Eosinophil progenitor levels are increased in patients with active pediatric eosinophilic esophagitis.

J Allergy Clin Immunol. 2016 May 4;

Authors: Morris DW, Stucke EM, Martin LJ, Abonia JP, Mukkada VA, Putnam PE, Rothenberg ME, Fulkerson PC

PMID: 27199214 [PubMed - as supplied by publisher]

[Bouveret syndrome: a case report and literature review].

Rozhl Chir. 2016;95(4):164-7

Authors: Kocián P, Bocková M, Schwarz J

Abstract
UNLABELLED: Bouveret syndrome is a gastric outlet obstruction caused by impaction of a gallstone that passes through a cholecystoduodenal or cholecystogastric fistula. It is a rare disease, most common in elderly women with multiple comorbidities and high surgical risk. The diagnosis can be made either radiologically or endoscopically. Endoscopic extraction is the preferred therapeutic option. Surgical intervention is indicated when endoscopic methods fail. We describe a case of Bouveret syndrome in a 79 years old woman. The report is followed by a review of literature on the diagnostics and treatment of this rare syndrome.
KEY WORDS: gallstones bilioenteric fistula gallstone ileus duodenal obstruction Bouveret syndrome.

PMID: 27226271 [PubMed - in process]

Efficacy and safety of regenerative cell therapy for pulmonary arterial hypertension in animal models: a preclinical systematic review protocol.

Syst Rev. 2016;5(1):89

Authors: Suen CM, Zhai A, Lalu MM, Welsh C, Levac BM, Fergusson D, McIntyre L, Stewart DJ

Abstract
BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease (15 cases per million) that is characterized by widespread loss of the pulmonary microcirculation and elevated pulmonary vascular resistance leading to pathological right ventricular remodeling and ultimately right heart failure. Regenerative cell therapies (i.e., therapies involving cells with stem or progenitor-like properties) could potentially restore the effective lung microcirculation and provide a curative therapy for PAH. Preclinical evidence suggests that regenerative cell therapy using endothelial progenitor cells or mesenchymal stem cells may be beneficial in the treatment of PAH. These findings have led to the completion of a small number of human clinical trials, albeit with modest effect compared to animal studies. The objective of this systematic review is to compare the efficacy and safety of regenerative cell therapies in preclinical models of PAH as well as assess study quality to inform future clinical studies.
METHODS: We will include preclinical studies of PAH in which a regenerative cell type was administered and outcomes compared to a disease control. The primary outcome will be pulmonary hemodynamics as assessed by measurement of right ventricular systolic pressure and/or mean pulmonary arterial pressure. Secondary outcomes will include mortality, survival, right ventricular remodeling, pulmonary vascular resistance, cardiac output, cardiac index, pulmonary acceleration time, tricuspid annular systolic excursion, and right ventricular wall thickness. Electronic searches of MEDLINE and EMBASE databases will be constructed and reviewed by the Peer Review of Electronic Search Strategies (PRESS) process. Search results will be screened independently in duplicate. Data from eligible studies will be extracted, pooled, and analyzed using random effects models. Risk of bias will be assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool, and individual study reporting will be assessed according to an itemized checklist based on the Animal Research: Reporting of In vivo Experiments (ARRIVE) guidelines.
DISCUSSION: This systematic review will examine the efficacy and safety of regenerative cell therapy in preclinical models of PAH. As well, the literature will be assessed for study quality and risk of bias. The results will guide the design of future clinical trials and preclinical animal studies.
SYSTEMATIC REVIEW REGISTRATION: CAMARADES ( http://www.dcn.ed.ac.uk/camarades/SyRF/Protocols.htm ).

PMID: 27225668 [PubMed - in process]

Nation-wide epidemiological study of Japanese patients with rare viral myelopathy using novel registration system (HAM-net).

Orphanet J Rare Dis. 2016;11(1):69

Authors: Coler-Reilly AL, Yagishita N, Suzuki H, Sato T, Araya N, Inoue E, Takata A, Yamano Y

Abstract
BACKGROUND: At least one million people are infected with human T-lymphotropic virus type 1 (HTLV-1) in Japan, a small percentage of whom develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T-cell leukemia/lymphoma (ATLL). Patients with HAM/TSP suffer from progressively worsening myelopathic symptoms, such as motor disability and bladder dysfunction, and may become wheelchair-bound or even bedridden.
METHODS: To learn more about this rare, debilitating disease, we established the national registration system "HAM-net" in March 2012. We continuously obtain detailed data from enrolled patients using the registration forms and an annual telephone interview. In this retrospective study, we describe the demographics and clinical histories of 383 registered patients from all over Japan.
RESULTS: Patients were diagnosed at a median of 53 years old, long after disease onset at 45. Most (55.3 %) were originally from the southernmost regions, Kyushu and Okinawa. The main initial symptoms were difficulty walking (81.9 %), urinary dysfunction (38.5 %), and lower limb sensory disturbances (13.9 %). Many patients reported frequent leg numbness and leg pain, and the vast majority required medical intervention for urinary symptoms and constipation. A median of 8 years elapsed from the onset of motor symptoms to Osame Motor Disability Score (OMDS) 5 (requiring unilateral support), 12.5 years to OMDS 6 (requiring bilateral support), and 18 years to OMDS 9 (unable to walk). Health Assessment Questionnaire - Disability Index (HAQ-DI) tasks related to mobility, as opposed to hand motions, were very difficult for HAM/TSP patients and well-correlated with OMDS. Scores on the MOS 36-Item Short-Form Health Survey (SF-36) indicated that physical functioning was severely impaired in HAM/TSP patients. Patients with a history of blood transfusion (19.1 %) were older and suffered from more severe disability as indicated by their high HAQ-DI scores. Patients with a family history of HAM/TSP (8.4 %) were younger and had relatively mild symptoms given their long disease durations; many (15.6 %) also had a relative with ATLL.
CONCLUSIONS: The HAM-net national registration system has been an effective tool for gathering personal and clinical data from HAM/TSP patients scattered throughout Japan. We expect to conduct many retrospective and prospective epidemiological studies using HAM-net in the future.

PMID: 27225443 [PubMed - in process]

Quantifying benefit-risk preferences for new medicines in rare disease patients and caregivers.

Orphanet J Rare Dis. 2016;11(1):70

Authors: Morel T, Aymé S, Cassiman D, Simoens S, Morgan M, Vandebroek M

Abstract
BACKGROUND: Rare disease patients and caregivers face uncommon, serious, debilitating conditions often characterised by poor prognosis and limited treatment options. This study aimed to explore what they consider of value when choosing between hypothetical therapeutic options and to quantify both their benefit-risk preferences and the influence of disease context.
METHODS: A mixed-methods survey with patients and caregivers was conducted in the United Kingdom across a range of rare diseases. Discrete-choice experiments that compared hypothetical treatment profiles of benefits and risks were used to measure respondent preferences across a set of seven attributes related to health outcomes, safety, and process of care. Bespoke questions on current disease management and the joint use of the 12-item WHODAS 2.0 questionnaire and of two Likert scales capturing self- and proxy-assessed disease-induced threat to life and impairment were implemented to describe disease context. Additionally, qualitative insights on the definitions of value and risk were collected from respondents.
RESULTS: Final study sample included 721 patients and 152 informal caregivers, across 52 rare diseases. When choosing between hypothetical novel treatments for rare diseases, respondents attributed most importance to drug response, risk of serious side effects, and the ability to conduct usual activities while on treatment. In contrast, attributes related to treatment modalities were the least important. Respondents expressed a willingness to accept risks in hopes of finding some benefit, such as a higher chance of drug response or greater health improvement potential. Increasing disease severity, impairment or disability, and the lack of effective therapeutic options were shown to raise significantly the willingness to gain benefit through increased risk.
CONCLUSIONS: This is the first study performing a quantitative discrete choice experiment amongst patients and caregivers across 52 rare conditions. It enables a more detailed understanding of the relationship between disease context, treatment attributes and the degree of risk respondents are willing to take to gain a specific degree of benefit. Researchers of novel therapeutics for rare diseases should be encouraged to invest in preference elicitation studies to generate rigorous patient evidence and specific regulatory guidance should be issued to acknowledge their importance and their use in marketing authorisations.

PMID: 27225337 [PubMed - in process]

Crowd Sourcing.

J Med Pract Manage. 2016 Jan-Feb;31(4):238-9

Authors: Baum N

Abstract
The Internet has contributed new words and slang to our daily vernacular. A few terms, such as tweeting, texting, sexting, blogging, and googling, have become common in most vocabularies and in many languages, and are now included in the dictionary. A new buzzword making the rounds in industry is crowd sourcing, which involves outsourcing an activity, task, or problem by sending it to people or groups outside a business or a practice. Crowd sourcing allows doctors and practices to tap the wisdom of many instead of relying only on the few members of their close-knit group. This article defines "crowd sourcing," offers examples, and explains how to get started with this approach that can increase your ability to finish a task or solve problems that you don't have the time or expertise to accomplish.

PMID: 27039640 [PubMed - indexed for MEDLINE]

New practical definitions for the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Ann Neurol. 2015 Dec;78(6):871-86

Authors: Pilliod J, Moutton S, Lavie J, Maurat E, Hubert C, Bellance N, Anheim M, Forlani S, Mochel F, N'Guyen K, Thauvin-Robinet C, Verny C, Milea D, Lesca G, Koenig M, Rodriguez D, Houcinat N, Van-Gils J, Durand CM, Guichet A, Barth M, Bonneau D, Convers P, Maillart E, Guyant-Marechal L, Hannequin D, Fromager G, Afenjar A, Chantot-Bastaraud S, Valence S, Charles P, Berquin P, Rooryck C, Bouron J, Brice A, Lacombe D, Rossignol R, Stevanin G, Benard G, Burglen L, Durr A, Goizet C, Coupry I

Abstract
OBJECTIVE: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is caused by mutations in the SACS gene. SACS encodes sacsin, a protein whose function remains unknown, despite the description of numerous protein domains and the recent focus on its potential role in the regulation of mitochondrial physiology. This study aimed to identify new mutations in a large population of ataxic patients and to functionally analyze their cellular effects in the mitochondrial compartment.
METHODS: A total of 321 index patients with spastic ataxia selected from the SPATAX network were analyzed by direct sequencing of the SACS gene, and 156 patients from the ATAXIC project presenting with congenital ataxia were investigated either by targeted or whole exome sequencing. For functional analyses, primary cultures of fibroblasts were obtained from 11 patients carrying either mono- or biallelic variants, including 1 case harboring a large deletion encompassing the entire SACS gene.
RESULTS: We identified biallelic SACS variants in 33 patients from SPATAX, and in 5 nonprogressive ataxia patients from ATAXIC. Moreover, a drastic and recurrent alteration of the mitochondrial network was observed in 10 of the 11 patients tested.
INTERPRETATION: Our results permit extension of the clinical and mutational spectrum of ARSACS patients. Moreover, we suggest that the observed mitochondrial network anomalies could be used as a trait biomarker for the diagnosis of ARSACS when SACS molecular results are difficult to interpret (ie, missense variants and heterozygous truncating variant). Based on our findings, we propose new diagnostic definitions for ARSACS using clinical, genetic, and cellular criteria.

PMID: 26288984 [PubMed - indexed for MEDLINE]

Routine nail clipping leads to the diagnosis of amelanotic nail unit melanoma in a young construction worker.

J Cutan Pathol. 2015 Aug;42(8):505-9

Authors: Boni A, Chu EY, Rubin AI

PMID: 26272255 [PubMed - indexed for MEDLINE]

Noteworthy Professional News.

Adv Neonatal Care. 2015 Aug;15(4):235-6

Authors:

PMID: 26225589 [PubMed - indexed for MEDLINE]

Prenatal diagnosis of orbital melanotic neuroectodermal tumor in infancy.

Ultrasound Obstet Gynecol. 2015 Aug;46(2):249-50

Authors: Koob M, Fayard C, Pariente D, Adamsbaum C, Franchi-Abella S

PMID: 25594399 [PubMed - indexed for MEDLINE]

Fluorescence-based bioassays for the detection and evaluation of food materials.

Sensors (Basel). 2015;15(10):25831-67

Authors: Nishi K, Isobe S, Zhu Y, Kiyama R

Abstract
We summarize here the recent progress in fluorescence-based bioassays for the detection and evaluation of food materials by focusing on fluorescent dyes used in bioassays and applications of these assays for food safety, quality and efficacy. Fluorescent dyes have been used in various bioassays, such as biosensing, cell assay, energy transfer-based assay, probing, protein/immunological assay and microarray/biochip assay. Among the arrays used in microarray/biochip assay, fluorescence-based microarrays/biochips, such as antibody/protein microarrays, bead/suspension arrays, capillary/sensor arrays, DNA microarrays/polymerase chain reaction (PCR)-based arrays, glycan/lectin arrays, immunoassay/enzyme-linked immunosorbent assay (ELISA)-based arrays, microfluidic chips and tissue arrays, have been developed and used for the assessment of allergy/poisoning/toxicity, contamination and efficacy/mechanism, and quality control/safety. DNA microarray assays have been used widely for food safety and quality as well as searches for active components. DNA microarray-based gene expression profiling may be useful for such purposes due to its advantages in the evaluation of pathway-based intracellular signaling in response to food materials.

PMID: 26473869 [PubMed - indexed for MEDLINE]

Principles of Systems Biology-No. 5.

Cell Syst. 2016 May 25;2(5):290-292

Authors:

Abstract
If systems biology is about understanding how links between components yield emergent phenomena, this month's Cell Systems Call (Cell Systems 1, 307) contains a veritable bounty of examples, showcasing the breadth of the field from systems oceanography to molecular evolution to the influence of cellular niche microenvironments on stem cell development.

PMID: 27228344 [PubMed - as supplied by publisher]

TissueMiner: a multiscale analysis toolkit to quantify how cellular processes create tissue dynamics.

Elife. 2016 May 26;5

Authors: Etournay R, Merkel M, Popovi M, Brandl H, Dye NA, Aigouy B, Salbreux G, Eaton S, Jülicher F

Abstract
Segmentation and tracking of cells in long-term time-lapse experiments has emerged as a powerful method to understand how tissue shape changes emerge from the complex choreography of constituent cells. However, methods to store and interrogate the large datasets produced by these experiments are not widely available. Furthermore, recently developed methods for relating tissue shape changes to cell dynamics have not yet been widely applied by biologists because of their technical complexity. We therefore developed a database format that stores cellular connectivity and geometry information of deforming epithelial tissues, and computational tools to interrogate it and perform multi-scale analysis of morphogenesis. We provide tutorials for this computational framework, called TissueMiner, and demonstrate its capabilities by comparing cell and tissue dynamics in vein and inter-vein subregions of the Drosophila pupal wing. These analyses reveal an unexpected role for convergent extension in shaping wing veins.

PMID: 27228153 [PubMed - as supplied by publisher]

Recent Progress on Systems and Synthetic Biology Approaches to Engineer Fungi As Microbial Cell Factories.

Curr Genomics. 2016 Apr;17(2):85-98

Authors: Amores GR, Guazzaroni ME, Arruda LM, Silva-Rocha R

Abstract
Filamentous fungi are remarkable organisms naturally specialized in deconstructing plant biomass and this feature has a tremendous potential for biofuel production from renewable sources. The past decades have been marked by a remarkable progress in the genetic engineering of fungi to generate industry-compatible strains needed for some biotech applications. In this sense, progress in this field has been marked by the utilization of high-throughput techniques to gain deep understanding of the molecular machinery controlling the physiology of these organisms, starting thus the Systems Biology era of fungi. Additionally, genetic engineering has been extensively applied to modify wellcharacterized promoters in order to construct new expression systems with enhanced performance under the conditions of interest. In this review, we discuss some aspects related to significant progress in the understating and engineering of fungi for biotechnological applications, with special focus on the construction of synthetic promoters and circuits in organisms relevant for industry. Different engineering approaches are shown, and their potential and limitations for the construction of complex synthetic circuits in these organisms are examined. Finally, we discuss the impact of engineered promoter architecture in the single-cell behavior of the system, an often-neglected relationship with a tremendous impact in the final performance of the process of interest. We expect to provide here some new directions to drive future research directed to the construction of high-performance, engineered fungal strains working as microbial cell factories.

PMID: 27226765 [PubMed]

Complement membrane attack and tumourigenesis: a systems biology approach.

J Biol Chem. 2016 May 19;

Authors: Towner LD, Wheat RA, Hughes TR, Morgan BP

Abstract
Tumour development driven by inflammation is now an established phenomenon but the role that complement plays remains uncertain. Recent evidence has suggested that various components of the complement (C) cascade may influence tumour development in disparate ways; however, little attention has been paid to that of the membrane attack complex (MAC). This is despite abundant evidence documenting the effects of this complex on cell behaviour, including cell activation, protection from/induction of apoptosis, release of inflammatory cytokines, growth factors and ECM components and regulators and the triggering of the NLRP3 inflammasome. Here we present a novel approach to this issue by using global gene expression studies in conjunction with a systems biology analysis. Using network analysis of MAC responsive expression changes we demonstrated a cluster of co-regulated genes known to have their impact in the extracellular space and on the supporting stroma and with well-characterized tumour promoting roles. Network analysis highlighted the central role for EGFR activation in mediating the observed responses to MAC exposure. Overall, the study sheds light on the mechanisms by which sublytic MAC causes tumour cell responses and exposes a gene expression signature that implicates MAC as a driver of tumour progression. These findings have implications for understanding of the roles of C and the MAC in tumour development and progression which in turn will inform future therapeutic strategies in cancer.

PMID: 27226542 [PubMed - as supplied by publisher]

Redox regulation of vascular remodeling.

Cell Mol Life Sci. 2016 Jan;73(2):349-63

Authors: Karimi Galougahi K, Ashley EA, Ali ZA

Abstract
Vascular remodeling is a dynamic process of structural and functional changes in response to biochemical and biomechanical signals in a complex in vivo milieu. While inherently adaptive, dysregulation leads to maladaptive remodeling. Reactive oxygen species participate in homeostatic cell signaling in tightly regulated- and compartmentalized cellular circuits. It is well established that perturbations in oxidation-reduction (redox) homeostasis can lead to a state of oxidative-, and more recently, reductive stress. We provide an overview of the redox signaling in the vasculature and review the role of oxidative- and reductive stress in maladaptive vascular remodeling. Particular emphasis has been placed on essential processes that determine phenotype modulation, migration and fate of the main cell types in the vessel wall. Recent advances in systems biology and the translational opportunities they may provide to specifically target the redox pathways driving pathological vascular remodeling are discussed.

PMID: 26483132 [PubMed - indexed for MEDLINE]

Leveraging Social Media to Promote Public Health Knowledge: Example of Cancer Awareness via Twitter.

JMIR Public Health Surveill. 2016 Jan-Jun;2(1):e17

Authors: Xu S, Markson C, Costello KL, Xing CY, Demissie K, Llanos AA

Abstract
BACKGROUND: As social media becomes increasingly popular online venues for engaging in communication about public health issues, it is important to understand how users promote knowledge and awareness about specific topics.
OBJECTIVE: The aim of this study is to examine the frequency of discussion and differences by race and ethnicity of cancer-related topics among unique users via Twitter.
METHODS: Tweets were collected from April 1, 2014 through January 21, 2015 using the Twitter public streaming Application Programming Interface (API) to collect 1% of public tweets. Twitter users were classified into racial and ethnic groups using a new text mining approach applied to English-only tweets. Each ethnic group was then analyzed for frequency in cancer-related terms within user timelines, investigated for changes over time and across groups, and measured for statistical significance.
RESULTS: Observable usage patterns of the terms "cancer", "breast cancer", "prostate cancer", and "lung cancer" between Caucasian and African American groups were evident across the study period. We observed some variation in the frequency of term usage during months known to be labeled as cancer awareness months, particularly September, October, and November. Interestingly, we found that of the terms studied, "colorectal cancer" received the least Twitter attention.
CONCLUSIONS: The findings of the study provide evidence that social media can serve as a very powerful and important tool in implementing and disseminating critical prevention, screening, and treatment messages to the community in real-time. The study also introduced and tested a new methodology of identifying race and ethnicity among users of the social media. Study findings highlight the potential benefits of social media as a tool in reducing racial and ethnic disparities.

PMID: 27227152 [PubMed]

Bioinformatic Studies to Predict MicroRNAs with the Potential of Uncoupling RECK Expression from Epithelial-Mesenchymal Transition in Cancer Cells.

Cancer Inform. 2016;15:91-102

Authors: Wang Z, Murakami R, Yuki K, Yoshida Y, Noda M

Abstract
RECK is downregulated in many tumors, and forced RECK expression in tumor cells often results in suppression of malignant phenotypes. Recent findings suggest that RECK is upregulated after epithelial-mesenchymal transition (EMT) in normal epithelium-derived cells but not in cancer cells. Since several microRNAs (miRs) are known to target RECK mRNA, we hypothesized that certain miR(s) may be involved in this suppression of RECK upregulation after EMT in cancer cells. To test this hypothesis, we used three approaches: (1) text mining to find miRs relevant to EMT in cancer cells, (2) predicting miR targets using four algorithms, and (3) comparing miR-seq data and RECK mRNA data using a novel non-parametric method. These approaches identified the miR-183-96-182 cluster as a strong candidate. We also looked for transcription factors and signaling molecules that may promote cancer EMT, miR-183-96-182 upregulation, and RECK downregulation. Here we describe our methods, findings, and a testable hypothesis on how RECK expression could be regulated in cancer cells after EMT.

PMID: 27226706 [PubMed]

Antiviral activity of doxycycline against vesicular stomatitis virus in vitro.

FEMS Microbiol Lett. 2015 Nov;362(22)

Authors: Wu ZC, Wang X, Wei JC, Li BB, Shao DH, Li YM, Liu K, Shi YY, Zhou B, Qiu YF, Ma ZY

Abstract
Doxycycline (Dox) is a tetracycline derivative with broad-spectrum antimicrobial activities that is used as an effector substance in inducible gene-expression systems. We investigated the antiviral activity of Dox against vesicular stomatitis virus (VSV) infection in cultured H1299 cells. Dox at concentrations of 1.0-2.0 μg ml(-1) significantly inhibited VSV replication and the VSV-induced cytopathic effect in dose-dependent manners, suggesting that Dox may have broader activity in inhibiting viral replication, in addition to its well-defined bacteriostatic activity. Dox exerted its antiviral effect at the early-mid stage of VSV infection, suggesting that it did not interfere with VSV infectivity, adsorption, or entry into target cells. These results indicate that Dox can inhibit VSV infection and may therefore have potential applications for the treatment of viral infections.

PMID: 26459887 [PubMed - indexed for MEDLINE]

Metastatic malignant struma ovarii with coexistence of Hashimoto's thyroiditis.

Endocrinol Diabetes Metab Case Rep. 2016;:160030

Authors: Russo M, Marturano I, Masucci R, Caruso M, Fornito MC, Tumino D, Tavarelli M, Squatrito S, Pellegriti G

Abstract
Struma ovarii is a rare ovarian teratoma characterized by the presence of thyroid tissue as the major component. Malignant transformation of the thyroidal component (malignant struma ovarii) has been reported in approximately 5% of struma ovarii. The management and follow-up of this unusual disease remain controversial. We report the case of a woman with a history of autoimmune thyroiditis and a previous resection of a benign struma ovarii that underwent hystero-annexiectomy for malignant struma ovarii with multiple papillary thyroid cancer foci and peritoneal involvement. Total thyroidectomy and subsequent radioiodine treatment lead to complete disease remission after 104 months of follow-up. The diagnosis and natural progression of malignant struma ovarii are difficult to discern, and relapses can occur several years after diagnosis. A multidisciplinary approach is mandatory; after surgical excision of malignant struma, thyroidectomy in combination with (131)I therapy should be considered after risk stratification in accordance with a standard approach in differentiated thyroid cancer patients.
LEARNING POINTS: Malignant struma ovarii is a rare disease; diagnosis is difficult and management is not well defined.Predominant sites of metastasis are adjacent pelvic structures.Thyroidectomy and (131)I therapy should be considered after risk stratification in accordance with standard approaches in DTC patients.

PMID: 27224256 [PubMed - as supplied by publisher]