bluuebunny/crossref_metadata_2025 huggingface dataset:
A Hot Spots Ignition Probability Model for Low‐Velocity Impacted Explosive Particles Based on the Particle Size and Distribution
Authors: Guo Hong-fu , Wu Yan-qing , Huang Feng-lei
Published: February 2017

Particle size and distribution play an important role in ignition. The size and distribution of the cyclotetramethylene tetranitramine (HMX) particles were investigated by Laser Particle Size Analyzer Malvern MS2000 before experiment and calculation. The mean size of particles is 161 μm. Minimum and maximum sizes are 80 μm and 263 μm, respectively. The distribution function is like a quadratic function. Based on the distribution of micron scale explosive particles, a microscopic model is established to describe the process of ignition of HMX particles under drop weight. Both temperature of contact zones and ignition probability of powder explosive can be predicted. The calculated results show that the temperature of the contact zones between the particles and the drop weight surface increases faster and higher than that of the contact zones between two neighboring particles. For HMX particles, with all other conditions being kept constant, if the drop height is less than 0.1 m, ignition probability will be close to 0. When the drop heights are 0.2 m and 0.3 m, the ignition probability is 0.27 and 0.64, respectively, whereas when the drop height is more than 0.4 m, ignition probability will be close to 0.82. In comparison with experimental results, the two curves are reasonably close to each other, which indicates our model has a certain degree of rationality.
Simultaneous Papillary Carcinoma in Thyroglossal Duct Cyst and Thyroid
Authors: Penna Gustavo Cancela e , Mendes Henrique Gomes , Kraft Adele O. , Berenstein Cynthia Koeppel , Fonseca Bernardo , Martorina Wagner José , de Souza Andreise Laurian N. R. , Meyer de Moraes Gustavo , Rajão Kamilla Maria Araújo Brandão , Sousa Bárbara Érika Caldeira Araújo
Published: February 2017

Thyroglossal duct cyst (TDC) is a cystic expansion of a remnant of the thyroglossal duct tract. Carcinomas in the TDC are extremely rare and are usually an incidental finding after the Sistrunk procedure. In this report, an unusual case of a 36-year-old woman with concurrent papillary thyroid carcinoma arising in the TDC and on the thyroid gland is presented, followed by a discussion of the controversies surrounding the possible origins of a papillary carcinoma in the TDC, as well as the current management options.
Meta-Analysis of the Relationship between Deep Brain Stimulation in Patients with Parkinson’s Disease and Performance in Evaluation Tests for Executive Brain Functions
Authors: Martínez-Martínez A. M. , Aguilar O. M. , Acevedo-Triana C. A.
Published: February 2017

Parkinson’s disease (PD) is a neurodegenerative condition, which compromises the motor functions and causes the alteration of some executive brain functions. The presence of changes in cognitive symptoms in PD could be due to the procedure of deep brain stimulation (DBS). We searched in several databases for studies that compared performance in executive function tests before and after the DBS procedure in PE and then performed a meta-analysis. After the initial search, there were 15 articles that specifically evaluated the functions of verbal fluency, working memory, cognitive flexibility, abstract thinking, and inhibition. It was found that there were differences in the evaluation of the cognitive functions in terms of the protocols, which generated heterogeneity in the results of the meta-analysis. Likewise, a tendency to diminish functions like verbal fluency and inhibition was found, being this consistent with similar studies. In the other functions evaluated, no difference was found between pre- and postsurgery scores. Monitoring of this type of function is recommended after the procedure.
Mesenchymal Stromal Cell Therapy in Crohn's Disease
Authors: Forbes Geoffrey M.
Published: February 2017

Background: Mesenchymal stromal cells (MSC) are multipotent adult stem cells with immunomodulatory properties. They uniquely express HLA class I antigen at a low level, and do not express HLA class II. Hence, for allogeneic administration, donor to recipient matching is not required; yet a prolonged chimeric state does not occur. Contrary to haematopoietic stem cell transplantation, cytotoxic drug therapy is not required to harvest, or administer, cells. Key Messages: MSC are obtained from marrow, adipose tissue or placenta. In our centre, MSC are isolated from a 10 ml donor marrow aspirate, by virtue of their adherence to plastic. They are expanded in culture, cryopreserved, and subjected to strict quality controls before release for intravenous administration. These activities occur in a dedicated, nationally accredited, laboratory. Initial observations of allogeneic MSC efficacy were in graft-versus-host disease. Both autologous and allogeneic MSC have since been evaluated in biologic refractory luminal and fistulising Crohn's disease (CD). Data from early-phase studies have suggested efficacy for luminal disease when allogeneic MSC were given intravenously and also suggested efficacy for fistulising disease when either allogeneic or autologous MSC were administered into fistulas. MSC treatment is not reported to have caused serious adverse events. Although in vitro criteria for defining MSC exist, a major challenge lies in how to define MSC for clinical use. MSC function in vivo is likely to be dependent upon donor immunological characteristics, and widely varying manufacturing processes between laboratories. MSC dose, frequency of administration, stage of disease, and presence of concomitant immunosuppression also require to be defined. Conclusions: MSC therapy may have future utility in CD, but considerable work is first required to determine appropriate phenotypic and functional characteristics of administered cells.
Crohn's Disease and Intestinal Transplantation
Authors: Drastich Pavel , Oliverius Martin
Published: February 2017

Background: Most patients with Crohn's disease (CD) require one or more operations during their lifetime. Repeated resections and surgical complications may result in short gut in a subset of patients, typically those with extensive small bowel disease or a penetrating CD phenotype. The effects of short bowel syndrome (SBS) can range in seriousness from mild to life-threatening advanced intestinal failure. Worldwide, CD is the second leading indication for intestinal transplantation (ITx) in SBS, but the overall incidence of ITx is quite low. Key Messages: Currently, total parenteral nutrition (TPN) is the preferred treatment option for patients with SBS because of its superior survival outcome. However, TPN can fail from loss of venous access due to catheter-associated thromboses, recurrent catheter-related blood stream infections, or intestinal-failure-associated liver dysfunction. Three types of transplantations are available for CD patients - small bowel alone, liver plus small bowel and multivisceral, which includes other intra-abdominal organs. An abdominal wall transplant is required in case of abdominal wall defects or lack of free intra-abdominal space. The current 5-year survival rate of 54% following ITx of the isolated small bowel appears worse than that associated with TPN. However, outcomes are substantially improving because of surgical and technical advances and progress in medical therapy. On the other hand, ITx carries the risk of both complications (e.g., rejection, infections, and post transplant lymphoproliferative disorders) and adverse events associated with immunosuppression. CD recurrence has been reported in a few patients, but this primarily histologic recurrence might not be of great clinical importance. Conclusions: ITx has become a well-established treatment for those who fail on TPN and who have life-threatening complications. Fortunately, it concerns only a small proportion of CD patients, but it does offer reasonable survival and quality of life. Primary management of patients with small bowel failure should be provided by a center experienced in medical intestinal rehabilitation, nutrition, and transplantation of other solid organs.
Botulinum Toxin Off-Label Use in Dermatology: A Review
Authors: Campanati Anna , Martina Emanuela , Giuliodori Katia , Consales Veronica , Bobyr Ivan , Offidani Annamaria
Published: February 2017

Background: Botulinum toxin is a neurotoxin produced by the bacterium Clostridium botulinum which causes a flaccid muscle paralysis. It is currently used for aesthetic treatments and in the focal hyperhidrosis. Recently, botulinum toxin has also been used experimentally in many other dermatological conditions with good results. Objective: To review and analyze the possible botulinum toxin off-label applications published. Methods: A retrospective review of the published data was conducted. Conclusions: this potent drug can lead to several off-label indications of interest for dermatologists. Further clinical trials are still needed to better understand the real efficacy and safety of these applications and to standardize injection and dose protocols.
Feasibility of Preoperative Chemotherapy with Docetaxel, Cisplatin, and 5-Fluorouracil versus Adriamycin, Cisplatin, and 5-Fluorouracil for Resectable Advanced Esophageal Cancer
Authors: Shiraishi Osamu , Yamasaki Makoto , Makino Tomoki , Motoori Masaaki , Miyata Hiroshi , Shinkai Masayuki , Kimura Yutaka , Hirao Motohiro , Fujitani Kazumasa , Tamura Shigeyuki , Kobayashi Kenji , Yano Masahiko , Doki Yuichiro , Yasuda Takushi
Published: February 2017

Background: Neoadjuvant chemotherapy for resectable advanced esophageal squamous cell carcinoma (ESCC) requires reassessment. We have conducted a trial aiming at the comparison between DCF and ACF concerning perioperative adverse events. Methods: Patients were randomly assigned to receive either DCF [docetaxel 70 mg/m2, cisplatin 70 mg/m2 on day 1, and 5-fluorouracil (5-FU) 700 mg/m2 for 5 days] every 3 weeks or ACF (adriamycin 35 mg/m2, cisplatin 70 mg/m2 on day 1, and 5-FU 700 mg/m2 for 7 days) every 4 weeks. Each group consisted of 81 patients. Two cycles of preoperative chemotherapy were planned, after which patients underwent subtotal esophagectomy via a right thoracotomy with lymphadenectomy. Chemotherapy- and surgery-related adverse effects were assessed. Results: Grade 3-4 neutropenia and febrile neutropenia occurred in 90 and 39% of patients, respectively, in the DCF group compared with 69 and 17% of patients, respectively, in the ACF group (p < 0.01). Perioperative complications did not differ significantly between the groups. The overall response rates of DCF and ACF were 61 and 40%, respectively, while the histopathological complete responses were 15 and 3%, respectively (p < 0.01). Conclusion: The DCF and ACF regimens were found to be equally feasible in patients with resectable advanced ESCC; however, DCF delivered an antitumor effect and therefore potentially improved the long-term outcomes.
EGFR Inhibitors in Patients with Advanced Squamous Cell Anal Carcinomas: A Single-Institution Experience
Authors: Kim Dae Won , Byer Jennifer , Kothari Nishi , Mahipal Amit , Chang Yound Doo , Kim Richard D.
Published: February 2017

Background: Although squamous cell anal carcinomas are relatively rare, their incidence has been increasing steadily. Because of the limited data, treatment of metastatic disease is a major therapeutic challenge. In this study, we report the safety and efficacy of epidermal growth factor receptor (EGFR) inhibitors in patients with advanced squamous cell anal carcinomas. Method: A retrospective analysis was conducted using the Moffitt Cancer Tumor Registry from January 2009 to January 2014. Eligible patients had diagnosis of advanced squamous cell anal carcinomas and received an EGFR inhibitor as part of their treatment. Result: A total of 13 patients were identified for analysis. All of them received concurrent chemoradiation as initial treatment and subsequently had recurrence. Five patients received single agent cetuximab or panitumumab, and the others received cetuximab or panitumumab with irinotecan or FOLFIRI. The objective response rate was 30.8% including 1 complete response, and the disease control rate was 46.2%. With a median follow-up of 9.6 months, the median progression-free survival and median overall survival were 4.4 months and 11.4 months, respectively. Conclusion: Our analysis suggests that EGFR inhibitors have potential efficacy and are reasonably well tolerated in patients with squamous cell anal carcinomas. These findings warrant further evaluation in a large prospective trial.
Extranodal Marginal Zone Lymphoma of Ocular Adnexa: Outcomes following Radiation Therapy
Authors: Platt Sean , Al Zahrani Yahya , Singh Nakul , Hill Brian , Cherian Sheen , Singh Arun D.
Published: February 2017

Aim: The aim of this study was to report outcomes following radiation therapy in patients with biopsy-proven extranodal marginal zone lymphoma of the ocular adnexa and uvea. Methods: Records from a single institution were retrospectively reviewed from January 1997 to December 2015. The mean follow-up duration was 38 months (range 0-194). Radiation therapy was administered to 77 eyes (60 patients); 57 of the 77 eyes (74%) were treated with radiation only (range 20-36 Gy, median 15 fractions). Radiation cataract, radiation retinopathy, and optic neuropathy assessments were performed on all eyes treated with radiation. Results: 100% of the 47 patients treated with radiation therapy only had local control with an average dose of 26.5 Gy (median 25.2 [range 20-36] Gy; 150-200 cGy per fraction). Four patients lost 2 lines or more of vision after radiation. The most common complication of radiation therapy was cataract formation/progression in 19 eyes (25%). Radiation retinopathy was observed only in 1 patient (1%). Conclusion: Our results confirm that radiation therapy (median 25 Gy) for extranodal marginal zone lymphoma of the ocular adnexa is associated with high local control and low risk of visually significant complications.
Alexithymia and Plaque Psoriasis: Preliminary Investigation in a Clinical Sample of 250 Patients
Authors: Talamonti Marina , Galluzzo Marco , Servoli Stella , D'Adamio Simone , Bianchi Luca
Published: February 2017

Background/Aims: Psoriasis as a dermatological disorder has complex effects on mental health and the psychological status of the patient. Many authors proposed that assessing how psoriasis affects a patient's life is better than a body surface area measurement for delineating psoriasis severity. Alexithymia is a personality dimension characterized by difficulty identifying feelings, difficulty describing feelings, and externally oriented thinking observed in many clinical conditions, especially in psychosomatic disorders. This study aimed to determine the prevalence of alexithymia in patients with plaque psoriasis compared with healthy participants, while taking into consideration demographic and clinical variables. Methods: We enrolled 250 patients with chronic plaque psoriasis, naïve to any systemic treatment, and 215 healthy individuals. The 20-item Toronto Alexithymia Scale (TAS-20) was used to assess alexithymia. Data analysis was done. Results: The mean TAS score was 53.5 (±15.3) for the patient group and 45.1 (±10.8) for controls (p < 0.0001). Compared to controls, the psoriasis group showed significant alexithymic features (32.4 vs. 9.3%), and no significant differences of alexithymia between patients with severe and mild psoriasis were observed. A significant relationship was determined between alexithymia and female gender and sensitive area involvement, such as the face, hands, and genital area. Conclusion: This study suggests that the assessment of alexithymia should be a part of the comprehensive care of patients with moderate to severe psoriasis. For this purpose, the TAS-20 is a useful and simple tool to be used in daily clinical practice.
Pattern and Dynamics of Distant Metastases in Metastatic Colorectal Cancer
Authors: Holch Julian Walter , Demmer Maximilian , Lamersdorf Charlotte , Michl Marlies , Schulz Christoph , von Einem Jobst Christian , Modest Dominik Paul , Heinemann Volker
Published: February 2017

Background: Few studies report the incidence of metastatic patterns in colorectal cancer. Furthermore, little is known about dynamic aspects of these metastases during the course of disease. Methods: This retrospective cohort study involved 385 patients who received anti-tumor treatment at our institution (Department of Medical Oncology, University Hospital Grosshadern, Ludwig-Maximilians-University Munich, Germany) for metastatic colorectal adenocarcinoma between 2007 and 2014. We reviewed all available imaging results of these patients to document the presence and detailed localization of metastases. Results: Most of the evaluated patients were initially diagnosed with metastases in the liver (70%), followed by the lungs (24%), distant lymph nodes (16%), and peritoneum (15%), besides rare anatomical sites (<5%). Colon and rectal cancer as well as synchronous and metachronous metastases differed with regard to the pattern of individual metastatic sites. The median time to first progressive disease (PD) with new metastases was 12.6 months. The time intervals between first and second as well as second and third PD with new metastases were comparable with 10.5 and 10.8 months, respectively. At initial diagnosis, the mean number of metastatic sites was 1.4 and increased to 2.6 at the third PD with new metastases. For patients with initially one metastatic site, the mean number increased to 2.2. Conclusion: The present analysis provides detailed information on the pattern and evolution of colorectal cancer metastases over time. Thus, it may establish the basis for prospective future research in this field.
Oligometastatic Disease in Colorectal Cancer - How to Proceed
Authors: Aigner Felix , Pratschke Johann , Schmelzle Moritz
Published: February 2017

Background: Oligometastatic disease in colorectal cancer may affect the liver, lung, and peritoneum. This review mainly focuses on colorectal liver metastases (CRLM) and highlights recommendations and therapeutic strategies drawn from the current literature and consensus conferences. The following data address a paradigm shift in surgical approaches to CRLM, pushing the limits of multimodal treatment concepts. Methods: A systematic review of the relevant literature on multimodal treatment strategies for synchronous and metachronous CRLM is presented. Results: The choice of treatment strategy depends on the clinical scenario; however, perioperative chemotherapy and the liver-first concept in synchronous CRLM are favored with subsequent partial extended liver resection with or without various augmentation techniques for liver surgery. Conclusion: Surgical strategies should be strongly defined with regard to an adequate liver remnant. All patients with synchronous CRLM should be evaluated by a multidisciplinary team.
Neuroendocrine Cancer, Therapeutic Strategies in G3 Cancers
Authors: Rinke Anja , Gress Thomas M.
Published: February 2017

Background: According to the latest WHO classification, neuroendocrine neoplasm (NEN) G3 of the gastrointestinal tract is defined by a proliferation index Ki67 above 20%. Gastrointestinal neuroendocrine carcinoma (NEC) is a rare and highly aggressive malignancy and despite responsiveness to chemotherapy, overall survival is poor. In the last 3-4 years, the heterogeneity of the NEN G3 group has become evident. Summary: In addition to the proliferative activity, the tumour differentiation seems to play a major role, further dividing the NEN G3 group into neuroendocrine tumour (NET) G3 and NEC. NET G3 often arise in the pancreas, and their median proliferation rate is lower and prognosis is better as compared to NEC. However, NET G3 show a limited response to platinum-based chemotherapy. Lack of specific data for NET G3 hampers clear therapeutic recommendations. Cisplatin combined with etoposide is the established standard regimen for advanced gastrointestinal NEC. Substituting carboplatin for cisplatin or irinotecan for etoposide is considered alternative first-line regimen. There is no standard second-line treatment; options are discussed within this review. Key Points: (1) In NEN G3, the distinction between NET G3 and NEC G3 is clinically and prognostically meaningful. (2) Platinum-based chemotherapy remains the recommended first-line treatment in metastasized NEC patients. (3) There is no established standard for NET G3; treatments established for NET G2 such as temozolomide-based chemotherapy or peptide receptor radiotherapy may be considered. (4) Specific trials for NET G3 are necessary. (5) New therapies for NEC are urgently needed. Checkpoint inhibitors should be evaluated.
Two Cases of Mistaken Polyuria and Nephrocalcinosis in Infants with Glucose-Galactose Malabsorption: A Possible Role of 1,25(OH)2D3
Authors: Fiscaletti Melissa , Lebel Marie-Jeanne , Alos Nathalie , Benoit Geneviève , Jantchou Prévost
Published: February 2017

Background/Aims: Glucose-galactose malabsorption (GGM) is a rare and potentially fatal disorder. The autosomal recessive mutation of the SGLT1 gene interferes with the active glucose transport in the gut resulting in osmotic diarrhea and failure to thrive (FTT). Two nonrelated infants with GGM are presented as well as a novel mutation in SGLT1. Case Presentation: The first case consulted for FTT and presented with hypercalcemia and hypercalciuria. His mother had self-medicated with high doses of vitamin D. The second case consulted for macroscopic hematuria, and presented with dehydration and secondary acute kidney injury. In both cases, the profuse diarrhea, initially mistaken for polyuria, promptly resolved after the introduction of glucose-galactose-free milk. Investigations showed bilateral nephrocalcinosis and high levels of 1,25(OH)2D3 in both patients. We hypothesize that the upregulation of epithelial calcium channels (TRPV6) and 1,25(OH)2D3 are possible factors involved in the pathophysiology of nephrocalcinosis sometimes seen in GGM. Furthermore, a novel intronic SGLT1 mutation (c.207+2dup) is described. Conclusion: These 2 cases demonstrate that a malabsorption disorder such as GGM can present with nephrocalcinosis and/or hypercalcemia, with increased 1,25(OH)2D3 levels in infants. Prompt recognition of GGM is sometimes difficult but crucial.
Three-Dimensional Imaging-Based Web Application for Predicting Tracheal Tube Depth in Preterm Neonates
Authors: Tupprasoot Raksa , Langan Dean , Hutchinson J. Ciaran , Barrett Hannah , Sury Michael R.J. , Arthurs Owen J.
Published: February 2017

Background: Positioning a tracheal tube (TT) to the correct depth in preterm infants is challenging. Currently, there is no reliable single-predictor model for neonates applicable to the whole range of size or age. Objective: In this study, we used post-mortem magnetic resonance imaging (PMMRI) of preterm infants to measure tracheal dimensions and to develop a clinical guide for TT positioning. Methods: We measured tracheal length (TL) and tracheal diameter (TD) in a cohort of normal neonates and foetuses that underwent PMMRI (cause of death unexplained). The distance between the lips and the mid-tracheal point, i.e., the mid-tracheal length (mid-TL), and the TD measurement were obtained. We produced univariate prediction models of mid-TL and TD, using gestational age (GA), foot length (FL), crown-rump length (CRL) and body weight (BW) as potential predictors, as well as multiple prediction models for mid-TL. Results: Tracheal measurements were performed in 117 cases, with a mean GA of 28.8 weeks (range 14-42 weeks). The best linear association was between mid-TL and FL (mid-TL = FL × 0.914 + 1.859; R2 = 0.94), but was improved by multivariate regression models. We developed a prediction tool using only GA and BW (R2 = 0.92), and all four predictors (GA, BW, FL and CRL; R2 = 0.94) which is now available as a web-based application via the Internet. Conclusion: Post-mortem imaging data provide estimates of TT insertion depth. Our prediction tool based on age and BW can be used at the bedside and is ready to be tested in clinical practice.
Effects of Monochord Music on Heart Rate Variability and Self-Reports of Relaxation in Healthy Adults
Authors: Gäbel Christine , Garrido Natalia , Koenig Julian , Hillecke Thomas Karl , Warth Marco
Published: February 2017

Background: Music-based interventions are considered an effective and low-cost treatment option for stress-related symptoms. The present study aimed to examine the trajectories of the psychophysiological response in apparently healthy participants during a music-based relaxation intervention compared to a verbal relaxation exercise. Material and Methods: 70 participants were assigned to either receptive live music (experimental group) or a prerecorded verbal relaxation exercise (control group). Self-ratings of relaxation were assessed before and after each intervention on visual analogue scales and the Relaxation Inventory (RI). The heart rate variability (HRV) was continuously recorded throughout the sessions. Statistical analysis focused on HRV parameters indicative of parasympathetic cardiovascular outflow. Results: We found significant quadratic main effects for time on the mean R-R interval (heart rate), the high-frequency power of HRV (indicative of parasympathetic activity), and the self-ratings of relaxation in both groups. A significant group × time interaction was observed for the cognitive tension subscale of the RI. Conclusions: Participants in both groups showed psychophysiological changes indicative of greater relaxation over the course of the interventions. However, differences between groups were only marginal. Music might be effective in relieving stress and promoting relaxation by altering the autonomic nervous system function. Future studies need to explore the long-term outcomes of such interventions.
Exome Sequencing Identifies a Novel DES Mutation (R227C) in a Chinese Dilated Cardiomyopathy Family
Authors: Yu Rong , Liu Lv , Chen Chan , Shen Jin-Mei
Published: February 2017

Objectives: Dilated cardiomyopathy (DCM) is a common disease in the clinic, and it is the leading cause of heart failure and sudden cardiac death. Previous studies have proven that genetic factors play a crucial role in the occurrence of DCM; more than 50 disease genes including desmin (DES) have been identified to be associated with DCM. At present, most DES mutations are reported in desmin-related myofibrilla myopathy patients, but variants leading to isolated DCM are rarely reported. Methods: We applied whole-exome sequencing and cardiomyopathy-related gene filtering strategies to discover the genetic factors in a Chinese DCM family. Results: A novel mutation (c.679 C>T /p.R227C) in exon 3 of DES was identified and cosegregated with the affected members of a Chinese family with isolated DCM phenotypes (left ventricle and left atrial diameters). Conclusion: This mutation leads to a substitution of arginine by cysteine and it is predicted to be deleterious by bioinformatics programs. Our study not only contributes to the genetic diagnosis and counseling of families with DCM, but it also further proves that DES mutations may lead to isolated DCM and provides a new case for the study of the relationship between DES mutations and DCM.
The Course and Impact of Poststroke Insomnia in Stroke Survivors Aged 18 to 65 Years: Results from the Psychosocial Outcomes In StrokE (POISE) Study
Authors: Glozier Nick , Moullaali Tom J. , Sivertsen Børge , Kim Dukyeon , Mead Gillian , Jan Stephen , Li Qiang , Hackett Maree L.
Published: February 2017

Background: Insomnia symptoms are common in the population and have negative psychosocial and functional sequelae. There are no prospective studies of the course of such symptoms and their impact, if any, in stroke survivors. This prospective cohort study investigated insomnia after stroke in working-age adults and evaluated its impact on psychological and functional outcomes over the subsequent year. Methods: We prospectively recruited 441 young (<65 years) consecutive stroke survivors from 20 public hospitals in the New South Wales Stroke Service network. Participants were assessed by self-report and interview at 28 days, 6 months, and 12 months after stroke. Insomnia was defined using a common epidemiological measure of sleep disturbance and daytime consequences. Depression, anxiety, disability, and return to work were assessed through standardized measures. Results: The point prevalence of insomnia at each time point in the year after stroke was stable at 30–37% and more common in females. Fifty-eight (16%) of all participants reported “chronic” insomnia, with symptoms at both baseline and 6 months later. At 12 months, this group was more likely to be depressed (OR 6.75, 95% CI 2.78–16.4), anxious (OR 3.31, 95% CI 1.54–7.09), disabled (OR 3.60, 95% CI 2.07–6.25), and not have returned to work, compared to those without insomnia over the same period. Conclusions: Chronic insomnia has a negative effect on disability and return to work 1 year after stroke even after adjusting for demographic, psychiatric, and disability factors. Identifying and appropriately targeting insomnia through known effective treatments may improve functional outcomes after stroke.
Inherited Congenital Cataract: A Guide to Suspect the Genetic Etiology in the Cataract Genesis
Authors: Messina-Baas Olga , Cuevas-Covarrubias Sergio A.
Published: February 2017

Cataracts are the principal cause of treatable blindness worldwide. Inherited congenital cataract (CC) shows all types of inheritance patterns in a syndromic and nonsyndromic form. There are more than 100 genes associated with cataract with a predominance of autosomal dominant inheritance. A cataract is defined as an opacity of the lens producing a variation of the refractive index of the lens. This variation derives from modifications in the lens structure resulting in light scattering, frequently a consequence of a significant concentration of high-molecular-weight protein aggregates. The aim of this review is to introduce a guide to identify the gene involved in inherited CC. Due to the manifold clinical and genetic heterogeneity, we discarded the cataract phenotype as a cardinal sign; a 4-group classification with the genes implicated in inherited CC is proposed. We consider that this classification will assist in identifying the probable gene involved in inherited CC.
The Blood-Retinal Barrier in the Management of Retinal Disease: EURETINA Award Lecture
Authors: Cunha-Vaz José
Published: February 2017

Retinal diseases are the main causes of blindness in the Western world. Diabetic retinopathy and age-related macular degeneration continue to increase in prevalence and as main causes of vision loss. Intravitreal anti-VEGF and steroid injections have raised new expectations for their successful treatment. These agents act by stabilizing the blood-retinal barrier (BRB). Our group defined the BRB by identifying for the first time the tight junctions that unite retinal endothelial cells and are the basis for the inner BRB, an observation later confirmed in retinal pigment epithelial cells and in brain vessels. A major role of active transport processes was also identified. Today, the BRB is understood to play a fundamental role in retinal function in both health and disease. Retinal edema, an ubiquitous manifestation of retinal disease, is directly associated with breakdown of the BRB and with vision loss. In its most common form (i.e., vasogenic edema), due to breakdown of the BRB, Starling's law of capillary filtration may be used to interpret the mechanisms of fluid accumulation in the retina. The main factors involved in the development of retinal edema are BRB permeability, capillary hydrostatic pressure, tissue hydrostatic pressure, tissue osmotic pressure, and plasma osmotic pressure. In the clinical environment, breakdown of the BRB has been identified by fluorescein angiography and vitreous fluorometry, requiring the intravenous administration of fluorescein. An OCT-based method, OCT-Leakage, recently introduced by our group is capable of noninvasively identifying and quantifying sites of alteration of the BRB by mapping areas of lower-than-normal optical reflectivity, thus reflecting changes in the retinal extracellular fluid. We found good correspondence between the location of increased areas of low optical reflectivity identified by OCT-Leakage and the main sites of leakage on fluorescein angiography. Furthermore, with OCT-Leakage the areas of abnormal fluid accumulation can be identified in specific retinal layers, clearly offering more information than previously obtained with fluorescein angiography. OCT angiography has become available, replacing much of the information yielded by fluorescein angiography in a noninvasive manner. However, OCT angiography cannot visualize the leakage, i.e., the alteration of the BRB. OCT-Leakage is able to identify the locations of increases in extracellular fluid in the different layers of the retina. The complementarity of these 2 methods is of potential great interest for the diagnosis and management of several retinal diseases in which the presence and amount of fluid, as a marker of severity and activity, is paramount to treatment and management decisions in clinical practice.
Convergent Results from Neuropsychology and from Neuroimaging in Patients with Mild Cognitive Impairment
Authors: Eliassen Carl Fredrik , Reinvang Ivar , Selnes Per , Fladby Tormod , Hessen Erik
Published: February 2017

Background/Aims: To investigate the correspondence between neuropsychological single measures and variation in fludeoxyglucose positron emission tomography (FDG PET) glucose metabolism and magnetic resonance imaging (MRI) cortical thickness in mild cognitive impairment (MCI) patients. Methods: Forty-two elderly controls and 73 MCI subjects underwent FDG PET and MRI scanning. Backward regression analyses with PET and MRI regions were used as dependent variables, while Rey Auditory Verbal Memory Test (RAVLT) recall, Trail Making Test B (TMT B), and a composite test score (RAVLT learning and immediate recall, TMT A, COWAT, and letter-number sequencing) were used as predictor variables. Results: The composite score predicted variation in cortical metabolism; supplementary analyses showed that TMT B was significantly correlated with PET metabolism as well. RAVLT and TMT B were significant predictors of variation in MRI cortical thickness. Conclusion: Our results indicate that RAVLT and TMT B are sensitive to variation in Alzheimer disease neuroimaging markers.
Association of Growth Differentiation Factor 15 with Mortality in a Prospective Hemodialysis Cohort
Authors: You Amy S. , Kalantar-Zadeh Kamyar , Lerner Lorena , Nakata Tracy , Lopez Nancy , Lou Lidia , Veliz Mary , Soohoo Melissa , Jing Jennie , Zaldivar Frank , Gyuris Jeno , Nguyen Danh V. , Rhee Connie M.
Published: February 2017

Background/Aims: Cardiovascular disease and protein-energy wasting are among the strongest predictors of the high mortality of dialysis patients. In the general population, the novel cardiovascular and wasting biomarker, growth differentiation factor 15 (GDF15), is associated with decreased survival. However, little is known about GDF15 in dialysis patients. Methods: Among prevalent hemodialysis patients participating in a prospective study (October 2011 to August 2015), we examined the association of baseline GDF15 levels with all-cause mortality using unadjusted and case mix-adjusted death hazard ratios (HRs) that controlled for age, sex, race, ethnicity, diabetes, and dialysis vintage. Results: The mean age ± SD of the 203 patients included in the study was 53.2 ± 14.5 years, and the cohort included 41% females, 34% African-Americans, and 48% Hispanics. GDF15 levels (mean ± SD 5.94 ± 3.90 ng/mL; range 1.58-39.8 ng/mL) were higher among older patients and were inversely associated with serum creatinine concentrations as a surrogate for muscle mass. Each 1.0 ng/mL increase in GDF15 was associated with an approximately 17-18% higher mortality risk in the unadjusted and case mix models (p < 0.05). Increments of about 1 SD (a 4.0 ng/mL increase in GDF15) were associated with a nearly 2-fold higher death risk. The highest GDF15 tertile was associated with higher mortality risk (reference: lowest tertile): the HRs (95% CI) were 3.19 (1.35-7.55) and 2.45 (1.00-6.00) in the unadjusted and the case mix-adjusted model, respectively. These incremental death trends were confirmed in cubic spline models. Conclusion: Higher circulating GDF15 levels are associated with higher mortality risk in hemodialysis patients. Future studies are needed to determine whether GDF15 may represent a novel therapeutic target for cardiovascular disease, wasting, and death in this population.
Utilization of a Novel, Multi-Durometer Intracranial Distal Access Catheter: Nuances and Experience in 110 Consecutive Cases of Aneurysm Flow Diversion
Authors: Colby Geoffrey P. , Lin Li-Mei , Xu Risheng , Beaty Narlin , Bender Matthew T. , Jiang Bowen , Huang Judy , Tamargo Rafael J. , Coon Alexander L.
Published: February 2017

Background: Coaxial catheter support systems provide a safe and stable foundation in endovascular treatment of intracranial aneurysms. Increasingly, robust distal intracranial support is sought during complex neurointerventions. The AXS Catalyst 5 distal access catheter (Cat5) is a new intracranial catheter designed for improved trackability and stability. We report the first experience using Cat5 for aneurysm treatment by flow diversion. Methods: A single-center aneurysm database was reviewed for cases of aneurysm treatment with the Pipeline embolization device (PED) that utilized Cat5. Data were collected for patient demographics, aneurysm characteristics, procedural details, catheter positions, vessel tortuosity, and catheter related complications. Results: One hundred and ten cases of aneurysm flow diversion were successfully performed using Cat5. Patient age ranged from 21 to 86 years (mean 57 ± 12.5 years) with 84% women. Aneurysm size ranged from 2 to 28 mm (mean 5.7 ± 5.0 mm), with 97% in the anterior circulation. Twenty-four aneurysms (22%) were located beyond the ICA termination. Significant cervical carotid tortuosity was present in 26% of cases, and moderate to severe cavernous tortuosity (cavernous grade ≥2) in 45% of cases. Cat5 was tracked to the intended distal position in all cases with 100% technical success of PED implantation. No iatrogenic catheter-related vessel injury occurred, and major neurological morbidity occurred in 1 patient (1%). Summary: The Cat5 is a novel, multi-durometer cranial distal access catheter designed for use in tri-axial systems. We have demonstrated the utility of Cat5 in 110 successful cases of flow diversion with a wide range of complexity. This catheter is a new tool in the neurointerventionalist's armamentarium to achieve robust and atraumatic distal access.
Association between Various Brain Pathologies and Gait Disturbance
Authors: Wennberg Alexandra M.V. , Savica Rodolfo , Mielke Michelle M.
Published: February 2017

Background: Approximately 30% of older adults have disrupted gait. It is associated with increased risk of cognitive decline, disability, dementia, and death. Additionally, most older adults present with 1 or more neuropathologies at autopsy. Recently, there has been an effort to investigate the association between subclinical neuropathology and gait. Summary: We reviewed studies that investigated the association between gait and neuropathologies. Although all pathologies reviewed were associated with gait, grey matter atrophy was most consistently linked with poorer gait performance. Studies investigating the association between white matter and gait focused primarily on total white matter. Future research using more parsed regional analysis will provide more insight into this relationship. Evidence from studies investigating neuronal activity and gait suggests that gait disruption is associated with both under- and overactivation. Additional research is needed to delineate these conflicting results. Lastly, early evidence suggests that both amyloid and tau aggregation negatively impact multiple gait parameters, but additional studies are warranted. Overall, there was substantial methodological heterogeneity and a paucity of longitudinal studies. Key Messages: Longitudinal studies mapping changes in different types of neuropathology as they relate to changes in multiple gait parameters are needed to better understand trajectories of pathology and gait.
A New Perspective for Osteosarcoma Therapy: Proteasome Inhibition by MLN9708/2238 Successfully Induces Apoptosis and Cell Cycle Arrest and Attenuates the Invasion Ability of Osteosarcoma Cells in Vitro
Authors: Liu Renhao , Fu Chunjiang , Sun Jiabing , Wang Xvming , Geng Shuo , Wang Xiaoyu , Zou Jilong , Bi Zhenggang , Yang Chenglin
Published: February 2017

Background: The proteasome exists in all eukaryotic cells and provides the main route of intracellular proteins degradation involved in cell growth and apoptosis. Proteasome inhibition could block protein degradation pathways and disturb regulatory networks, possibly leading to profound effects on cell growth, particularly in cancer cells. A proteasome inhibitor with an appropriate toxicity index for malignant cells rather than normal cells would be an attractive anticancer therapy. Methods: The human osteosarcoma (OS) cell lines MG-63 and Saos-2 and normal osteoblast cells were used to study the antitumour activity of the proteasome inhibitor MLN9708/2238. Results: MLN2238 inhibited cell growth, induced cell cycle arrest and apoptosis, and attenuated the invasion abilities of MG-63 and Saos-2 cells, with little cytotoxicity to normal cells. In addition, MLN2238 promoted antitumour mechanisms including the accumulation of E2F1, P53, P21 and other negative G2/M checkpoint proteins; up-regulated the relative expression ratio of BAX/BCL-2, APAF-1 and pro-apoptotic proteins of the BCL-2 family; triggered mitochondrial outer membrane permeabilization (MOMP); down-regulated BCL-2 and XIAP; activated caspase3/8/9; and suppressed MMP2/9 expression and secretion levels. Conclusions: The proteasome may be a novel biochemical target for OS treatment in vitro. Our study provides a promising mechanistic framework for MLN9708/2238 in OS treatment, supporting its clinical development.
Higher Numbers of T-Bet+ Tumor-Infiltrating Lymphocytes Associate with Better Survival in Human Epithelial Ovarian Cancer
Authors: Xu Yun , Chen Lujun , Xu Bin , Xiong Yuqi , Yang Min , Rui Xiaohui , Shi Liangrong , Wu Changping , Jiang Jingting , Lu Binfeng
Published: February 2017

Background/Aims: T-bet, a member of the T-box family of transcription factors, is a key marker of type I immune response within the tumor microenvironment, and has been previously reported by us to serve as an important prognostic indicator for human gastric cancer patients and a potential biomarker for immunotherapy. In the present study, we aimed to assess the clinical significance and prognostic value of T-bet+ tumor-infiltrating lymphocytes in human epithelial ovarian cancer. Methods: The immunohistochemistry was used to analyze the infiltration density of T-bet+ lymphoid cells in human epithelial ovarian cancer tissues, and the flow cytometry analysis was used to further analyze the presence of T-bet+ tumor-infiltrating lymphocytes subgroups in cancer tissues. Results: Our immunohistochemistry analysis showed increased number of T-bet+ lymphoid cells in the human epithelial ovarian cancer tissues, and the flow cytometry analysis further demonstrated the presence of T-bet+ tumor-infiltrating lymphocytes subgroups including CD4+ , CD8+ T cells and NK cells. In addition, we also observed a significant association of T-bet+ tumor-infiltrating lymphocytes density in the tumor nest of cancer with not only serum CA125 levels but also with distant metastasis. However no association was observed with other characteristics like patients' age, pathological type, FIGO stage, tumor site and tumor size. Furthermore, the survival analysis showed that higher density of T-bet+ tumor-infiltrating lymphocytes both in tumor nest and tumor stroma of cancer tissues was significantly associated with better patient survival. In addition, the density of T-bet+ tumor-infiltrating lymphocytes in tumor nest appeared to be an independent risk factor for predicting patients’ postoperative prognoses. Conclusions: Our data indicated that the key transcription factor T-bet might play an important role in the type I immune cells mediated antitumor response, and the density of T-bet+ lymphocytes in human epithelial ovarian cancer tissues could serve as a prognostic predictor for ovarian cancer patients.
NEL-Like Molecule-1 (Nell1) Is Regulated by Bone Morphogenetic Protein 9 (BMP9) and Potentiates BMP9-Induced Osteogenic Differentiation at the Expense of Adipogenesis in Mesenchymal Stem Cells
Authors: Wang Jing , Liao Junyi , Zhang Fugui , Song Dongzhe , Lu Minpeng , Liu Jianxiang , Wei Qiang , Tang Shengli , Liu Hao , Fan Jiaming , Zou Yulong , Guo Dan , Huang Jiayi , Liu Feng , Ma Chao , Hu Xue , Li Li , Qu Xiangyang , Chen Liqun , Weng Yaguang , Lee Michael J. , He Tong-Chuan , Reid Russell R. , Zhang Jiye
Published: February 2017

Background: BMP9 induces both osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs). Nell1 is a secretory glycoprotein with osteoinductive and anti-adipogenic activities. We investigated the role of Nell1 in BMP9-induced osteogenesis and adipogenesis in MSCs. Methods: Previously characterized MSCs iMEFs were used. Overexpression of BMP9 and NELL1 or silencing of mouse Nell1 was mediated by adenoviral vectors. Early and late osteogenic and adipogenic markers were assessed by staining techniques and qPCR analysis. In vivo activity was assessed in an ectopic bone formation model of athymic mice. Results: We demonstrate that Nell1 expression was up-regulated by BMP9. Exogenous Nell1 potentiated BMP9-induced late stage osteogenic differentiation while inhibiting the early osteogenic marker. Forced Nell1 expression enhanced BMP9-induced osteogenic regulators/markers and inhibited BMP9-upregulated expression of adipogenic regulators/markers in MSCs. In vivo ectopic bone formation assay showed that exogenous Nell1 expression enhanced mineralization and maturity of BMP9-induced bone formation, while inhibiting BMP9-induced adipogenesis. Conversely, silencing Nell1 expression in BMP9-stimulated MSCs led to forming immature chondroid-like matrix. Conclusion: Our findings indicate that Nell1 can be up-regulated by BMP9, which in turn accelerates and augments BMP9-induced osteogenesis. Exogenous Nell1 may be exploited to enhance BMP9-induced bone formation while overcoming BMP9-induced adipogenesis in regenerative medicine.
Transformer Less Voltage Quadrupler Based DC-DC Converter with Coupled Inductor and PI Filter for Increased Voltage Gain and Efficiency
Authors: Sujitha C. , Ravi S. , Diarra Bakary , Chuma Joseph
Published: February 2017

In this paper a voltage quadrupler dc-dc converter with coupled inductor  and π filter is presented. The use of the coupled inductor reduces the high leakage inductance which is present in a transformer enabled converter.  The output ripples in the converter is reduced by providing a π filter.  The interleaved voltage quadrupler is used in this system in order to boost the output voltage. The voltage multiplier improves the output voltage gain.  The main advantage of this system is more voltage gain when compared with the transformer eneabled circuit and the overall efficiency of the system is improved. The circuit is simple to control. As a final point of this research, the simulation and the hardware investigational results are presented to demonstrate the effectiveness of this proposed converter.