant cost savings.
Results of Construction of Protective Loop Ileostomies and Reversal Surgery for Colorectal Surgery
Authors: Abegg R.M. , Brokelman W. , van Bebber I.P. , Bosscha K. , Prins H.A. , Lips D.J.
Published: April 2017

Background: Protective loop ileostomies in colorectal surgery are constructed to reduce morbidity and reinterventions related to the primary operation. However, ileostomies are associated with stoma-related morbidity and postoperative complications following reversal surgery. Dutch national data show increased use of loop ileostomies in colorectal surgery for cancer justifying an adequate assessment of its morbidity. This study was undertaken to investigate morbidity associated with protective loop ileostomies in colorectal surgery. Methods: Retrospectively, 118 consecutive patients undergoing left-sided colonic or rectal resection with protective loop ileostomy were included. Primary outcome was 30-day mortality. Secondary endpoints included total complication rate (including stoma-related morbidity), total reintervention risk, anastomotic leakage risk and total length of stay. Results: No mortality was observed. Overall major complication, reintervention and anastomotic leakage risk for colorectal surgery were 20, 20 and 3.9%, respectively. Combined length of stay for stoma-related morbidity and reversal surgery was 12.7 days. The risk for stoma-related morbidity was 35%, and the risk for nonelective reversal was 12%. Closure rate (mean follow-up of 15 months) was 87% with a mean interval of 125 days. Reversal surgery was not correlated with mortality but with major complications (11%) and reintervention risk, anastomotic leakage risk (3.8%) and a mean length of stay of 9 days. Conclusion: Construction of loop ileostomies in left-sided colonic or rectal resection is associated with a low risk for anastomotic leakage at the expense of substantial stoma-related morbidity and morbidity related to reversal surgery. More accurate identification of colorectal cancer patients benefitting from protective loop ileostomy seems to be warranted.
Oxaliplatin-Induced Leukocytoclastic Vasculitis under Adjuvant Chemotherapy for Colorectal Cancer: Two Cases of a Rare Adverse Event
Authors: Quack Henriette , Erpenbeck Luise , Wolff Hendrik A. , Sprenger Thilo , Seitz Cornelia S. , Schön Michael P. , Neumann Steffen , Stanek Kathrin , Ghadimi B. Michael , Michels Beate , Middel Peter , Schaefer Inga-Marie , Liersch Torsten , Conradi Lena-Christin
Published: April 2017

Leukocytoclastic vasculitis is a multicausal systemic inflammatory disease of the small vessels, histologically characterized by inflammation and deposition of both nuclear debris and fibrin in dermal postcapillary venules. The clinical picture typically involves palpable purpura of the lower legs and may be associated with general symptoms such as fatigue, arthralgia and fever. Involvement of the internal organs, most notably the kidneys, the central nervous system or the eyes, is possible and determines the prognosis. Oxaliplatin-induced leukocytoclastic vasculitis is a very rare event that limits treatment options in affected patients. We report 2 patients who developed the condition under chemotherapy for advanced rectal and metastatic colon carcinoma, respectively; a termination of the therapy was therefore necessary. While current therapies for colorectal cancer include the combination of multimodal treatment with new and targeted agents, rare and unusual side effects elicited by established agents also need to be taken into account for the clinical management.
Radiation Therapy for Chemotherapy-Resistant Recurrent Epithelial Ovarian Cancer
Authors: Machida Shizuo , Takei Yuji , Yoshida Chikako , Takahashi Yoshifumi , Koyanagi Takahiro , Sato Naoto , Taneichi Akiyo , Saga Yasushi , Fujiwara Hiroyuki , Suzuki Mitsuaki
Published: April 2017

Objectives: While radiation therapy is administered as a palliative treatment for recurrent ovarian cancer, it remains unclear whether it improves the prognosis. Methods: The effects and adverse events of radiation therapy for patients with recurrent epithelial ovarian cancer were investigated using medical records. Results: Herein, 46 subjects comprising 33 patients whose recurrent lesions were contained within the irradiation field (therapeutic radiation group; TRG) and 13 patients with some recurrent lesions outside the irradiation field (palliative radiation group; PRG) were included. The TRG achieved a response rate (RR) of 66%, a disease control rate (DCR) of 100%, a progression-free survival (PFS) of 10 months, and an overall survival (OS) of 20 months. The PFS after radiation therapy was significantly longer than that following chemotherapy received just before radiation therapy. The PFS of patients with recurrent intrapelvic lesions was longer than that of patients with some extrapelvic recurrence. There was no significant association between PFS after radiation therapy and the duration from the previous chemotherapy or histological type. The RR, DCR, PFS, and OS of the PRG were 30 and 90% and 2 and 6 months, respectively. Serious adverse events were rare. Conclusions: Radiation therapy is a potential option for chemotherapy-resistant, localized recurrent ovarian cancer.
A Pilot Study Exploring the Mechanisms Involved in the Longitudinal Propagation of Acute Aortic Dissection through Computational Fluid Dynamic Analysis
Authors: Zhang Yongxue , Lu Qingsheng , Feng Jiaxuan , Yu Peng , Zhang Suming , Teng Zhongzhao , Gillard Jonathan H. , Song Runze , Jing Zaiping
Published: April 2017

Objective: This study sought to elucidate the underlying hemodynamic mechanisms involved in the longitudinal propagation of acute, type-B aortic dissections. Methods: Three-dimensional patient-specific aortic geometry was reconstructed from computed tomography images of 3 cases, followed by computational fluid dynamic analysis using finite-element analysis modeling. Three models were reconstructed; the normal-aortic model (from a healthy volunteer), the visceral-involvement model (from a patient whose visceral arteries were involved) and the progression model (from a patient whose visceral arteries were intact at admission). Wall pressure distribution was analyzed in all three models. Results: In the systolic phase of a cardiac cycle, the wall pressure dropped from the proximal to the distal aorta within the true lumen. This pressure gradient was observed in all three models. A milder pressure gradient was seen in the false lumen in the visceral-involvement model, whereas the pressure in the false lumen remained almost constant in the progression model. The dyssynchrony of the pressure gradients in the true and false lumens caused an imbalance in pressure between the two lumens. Conclusion: The interluminal pressure differential may be a contributing factor in the compression of the true lumen and the cleavage force of the aortic wall, leading to the longitudinal propagation of the dissection.
Continuous ECG Monitoring for Tracking Down Atrial Fibrillation after Stroke: Holter or Automated Analysis Strategy?
Authors: Suissa Laurent , Lachaud Sylvain , Mahagne Marie-Hélène
Published: April 2017

Background: Tracking down atrial fibrillation (AF) in the stroke unit is a relevant challenge for the prevention of recurrent AF-related stroke. The optimal terms of use of continuous ECG monitoring (CEM) are unknown. We compared 24-hour routine Holter ECG with two different CEM analysis strategies for AF detection. Methods: We prospectively enrolled consecutive ischemic stroke patients. All AF-naïve patients received CEM during hospitalization. Two methods for reading CEM data were compared: manual analysis using the Holter function (hCEM) and semiautomated analysis using software (aCEM). The McNemar test was used to compare AF detection rates. Results: Of the 362 patients included, 58 (16.0%) were non-AF-naïve patients and 304 were AF-naïve patients. AF-Naïve patients underwent CEM with a median duration of 5.3 days (3.4-9.7). We detected 22 new AF cases (7.2%) with first-24-hour hCEM, 31 (10.2%) with aCEM, and 42 (13.8%) with hCEM. hCEM and aCEM both significantly increased the AF detection rate compared to first-24-hour hCEM. hCEM detected more new AF cases than aCEM (+3.6%, p = 0.003). Conclusions: In stroke patients, early and prolonged aCEM and hCEM both increase the AF detection rate compared to first-24-hour hCEM. hCEM gives the best AF detection rate. We suggest that in aCEM, detection based only on the ventricular rhythm analysis explains its lower specificity and sensitivity.
Association of Antenatal Corticosteroids and the Mode of Delivery with the Mortality and Morbidity of Infants Weighing Less than 1,500 g at Birth in Japan
Authors: Sasaki Yoshihito , Ikeda Tomoaki , Nishimura Kunihiro , Katsuragi Shinji , Sengoku Kazuo , Kusuda Satoshi , Fujimura Masanori
Published: April 2017

Objective: This study aimed to re-evaluate the effectiveness of antenatal corticosteroids (ACS) and to analyze the association between ACS and the mode of delivery in the context of perinatal morbidity and mortality in very-low-birth-weight (VLBW) infants. Study Design: This retrospective cohort study involved 15,765 VLBW infants born between 2003 and 2008 at less than 34 weeks of gestation and weighing less than 1,500 g at birth. Data were obtained from the Japanese neonatal research network database. Univariate and multivariate logistic regression analyses were performed to evaluate the impact of ACS and mode of delivery on the risk of infant mortality and morbidity. Results: Administration of ACS was associated with decreases in mortality rate, intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP), and was not associated with the incidence of respiratory distress syndrome (RDS), periventricular leukomalacia or necrotizing enterocolitis (NEC). When the administration of ACS was analyzed in the context of different modes of delivery, the incidence of IVH and ROP tended to decrease with cesarean section deliveries, whereas the incidence of RDS tended to decrease and the incidence of NEC tended to increase for infants delivered vaginally. The incidence of chronic lung disease tended to increase in association with both delivery methods. Conclusions: This large cohort study reconfirms that ACS treatment is associated with decreases in infant mortality and severe morbidity. Furthermore, the delivery method may be associated with severe morbidity in VLBW infants exposed to ACS.
Distribution Analyses of Acquired Melanocytic Naevi on the Trunk
Authors: Blake Tristan , McClenahan Phil , Duffy David , Schaider Helmut , McEniery Elizabeth , Soyer H. Peter
Published: April 2017

Acquired melanocytic naevi (AMN) are a well-known risk factor for the development of melanoma. Whereas previous studies have reviewed AMN distributions on individual body sites, the clinical distribution of AMN on the adult trunk has not been thoroughly investigated. We studied 40 participants with 1,282 naevi >5 mm, of which 781 were located on the trunk. Remarkably, 70% of these truncal naevi were located on the back and we produced a continuous mathematical description of decreasing naevus frequency moving dorsolaterally from the back midline. Furthermore we found that for both sexes the mean naevus size was larger on the front as well as on the lower trunk. This distinct pattern, whilst probably being unwritten knowledge (in the dermatology domain), has not been discussed before.
Sildenafil Stimulates and Dexamethasone Inhibits Pulmonary Vascular Development in Congenital Diaphragmatic Hernia Rat Lungs
Authors: Kattan Javier , Céspedes Carlos , González Alvaro , Vio Carlos P.
Published: April 2017

Background: A predictor of neonatal mortality in infants with congenital diaphragmatic hernia (CDH) is disrupted pulmonary vascular development, clinically expressed as pulmonary hypertension. Objective: To determine if prenatal corticosteroids and phosphodiesterase-5 (PDE-5) inhibitors have a beneficial effect on pulmonary vascular development in CDH lungs. Methods: We induced CDH in fetal rats by giving nitrofen. We then exposed them to dexamethasone or to sildenafil. We separated them into three groups: (1) DEX, 4 pregnant rats received dexamethasone at days E16, E18 and E20; (2) SILD, 4 pregnant rats received sildenafil and L-arginine between E14 and E22, and (3) placebo. We then analyzed the lung of each fetus with CDH at E22. We examined the number of arterioles and arteries, and their percent of medial wall thickness (%MWT). Results: We obtained 30 CDH-positive fetuses. We analyzed 3,560 arterioles and 211 arteries. SILD showed a significant increase in the number of arterioles, but no significant increase in the number of arteries. No change was noted in the arteriolar %MWT. In contrast, DEX showed significant decreases in the number of arterioles and arteries and a significant increase in %MWT. Conclusions: PDE-5 inhibitors may improve pulmonary arteriolar development in fetuses with CDH. In contrast, prenatal corticosteroids could have deleterious effects on arteriolar and arterial development in CDH lungs.
Dermal Xenobiotic Metabolism: A Comparison between Native Human Skin, Four in vitro Skin Test Systems and a Liver System
Authors: Wiegand Christian , Hewitt Nicola J. , Merk Hans F. , Reisinger Kerstin
Published: April 2017

The xenobiotic metabolism of 4 in vitro human skin test systems (2D and 3D) was compared with that of the native human skin samples from which the skin test systems had been produced. In total 3 skin samples were investigated, each from a different donor to exclude variability due to gender, donor or tissue supplier. In addition, the skin cultures were compared with a surrogate of the liver. Basal and induced phase I and phase II enzymes were analyzed regarding gene/protein expression as well as enzyme activity. The distinctions between the different test systems and the two dermal compartments (epidermis and dermis) were more noticeable than any donor variability. The 3D models of skin and liver mirrored the in vivo situation more realistically than did the monolayer cultures. Phase I metabolism was more pronounced in the hepatic model, whereas phase II metabolism was more prominent in the reconstructed skin. These results show that reconstructed skin models are a valuable tool for organ-specific safety assessment with regard to xenobiotic metabolism.
Spinal Accessory Neuropathy following Dual Tunneling of Lead Extensions for Motor Cortex Stimulation
Authors: Lipinski Lindsay J. , Van Gompel Jamie , Smith Jay , Spinner Robert J.
Published: April 2017

Background: Spinal accessory nerve (SAN) injury is a known complication of surgery involving the posterior cervical triangle. Because the nerve lies in a plane that is traversed by extension leads for neuromodulation, the SAN is at risk during tunneling for these procedures. Methods: We report a 50-year-old man who developed spinal accessory neuropathy after tunneling of two sets of extension leads through his neck to connect to the pulse generator at the chest wall. Immediately postoperatively, he developed severe right shoulder pain and trapezius weakness manifested as decreased shoulder abduction and scapular winging. Results: Electromyography 2 months later confirmed a SAN injury. Ultrasonography demonstrated the SAN to be angulated between the two sets of extension leads in the posterior cervical triangle. Operative exploration confirmed this finding. Neurolysis was performed and the deep extension lead was relocated superficial to the nerve. Postoperatively, the patient had immediate resolution of his shoulder pain and an improved range of motion. Conclusion: As the indications for neuromodulation continue to grow, tunneling may be performed more frequently. It is our belief that the second pass through the neck of a dual extension lead system may inadvertently be directed deeply and poses an increased risk to the SAN.
B-Cell Malignant Lymphoma Presenting as Otitis Media and Mastoiditis Associated with Sinus Thrombosis
Authors: Saito Atsushi , Jia Wenting , Sasaki Tatsuya , Mizukami Hiroki , Sasaki Akira , Shinkawa Hideichi , Nishijima Michiharu
Published: April 2017

Cerebral venous thrombosis as a manifestation of paraneoplastic angitis and otitis media, revealing non-Hodgkin B-cell lymphoma (NHBL), is extremely rare. A 57-year-old woman presented with headache, auditory disturbance and recalcitrant otitis media. Magnetic resonance imaging showed brain edema in the temporal lobe and transverse sinus thrombosis. External drainage under antibiotic treatment was repeated based on a diagnosis of invasive otitis media and mastoiditis associated with infectious sinus thrombosis, but the condition deteriorated progressively. Open surgery for otitis media was performed 6 years after the initial symptoms and after a tumorous lesion had been detected in the middle ear. Pathological findings revealed NHBL. We report a rare case of NHBL presenting as otitis media and mastoiditis associated with sinus thrombosis, and a literature review.
A Randomized Phase II Trial of Gemcitabine plus Carboplatin: Biweekly versus Standard Schedules in Patients with Advanced Non-Small Cell Lung Cancer
Authors: Hasegawa Yukihiro , Miura Dai , Kitamura Chiho , Suzuki Takaya , Kobayashi Kazuma , Sato Nobuyuki
Published: April 2017

Objective: Gemcitabine combined with carboplatin (GC) is a widely used regimen for advanced non-small cell lung cancer (NSCLC), but clinical outcome is still hampered by its toxicity. We conducted a randomized phase II study of GC and compared biweekly versus standard schedules in patients with advanced NSCLC with respect to toxicity and outcome. Methods: Forty patients with stage IIIB or IV NSCLC were randomized to receive either a biweekly regimen of GC [gemcitabine (1,000 mg/m2 on days 1 and 14) and carboplatin (area under the concentration-time curve, AUC = 3 on days 1 and 14)] every 28 days or a standard regimen of GC [gemcitabine (1,000 mg/m2 on days 1 and 8) and carboplatin (AUC = 5 on day 1)] every 21 days. These cycles were repeated until disease progression. Results: Response rates were 55% for the biweekly regimen and 40% for the standard regimen. Median overall and progression-free survival times were 19.7 and 6.2 months, respectively, for the biweekly regimen, and 11.8 and 2.8 months, respectively, for the standard GC regimen. Hematologic toxicity was prominent. However, the incidence of grade 1 or 2 thrombocytopenia was significantly lower in the biweekly than in the standard GC regimen (p < 0.05). Nonhematologic toxicity was mild. Conclusion: A biweekly GC regimen was better tolerated than a standard GC regimen in patients with advanced NSCLC.
The Immune Microenvironment: A Major Player in Human Cancers
Authors: Fridman W.H. , Remark R. , Goc J. , Giraldo N.A. , Becht E. , Hammond Scott A. , Damotte D. , Dieu-Nosjean M.-C. , Sautès-Fridman Catherine
Published: April 2017

Cancer is a major public health issue and figures among the leading causes of death in the world. Cancer development is a long process, involving the mutation, amplification or deletion of genes and chromosomal rearrangements. The transformed cells change morphologically, enlarge, become invasive and finally detach from the primary tumor to metastasize in other organs through the blood and/or lymph. During this process, the tumor cells interact with their microenvironment, which is complex and composed of stromal and immune cells that penetrate the tumor site via blood vessels and lymphoid capillaries. All subsets of immune cells can be found in tumors, but their respective density, functionality and organization vary from one type of tumor to another. Whereas inflammatory cells play a protumoral role, there is a large body of evidence of effector memory T cells controlling tumor invasion and metastasis. Thus, high densities of memory Th1/CD8 cytotoxic T cells in the primary tumors correlate with good prognosis in most tumor types. Tertiary lymphoid structures, which contain mature dendritic cells (DC) in a T cell zone, proliferating B cells and follicular DC, are found in the tumor stroma and they correlate with intratumoral Th1/CD8 T cell and B cell infiltration. Eventually, tumors undergo genetic and epigenetic modifications that allow them to escape being controlled by the immune system. This comprehensive review describes the immune contexture of human primary and metastatic tumors, how it impacts on patient outcomes and how it could be used as a predictive biomarker and guide immunotherapies.
Clinical Effects of Oseltamivir, Zanamivir, Laninamivir and Peramivir on Seasonal Influenza Infection in Outpatients in Japan during the Winter of 2012-2013
Authors: Takemoto Yuji , Asai Teizaburo , Ikezoe Itsuo , Yano Takako , Ichikawa Masahiro , Miyagawa Shogo , Matsumoto Jun
Published: April 2017

Background: The neuraminidase inhibitors (NAIs) oseltamivir, zanamivir, laninamivir and peramivir are available in Japan. However, the selective use of NAIs for treating outpatients with influenza has not been clearly defined. Methods: We assigned 191 patients with influenza to 4 groups, each treated with a different NAI, and then compared how long it took to alleviate fever and other symptoms and to eliminate the virus. Results: Alleviation of fever occurred significantly sooner with peramivir than with either zanamivir (p = 0.0002) or oseltamivir (p = 0.0059), but was not significantly different from that with laninamivir (p = 0.0457; p < 0.0083). Other symptoms were also alleviated sooner by peramivir than by the other 3 NAIs. Conclusions: The ability of each NAI to alleviate influenza symptoms and fever varied. The appropriate use of NAIs requires further study.
Aberrant Methylation of the VIM Promoter in Uterine Cervical Squamous Cell Carcinoma
Authors: Lee Min-Kyung , Jeong Eun-Mi , Kim Jae Hyung , Rho Seung Bae , Lee Eun-Ju
Published: April 2017

Objectives: To identify prognosis-associated methylation markers of uterine cervical squamous cell carcinoma (SCC) and to verify potential clinical correlations. Methods: A genome-wide methylation array was performed using tissue samples of stage Ib1 (n = 9) and IIa (n = 5) tumors. Methylation levels were quantitatively evaluated by pyrosequencing for 54 tissue samples from SCC patients and 22 samples from normal controls. Clinicopathologic findings were obtained from medical records. Correlation or t test statistics were used to analyze the relationships between methylation levels and clinical features. Survival data were estimated using the Kaplan-Meier method and compared to the log-rank test. Results: The methylation array identified 32 genes with distinct differences (p < 0.01) between stage Ib1 and IIa disease, and VIM was selected for further evaluation. Pyrosequencing analysis revealed that 40.7% of carcinoma samples had a higher methylation level in the VIM gene compared to the normal controls. VIM methylation status, low FIGO stage, and lack of parametrial involvement were significantly associated with longer disease-free survival (p = 0.036, p = 0.028, and p = 0.001, respectively). Conclusions: We profiled 32 genes that might be associated with prognosis in cervical cancer. We further revealed that the VIM gene is frequently methylated in cervical SCC and that its methylation might predict a favorable prognosis.
Assessment of Impact of Training in Improving Knowledge of Blood Transfusion among Clinicians
Authors: Kaur Paramjit , Kaur Gagandeep , Kaur Ravneet , Sood Tanvi
Published: April 2017

Background: Blood is a precious resource that needs to be prescribed, handled, stored and transfused as per guidelines to ensure recipient safety. The present study aims to assess the basic knowledge of clinicians pertaining to safe transfusion practice, impart relevant training, and assess the impact of such training programs. Methods: A total of 25 fresh bachelor of medicine and bachelor of surgery graduates were enrolled for the study. The participants were given a pre-assessment questionnaire related to the entire transfusion chain followed by interactive training of the participants and post-training re-assessment. Results: The mean score in the pre-training assessment was 51% while in the post-training assessment the mean score was 85.4%; the difference was statistically significant. There were significant differences in knowledge pertaining to storage temperature, shelf life of red cells and platelets, alternate group choice for fresh frozen plasma, and documentation of transfusion reaction. The participants had inadequate knowledge pertaining to cross-match procedure and management of transfusion reactions. Conclusion: The study assessed the knowledge and awareness of clinicians regarding blood transfusion practice. Mandatory training and inclusion of transfusion medicine as a subject at undergraduate level can help in improving transfusion practice and ensuring recipient safety.
Serum Protein S100β is a Diagnostic Biomarker for Distinguishing Posterior Circulation Stroke from Vertigo of Nonvascular Causes
Authors: Purrucker Jan C. , Herrmann Oliver , Lutsch Julia K. , Zorn Markus , Schwaninger Markus , Bruckner Tom , Auffarth Gerd U. , Veltkamp Roland
Published: April 2017

Background: In patients presenting with acute vertigo or dizziness, identifying the posterior fossa stroke as the underlying cause can be a major challenge. We therefore evaluated the serum biomarkers for the differential diagnosis of nonvascular vertigo and posterior circulation stroke. Methods: Of a total of 80 patients, 31 patients had an ischemic stroke in the posterior circulation and 12 infratentorial hemorrhage. Findings in these patients were compared with those in 22 patients with vertigo of nonvascular origin and 15 matched control patients without neurological symptoms. Blood samples drawn <24 h after symptom onset were analyzed for S100 calcium-binding protein B (S100β), matrix metalloproteinase 9 (MMP-9), soluble vascular cellular adhesion molecule-1 (sVCAM-1), and glial fibrillary acidic protein (GFAP). Results/Conclusion: Serum levels of S100β were significantly higher in stroke patients than in nonvascular vertigo patients. Serum concentrations of MMP-9 tended to be higher in stroke patients, whereas no significant differences among groups were found for sVCAM-1 and GFAP. Receiver-operating characteristic analysis revealed a sensitivity of 94.4% and a specificity of 31.8% for detecting stroke in patients presenting with vertigo for S100β. S100β may serve as a biomarker for distinguishing between vertigo of vascular causes and nonvascular, acute vertigo.
Serum hs-CRP Levels are Increased in de Novo Parkinson's Disease Independently from Age of Onset
Authors: Song In-Uk , Cho Hyun-Ji , Kim Jung-Seok , Park In-Seok , Lee Kwang-Soo
Published: April 2017

Background: Microglia in the brain are the counterpart of macrophages and it functions as a first defense in the brain. The double-edged feature of microglia has explained that the inflammatory state of microglia in aged brains induces them to over-respond to small stimuli that are otherwise well controlled in young brains. The clinical effect of microglia in patients with Parkinson's disease (PD) is poorly defined. This prospective study assessed the peripheral concentrations of hs-CRP, a protein able to reflect neuroinflammation in the CNS, in de novo PD patients with varying ages of onset. Methods: We examined 435 patients with de novo PD and 221 healthy subjects and the differences in hs-CRP between these groups were investigated. The PD group was classified into 4 subgroups according to the age of de novo PD to investigate the relationship between hs-CRP and the aging process in de novo PD. Results: There were significantly higher serum hs-CRP levels in patients with PD compared with healthy subjects. A post-hoc analysis of the 4 PD subgroups showed no significant differences in serum hs-CRP level. Conclusion: We assumed that neuroinflammatory reactions play a role in the pathogenesis of PD, but found no clinical evidence of a neuroprotective effect against PD in young brains. To clarify the role of microglia and aging in the pathogenesis of PD, future longitudinal studies involving a large cohort are required.
Paeonol Attenuates Advanced Oxidation Protein Product-Induced Oxidative Stress Injury in THP-1 Macrophages
Authors: Ping Mao , Xiao Wei , Mo Liqian , Xiao Xiaoyan , Song Shaolian , Tang Waijiao , Yang Xixiao
Published: April 2017

Background: Paeonol (2'-hydroxy-4'-methoxyacetophenone) is thought to possess a broad range of clinically curative effects that are likely mediated by its anti-inflammatory and antioxidant activities. Aims: To elucidate the efficacy of paeonol's anti-inflammatory and antioxidant activities and the underlying mechanism of paeonol in advanced oxidation protein product (AOPP) stimulation of THP-1 macrophages. Materials and Methods: After incubating cells with AOPP plus paeonol, nitric oxide (NO) production and the levels of inducible NO synthase (iNOS), receptor for advanced glycation end products (RAGE), CD36, scavenger receptor (SR)-A, and SR-B1 were calculated. Moreover, THP-1 macrophages were preincubated with paeonol, the free radical scavenger N-acetylcysteine (NAC), NADPH oxidase inhibitors [apocynin, diphenylene iodonium (DPI)], and the specific inhibitor of nuclear factor-κB pyrrolidine dithiocarbamate (PDTC) prior to incubation with AOPP, and the levels of intracellular reactive oxygen species (ROS) production and tumor necrosis factor-a (TNF-a), interleukin (IL)-1ß, IL-6, and monocyte chemotactic protein 1 (MCP-1) were determined. Results: Paeonol increased NO production and the mRNA level of iNOS, whereas it decreased ROS production. ROS production was also effectively attenuated by apocynin, DPI, NAC, and PDTC. Furthermore, these inhibitors and paeonol could downregulate the mRNA and protein levels of proinflammatory cytokines (TNF-a, IL-1ß, IL-6, and MCP-1). Paeonol significantly reduced the expression levels of RAGE and CD36 but increased the expression levels of SR-A and SR-B1. Conclusions: These results indicate that paeonol can decrease proinflammatory cytokines in THP-1 macrophages, likely through RAGE-, CD36-, SR-A-, and SR-B1-mediated signals involving NADPH oxidase-dependent ROS generation. This suggests that paeonol can be used as a therapeutic agent for diseases contributing to oxidative stress injury.
Preventive Effect of Baicalein on Methamphetamine-Induced Amnesia in the Passive Avoidance Test in Mice
Authors: Wong Yi-Kuei , Chou Ming-Kuan , Shen Yuh-Chiang , Wang Yea-Hwey , Yen Jiin-Cherng , Chen Chieh-Fu , Lin Shi-Kwang , Liao Jyh-Fei
Published: April 2017

Background/Aims: Methamphetamine abuse may produce cognitive impairment. Baicalein, a bioactive flavonoid, has antioxidative, anti-inflammatory and neuroprotective effects. This study examined the effects of baicalein pretreatment on memory performance in the passive avoidance test after either one dose or an acute binge of methamphetamine in Institute of Cancer Research (ICR) mice. Methods: Methamphetamine was administered by intraperitoneal (i.p.) injection of either one dose (3 mg/kg) or an acute binge (3 mg/kg, 4 i.p. injections at 2-hour intervals). The effects of baicalein pretreatment (1 mg/kg, i.p.) on methamphetamine-induced changes of locomotor activity and memory performance were compared with those of eticlopride, a selective dopamine D2 receptor antagonist. The effects of baicalein on acute binge methamphetamine-induced oxidative stress (malondialdehyde- and nitrotyrosine-modified protein production) in the mouse hippocampus were also examined. Results: One-dose methamphetamine treatment (i.p., 30 min before or immediately after the training trial) induced hyperlocomotion and amnesia in mice, which were blocked by eticlopride but not by baicalein pretreatment. The memory performance in mice was impaired 5 days after acute binge methamphetamine, which was significantly attenuated by baicalein but not by eticlopride pretreatment. Baicalein pretreatment also attenuated acute binge methamphetamine-induced oxidative stress in the mouse hippocampus. Conclusions: Baicalein exhibits antioxidative and neuroprotective effects in attenuating acute binge methamphetamine-induced memory deficits and oxidative hippocampal damage.
Analgesic Effects of Morphine in Combination with Adjuvant Drugs in Rats
Authors: Leppert Wojciech , Okulicz-Kozaryn Irena , Kaminska Ewa , Szulc Michal , Mikolajczak Przemyslaw
Published: April 2017

Background: Morphine is co-administered with adjuvant drugs to treat pain, nausea, vomiting, dyspnoea and delirium in cancer patients. Aim of the Study: To investigate analgesic effects of morphine when co-administered with adjuvant drugs. Material and Methods: Two-month-old male Wistar rats received single morphine doses alone (0.45 and 0.9 mg/kg) or with midazolam (0.3 mg/kg), haloperidol (0.15 and 0.45 mg/kg), levomepromazine (0.35 mg/kg), metoclopramide (1.0 mg/kg), and hyoscine butylbromide (1.7 mg/kg) as single subcutaneous injections. Analgesia was measured by the tail-flick test after 15, 30, 45, 60, and 90 min of drug administration. In the case of significant analgesia enhancement, analgesic and sedative effects were explored in 3-, 5-, 6-, 8-, and 11-month-old rats. Results: Significant morphine (0.9 mg/kg) analgesia enhancement was observed 60 min after haloperidol (0.15 and 0.45 mg/kg) and hyoscine butylbromide co-administration. The addition of haloperidol to morphine significantly increased analgesia in 6-, 8- and 11-month-old rats while in the case of hyoscine butylbromide co-administration this effect was observed only in 11-month-old rats. Conclusions: Haloperidol and hyoscine butylbromide enhanced morphine analgesia. Future studies may explore the repeated administration of these drug combinations in rats and humans. i 2014 S. Karger AG, Basel
Short-Term Preseasonal Immunotherapy: Is Early Clinical Efficacy Related to the Basophil Response?
Authors: Kepil Özdemir Seçil , Sin Betül Ayşe , Güloğlu Deniz , İkincioğulları Aydan , Gençtürk Zeynep , Mısırlıgil Zeynep
Published: April 2017

Background: An aluminum hydroxide-adsorbed depot allergoid preparation of six-grass pollen allergens has been developed for short-term preseasonal immunotherapy in pollinosis. However, only limited knowledge exists about its immunological and clinical effects. The aim of this study was to evaluate the basophil response, which can explain early clinical findings of short-term preseasonal allergoid immunotherapy in allergic rhinitis. Methods: In a double-blind, placebo-controlled study, 31 patients allergic to grass pollens received one course of short-term preseasonal allergoid immunotherapy or placebo. Immunogenicity was assessed by the levels of specific IgG4, IgE antibodies and an allergen-induced CD203c basophil activation test. The primary clinical end point was the combined symptom and medication score/average combined score (ACS). Results: There was a 52.9% difference in ACS between the treatment and placebo groups in favor of immunotherapy (p = 0.01). Active treatment induced Phleum pratense-specific IgG4 and IgE antibodies (p < 0.05). A decrease in allergen-induced basophil activation at submaximal allergen concentrations was demonstrated at the end of immunotherapy and at the peak of the grass pollen season after immunotherapy. Conclusions: This study shows that grass pollen-allergic patients treated with one course of short-term preseasonal allergoid immunotherapy exhibit a decrease in allergen-induced basophil activation, an increase in allergen-specific IgG4 antibodies and early clinical improvement.
Antioxidant Treatment Prevents Serum Deprivation- and TNF-α-Induced Endothelial Dysfunction through the Inhibition of NADPH Oxidase 4 and the Restoration of β-Oxidation
Authors: Scioli Maria Giovanna , Bielli Alessandra , Agostinelli Sara , Tarquini Chiara , Arcuri Gaetano , Ferlosio Amedeo , Costanza Gaetana , Doldo Elena , Orlandi Augusto
Published: April 2017

Aims: Oxidative stress plays a pivotal role in the impaired endothelial function occurring in vascular diseases. Antioxidant strategies induce a clinical advantage in patients with endothelial dysfunction and atherosclerosis and protect from oxidative damage, but the underlying molecular mechanisms have been poorly evaluated. The aim of this study was to analyze the effects and mechanisms of action of antioxidant regimens on endothelial function. Methods and Results: Antioxidant efficacy of N-acetylcysteine, ascorbic acid and propionyl-L-carnitine was evaluated in serum-deprived and TNF-α-stimulated human umbilical vein endothelial cells in vitro. Cell adhesion molecule (CAM) expression was evaluated by blot and real-time PCR, and inflammatory cytokine secretion was evaluated by ELISA; leukocyte adhesion and reactive oxygen species assays and NADPH oxidase 4 isoform (Nox4) expression analyses by blots were also performed. Antioxidant pretreatment restored serum-deprived and TNF-α-induced impaired mitochondrial β-oxidation by reducing flavin adenine dinucleotide level and counteracting increased CAM and Nox4 expression, leukocyte adhesion and inflammatory cytokine secretion. Specific inhibition by plumbagin and siNox4 prevented TNF-α- and serum deprivation-induced detrimental effects, confirming that endothelial oxidative stress and inflammation were Nox4 dependent. Conclusions: Our findings documented Nox4 as a main actor in oxidative stress-induced endothelial dysfunction and further clarify the molecular basis of antioxidant treatment efficacy. © 2014 S. Karger AG, Basel
Neighbourhood Deprivation, Individual-Level Familial and Socio-Demographic Factors and Diagnosed Childhood Obesity: A Nationwide Multilevel Study from Sweden
Authors: Li Xinjun , Memarian Ensieh , Sundquist Jan , Zöller Bengt , Sundquist Kristina
Published: April 2017

Objectives: To examine whether there is an association between neighbourhood deprivation and diagnosed childhood obesity, after accounting for family- and individual-level socio-demographic characteristics. Methods: An open cohort of all children aged 0-14 years was followed between January 1, 2000 and December 31, 2010. Childhood residential locations were geocoded and classified according to neighbourhood deprivation. Data were analysed by multilevel logistic regression, with family- and individual-level characteristics at the first level and level of neighbourhood deprivation at the second level. Results: During the study period, among a total of 948,062 children, 10,799 were diagnosed with childhood obesity. Age-adjusted cumulative incidence for diagnosed childhood obesity increased with increasing level of neighbourhood deprivation. Incidence of diagnosed childhood obesity increased with increasing neighbourhood-level deprivation across all family and individual-level socio-demographic categories. The odds ratio (OR) for diagnosed childhood obesity for those living in high-deprivation neighbourhoods versus those living in low-deprivation neighbourhoods was 2.44 (95% confidence interval (CI) = 2.22-2.68). High neighbourhood deprivation remained significantly associated with higher odds of diagnosed childhood obesity after adjustment for family- and individual-level socio-demographic characteristics (OR = 1.70, 95% CI = 1.55-1.89). Age, middle level family income, maternal marital status, low level education, living in large cities, advanced paternal and maternal age, family history of obesity, parental history of diabetes, chronic obstructive pulmonary disease, alcoholism and personal history of diabetes were all associated with higher odds of diagnosed childhood obesity. Conclusions: Our results suggest that neighbourhood characteristics affect the odds of diagnosed childhood obesity independently of family- and individual-level socio-demographic characteristics.
Persistent Aura with Small Occipital Cortical Infarction: Implications for Migraine Pathophysiology
Authors: Thissen Sam , Koehler Peter J.
Published: April 2017

Objective: The pathophysiology of migraine with aura is thought to be related to cortical spreading depression and cortical hypersensitivity, in which inhibitory interneurons may play a role. Persistent migraine aura (PMA) without infarction is defined as auras that last longer than 1 week in the absence of infarction. We describe a case of persistent aura with a small occipital cortical infarction and discuss implications of this case and PMA for pathophysiological concepts of migrainous auras. Methods: We present a case and discuss the implications for pathophysiological concepts. Results: The case presented cannot be diagnosed as PMA as the patient was found to have an occipital cortical infarction with hypoactivity on fluorodeoxyglucose-positron emission tomography. Nevertheless, the patient suffered from persistent aura (with infarction). We argue that the infarction may have been responsible for an increased imbalance in one of the primary visual cortex networks that was already hyperexcitable due to the migraine aura condition. Conclusion: PMA with occipital infarction has not been reported previously. We believe the findings of the present case and PMA cases reported in the past may support the intracortical disinhibition hypothesis in migraine.
Incidence of and Risk Factors for Alzheimer's Disease and Mild Cognitive Impairment in Korean Elderly
Authors: Bae Jong Bin , Kim You Joung , Han Ji Won , Kim Tae Hui , Park Joon Hyuk , Lee Seok Bum , Lee Jung Jae , Jeong Hyun Ghang , Kim Jeong Lan , Jhoo Jin Hyeong , Yoon Jong Chul , Kim Ki Woong
Published: April 2017

Background/Aims: Knowledge of incidence rates and risk factors is essential for the development of strategies to treat patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Methods: A subpopulation of the Nationwide Survey on Dementia Epidemiology (460 Korean subjects aged ≥65 years from 2 rural and 2 urban districts) was followed up for 3.5 years. The age-specific incidence was estimated and risk factors were identified. Results: The age-standardized incidence of AD and MCI was 7.9 and 28.1 cases per 1,000 person-years, respectively. MCI was associated with a 6-fold increased risk of AD. Depression was a risk factor for AD with MCI. Age, lack of formal education, illiteracy, rural residence, and marital status were associated with the risk of AD. Conclusion: Strategies to control modifiable risk factors should be implemented to decrease the incidence of AD. © 2014 S. Karger AG, Basel