bluuebunny/crossref_metadata_2025 huggingface dataset:
Targets and Candidate Agents for Type 2 Diabetes Treatment with Computational Bioinformatics Approach
Authors: Wang Qiong , Zhao Zhigang , Shang Jing , Xia Wei
Published: October 2014

We sought to explore the molecular mechanism of type 2 diabetes (T2D) and identify potential drug targets and candidate agents for T2D treatment. The differentially expressed genes (DEGs) were assessed between human pancreatic islets with T2D and normal islets. The dysfunctional pathways, the potential transcription factor, and microRNA targets were analyzed by bioinformatics methods. Moreover, a group of bioactive small molecules were identified based on the connectivity map database. The pathways of Eicosanoid Synthesis, TGF-beta signaling pathway, Prostaglandin Synthesis and Regulation, and Integrated Pancreatic Cancer Pathway were found to be significantly dysregulated in the progression of T2D. The genes ofZADH2(zinc binding alcohol dehydrogenase domain containing 2),BTBD3(BTB (POZ) domain containing 3), Cul3-based ligases,  LTBP1(latent-transforming growth factor beta binding protein 1),PDGFRA(alpha-type platelet-derived growth factor receptor), andFST(follistatin) were determined to be significant nodes regulated by potential transcription factors and microRNAs. Besides, two small molecules (sanguinarine and DL-thiorphan) were identified to be capable of reverse T2D. In the present study, a systematic understanding for the mechanism underlying T2D development was provided with biological informatics methods. The significant nodes and bioactive small molecules may be drug targets and candidate agents for T2D treatment.
Effect of Aerobic Exercise Training on MDA and TNF-αLevels in Patients with Type 2 Diabetes Mellitus
Authors: Arslan Mihriban , Ipekci Suleyman Hilmi , Kebapcilar Levent , Dogan Dede Nesrin , Kurban Sevil , Erbay Ekrem , Gonen Mustafa Sait
Published: October 2014

Objective.Diabetes mellitus (DM) is associated with low-grade inflammation. The benefits of regular exercise for the DM are well established, whereas less is known about the impact of aerobic exercise on malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) in the DM.Methods.We randomised 64 participants, who do not exercise regularly, without any diabetic chronic complications in parallel to 12 weeks of aerobic exercise (three times per week,n=31) and no exercise (control;n=33). Plasma levels of soluble TNF-αand MDA levels were measured before-after physical training programme and control group.Results.Sixty-four patients with type 2 diabetes mellitus were analysed. When comparing the two groups of patients with age, gender, hemoglobin A1c (HbA1c) levels, lipid profile, waist circumference, body mass index (BMI) and class of treatment for diabetes were not different between groups. While soluble TNF-αremained essentially unaffected by physical training, plasma concentrations of MDA markedly decreased(P<0.05); physical training also decreased body weight, waist circumference, and blood pressure(P<0.05).Conclusion.Exercise training favorably affected body weight, waist circumference, and blood pressure. A three-weekly, 12-week, aerobic-training programme, without a concomitant weight loss diet, was associated with significant decrease in MDA levels in type 2 diabetic individuals.
Enhanced Photocatalytic Activity of W‐Doped and W‐La‐Codoped TiO2 Nanomaterials under Simulated Sunlight
Authors: Hua Chenghe , Dong Xiaoli , Wang Xiuying , Xue Mang , Zhang Xiufang , Ma Hongchao
Published: October 2014

W‐doped TiO2 and W‐La‐codoped TiO2 nanomaterials were successfully synthesized via the sol‐gel method. The products were characterized by X‐ray diffraction, UV‐vis diffuse reflectance spectrophotometer, transmission electron microscopy, and X‐ray photoelectron spectroscopy. The presence of W and La results in significant red shift of absorption edge for TiO2‐based nanomaterials. The weight ratios of La and W in the composites play important roles in the absorption edge for TiO2‐based nanomaterials. The photocatalytic activities of both W‐doped TiO2 and W‐La‐codoped TiO2 photocatalysts for decolorization of methyl orange solution were evaluated under simulated sunlight irradiation. The results showed that both W‐doped and W‐La‐codoped can effectively improve the photocatalytic behaviors of TiO2 nanomaterials ascribed to the improved photoinduced charge carriers separation, enhanced light absorption, and large surface area. Furthermore, W‐La‐codoped TiO2 exhibited higher photocatalytic activity than W‐doped TiO2. Considering their high photocatalytic activity, the doped TiO2 nanomaterials could be applied in wastewater treatment and environmental purification.
The Elusive Role of the Left Temporal Pole (BA38) in Language: A Preliminary Meta-Analytic Connectivity Study
Authors: Ardila Alfredo , Bernal Byron , Rosselli Monica
Published: October 2014

It has been suggested that the left temporal pole (Brodmann area 38 (BA38)) participates in diverse language functions, including semantic processing, speech comprehension, and naming. Utilizing the activation likelihood estimation (ALE), a meta-analytic connectivity study was conducted to further our understanding on the role of BA38 in language. Departing from the BrainMap functional database, 11 papers corresponding to 12 paradigms including 201 participants were selected. Initially, P<0.01 was employed as the significance level, resulting in the presence of four different activation clusters. However, when the significance level was lowered to P<0.05, sixteen activation clusters appeared, including classical language areas such as Broca’s and Wernicke’s areas. It was concluded that (1) this meta-analytic connectivity study suggests the presence of two major connection circuits involving BA38; one is related to language, while the other may be involved in visuospatial and integrative audiovisual functions. Furthermore, (2) BA38 also contributes to various brain networks supporting linguistic processes related not only to language comprehension but also to language production.
The Influence of Aggregate Size and Binder Material on the Properties of Pervious Concrete
Authors: Fu Tun Chi , Yeih Weichung , Chang Jiang Jhy , Huang Ran
Published: October 2014

Specimens were prepared by altering parameters such as aggregate sizes, binder materials, and the amounts of binder used and were subsequently tested by using permeability, porosity, mechanical strength, and soundness tests. The results indicated that the water permeability coefficient and connected porosity decreased as the amount of binder used increased and increased with increasing aggregate size. In the mechanical strength test, the compressive, splitting tensile, and flexural strengths increased as the amount of binder used increased and decreased with the increase of aggregate size. Highly viscous binder enhanced compressive strength, water permeability, and the resistance to sulfate attacks. In the mechanics and sulfate soundness tests, the mix proportion of alkali-activated slag paste used in this study exhibited a superior performance than the Portland cement pervious concrete (the control) did, but the difference in water permeability between the two types of concrete was insignificant. The mix proportions of cement paste containing 20% and 30% silica fume exhibited less mechanical strength than the control did. Moreover, compared with the control, the cement paste containing silica fume demonstrated poor resistance to sulfate attacks, and the difference in the water permeability between such specimen and the control was not noticeable.
The Effect of Topical Application of Royal Jelly on Chemoradiotherapy-Induced Mucositis in Head and Neck Cancer: A Preliminary Study
Authors: Yamauchi Kohichi , Kogashiwa Yasunao , Moro Yorihisa , Kohno Naoyuki
Published: October 2014

Purpose. One of the common side effects experienced by head and neck cancer patients on chemoradiotherapy is mucositis. Severe mucositis may be controllable by limiting cancer therapy, but it has resulted in decreasing the completion rate of chemoradiotherapy. The efficacy of royal jelly (RJ) as prophylaxis against chemoradiotherapy-induced mucositis was evaluated through clinical scoring of oral and pharyngeal mucositis.Methods. In this randomized, single-blind (physician-blind), clinical trial, 13 patients with head and neck cancer requiring chemoradiation were randomly assigned to two groups. Seven patients assigned to the study group received RJ, and 6 patients were assigned to the control group. RJ group patients took RJ three times per day during treatment. The patients in both groups were evaluated twice a week for the development of mucositis using Common Terminology Criteria for Adverse Events version 3.0.Results. A significant reduction in mucositis was seen among RJ-treated patients compared with controls (P<0.001).Conclusion. This study demonstrated that prophylactic use of RJ was effective in reducing mucositis induced by chemoradiotherapy in head and neck cancer patients. However, further studies are needed because of the small sample size and the absence of double blinding.
Infantile Hemangioma-Like Vascular Lesion in a 26-Year-Old Woman after Abortion
Authors: Lu Yang , Wang Shu Jun , Li Xin , Hu Li , Zhang Wen Jie , Li Wei
Published: October 2014

A 26-year-old woman (G2P1A1) presented with a 5-week history of multiple red marks on her body after a therapeutic abortion. A physical examination found 15 palpable red marks on her head, neck, chest, arms and legs. Proliferating endothelial cells, which expressed CD31, CD34, von Willebrand factor, but not Glut-1 and merosin, were observed in the lesional area by histopathological analyses. Histocompatibility antigen typing of 2 lesions was identical to a sample from peripheral blood. Accelerated regression was observed in 2 lesions treated by intralesional injection of betamethasone, while spontaneous regression was observed within 9 months in the remaining lesions without any treatment. Rapid growth, spontaneous regression and histological analyses in this case support the diagnosis of ‘infantile hemangioma-like vascular lesion'.
Influence of Intravitreal Triamcinolone Acetonide Injection in Scleral Buckling Surgery for Macula-Off Retinal Detachment
Authors: Mirshahi Ahmad , Karkhaneh Reza , Zamani Amir Javad , Movassat Morteza , Azadi Pejvak
Published: October 2014

Purpose: To investigate the effect of intravitreal triamcinolone acetonide injection on the resolution of subretinal fluid (SRF), and its correlation with visual outcome after scleral buckle (SB) surgery. Methods: A prospective consecutive case series was conducted in patients who underwent SB surgery for macula-off rhegmatogenous retinal detachment (RRD) at Farabi Eye Hospital from February 1, 2012 to August 30, 2013. Exclusion criteria included previous ocular surgery (e.g. primary surgical failure) except cataract surgery, recurrent retinal detachment, macular hole, epiretinal membrane, proliferative vitreoretinopathy grade C, history of trauma, other retinal diseases, and diabetes mellitus. Patients were assigned to two groups. In group 1, patients received 2 mg of intravitreal triamcinolone acetonide injection at the end of surgery while patients in group 2 received intravitreal balanced saline solution for balancing the intraocular pressure (IOP). Patients were followed up at 1 day, 1 week, 1 month, 2 months and 3 months after the surgery by best-corrected visual acuity (BCVA), slitlamp examination, indirect ophthalmoscopy and optical coherence tomography (OCT). OCT (Heidelberg Engineering, Heidelberg, Germany) was used at all visits except day 1 after the surgery. Student's t test and χ2 tests were used for comparisons; p value ≤0.05 was considered significant. Results: Sixty-two eyes of 62 patients were enrolled in the study. There were 33 male patients (53%) and 29 female patients (47%). The average age was 43.8 years (18-72 years). The mean duration of symptoms was 34.7 ± 46.8 days. There were 29 eyes in group 1 and 33 eyes in group 2. Twelve weeks after the operation, 25 patients (40%) had SRF beneath the macula, but there was no significant difference (p = 0.24, χ2 test) between the two groups. Improvement in BCVA in both groups was statistically significant (p ≤ 0.001) but did not differ between the two groups (p = 0.09) apart from week 12, in which the improvement in group 1 was significantly higher (p = 0.03). The incidence of cystoid macular edema did not differ in a statistically significant way between the groups (p = 0.19). IOP in 4 (15%) patients in group 1 rose above 21 mm Hg but responded quickly to 2 weeks of topical antiglaucoma medication. There was no cataract progression in either group. There was no correlation between the incidence of persistent SRF and the extent of detachment in both groups (p = 0.83). There was no surgical failure or redetachment in either group during the study period. Conclusion: Single-dose intravitreal triamcinolone may increase the final BCVA in macula-off RRD patients despite persistent SRF, suggesting the anti-inflammatory role of this drug.
An Internet-Based Ecological Momentary Assessment Study Relying on Participants' Own Mobile Phones: Insights from a Study with Young Adult Smokers
Authors: Thrul Johannes , Bühler Anneke , Ferguson Stuart G.
Published: October 2014

Background: In this paper we describe a novel Internet-based cell phone-optimized assessment technique (ICAT) to conduct an ecological momentary assessment (EMA) study. Participants could access the assessment instrument via the web browsers of their mobile phones. Methods: We report results from 92 young adult smokers (18-25 years old) who completed the baseline assessment and the first of 4 waves (3 days/wave) of EMA. Random prompts were issued via text messages sent to the participants. The participants were also instructed to self-initiate reports of smoking situations. Results: Compliance with the study protocols was low. In total, the participants completed 885 assessments during the 3 days of monitoring. Only 50.2% of random prompts were responded to, and 52.4% of those were completed within the first 10 min after issuing. Furthermore, reports of smoking situations were rarely self-initiated. In a multivariate regression analysis, age (positively) and female gender (negatively) predicted the number of completed assessments. Conclusions: This study adds to the limited experiences made with ICAT in substance use research. Similar to the few prior ICAT studies, compliance was low compared to traditional EMA studies. While using ICAT is technically feasible, specific improvements should be implemented to tap ICAT's full potential in future studies.
Role of Inflammation in Diabetic Macular Edema
Authors: Noma Hidetaka , Mimura Tatsuya , Yasuda Kanako , Shimura Masahiko
Published: October 2014

Vitreous fluid levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor (sVEGFR)-2, soluble intercellular adhesion molecule (sICAM)-1, monocyte chemotactic protein (MCP)-1 and pentraxin 3 (PTX3) were measured by enzyme-linked immunosorbent assay in 36 patients with diabetic macular edema (DME) and 15 patients with macular hole (MH). Aqueous flare values were measured with a laser flare meter, and macular edema was examined by optical coherence tomography. Vitreous fluid levels of VEGF, sVEGFR-2, sICAM-1, MCP-1 and PTX3 were significantly higher in the patients with DME than in those with MH. There was a significant correlation between the vitreous fluid level of sVEGFR-2 and the levels of sICAM-1, MCP-1 and PTX3. The aqueous flare value was significantly correlated with the vitreous fluid levels of sVEGFR-2, sICAM-1, MCP-1 and PTX3. These findings suggest that inflammatory factors may induce an increase in vascular permeability and disrupt the blood-aqueous barrier in DME patients.
Second-Trimester Placental Volume and Vascular Indices in the Prediction of Small-for-Gestational-Age Neonates
Authors: Fang Shih-Wen , Ou Chia-Yu , Tsai Ching-Chang , Fu Hung-Chun , Cheng Hsin-Hsin , Cheng Bi-Hua , Chang Ming-Shan , Hsu Te-Yao
Published: October 2014

Objective: To evaluate the ability of second-trimester placental volume and vascular indices to predict small-for-gestational-age (SGA) birth weight pregnancies. Material and Methods: Women with singleton pregnancies were prospectively evaluated at 17-20 weeks of gestation. Second-trimester placental volume and vascular indices were obtained and calculated using volume organ computer-aided analysis and three-dimensional (3D) power Doppler ultrasound. Participants were followed until delivery and their medical records were reviewed, including maternal age, parity and pregestational body weight and body height, as well as the gestational age, birth weight and gender of the fetus. Results: Of the 163 women with complete follow-up, 20 gave birth to SGA and 143 to appropriate-for-gestational-age (AGA) neonates. The mean second-trimester placental volume was significantly lower in the SGA than in the AGA group (170.6 ± 49.8 vs. 213.5 ± 75.8 cm3, p = 0.015). None of the vascular indices, including the vascularization index, flow index and vascularization flow index, differed significantly between the two groups. We also found that the optimum cutoff for placental volume at a gestational age of 17-18 weeks was 189.7 cm3. Discussion: Second-trimester placental volume was positively correlated with neonatal birth weight. Second-trimester placental volume measured on 3D ultrasound may be predictive of SGA neonates.
Atherosclerotic Plaque Morphology Indicates Clinical Symptoms of Plaque Progression
Authors: Feng Tian , Yundai Chen , Ying Zhou , Jing Wang , Tao Zhang
Published: October 2014

Objective: This study aimed to evaluate the relationship between plaque morphology and the plaque progression (PP) that occurs despite routine medical therapy and better risk-factor control. Methods: A total of 183 patients who received baseline and follow-up coronary angiography were divided into 2 groups, the PP group (n = 78) and the non-PP group (n = 105). Optical coherence tomography (OCT) was performed after baseline coronary angiography. The plaque characteristics were noted and the fibrous cap thickness was measured at the thinnest point of each plaque. Macrophages in the fibrous cap were detected, and the macrophage content was measured based on the signal attenuation. Results: The level of high-sensitivity C-reactive protein was higher in the PP group (p = 0.001). The OCT examination showed that the proportion of lipid-rich plaques in the PP group was higher than that in the non-PP group (p < 0.001). Calcified plaques were detected frequently in the non-PP group (p < 0.001). Macrophages in the fibrous cap were detected frequently in the PP group (p < 0.001), and the macrophage content was significantly greater than that in the non-PP group (p < 0.001). Conclusion: Lipid-rich plaques with large numbers of macrophages were prone to PP, whereas the progression of calcified plaques was rare.
Diethylstilboestrol (1 mg) in the Management of Castration-Resistant Prostate Cancer
Authors: Turo Rafal , Tan Kenny , Thygesen Helene , Sundaram Subramanian K. , Chahal Rohit , Prescott Stephen , Cross William R.
Published: October 2014

Objective: To investigate the efficacy of diethylstilboestrol (DES) in patients with advanced prostate cancer refractory to androgen suppression. Methods: This retrospective study comprises 194 patients with prostate cancer treated with DES (1 mg daily) between 1976 and 2010. Study outcome parameters included demographic data, tumour characteristics, treatment history, prostate-specific antigen (PSA) responses, radiologic studies, adverse events and overall survival. Results: At initiation of oestrogen therapy the mean patient age was 69 years (range: 48-89) and the median PSA was 96 ng/ml (range: 1.9-9,500). The median duration of prior prostate cancer treatment was 29 months (range: 1-365). DES was the second-line treatment in 58 patients and the third/fourth-line therapy in 136 men. A formal (≥50%) PSA response was observed in 95 patients (48.9%) and the median time to progression (TTP) was 250 days (95% CI, 180-360) for this group. An additional 62 patients (31.9%) had a partial PSA response with a median TTP of 150 days (95% CI, 92-180). Thirty-seven patients (19.1%) did not have a PSA response and the median TTP was 90 days (95% CI, 90-97). The median overall survival from the start of oestrogen therapy for the entire cohort was 576 days (95% CI, 482-690). The median overall survival of patients who had a formal (≥50%), partial (<50%) and no PSA response was 756 (95% CI, 670-1,429), 428 (95% CI, 340-630) and 329 (95% CI, 287-510) days, respectively. Thirty-nine patients (20.1%) were still alive at the end of the study. No treatment-related deaths occurred. Conclusions: In the age of chemotherapy this study highlights the efficacy of oestrogen therapy in castration-refractory prostate cancer. The optimal point in the therapeutic pathway at which DES should be prescribed remains to be established.
End-Word Dysfluencies in Young Children: A Clinical Report
Authors: MacMillan Verity , Kokolakis Artemi , Sheedy Stacey , Packman Ann
Published: October 2014

Objective: We report on 12 children with end-word dysfluencies (EWDs). Our aim was to document this little-reported type of dysfluency and to develop a possible explanation for them and how they relate to developmental stuttering. Method: Audio recordings were made for 9 of the 12 children in the study. The EWDs were identified by consensus of two specialist speech pathologists and confirmed on acoustic displays. A segment of participant 1's speech was transcribed, including phonetic transcription of EWDs. Results: The EWDs typically consisted of repetitions of the nucleus and/or the coda. However, there were also some EWDs that consisted of fixed postures on the nucleus (when in final position) or coda. We also report on the infrequent occurrence of broken words. Ten of the 12 children also stuttered, with 9 of them coming from four families, each with a history of stuttering. Conclusion: This study indicates that EWDs may be more prevalent than previously thought, but they may go largely unnoticed due to their perceptually fleeting nature. The hypothesis was developed that EWDs be regarded as another type of developmental dysfluency, along with stuttering and cluttering. Ideas for further research are suggested. © 2014 S. Karger AG, Basel
Prevalence of and Potential Influencing Factors for Alcohol Dependence in Europe
Authors: Rehm Jürgen , Anderson Peter , Barry Joe , Dimitrov Plamen , Elekes Zsuzsanna , Feijão Fernanda , Frick Ulrich , Gual Antoni , Gmel, Jr. Gerrit , Kraus Ludwig , Marmet Simon , Raninen Jonas , Rehm Maximilien X. , Scafato Emanuele , Shield Kevin D. , Trapencieris Marcis , Gmel Gerhard
Published: October 2014

Alcohol use disorders (AUDs), and alcohol dependence (AD) in particular, are prevalent and associated with a large burden of disability and mortality. The aim of this study was to estimate prevalence of AD in the European Union (EU), Iceland, Norway, and Switzerland for the year 2010, and to investigate potential influencing factors. The 1-year prevalence of AD in the EU was estimated at 3.4% among people 18-64 years of age in Europe (women 1.7%, men 5.2%), resulting in close to 11 million affected people. Taking into account all people of all ages, AD, abuse and harmful use resulted in an estimate of 23 million affected people. Prevalence of AD varied widely between European countries, and was significantly impacted by drinking cultures and social norms. Correlations with level of drinking and other drinking variables and with major known outcomes of heavy drinking, such as liver cirrhosis or injury, were moderate. These results suggest a need to rethink the definition of AUDs.
The Origins of the Treatment of Traumatic Spinal Injuries
Authors: Weiner Marie-France , Silver John Russell
Published: October 2014

Background: It is widely acknowledged that Donald Munro in the United States (1936) and Ludwig Guttmann in the United Kingdom (1944) are the founders of the modern treatment of spinal injuries. However, Germany was the birthplace of neuropathology and led the field in neurology and psychiatry. The first effective spinal injury units were established by Wilhelm Wagner in Königshütte, Silesia and Emil Kocher in Bern, Switzerland at the end of the 19th century. Summary: The modern principles of spinal injury treatment emanated from the work carried out by Wagner and Kocher. This knowledge was applied during the First World War in Germany, France, Austria, Switzerland and the United Kingdom. Marburg established a unit in Vienna, Dr. and Mrs. Déjerine and their team of French doctors treated casualties from the First World War and, in the United Kingdom, Gordon Holmes, George Riddoch and Henry Head treated soldiers suffering from spinal injuries in specialised units. After the war these units closed down, doctors went back to their previous occupations and the expertise gained was lost or, in the case of Germany, suppressed. It was only in 1939 when Ludwig Guttmann, a Jewish refugee, arrived in the United Kingdom that this specialised knowledge was used to set up satisfactory treatment. Key Messages: Many of the key principles of treatment for spinal injuries were developed at the end of the 19th century and during the First World War but units closed down and the knowledge gained was forgotten. With the advent of the Second World War, German refugees, many of whom had worked in the field of neurology (including Ludwig Guttmann), came to the United Kingdom armed with a thorough training in neurology and rehabilitation and applied these principles to the treatment of spinal injuries for the benefit of the country which gave them refuge.
The Overtreatment Risk of See-and-Treat Strategy in Management of Abnormal Cervical Cytology
Authors: Kim Ji Ye , Lee Doo Haeng , Kang Jun Hyeok , Kim Kye Hyun , Lee Kyo Won , Kim Woo Young
Published: October 2014

Background: To evaluate the feasibility of conization without a prior punch biopsy for patients with abnormal cytology. Methods: A retrospective review was performed for 700 patients who underwent conization at a single institution from January 2003 to August 2012. Each of these patients was assigned to one of two groups, either the ‘see-and-treat' group or the ‘three-step' group, depending on whether the patient had undergone a punch biopsy before conization or not. The final histologic results of two groups were compared. Results: The overtreatment risk was higher in the ‘see-and-treat' group in patients with atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (ASCUS/LSIL) cytology (64.7% in the ‘see-and-treat' group vs. 36.5% in the ‘three-step' group; p = 0.001). There was no significant statistical difference in the rate of cervical dysplasia or invasive carcinoma in patients with high-grade squamous intraepithelial lesion (HSIL) cytology between groups (91.8% in the ‘see-and-treat' group vs. 93.5% in the ‘three-step' group; p = 0.793). Conclusion: The patients with HSIL on cytology can be managed by a ‘see-and-treat' strategy with a low risk of overtreatment. On the other hand, the ‘three-step' management is more appropriate in patients with ASCUS/LSIL cytology.
The Weaned Pig as a Model for Doxorubicin-Induced Mucositis
Authors: Martin Jamee , Howard Scott C. , Pillai Asha , Vogel Peter , Naren Anjaparavanda P. , Davis Steven , Ringwald-Smith Karen , Buddington Karyl , Buddington Randal K.
Published: October 2014

Background: Chemotherapy-induced mucositis (CIM) complicates cancer therapy and limits maximum tolerated doses and efficacy. Rodent models do not reproducibly mimic clinical CIM, so alternative models are needed. Methods: CIM severity was assessed after weaned pigs were treated with doxorubicin (5 and 3.75 mg/kg) using clinical observations, laboratory parameters and gastrointestinal structure and functions. Bovine colostrum was provided as an experimental intervention to the pigs treated receiving the 3.75 mg/kg dose. Results: Doxorubin at 3.75 mg/kg decreased food intake and weight gain (p < 0.05) and caused diarrhea and vomiting that coincided with damage to the small intestine mucosa based on histological scoring (p < 0.05). It resulted in higher serum TNF-α concentrations, increased chloride secretion and reduced brush border membrane disaccharidase activities and carrier-mediated glucose uptake (all p < 0.05). The gastrointestinal damage and dysfunction resemble the clinical and laboratory features of CIM in humans; these can be partially prevented by providing cow colostrum. Conclusion: The weaned pig is a relevant large animal for studying CIM and evaluating existing and experimental interventions for mucositis.
Uptake of Noninvasive Prenatal Testing in Chinese Women following Positive Down Syndrome Screening
Authors: Poon C.F. , Tse W.C. , Kou K.O. , Leung K.Y.
Published: October 2014

Objectives: To investigate how the introduction of noninvasive prenatal testing (NIPT) influenced women's testing choices following a positive Down syndrome screening. Methods: A retrospective study was conducted to compare differences in the uptake rates of invasive prenatal diagnosis (IPD) or no testing in one public hospital 1 year before (pre-NIPT) and 1 and 2 years after the introduction of NIPT in private in August 2011 using descriptive analysis and a χ2 test. Conventional screening was funded publicly, but NIPT was not. Multivariable binary logistic regression was used to determine factors affecting choices. Results: In pre-NIPT and in years 1 and 2 after the introduction of NIPT, 306, 362 and 401 women who screened positive were seen, respectively. In year 1 and year 2, 12.6 and 26.7% of them underwent NIPT while IPD was decreased by 16.3 and 25.6%, respectively (p < 0.001). Both chorionic villus sampling and amniocentesis decreased in year 1, but only the former in year 2. However, the rate of declining further testing was similar before and after NIPT (p = 0.213). In multivariable analysis, first trimester screening, nulliparity and working women were significant predictors of accepting NIPT, while only nulliparity was a predictor of declining IPD (OR = 0.61). Conclusions: Introduction of NIPT resulted in a significant decrease in IPD for 2 consecutive years.
Estimated Prevalence and Incidence of Multiple Sclerosis in Iran
Authors: Etemadifar Masoud , Izadi Sadegh , Nikseresht Alireza , Sharifian Maryam , Sahraian Mohammad Ali , Nasr Zahra
Published: October 2014

Background: Multiple Sclerosis (MS) is a chronic demyelinating disease of the central nervous system and its epidemiology has changed in recent years. Previously, Iran was considered to have a low MS prevalence. In this study, we aimed to update the prevalence and incidence of MS in Iran. Patients and Methods: This study was conducted based on the data derived from the new report of Iran's Ministry Of Health and Medical Education (MOHME) regarding the patients who have registered to obtain support for treatment in Iran till the end of 2013. Results: Among the 42,200 registered patients, 32,477 were female and 9,723 were male (sex ratio: 3.34: 1), and 4,545 were diagnosed in 2013. This resulted in a prevalence of 54.51 and an incidence of 5.87 per 100,000. Conclusion: According to our study results, Iran has a medium-to-high prevalence rate of MS. According to the previous epidemiologic studies from Iran, it seems that the prevalence of MS significantly has increased during recent years. This rate is similar to what is seen in many western countries.
Determination of Infective Dose of H9N2 Avian Influenza Virus in Different Routes: Aerosol, Intranasal, and Gastrointestinal
Authors: Yao Meiling , Lv Jing , Huang Rong , Yang Yan , Chai Tongjie
Published: October 2014

Background: Low pathogenic H9N2 avian influenza virus (AIV) has been spreading worldwide, leading to huge economic losses to poultry husbandry, but few studies were concerned about its aerosol infection. Methods: This study compared the infective doses of H9N2 AIV to chickens by three different routes, aerosol infection, intranasal and gastrointestinal infection, and determination of the results was conducted by detecting virus shedding and seroconversion of chickens. Results: The results indicated that chickens were susceptible to H9N2 AIV with a different infection rate which depended on the route of inoculation. H9N2 AIV media aerosol-infective dose (aID50) to chickens was about 491 TCID50, intranasal infection was 398 TCID50, and gastrointestinal infection was 19,952 TCID50. Conclusion: The infection ability of H9N2 AIV to chickens was related to its way of invading. The respiratory infection ability was about 40 times more effective than gastrointestinal infection, which suggested that urgent attention should be paid to environmental disinfection to block airborne transmission of influenza virus.
Pre- and Postshunting Magnetization Transfer Ratios Are in Accordance with Neurological and Behavioral Changes in Hydrocephalic Immature Rats
Authors: Rocha Catalão Carlos Henrique , Leme Correa Diego Augusto , Bernardino Garcia Camila Araújo , dos Santos Antonio Carlos , Garrido Salmon Carlos Ernesto , Alves Rocha Maria José , da Silva Lopes Luiza
Published: October 2014

Hydrocephalus is a common neurological condition in children characterized by an imbalance between the production and absorption of cerebrospinal fluid (CSF), causing abnormal fluid accumulation in the brain cavities. Shunt systems have been used to drain excess CSF and to prevent progressive ventricular enlargement. However, despite improvements in these systems, neurological and structural changes cannot always be reversed. Our aim was to evaluate the magnetization transfer ratio as a biomarker for the effectiveness of a CSF shunt system to treat neurological and behavioral disorders observed in experimental hydrocephalus. Seven-day-old Wistar rats were used in this study. The pups were subjected to hydrocephalus induction via 20% kaolin intracisternal injection. After confirmation of ventriculomegaly by magnetic resonance imaging (MRI), a group of animals underwent placement of a ventriculosubcutaneous shunt (VSS). The reduction in ventricular size in hydrocephalic rats operated with functional VSS was observed as a decrease in ventricular ratio values and preservation of the corpus callosum thickness. Magnetization transfer values were significantly increased and matched to the recovery process of axonal myelination observed based on more-intense blue staining by solochrome cyanin. The histopathological analysis revealed a reduction in reactive astrocytes by means of GFAP immunostaining. The hydrocephalic rats operated with functional VSS also showed significant progress in motor and exploratory activities, similar to the control animals, at the end of the experiment. In conclusion, the VSS system employed 7 days after hydrocephalus induction was able to prevent structural damage and restore the axonal myelination process in periventricular structures by stabilizing and reducing the ventricular enlargement, and the results are in accordance with the magnetization transfer ratio in MRI.
Determination of the Preferred Conditions for the Isolated Perfusion of Porcine Kidneys
Authors: Mancina Elina , Kalenski Julia , Paschenda Pascal , Beckers Christian , Bleilevens Christian , Boor Peter , Doorschodt Benedict M. , Tolba René H.
Published: October 2014

Background: The isolated perfused porcine kidney (IPPK) model has been the method of choice for the early preclinical evaluation of kidney graft preservation techniques. The preferred reperfusion conditions have not yet been determined. Here, we examined the effects of pressure- or flow-controlled perfusion and oxygenation by pure oxygen or carbogen (95% O2/5% CO2) on normothermic reperfusion in the IPPK model. Methods: Porcine kidneys were cold-stored for 24 h in histidine-tryptophan-ketoglutarate solution and reperfused for 1 h with normothermic whole blood/Krebs-Henseleit buffer medium (20/80%). Kidneys (n = 5/group) were flow-controlled reperfused with pure oxygen (1 ml/min/g; Flow-O2) or pressure-controlled reperfused (85 mm Hg mean arterial pressure) and oxygenated with either pure oxygen (Pressure-O2) or carbogen (Pressure-O2/CO2). Renal function and damage were assessed during reperfusion and NGAL and HIF-1α levels were analyzed using an ELISA. Results: Pressure-O2 and Pressure-O2/CO2 were associated with significantly better renal hemodynamics and acid-base homeostasis compared to Flow-O2. Urine protein concentrations and the fractional excretion of sodium were lower with both Pressure-O2 and Pressure-O2/CO2 than with Flow-O2. NGAL and HIF-1α levels were also lower with Pressure-O2 and Pressure-O2/CO2 than with Flow-O2. Only Pressure-O2/CO2 could demonstrate a significantly increased urine production compared to Flow-O2. The structural integrity was well preserved in the Pressure-O2 and Pressure-O2/CO2 groups, whereas diffuse and global glomerular destruction was observed in the Flow-O2 group. Conclusion: In the IPPK model, the application of pressure-controlled reperfusion with carbogen oxygenation, and to a lesser extent with pure oxygen, maintained physiological renal function for 1 h, thus providing a reliable and reproducible ex vivo evaluation of kidney preservation quality.
Clinical Application of Pharmacogenomics: The Example of HLA-Based Drug-Induced Toxicity
Authors: Lee Ming Ta Michael , Mahasirimongkol Surakameth , Zhang Yanfei , Suwankesawong Wimon , Chaikledkaew Usa , Pavlidis Cristiana , Patrinos George P. , Chantratita Wasun
Published: October 2014

Pharmacogenomics is gradually becoming more and more indispensable in modern medicine. In several cases, a pharmacogenomics test may alleviate serious drug-induced adverse reactions, if it precedes drug prescription. In this article, we provide an overview of the well-established HLA-based carbamazepine- and allopurinol-induced adverse reactions, as one of the most characteristic examples of the clinical application of pharmacogenomics, highlighting its regional impact in Southeast Asian populations in preventing adverse reactions of certain drug/allele pairs. This example provides useful insights towards evidence generation for policy implementation, including economic evaluation analysis, the implementation of pharmacogenomics testing procedures and monitoring of policy effectiveness, hence serving, per se or in the context of international collaborative efforts, as a model for similar cases in several national healthcare systems worldwide.
Antiangiogenic Effect of Itraconazole on Corneal Neovascularization: A Pilot Experimental Investigation
Authors: Goktas Sertan , Sakarya Rabia , Erdogan Ender , Sakarya Yasar , Ozcimen Muammer , Dursunoglu Duygu , Kocacan Metin , Alpfidan Ismail , Erdogan Erkan , Bukus Abdulkadir , Ivacık Ismail Senol
Published: October 2014

Purpose: To investigate the antiangiogenic effect of itraconazole for the prevention of experimentally induced corneal neovascularization and whether the efficacy depends on the route of administration. Materials and Methods: Thirty-six rats were randomly divided into 6 groups with 6 rats in each group. Chemical cauterization of the cornea was performed using silver nitrate/potassium nitrate sticks, and the rats were subsequently treated daily with topical (10 mg/ml), subconjunctival (10 mg/ml) or intraperitoneal (19 mg/kg) itraconazole for 7 days. Control rats received topical, subconjunctival or intraperitoneal 0.9% saline. On the 8th day of the experiment, the rat corneas were photographed to determine the percentage area of the cornea covered by neovascularization. The maximum density of corneal neovascularization was determined by microscopy. Results: The median percentage of corneal neovascularization for group 1 was 31.5% (95% confidence interval, 27.5-35.5%); in group 3, it was 32% (23.5-39.8%); in group 5, it was 47% (36.3-60.0%). The percentages of corneal neovascularization in groups 2, 4 and 6 (the control groups) were 70% (95% confidence interval, 60.7-77.3%), 69% (63.0-77.7%) and 68% (56.5-78.5%), respectively. The area of neovascularization was smaller after itraconazole treatment as compared to saline treatment. Further, the area of neovascularization was smaller after topical and subconjunctival administration than after intraperitoneal administration. Histological evaluation of the corneas showed the most extensive corneal neovascularization in the control group. No local or systemic adverse effects were seen from either treatment group. Conclusion: Itraconazole reduces corneal neovascularization shortly after chemical burn. However, a larger experimental study is necessary to confirm the data of this investigation.
Ustekinumab Improves Psoriasis without Suppressing Tumor Antigen-Specific Cytotoxic T Lymphocytes
Authors: Narita Miwako , Nishizawa Yoshinori , Iwaya Shunpei , Oiwa Eri , Iwabuchi Minami , Uchiyama Takayoshi , Matsuyama Asako , Masuko Masayoshi , Takahashi Masuhiro
Published: October 2014

Background: Ustekinumab is currently used for the treatment of psoriasis with remarkable efficiency. However, worries about the development of malignancies in ustekinumab-treated patients have not been completely resolved because of the major role of IL-12 and IL-23 in tumor immunity. In the present study, we tried to elucidate the effects of ustekinumab on antigen-specific tumor immunity. Methods: After approval by the institutional ethical committee, a 56-year-old male volunteer with psoriasis was administered with 20 doses of WT1 peptide. WT1-specific cytotoxic T lymphocytes (CTLs) were evaluated by WT1 tetramer assay after mixed lymphocyte peptide culture. Results: WT1 tetramer+ T cells with cytotoxic ability appeared in the blood after peptide administration and the frequency of WT1 tetramer+ T cells increased to more than 15 in 106 CD8+ T cells. Thirty months after stopping WT1 administration, the patient commenced treatment with ustekinumab for psoriasis at weeks 0 and 4, and every 12 weeks thereafter. Psoriasis plaques were almost cleared up and the response to ustekinumab has so far lasted for 30 months. The frequency of WT1 tetramer+ T cells has not changed since the initiation of ustekinumab treatment. The effects of ustekinumab on the antigen-presenting and CTL-inducing abilities of dendritic cells were explored in vitro, revealing limited effects on both immune functions. Conclusions: These in vivo/vitro findings imply that ustekinumab improves psoriasis without suppressing tumor antigen-specific CTLs and support the data of recent clinical trials showing no increased incidence of malignancies with ustekinumab treatment.
Lack of Association between XPF Polymorphisms and Gastric Cancer Risk: A Meta-Analysis
Authors: Lin Jiaying , Hu Bing , Wang Man
Published: October 2014

SummaryBackground: Xeroderma pigmentosum complementation group F (XPF or ERCC4) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. Several epidemiological studies have examined associations between XPF polymorphisms and gastric cancers risk, but the findings remain inconclusive. Therefore, we conducted the present meta-analysis to obtain the most reliable estimate of the association. Methods: PubMed, Embase, Web of Science, and Wanfang were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were extracted and pooled to assess the strength of the association between 3 commonly studied polymorphisms of XPF (rs744154, rs6498486, rs1799801) and gastric cancer risk. The pooled ORs were performed for the co-dominant model (homozygous and heterozygous), dominant model, and recessive model. 3 studies on rs744154, 3 studies on rs6498486, and 4 studies on rs1799801 were included in our meta-analysis. Results: Our results show that the genotype distribution of the 3 polymorphisms was not associated with risk of gastric cancer in all genetic models. Conclusion: This meta-analysis suggests that the 3 common XPF polymorphisms rs744154, rs6498486, and rs1799801 are not associated with gastric cancer risk. However, large-sample and representative population-based studies with homogeneous gastric cancer patients and well-matched controls are warranted to confirm this finding.
Age Is Not Associated with Hospital Admission or Uncontrolled Symptoms of Asthma if Proper Treatment Is Offered
Authors: Ponte Eduardo Vieira , Stelmach Rafael , Franco Rosana , Souza-Machado Carolina , Souza-Machado Adelmir , Cruz Alvaro A.
Published: October 2014

Background: Aging modifies immune response and respiratory physiology. Few studies evaluate the effect of age on asthma. The aim of our study was to evaluate whether age is associated with uncontrolled symptoms and hospital admissions due to asthma in a setting where patients were receiving proper treatment. Methods: We enrolled 401 patients with uncontrolled asthma who were inhaled corticosteroid-naive. The follow-up period was 1 year. They received medications for asthma, performed spirometry, a symptoms questionnaire, and all emergency room visits and hospital admissions due to asthma were reported. The primary end point was hospital admission during the follow-up period. Results: Baseline data demonstrated that subjects >55 years of age had a later onset of asthma and a longer duration of symptoms. Adjusted logistic regression models demonstrated that older age at enrollment did not predict asthma control in the follow-up: hospital admission due to asthma [odds ratio (OR) 1.7 and 95% confidence interval (CI) 0.6-4.7], symptoms score (OR 0.6 and 95% CI 0.3-1.1) and emergency room visits due to asthma (OR 0.9 and 95% CI 0.6-1.3). Older age was associated with worse lung function (OR 1.8 and 95% CI 1.1-3.3). Conclusion: This study allows us to conclude that older age is associated with a later onset of asthma and a longer duration of symptoms. Age does not predict hospital admissions or poor control of asthma symptoms if proper treatment is offered. It does, however, predict worse lung function.
Granzyme H Is a Novel Protease Expressed by Human Mast Cells
Authors: Rönnberg Elin , Calounova Gabriela , Sutton Vivien R. , Trapani Joseph A. , Rollman Ola , Hagforsen Eva , Pejler Gunnar
Published: October 2014

Background: Many of the functions attributed to mast cells depend on the various pro-inflammatory mediators that are secreted upon mast cell activation. These include a panel of mast cell-specific proteases. In addition, recent studies have indicated that murine mast cells also express granzyme D, a protease previously thought to be confined to cytotoxic lymphocytes. Here, we address the human relevance of the latter findings by investigating whether human mast cells express granzyme H, the granzyme that may represent the functional counterpart to murine granzyme D. Methods: Cord blood-derived mast cells, LAD2 cells and skin mast cells in situ were evaluated for their expression of granzymes using quantitative PCR, Western blot analysis and immunostaining. Mast cells were activated by either calcium ionophore stimulation or IgE receptor cross-linking. Results: Cord blood-derived mast cells and LAD2 cells were shown to express granzyme H and B mRNA, while granzyme A, K and M expression was undetectable. Mast cell activation by either calcium ionophore or IgE receptor cross-linking caused down-regulated expression of granzyme H. In contrast, granzyme B expression was up-regulated by the same stimuli. Granzyme H expression was also confirmed at the protein level, as shown by both Western blot analysis and confocal microscopy. Further, we show that granzyme H is expressed by human skin mast cells in situ. Conclusions: The present findings implicate granzyme H as a novel protease expressed by human mast cells and support earlier findings obtained in natural killer cells suggesting that granzymes B and H are reciprocally regulated.