bluuebunny/crossref_metadata_2025 huggingface dataset:
Acupuncture for the Treatment of Oculomotor Paralysis: A Pilot Randomised Controlled Trial
Authors: Bi Jia-Qi , Li Wei , Yang Qi , Li Bao-lin , Meng Qing-Gang , Liu Yu-fu
Published: May 2016

This study consisted of a single centre randomised controlled trial with two parallel arms: an acupuncture group (n = 20) with 27 affected eyes and a sham group (n = 20) with 23 affected eyes. Participants in the acupuncture group received acupuncture treatment once daily, three times weekly for four weeks. Participants assigned to the control group received sham acupuncture, the same protocol as that used for the acupuncture group but without insertion of needles into the skin. The primary outcome measure was the cervical range of motion (CROM) score. Secondary outcome measures were the palpebral fissure size, response rate, and adverse events. All 40 participants completed the study. In the comparison of acupuncture and sham acupuncture, a significant difference was observed between acupuncture and sham acupuncture in CROM score (21.37 ± 15.16 and 32.21 ± 19.54, resp.) (P < 0.05) and palpebral fissure size (7.19 ± 2.94 and 5.41 ± 2.45, resp.) (P < 0.05). Response rate was also significantly different in the acupuncture group (P < 0.05). No adverse events were reported in both groups in this study. In summary, it was demonstrated that acupuncture had a feasibility positive effect on oculomotor paralysis.
Online Ensemble Using Adaptive Windowing for Data Streams with Concept Drift
Authors: Sun Yange , Wang Zhihai , Liu Haiyang , Du Chao , Yuan Jidong
Published: May 2016

Data streams, which can be considered as one of the primary sources of what is called big data, arrive continuously with high speed. The biggest challenge in data streams mining is to deal with concept drifts, during which ensemble methods are widely employed. The ensembles for handling concept drift can be categorized into two different approaches: online and block-based approaches. The primary disadvantage of the block-based ensembles lies in the difficulty of tuning the block size to provide a tradeoff between fast reactions to drifts. Motivated by this challenge, we put forward an online ensemble paradigm, which aims to combine the best elements of block-based weighting and online processing. The algorithm uses the adaptive windowing as a change detector. Once a change is detected, a new classifier is built replacing the worst one in the ensemble. By experimental evaluations on both synthetic and real-world datasets, our method performs significantly better than other ensemble approaches.
Evaluation of Bioinformatic Programmes for the Analysis of Variants within Splice Site Consensus Regions
Authors: Tang Rongying , Prosser Debra O. , Love Donald R.
Published: May 2016

The increasing diagnostic use of gene sequencing has led to an expanding dataset of novel variants that lie within consensus splice junctions. The challenge for diagnostic laboratories is the evaluation of these variants in order to determine if they affect splicing or are merely benign. A common evaluation strategy is to use in silico analysis, and it is here that a number of programmes are available online; however, currently, there are no consensus guidelines on the selection of programmes or protocols to interpret the prediction results. Using a collection of 222 pathogenic mutations and 50 benign polymorphisms, we evaluated the sensitivity and specificity of four in silico programmes in predicting the effect of each variant on splicing. The programmes comprised Human Splice Finder (HSF), Max Entropy Scan (MES), NNSplice, and ASSP. The MES and ASSP programmes gave the highest performance based on Receiver Operator Curve analysis, with an optimal cut-off of score reduction of 10%. The study also showed that the sensitivity of prediction is affected by the level of conservation of individual positions, with in silico predictions for variants at positions -4 and +7 within consensus splice sites being largely uninformative.
Cetuximab and Cisplatin Show Different Combination Effect in Nasopharyngeal Carcinoma Cells Lines via Inactivation of EGFR/AKT Signaling Pathway
Authors: Gu Jiajia , Yin Li , Wu Jing , Zhang Nan , Huang Teng , Ding Kai , Cao Haixia , Xu Lin , He Xia
Published: May 2016

Nasopharyngeal carcinoma (NPC) is a common malignant cancer in South China. Cisplatin is a classical chemotherapeutic employed for NPC treatment. Despite the use of cisplatin-based concurrent chemoradiotherapy, distant failure still confuses clinicians and the outcome of metastatic NPC remains disappointing. Hence, a potent systemic therapy is needed for this cancer. Epidermal growth factor receptor (EGFR) represents a promising new therapeutic target in cancer. We predicted that combining the conventional cytotoxic drug cisplatin with the novel molecular-targeted agent cetuximab demonstrates a strong antitumor effect on NPC cells. In this study, we selected HNE1 and CNE2 cells, which have been proved to possess different EGFR expression levels, to validate our conjecture. The two-drug regimen showed a significant synergistic effect in HNE1 cells but an additive effect in CNE2 cells. Our results showed that cisplatin-induced apoptosis was significantly enhanced by cetuximab in the high EGFR-expressing HNE1 cells but not in CNE2 cells. Further molecular mechanism study indicated that the EGFR/AKT pathway may play an important role in cell apoptosis via the mitochondrial-mediated intrinsic pathway and lead to the different antitumor effects of this two-drug regimen between HNE1 and CNE2 cells. Thus, the regimen may be applied in personalized NPC treatments.
Immunohistochemical Expression of VEGF and Podoplanin in Uterine Cervical Squamous Intraepithelial Lesions
Authors: Belfort-Mattos Patrícia Napoli , Focchi Gustavo Rubino de Azevedo , Ribalta Julisa Chamorro Lascasas , Megale De Lima Tatiana , Nogueira Carvalho Carmen Regina , Kesselring Tso Fernanda , De Góis Speck Neila Maria
Published: May 2016

VEGF and podoplanin (PDPN) have been identified as angiogenesis and/or lymphangiogenesis regulators and might be essential to restrict tumor growth, progression, and metastasis. In the present study, we evaluate the association between the expression of these markers and CIN grade. Immunohistochemistry was performed in 234 uterine cervical samples using conventional histologic sections or TMA with the monoclonal antibodies to VEGF (C-1 clone) and podoplanin (D2-40 clone). Positive-staining rates of VEGF in 191 CIN specimens were significantly associated with histological grade (P<0.001). Negative and/or focal immunostaining for PDPN were more frequent in CIN 3 (P=0.016). We found that patients with CIN 3 more frequently had strong and more diffuse staining for VEGF and diminished staining for PDPN (P=0.018). Strong and more diffuse VEGF immunoexpressions in CIN 2 and CIN 3 were detected when compared to CIN 1. Negative and/or focal PDPN immunoexpression appear to be more frequent in CIN 3. Moderate to strong VEGF expression may be a tendency among patients with high-grade lesions and diminished PDPN expression.
Synthesis and Characterization of Uniform Spherical Nanoporous TiO2Aerogel Templated by Cellulose Alcohol-Gel with Enhanced Photocatalytic Activity
Authors: Liu Zhiming , Wu Peng , Yang Shaoli , Wang Haiying , Jin Chunde
Published: May 2016

The spherical nanoporous TiO2aerogels were prepared by a simple ethanol-thermal method, using spherical cellulose alcohol-gel as the template. The morphology, crystalline structure, pore size, specific surface area, and the photocatalytic activity of obtained TiO2aerogel were separately characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), N2adsorption-desorption isotherms, and double beam UV-VIS spectrophotometer. The characteristics of TiO2aerogels presented uniform sphere shape, good internal structural morphology, high specific surface area (ranging from 111.88 to 149.95 m2/g), and good crystalline anatase phase. Moreover, methyl orange dye was used as the target pollutant to characterize the photocatalytic activities and the adsorption performance. The photocatalytic experiment shows that the obtained spherical TiO2aerogels had a higher degradation ratio of 92.9% on methyl orange dye compared with aspherical TiO2aerogels prepared from other concentrations of tetrabutyl orthotitanate (TBOT).
Dicer Elicits Paclitaxel Chemosensitization and Suppresses Cancer Stemness in Breast Cancer by Repressing AXL
Authors: Chang Ting-Yu , Chen Hsin-An , Chiu Ching-Feng , Chang Yi-Wen , Kuo Tsang-Chih , Tseng Po-Chun , Wang Weu , Hung Mien-Chie , Su Jen-Liang
Published: May 2016

Paclitaxel is a standard-of-care chemotherapy for breast cancer, despite the increasing recognition of its poor effectiveness in the treatment of patients with advanced disease. Here, we report that adenovirus-type 5 E1A-mediated elevation of the miRNA-processing enzyme Dicer is sufficient to enhance paclitaxel sensitization and reduce cancer stem-like cell properties in this setting. Elevating Dicer expression increased levels of the AXL kinase targeting miRNA miR-494, thereby repressing AXL expression to increase paclitaxel sensitivity. We found that Dicer expression was regulated at the transcription level by E1A, through activation of an MAPK14/CEBPα pathway. Our findings define a mechanism of E1A-mediated chemosensitization for paclitaxel, which is based upon the suppression of breast cancer stem-like cells, with potential implications for the diagnosis and treatment of breast cancer patients. Cancer Res; 76(13); 3916–28. ©2016 AACR.
A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor–Resistant Lung Tumors
Authors: Moores Sheri L. , Chiu Mark L. , Bushey Barbara S. , Chevalier Kristen , Luistro Leopoldo , Dorn Keri , Brezski Randall J. , Haytko Peter , Kelly Thomas , Wu Sheng-Jiun , Martin Pauline L. , Neijssen Joost , Parren Paul W.H.I. , Schuurman Janine , Attar Ricardo M. , Laquerre Sylvie , Lorenzi Matthew V. , Anderson G. Mark
Published: May 2016

Non–small cell lung cancers (NSCLC) with activating EGFR mutations become resistant to tyrosine kinase inhibitors (TKI), often through second-site mutations in EGFR (T790M) and/or activation of the cMet pathway. We engineered a bispecific EGFR-cMet antibody (JNJ-61186372) with multiple mechanisms of action to inhibit primary/secondary EGFR mutations and the cMet pathway. JNJ-61186372 blocked ligand-induced phosphorylation of EGFR and cMet and inhibited phospho-ERK and phospho-AKT more potently than the combination of single receptor–binding antibodies. In NSCLC tumor models driven by EGFR and/or cMet, JNJ-61186372 treatment resulted in tumor regression through inhibition of signaling/receptor downmodulation and Fc-driven effector interactions. Complete and durable regression of human lung xenograft tumors was observed with the combination of JNJ-61186372 and a third-generation EGFR TKI. Interestingly, treatment of cynomolgus monkeys with JNJ-61186372 resulted in no major toxicities, including absence of skin rash observed with other EGFR-directed agents. These results highlight the differentiated potential of JNJ-61186372 to inhibit the spectrum of mutations driving EGFR TKI resistance in NSCLC. Cancer Res; 76(13); 3942–53. ©2016 AACR.
Genomic Landscape Established by Allelic Imbalance in the Cancerization Field of a Normal Appearing Airway
Authors: Jakubek Yasminka , Lang Wenhua , Vattathil Selina , Garcia Melinda , Xu Li , Huang Lili , Yoo Suk-Young , Shen Li , Lu Wei , Chow Chi-Wan , Weber Zachary , Davies Gareth , Huang Jing , Behrens Carmen , Kalhor Neda , Moran Cesar , Fujimoto Junya , Mehran Reza , El-Zein Randa , Swisher Stephen G. , Wang Jing , Fowler Jerry , Spira Avrum E. , Ehli Erik A. , Wistuba Ignacio I. , Scheet Paul , Kadara Humam
Published: May 2016

Visually normal cells adjacent to, and extending from, tumors of the lung may carry molecular alterations characteristics of the tumor itself, an effect referred to as airway field of cancerization. This airway field has been postulated as a model for early events in lung cancer pathogenesis. Yet the genomic landscape of somatically acquired molecular alterations in airway epithelia of lung cancer patients has remained unknown. To begin to fill this void, we sought to comprehensively characterize the genomic architecture of chromosomal alterations inducing allelic imbalance (AI) in the airway field of the most common type of lung tumors, non–small cell lung cancer (NSCLC). To do so, we conducted a genome-wide survey of multiple spatially distributed normal-appearing airways, multiregion tumor specimens, and uninvolved normal tissues or blood from 45 patients with early-stage NSCLC. We detected alterations in airway epithelia from 22 patients, with an increased frequency in NSCLCs of squamous histology. Our data also indicated a spatial gradient of AI in samples at closer proximity to the NSCLC. Chromosome 9 displayed the highest levels of AI and comprised recurrent independent events. Furthermore, the airway field AI included oncogenic gains and tumor suppressor losses in known NSCLC drivers. Our results demonstrate that genome-wide AI is common in the airway field of cancerization, providing insights into early events in the pathogenesis of NSCLC that may comprise targets for early treatment and chemoprevention. Cancer Res; 76(13); 3676–83. ©2016 AACR.
Novel ß-HPV49 Transgenic Mouse Model of Upper Digestive Tract Cancer
Authors: Viarisio Daniele , Müller-Decker Karin , Zanna Paola , Kloz Ulrich , Aengeneyndt Birgit , Accardi Rosita , Flechtenmacher Christa , Gissmann Lutz , Tommasino Massimo
Published: May 2016

The beta genus of human papillomaviruses (ß-HPV) includes approximately 50 different viral types that are subdivided into five species (ß-1 through ß-5). Nonmelanoma cancers may involve some ß-1 and ß-2 HPV types, but the biology of most ß-HPV types and their possible connections to human disease are still little characterized. In this study, we studied the effects of ß-3 type HPV49 in a novel transgenic (Tg) mouse model, using a cytokeratin K14 promoter to drive expression of the E6 and E7 genes from this virus in the basal skin epidermis and the mucosal epithelia of the digestive tract (K14 HPV49 E6/E7-Tg mice). Viral oncogene expression only marginally increased cellular proliferation in the epidermis of Tg animals, compared with wild-type littermates, and we observed no spontaneous tumor formation during their entire lifespan. However, we found that K14 HPV49 E6/E7-Tg mice were highly susceptible to upper digestive tract carcinogenesis upon initiation with 4-nitroquinoline 1-oxide (4NQO). This was a selective effect, as the same mice did not exhibit any skin lesions after chronic UV irradiation. Opposite results were observed in an analogous Tg model expressing the ß-2 HPV38 E6 and E7 oncogenes at the same anatomic sites. While these mice were highly susceptible to UV-induced skin carcinogenesis, as previously shown, they were little affected by 4NQO treatment. Overall, our findings highlight important differences in the biologic properties of certain ß-type HPV that affect their impact on carcinogenesis in an anatomic site-specific manner. Cancer Res; 76(14); 4216–25. ©2016 AACR.
BRAF Status in Personalizing Treatment Approaches for Pediatric Gliomas
Authors: Olow Aleksandra , Mueller Sabine , Yang Xiaodong , Hashizume Rintaro , Meyerowitz Justin , Weiss William , Resnick Adam C. , Waanders Angela J. , Stalpers Lukas J.A. , Berger Mitchel S. , Gupta Nalin , James C. David , Petritsch Claudia K. , Haas-Kogan Daphne A.
Published: May 2016

Purpose: Alteration of the BRAF/MEK/MAPK pathway is the hallmark of pediatric low-grade gliomas (PLGGs), and mTOR activation has been documented in the majority of these tumors. We investigated combinations of MEK1/2, BRAFV600E and mTOR inhibitors in gliomas carrying specific genetic alterations of the MAPK pathway.

Experimental Design: We used human glioma lines containing BRAFV600E (adult high-grade: AM-38, DBTRG, PLGG: BT40), or wild-type BRAF (pediatric high-grade: SF188, SF9427, SF8628) and isogenic systems of KIAA1549:BRAF-expressing NIH/3T3 cells and BRAFV600E-expressing murine brain cells. Signaling inhibitors included everolimus (mTOR), PLX4720 (BRAFV600E), and AZD6244 (MEK1/2). Proliferation was determined using ATP-based assays. In vivo inhibitor activities were assessed in the BT40 PLGG xenograft model.

Results: In BRAFV600E cells, the three possible doublet combinations of AZD6244, everolimus, and PLX4720 exhibited significantly greater effects on cell viability. In BRAFWT cells, everolimus + AZD6244 was superior compared with respective monotherapies. Similar results were found using isogenic murine cells. In KIAA1549:BRAF cells, MEK1/2 inhibition reduced cell viability and S-phase content, effects that were modestly augmented by mTOR inhibition. In vivo experiments in the BRAFV600E pediatric xenograft model BT40 showed the greatest survival advantage in mice treated with AZD6244 + PLX4720 (P < 0.01).

Conclusions: In BRAFV600E tumors, combination of AZD6244 + PLX4720 is superior to monotherapy and to other combinatorial approaches. In BRAFWT pediatric gliomas, everolimus + AZD6244 is superior to either agent alone. KIAA1549:BRAF-expressing tumors display marked sensitivity to MEK1/2 inhibition. Application of these results to PLGG treatment must be exercised with caution because the dearth of PLGG models necessitated only a single patient-derived PLGG (BT40) in this study. Clin Cancer Res; 22(21); 5312–21. ©2016 AACR.
A New Class of Antibody–Drug Conjugates with Potent DNA Alkylating Activity
Authors: Miller Michael L. , Fishkin Nathan E. , Li Wei , Whiteman Kathleen R. , Kovtun Yelena , Reid Emily E. , Archer Katie E. , Maloney Erin K. , Audette Charlene A. , Mayo Michele F. , Wilhelm Alan , Modafferi Holly A. , Singh Rajeeva , Pinkas Jan , Goldmacher Victor , Lambert John M. , Chari Ravi V.J.
Published: May 2016

The promise of tumor-selective delivery of cytotoxic agents in the form of antibody–drug conjugates (ADC) has now been realized, evidenced by the approval of two ADCs, both of which incorporate highly cytotoxic tubulin-interacting agents, for cancer therapy. An ongoing challenge remains in identifying potent agents with alternative mechanisms of cell killing that can provide ADCs with high therapeutic indices and favorable tolerability. Here, we describe the development of a new class of potent DNA alkylating agents that meets these objectives. Through chemical design, we changed the mechanism of action of our novel DNA cross-linking agent to a monofunctional DNA alkylator. This modification, coupled with linker optimization, generated ADCs that were well tolerated in mice and demonstrated robust antitumor activity in multiple tumor models at doses 1.5% to 3.5% of maximally tolerated levels. These properties underscore the considerable potential of these purpose-created, unique DNA-interacting conjugates for broadening the clinical application of ADC technology. Mol Cancer Ther; 15(8); 1870–8. ©2016 AACR.
Somatotype in Alzheimer’s Disease
Authors: Buffa Roberto , Lodde Marco , Floris Giovanni , Zaru Cristina , Putzu Paolo F. , Marini Elisabetta
Published: May 2016

Background: The clinical picture of Alzheimer’s disease includes anthropometric and body composition variations. Somatotyping is a practical non-invasive method to assess body type. Objective: The objective of this study was to describe the somatotype of a sample of Alzheimer’s patients. Methods: The sample consisted of 55 Alzheimer disease individuals in the mild-moderate stage (17 men, mean age = 76.9 ± 7.2 years; 38 women, mean age = 79.6 ± 6.4 years). The pathological subjects were compared with a control group consisting of 280 healthy individuals (134 men, mean age = 74.2 ± 7.3 years; 146 women, mean age = 74.9 ± 7.4 years). The Heath-Carter somatotype was applied. Results: The Alzheimer patients (mean somatotype: 6.1–5.5–0.8 in men, 7.0–5.3–0.7 in women) are less mesomorphic and more ectomorphic than the controls (mean somatotype: 6.1–6.3–0.6 in men, 7.7–6.3–0.4 in women), the differences being significant in women (mesomorphy, p = 0.000; ectomorphy, p = 0.012). Conclusion: Alzheimer patients show peculiar somatometric characteristics. The somatotype technique could represent a suitable tool for the study and monitoring of physical variations.
Pronation Test: Eyes Closed or Open?
Authors: Togay Işıkay Canan , Şener H. Özden
Published: May 2016

Background: The pronation test reveals slight paresis in the upper limbs. Patients hold their arms outstretched in front of them with the hands supinated while they keep their eyes closed. Position changes such as pronation, abduction, or drift indicate a positive pronation test. However, proprioceptive disorders also result in position changes when the eyes are closed. Aim: To evaluate the effects of vision on the pronation test and the relation of test results to electrophysiological findings. Methods: Sixteen patients with slight unilateral paresis due to recent stroke were included in the study. Two pronation tests, one while the patients’ eyes were open and the other while the eyes were closed (in randomized order), were performed in all patients and recorded with a video camera. Two neurologists double-blinded to the position of the patients’ eyes then assessed the position changes in each recording. Electrophysiological examination included median sensory and motor evoked potentials in both upper limbs. Sensory and motor central conduction times (CCTs) were determined for all patients. Results: Assessments of position changes by two physicians were concordant. Ten patients had position changes more evident in the pronation test with the eyes closed (group 1), while 6 patients had similar position changes in both tests (group 2). Motor CCT difference between two sides was similar in the two groups. However, sensory CCT difference longer than 1.0 ms was significantly more frequent in group 1 (p < 0.01). Conclusion: All patients who developed more obvious position changes during the pronation test with eyes closed had sensory CCT abnormalities. Therefore, we suggest that patients should keep their eyes open and then close them during the pronation test in order to distinguish motor or proprioceptive involvement.
Cerebrovascular Reactivity in Degenerative and Vascular Dementia: A Transcranial Doppler Study
Authors: Vicenzini Edoardo , Ricciardi Maria Chiara , Altieri Marta , Puccinelli Francesco , Bonaffini Novella , Di Piero Vittorio , Lenzi Gian Luigi
Published: May 2016

Background: An impairment of cerebral microvessels is reported both in normal ageing and in senescence-associated processes, as well as in Alzheimer’s disease (AD) and vascular dementia (VaD). The aim of this study was to explore cerebral hemodynamics by transcranial Doppler in VaD and AD, compared with age-matched control subjects. Methods: Transcranial Doppler was investigated in all patients in the basal condition. Cerebral vasoreactivity to hyper- and hypocapnia was evaluated with CO2 mixture inhalation followed by hyperventilation. Results: We studied 60 AD and 58 VaD patients and 62 nondemented controls. Both AD and VaD subjects showed lower flow velocities (FV) and higher pulsatility indices (PI) as compared with controls. Lower total vasomotor reactivity and lower response to hypercapnia were observed in the AD and VaD groups as compared with controls. AD and VaD patients did not show significant differences in FV, PI values or cerebral vasoreactivity. Conclusions: Reduced FV and increased PI with a significant vasoreactivity reduction in VaD and AD patients are indicators of impairment of cerebral microvasculature circulation in both diseases. The identification of vascular function impairment in all kinds of dementia could be of help in identifying patients who would thus benefit more from specific therapeutic approaches.
Combined Effect of Apolipoprotein E Genotype and Past Fertility on Age at Onset of Alzheimer’s Disease in Women
Authors: Corbo Rosa Maria , Gambina Giuseppe , Ulizzi Laura , Monini Patrizia , Broggio Elisabetta , Rosano Aldo , Scacchi Renato
Published: May 2016

Background: Various risk factors influence the development of Alzheimer’s disease (AD). Apolipoprotein E (APOE) e*4 allele has a major role in AD susceptibility and its presence reduces age at AD onset. APOE is also thought to influence human reproduction, and common APOE genotypes seem to be associated with differential fertility. With this study, we investigated possible relationships between APOE genotype, past fertility, and AD onset age. Methods:APOE genotypes were determined in a sample of 176 women with sporadic AD. The number of children each woman had delivered was recorded. Results: A comparison of APOE genotype distribution in parous and nulliparous AD women confirmed that the e*3/e*3 genotype is associated with higher fertility and the e*4-carrying genotypes with lower fertility. When the combined effects of fertility and APOE genotypes on AD onset age were analyzed, parity was found to be associated with a significantly lower AD onset age (73.8 ± 6.2 years) than nulliparity (80.7 ± 5.0 years; p = 0.0007) among subjects carrying e*3/e*3 and e*3/e*2 genotypes. A similar effect was absent among e*4 carriers. Considering the high frequency of e*3/e*3 plus e*3/e*2 genotypes in Europe (range: 63–87%), past fertility may influence AD onset age in many women. Conclusion: Past fertility may have a relevant effect on AD onset age and this effect is influenced by APOE genotype.
Significance of Ceramide and DNA Ploidy in Laryngeal Carcinogenesis
Authors: Yuan Yasheng , Chi Fanglu , Wang Shuyi , Wang Zhengmin
Published: May 2016

Objective: To investigate the expression of ceramide produced by sphingomyelin and DNA ploidy in normal laryngeal mucosa, laryngeal precancerous lesions and laryngeal carcinoma. Methods: Eighty consecutive patients with leukoplakia larynx were identified from the archived pathology files of the Eye, Ear, Nose and Throat Hospital of Fudan University from 1990 to 2001. Among them, 23 patients developed laryngeal carcinoma. Flow cytometry and immunohistochemistry were performed to test DNA content and ceramide expression on normal tissue, precancerous lesions and laryngeal carcinoma. Results: Among 80 patients with laryngeal carcinoma, 23 cases were all aneuploids, and 57 diploids. Expression of ceramide decreased gradually from normal tissue via precancerous lesions to laryngeal carcinoma. Cell staining per high-power field was 400 ± 30, 180 ± 20, and 10 ± 10, respectively (p < 0.05, t test). The expression of ceramide in the DNA diploid cell was higher than that in the aneuploid cell (p < 0.05, t test). Conclusions: Ceramide, the second messenger in apoptosis, plays a significant role in the progression from precancerous lesion to carcinoma of the larynx. Reduction in ceramide may be the key factor in laryngeal carcinogenesis.
Modulation of Allergy Incidence in Icelandic Horses Is Associated with a Change in IL-4-Producing T Cells
Authors: Hamza E. , Doherr M.G. , Bertoni G. , Jungi T.W. , Marti E.
Published: May 2016

Background: Equine insect bite hypersensitivity (IBH) is an immediate-type hypersensitivity reaction provoked by insect-derived allergens. Icelandic horses living in Iceland do not have IBH due to absence of relevant insects, but acquire it at high frequency after being imported to mainland Europe. In contrast, their offspring born in mainland Europe has reduced IBH incidence. T helper 1 (Th1) and Th2 cells and cytokines were determined in Icelandic horses born in Iceland and on the continent and which either have IBH or are healthy. Methods: Peripheral blood mononuclear cells (PBMC) from these horses were stimulated for 18 h dur- ing summer and winter with polyclonal T cell stimuli, IBH allergen(s) or irrelevant allergen(s). Cells were analysed by flow cytometry for interferon-γ (IFN-γ) and interleukin-4 (IL-4); RNA was analysed for IFN-γ, IL-4, IL-5 and IL-13 mRNA. Results: During summer, but not during winter, IBH PBMC stimulated polyclonally showed reduced IFN-γ mRNA and IFN-γ-producing cells when compared with those of healthy horses, regardless of origin. PBMC stimulated polyclonally or with IBH allergen showed increased IL-4 mRNA levels and higher numbers of IL-4-producing cells when born in Iceland or showing IBH symptoms. IL-5 and IL-13 mRNA were modulated neither by disease nor by origin. Abrogation of IL-4 production in healthy horses born in mainland Europe may be due, at least in part, to IL-10. There was an increased level of IL-10 in supernatants from PBMC of healthy horses born in mainland Europe and stimulated polyclonally or with IBH allergen. Conclusions: Modulation of IBH incidence is governed by altered Th1/Th2 ratio, which might be influenced by IL-10.
Anterior Meningocele Misdiagnosed as an Ovarian Cyst
Authors: Fıçıcıoğlu C. , Baykal C. , Arıoğlu P. , Delier H. , Mercan A. , Özcan N.
Published: May 2016

Objective: An undiagnosed anterior meningocele may mimic an ovarian cyst. Careful evaluation and consultation must be the mainstay of surgery for adnexal masses. Results: A patient initially diagnosed as having an adnexal mass was discovered to have an anterior meningocele at surgery. In vitro fertilization plans were delayed to prevent complications during procedures.
In vitro Fertilization in Two Patients with Kartagener’s Syndrome and Infertility
Authors: Abu-Musa Antoine , Nassar Anwar , Usta Ihab
Published: May 2016

Women with Kartagener’s syndrome (KS) are at a risk for infertility because of the dyskinetic ciliary activity in the fallopian tubes. In vitro fertilization – embryo transfer (IVF-ET) is considered the treatment of choice for patients with tubal factor infertility. In the literature only 2 patients with KS were treated with IVF-ET, with only one pregnancy achieved. We report 2 patients with KS and infertility treated successfully with IVF-ET.
Impaired Vasorelaxation in Inbred Mice Is Associated with Alterations in Both Nitric Oxide and Super Oxide Pathways
Authors: Chen Chun , Korshunov Vyacheslav A. , Massett Michael P. , Yan Chen , Berk Bradford C.
Published: May 2016

Recently, we showed that genetic factors determine flow-dependent vascular remodeling. Among five inbred mouse strains, the SJL strain developed the largest intima in response to low flow. Because SJL mice have a spontaneous mutation in superoxide dismutase 2 (SOD-2) we tested the hypothesis that strain-specific variations in vascular function are due to alterations in redox and nitric oxide (NO) pathways. Vasorelaxation to acetylcholine was significantly impaired in aortic rings from SJL compared to C3H or FVB mice (up to 40%). Relaxation to the endothelium-independent vasodilator sodium nitroprusside (SNP) in SJL mice was also significantly impaired at low concentrations, with decreases in sensitivity and maximal relaxation to SNP compared to C3H and FVB mice. Western blot analyses showed significantly decreased expression (∼40%) of eNOS, PKG and SOD-2 proteins in SJL vasculature compared to C3H. Intact aortas from SJL showed significantly increased nitrotyrosine and decreased SOD-2 expression compared to C3H by immunohistochemistry. Basal levels of superoxide in aortas from SJL were not significantly different than C3H as measured by dihydroethidine. In summary, relatively small alterations in redox (SOD-2) and NO pathways (eNOS and PKG) may contribute to significantly impaired vasorelaxation in SJL mice.
Bilateral Serous Retinal Detachment Associated with Inferior Posterior Staphyloma Treated with Scleral Shortening and Vitrectomy
Authors: Kasai Akihito , Kanda Naotaka , Sekiryu Tetsuju
Published: May 2016

Purpose: We report a case of bilateral serous retinal detachment (SRD) associated with inferior posterior staphyloma (IPS) treated successfully with scleral shortening. Patient and Methods: A 63-year-old woman presented with bilateral visual loss due to an SRD with IPS. The best-corrected visual acuity levels were 0.6 (20/30) and 0.5 (20/40) in the right and left eye, respectively. The patient underwent vitrectomy and scleral shortening in the right eye. The lamellar scleral crescent was resected 4 mm in width from the 5- to 8-o'clock positions. Seven interrupted 5-0 polyester sutures were placed at the edge of the lamellar scleral crescent. After 25-gauge three-port vitrectomy, the sutures were tightened. Optical coherence tomography showed decreased curvature at the staphyloma border. The choroidal thickness decreased in the superior flat portion of the fundus and increased slightly in the staphyloma. The SRD resolved 3 months postoperatively. The best-corrected visual acuity in the right eye improved to 0.8 (20/25) 6 months postoperatively. Angiography 6 months postoperatively showed decreased diffuse dye leakage at the fovea in the right eye; indocyanine green angiography did not show marked changes. Discussion: Scleral shortening with vitrectomy changes the eye wall shape, may improve the retinal pigment epithelial integrity, and may be a treatment option for SRD with IPS.
Role of C-Reactive Protein Assessment as Early Predictor of Surgical Site Infections Development after Pancreaticoduodenectomy
Authors: Angiolini Maria Rachele , Gavazzi Francesca , Ridolfi Cristina , Moro Matteo , Morelli Paola , Montorsi Marco , Zerbi Alessandro
Published: May 2016

Background: Surgical site infections (SSIs) are extremely common in pancreatic surgery and explain its considerable morbidity and mortality, even in tertiary centers. Early detection of these complications, with the help of laboratory assays, improve clinical outcome. The aim of the present study is to evaluate C-reactive protein (CRP) diagnostic accuracy as early predictor of SSIs after pancreaticoduodenectomy (PD). Methodology: We considered 251 consecutive PD. We prospectively recorded preoperative clinical and anthropometric data, intraoperative details and the postoperative outcome. In the first pool of consecutive patients (n = 150), we analyzed CRP levels from postoperative day 1 to 7 and investigated the prediction of SSIs. We then validated the diagnostic accuracy on the following 101 consecutive cases. Results: At multivariate analysis, high BMI and preoperative biliary stenting appeared to be independently associated with SSIs and organ-space SSI development. The CRP cutoff of 17.27 mg/dl on postoperative day 3 (78% sensitivity, 79% specificity) and of 14.72 mg/dl on postoperative day 4 (87% sensitivity, 82% specificity) was in a position to predict the course of 78.2 and 80.2% of patients, respectively. Conclusions: CRP on postoperative days 3 and 4 seems able to predict postoperative course, selecting patients deserving intensification of diagnostic assessment; patients not satisfying these conditions could be reasonably directed toward early discharge.
Minimally Invasive Pancreatic Resection: Is It Really the Future?
Authors: Nappo G. , Perinel J. , El Bechwaty M. , Adham M.
Published: May 2016

The introduction and widespread application of minimally invasive surgery has been one of the most important innovations that radically changed the practice of surgery during the last few decades. The application to pancreatic surgery of minimally invasive approach has only recently emerged: both laparoscopic distal pancreatectomy (LDP) and laparoscopic pancreaticoduodenectomy (LPD) can be competently performed. LDP and LPD are advocated to improved perioperative outcomes, including decreased blood loss, shorter length of stay, reduced postoperative pain and expedited time to functional recovery. However, the indication to minimally invasive approach for pancreatic surgery is often benign or low-grade malignant pathologies. In this review, we summarize the current data on minimally invasive pancreatic surgery, focusing on indication, perioperative and oncological outcomes.
Ablation Strategies for Locally Advanced Pancreatic Cancer
Authors: Linecker Michael , Pfammatter Thomas , Kambakamba Patryk , DeOliveira Michelle L.
Published: May 2016

With the advent of novel and somewhat effective chemotherapy against pancreas cancer, several groups developed a new interest on locally advanced pancreatic cancer (LAPC). Unresectable tumors constitute up to 80% of pancreatic cancer (PC) at the time of diagnosis and are associated with a 5-year overall survival of less than 5%. To control those tumors locally, with perhaps improved patients survival, significant advances were made over the last 2 decades in the development of ablation methods including cryoablation, radiofrequency ablation, microwave ablation, high intensity focused ultrasound and irreversible electroporation (IRE). Many suggested a call for caution for possible severe or lethal complications in using such techniques on the pancreas. Most fears were on the heating or freezing of the pancreas, while non-thermal ablation (IRE) could offer safer approaches. The multimodal therapies along with high-resolution imaging guidance have created some enthusiasm toward ablation for LAPC. The impact of ablation techniques on primarily non-resectable PC remains, however, unclear.
Living Kidney Donors Who Develop Kidney Failure: Excerpts of Their Thoughts
Authors: Halverson Colin M.E. , Wang Jackie Y. , Poulson Michael , Karlin Jennifer , Crowley-Matoka Megan , Ross Lainie F.
Published: May 2016

Background: Psychosocial data about living kidney donors have been collected for almost 5 decades now. To date, however, no study has provided any psychosocial follow-up of donors who developed a serious health problem such as end-stage renal disease (ESRD). Methods: Donors who developed ESRD were invited to participate in a qualitative interview if they met one or both of the inclusion criteria: (1) developed ESRD within 10 years of donating and/or (2) lacked health insurance at the time of donation. We contacted 38 individuals who met these criteria, and 22 participated (58%). Two were subsequently excluded from analysis. Results: Twenty qualitative interviews were analyzed. Five findings are described: (1) donors describe the decision-making process as spontaneous and fast; (2) donors describe lack of appreciation for the need for post-donation self-care; (3) donors do not regret donating despite the adverse outcome; (4) donors advise future donors to have in place emotional and physical support post donation; and (5) donors appreciate the opportunity to tell their story from being a living donor to living with ESRD, which virtually all perceive as 2 separate unrelated events. Conclusions: Most donors are positive about their donation decision and experience and would donate again, despite developing ESRD themselves. They propose some important changes to the decision-making and informed-consent processes. Our data are reassuring regarding lack of donor regret, but highlight the need for living donor transplant programs to ensure that living donors understand their long-term risks and receive appropriate life-long follow-up care to minimize these risks.
Cell Block Preparation versus Liquid-Based Thin-Layer Cervical Cytology: A Comparative Study Evaluating Human Papillomavirus Testing by Hybrid Capture-2/Cervista, in situ Hybridization and p16 Immunohistochemistry
Authors: Tawfik Ossama , Davis Marilyn , Diaz Francisco J. , Fan Fang
Published: May 2016

Objective: Cell block (CB) preparations from residual liquid-based Pap samples have been shown to be of diagnostic value. In this study we evaluated human papillomavirus (HPV) in situ hybridization (ISH) and p16 immunohistochemistry (IHC) on CB preparations and compared the results with the primary diagnosis and standard HPV tests. Design: In total, 197 HE-stained CB slides prepared from CBs from residual Pap samples (152 ASCUS, 2 ASC-H, 32 LGSIL, 4 HGSIL, 1 AGUS and 6 normal) were analyzed. Hybrid Capture-2 (HC-2)/Cervista testing and HPV ISH and p16 IHC were performed on the CB samples. The test performance characteristics were compared with HPV and p16 assay performances. Results: The cellular architecture was well maintained in CBs with excellent consistency. HPV ISH testing had an excellent concordance with the HC-2/Cervista methods (85%) with high sensitivity (82.6%; 95% CI 75.9, 89.4) and specificity (89.3%). Of all the p16 tests, 38% were positive (60 out of 159 samples). The overall concordance between p16 and HC-2/Cervista (64%), or between p16 and ISH (68%), was lower than the concordance between ISH and HC-2/Cervista (85%). Conclusions: HPV ISH and p16 IHC testing is feasible, cost effective and practical. A combination of the two tests would ultimately improve diagnostic accuracy, leading to better therapeutic decisions.
Tumor Boards from the Perspective of Ambulant Oncological Care
Authors: Hermes-Moll Kerstin , Dengler Robert , Riese Christoph , Baumann Walter
Published: May 2016

Background: Cancer therapy requires the cooperation of physicians from different disciplines. At the core of the collaboration are ‘tumor boards' (also known as ‘multidisciplinary team meetings' and ‘tumor conferences'). However, there is limited health care research that addresses the multiple facets of such meetings. Material and Methods: Data were analyzed from 3 routinely conducted surveys comprising information from (i) office-based hematologists and oncologists, (ii) their patients, and (iii) quality indicators. Results: Most office-based oncologists stated that they participate in tumor boards taking place in hospitals. Although tumor boards are viewed as time intensive and lack financial compensation, they are considered as beneficial for patient care. Less than half of patients knew that their cases were discussed at a tumor board; those who knew rated the collaboration between their treating doctors as more positive, but also experienced slightly higher distress levels. The quality indicators showed that tumor board meetings were documented in three-quarters of the patient charts, but only half included the tumor board's recommendation. Conclusions: Participation in tumor boards is perceived as beneficial by oncologists and not just considered as a fulfillment of societies' recommendations or guidelines. The higher distress levels in patients who knew that their case was discussed at a tumor board may have occurred because more difficult cases are discussed at tumor boards and since the oncologists spend more time explaining the therapy process in complex cases, including the tumor board results.
Psychotherapie im Rahmen eines erfolgversprechenden Behandlungsplans für Depressionen: Die aktualisierte S3-Leitlinie/Nationale VersorgungsLeitlinie Unipolare Depression
Authors: Hautzinger Martin , Kühner Christine
Published: May 2016

Depressive Störungen zählen zu den häufigsten Beratungsanlässen und Erkrankungen in der Versorgung. Der vorliegende Beitrag gibt einen Überblick über die wichtigsten psychotherapierelevanten Aspekte der aktuellen Revision der S3-Leitlinie/Nationale VersorgungsLeitlinie Unipolare Depression, die im November 2015 veröffentlicht wurde.
Ressourcenaktivierung durch Perspektivwechsel. Stehen Sie doch einfach einmal auf! Ein Plädoyer für mehr Bewegung(en) in der Verhaltenstherapie
Authors: Roediger Eckhard
Published: May 2016

Hintergrund: Im Zustand emotionaler Aktivierung sind die Patienten in ihrem ich-syntonen Störungsattraktor fixiert. Mentale Perspektivwechsel haben eine zentrale Bedeutung für kognitive Neubewertungen. Durch körperliche Perspektivwechsel könnten vermutlich der Wechsel in andere Aktivierungszustände und die Aktivierung latent vorhandener Ressourcen im Sinne einer vertikalen Integration verschiedener Modalitäten umfassend unterstützt werden. Methode: Zehn teilweise aufeinander aufbauende Techniken mit verschiedenen Arten von Perspektivwechseln zum kontrollierten Balancieren zwischen emotionaler Aktivierung und Desidentifikation sowie Neubewertung werden dargestellt. Der Kontext ihrer Herkunft wird umrissen. Ergebnis: Diese komplexen Techniken ermöglichen in sehr dynamischer Weise die Aktivierung und Modifikation von Erlebens- und Verhaltensmustern, ohne die therapeutische Beziehung zu belasten. Schlussfolgerung: Diese Techniken der Beziehungsgestaltung und Prozesssteuerung könnten vermutlich unabhängig vom Störungsmodell bereits in der Therapieausbildung vermittelt werden.
Access to Medications for Cardiovascular Diseases in Low- and Middle-Income Countries
Authors: Wirtz Veronika J. , Kaplan Warren A. , Kwan Gene F. , Laing Richard O.
Published: May 2016

Cardiovascular diseases (CVD) represent the highest burden of disease globally. Medicines are a critical intervention used to prevent and treat CVD. This review describes access to medication for CVD from a health system perspective and strategies that have been used to promote access, including providing medicines at lower cost, improving medication supply, ensuring medicine quality, promoting appropriate use, and managing intellectual property issues. Using key evidence in published and gray literature and systematic reviews, we summarize advances in access to cardiovascular medicines using the 5 health system dimensions of access: availability, affordability, accessibility, acceptability, and quality of medicines. There are multiple barriers to access of CVD medicines, particularly in low- and middle-income countries. Low availability of CVD medicines has been reported in public and private healthcare facilities. When patients lack insurance and pay out of pocket to purchase medicines, medicines can be unaffordable. Accessibility and acceptability are low for medicines used in secondary prevention; increasing use is positively related to country income. Fixed-dose combinations have shown a positive effect on adherence and intermediate outcome measures such as blood pressure and cholesterol. We have a new opportunity to improve access to CVD medicines by using strategies such as efficient procurement of low-cost, quality-assured generic medicines, development of fixed-dose combination medicines, and promotion of adherence through insurance schemes that waive copayment for long-term medications. Monitoring progress at all levels, institutional, regional, national, and international, is vital to identifying gaps in access and implementing adequate policies.
The Association Between Antihypertensive Medication Nonadherence and Visit-to-Visit Variability of Blood Pressure
Authors: Kronish Ian M. , Lynch Amy I. , Oparil Suzanne , Whittle Jeff , Davis Barry R. , Simpson Lara M. , Krousel-Wood Marie , Cushman William C. , Chang Tara I. , Muntner Paul
Published: May 2016

Low adherence to antihypertensive medication has been hypothesized to increase visit-to-visit variability (VVV) of blood pressure (BP). We assessed the association between antihypertensive medication adherence and VVV of BP in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). VVV of BP was calculated using SD independent of mean, SD, and average real variability across study visits conducted 6 to 28 months after randomization. Participants who reported taking <80% of their antihypertensive medication at ≥1 study visits were categorized as nonadherent. Participants were followed up for cardiovascular events and mortality after the assessment of adherence and VVV of BP. SD independent of mean of BP was higher for nonadherent (n=2912) versus adherent (n=16 878) participants; 11.4±4.9 versus 10.5±4.5 for systolic BP; 6.8±2.8 versus 6.2±2.6 for diastolic BP (each
P
<0.001). SD independent of mean of BP remained higher among nonadherent than among adherent participants after multivariable adjustment (0.8 [95% confidence interval, 0.7–1.0] higher for systolic BP and 0.4 [95% confidence interval, 0.3–0.5] higher for diastolic BP]. SD and average real variability of systolic BP and diastolic BP were also higher among nonadherent than among adherent participants. Adjustment for nonadherence did not explain the association of VVV of BP with higher fatal coronary heart disease or nonfatal myocardial infarction, stroke, heart failure, or mortality risk. In conclusion, improving medication adherence may lower VVV of BP. However, VVV of BP is associated with cardiovascular outcomes independent of medication adherence.