Dental and dentofacial problems in a female child with Toriello-Carey -syndrome: changes in 3 years.

Spec Care Dentist. 2016 May 9;

Authors: Tirali RE, İlhan B, Şar Ç, Çehreli SB

Abstract
Toriello-Carey syndrome is a rare disease whose clinical manifestations are midline facial defects, laryngeal and pharyngeal hypoplasia, cardiac defect, and corpus callosum hypoplasia. Literature states that clinical manifestations are more evident in males. This is the second report in the literature which describes the dental and dentofacial -features in an 8-year-old female patient with Toriello-Carey syndrome.

PMID: 27159668 [PubMed - as supplied by publisher]

Paraneoplastic stiff person syndrome: Inpatient rehabilitation outcomes of a rare disease from two cancer rehabilitation programmes.

J Rehabil Med. 2016 May 3;

Authors: Robinson Smith S, Fu JB

Abstract
Paraneoplastic stiff person syndrome is a rare, but debilitating, manifestation of cancer, characterized by painful extremities, truncal and facial spasms. The resultant functional impairment may necessitate comprehensive rehabilitation and symptom management. This case series describes the acute inpatient rehabilitation courses of 2 patients at different tertiary care referral cancer rehabilitation programmes, including work-up and diagnosis, medical management of symptoms, and functional outcomes. Both patients had a reduction in symptom burden and an improvement in motor function as a result of multidisciplinary acute inpatient rehabilitation.

PMID: 27157044 [PubMed - as supplied by publisher]

Chronic recurrent multifocal osteomyelitis: a rare skeletal disorder.

BMJ Case Rep. 2015;2015

Authors: Aygun D, Barut K, Camcioglu Y, Kasapcopur O

Abstract
Chronic recurrent multifocal osteomyelitis (CRMO) is a rare non-infectious inflammatory bone disease of unknown aetiology. CRMO mainly affects the metaphyses of long bones and spine in children and young adolescents. It presents with recurrent episodes of bone pain and fever, resembling bacterial osteomyelitis, but cultures of lesions are sterile and it is unresponsive to antibiotic therapy. We report a case of a 3-year-old boy diagnosed with CRMO, who was initially treated for bacterial osteomyelitis, and received prolonged antibiotic therapy for chronic pain, and swelling of mandible and ulna. CRMO should be kept in mind in the differential diagnosis of chronic bone pain and osteomyelitis unresponsive to antibiotic treatment.

PMID: 26307646 [PubMed - indexed for MEDLINE]

Report on the EUROMAC McArdle Exercise Testing Workshop, Madrid, Spain, 11-12 July 2014.

Neuromuscul Disord. 2015 Sep;25(9):739-45

Authors: Quinlivan R, Lucia A, Scalco RS, Santalla A, Pattni J, Godfrey R, Marti R, Workshop Participants

PMID: 26159598 [PubMed - indexed for MEDLINE]

Breast: Sezary Syndrome: A Unique Presentation.

Breast J. 2015 Jul-Aug;21(4):423-7

Authors: Bedayat A, Mirzabeigi M, Yu H, Hultman R, MacMaster S

Abstract
Sezary syndrome is a subtype of cutaneous T cell lymphoma which usually presents as generalized skin disease with erytheroderma. Distal organ involvement is rare and is usually a late finding in the course of the disease. Breast involvement is extremely rare. Herein, we present a case report of a patient whose initial presentation involved an intramammary lymph node prior to the onset of more characteristic skin disease. Sezary syndrome was confirmed by cythopathologic findings.

PMID: 25939954 [PubMed - indexed for MEDLINE]

Activation of sirtuin 1 as therapy for the peroxisomal disease adrenoleukodystrophy.

Cell Death Differ. 2015 Nov;22(11):1742-53

Authors: Morató L, Ruiz M, Boada J, Calingasan NY, Galino J, Guilera C, Jové M, Naudí A, Ferrer I, Pamplona R, Serrano M, Portero-Otín M, Beal MF, Fourcade S, Pujol A

Abstract
Oxidative stress and mitochondrial failure are prominent factors in the axonal degeneration process. In this study, we demonstrate that sirtuin 1 (SIRT1), a key regulator of the mitochondrial function, is impaired in the axonopathy and peroxisomal disease X-linked adrenoleukodystrophy (X-ALD). We have restored SIRT1 activity using a dual strategy of resveratrol treatment or by the moderate transgenic overexpression of SIRT1 in a X-ALD mouse model. Both strategies normalized redox homeostasis, mitochondrial respiration, bioenergetic failure, axonal degeneration and associated locomotor disabilities in the X-ALD mice. These results indicate that the reactivation of SIRT1 may be a valuable strategy to treat X-ALD and other axonopathies in which the control of redox and energetic homeostasis is impaired.

PMID: 25822341 [PubMed - indexed for MEDLINE]

Use of Pharmacogenomics and Biomarkers in the Development of New Drugs for Alzheimer Disease in Japan.

Clin Ther. 2015 Aug;37(8):1627-31

Authors: Otsubo Y

Abstract
PURPOSE: Pharmacogenomics (PGx) and biomarkers have been utilized for improving the benefit/risk ratios of drugs and the efficiency of drug development. In the development of drugs for Alzheimer disease (AD), a number of clinical trials have failed to demonstrate clinical efficacy. To overcome this circumstance, the importance of using PGx/biomarkers for enhancing recruitment into clinical trials and for evaluating the efficacy of treatments has been increasingly recognized. In this article, the current status and examples of the use of PGx/biomarkers in Japan for drug development are explained.
METHODS: Guidelines, notifications, and administrative notices related to PGx/biomarkers were downloaded from the Web sites of the Pharmaceuticals and Medical Devices Agency (PMDA), the US Food and Drug Administration, and the European Medicines Agency. Data from clinical studies of AD drugs were obtained from the review reports of the PMDA. To analyze the current status of the use of PGx/biomarkers in Japan, "Issues to Consider in the Clinical Evaluation and Development of Drugs for Alzheimer's Disease (Interim Summary)" was also downloaded from PMDA Web site.
FINDINGS: There are 2 major measures of utilizing PGx/biomarkers for drug development: (1) biomarker qualification and (2) companion diagnostics. Recently, the PMDA issued a number of guidelines and notifications for their practical use. Although examples of qualified PGx/biomarkers and approved companion diagnostics are limited at present, it is expected that the use of PGx/biomarkers for the development of drugs against AD would increase.
IMPLICATIONS: For promoting the use of PGx/biomarkers in the development of drugs against AD, PGx/biomarkers should be qualified as early as possible. To that end, accumulating data on PGx/biomarkers from nonclinical or clinical trials and the concurrent development of reliable diagnostics in the early stage of the development process are indispensable. It is important to strengthen collaboration among the academia, industries, and regulatory agencies, followed by the establishment of an effective guideline in the area of AD.

PMID: 25963998 [PubMed - indexed for MEDLINE]

The Contribution of Transcriptomics to Biomarker Development in Systemic Vasculitis and SLE.

Curr Pharm Des. 2015;21(17):2225-35

Authors: Flint SM, McKinney EF, Lyons PA, Smith KG

Abstract
A small but increasing number of gene expression based biomarkers are becoming available for routine clinical use, principally in oncology and transplantation. These underscore the potential of gene expression arrays and RNA sequencing for biomarker development, but this potential has not yet been fully realized and most candidates do not progress beyond the initial report. The first part of this review examines the process of gene expression- based biomarker development, highlighting how systematic biases and confounding can significantly skew study outcomes. Adequate validation in an independent cohort remains the single best means of protecting against these concerns. The second part considers gene-expression based biomarkers in Systemic Lupus Erythematosus (SLE) and systemic vasculitis. The type 1 interferon inducible gene signature remains by far the most studied in autoimmune rheumatic disease. While initially presented as an objective, blood-based biomarker of active SLE, subsequent research has shown that it is not specific to SLE and that its association with disease activity is considerably more nuanced than first thought. Nonetheless, it is currently under evaluation in ongoing trials of anti-interferon therapy. Other candidate markers of note include a prognostic CD8+ T-cell gene signature validated in SLE and ANCA-associated vasculitis, and a disease activity biomarker for SLE derived from modules of tightly correlated genes.

PMID: 25771200 [PubMed - indexed for MEDLINE]

Providing family-centred care for rare diseases in maternity services: Parent satisfaction and preferences when dysmelia is identified.

Women Birth. 2016 May 4;

Authors: Johnson J, Adams-Spink G, Arndt T, Wijeratne D, Heyhoe J, Taylor P

Abstract
PROBLEM AND BACKGROUND: Dysmelia is usually detected prenatally or postnatally in maternity services. The provision of family-centred care for parents at the time of initial diagnosis is crucial to facilitate decision making, access to appropriate services, and the provision of parental care-giving, but no research has investigated parent experiences or preferences in this population.
AIMS: The current research aimed to address this by investigating satisfaction with service, occurrence of signposting and preferences in this group.
METHODS: Two online surveys were conducted. In the first survey (n=417), parents reported whether they were offered signposting information and their level of satisfaction with the service they received when initially diagnosed. In the second survey (n=130), a subgroup of participants who completed the first survey reported their preferences for signposting and health service access after diagnosis.
FINDINGS: On average, participants were less than satisfied with the service they received and only 27% were offered signposting information. Satisfaction was higher amongst parents who had been offered signposting information. 91% of parents said they would have wanted signposting information and 67% would have wanted access to a support group.
CONCLUSIONS: There is a need to improve the family-centeredness of care when dysmelia is identified. Offering signposting information to relevant third-sector organisations may increase parent satisfaction and address parent preferences. These findings could have implications for parents of children with other rare diseases identified in maternity services.

PMID: 27156021 [PubMed - as supplied by publisher]

[Pulmonary MALT lymphoma and paraneoplastic syndromes].

Rev Mal Respir. 2016 May 4;

Authors: Monge E, Coolen-Allou N, Mascarel P, Gazaille V

Abstract
INTRODUCTION: Primary pulmonary lymphoma is a rare disease; diagnosis is often delayed because of atypical clinical presentation and slow progression.
OBSERVATION: A 42-year-old woman consulted because of haemoptysis. Chest CT-scan showed multiple nodular calcified masses. A lung biopsy led to the diagnosis of pulmonary amyloidosis with pulmonary MALT lymphoma (mucosa-associated lymphoid tissue). The patient developed two paraneoplastic syndromes: a hypertrophic osteoarthropathy and mucinosis.
CONCLUSION: Multiple nodular amyloidosis can be a mode of presentation for pulmonary lymphoma. Paraneoplastic syndromes must be systematically considered and can help in early diagnosis of the disease and its relapse.

PMID: 27155897 [PubMed - as supplied by publisher]

Putting the Genome in Context: Gene-Environment Interactions in Type 2 Diabetes.

Curr Diab Rep. 2016 Jul;16(7):57

Authors: Franks PW, Paré G

Abstract
The genome is often the conduit through which environmental exposures convey their effects on health and disease. Whilst not all diseases act by directly perturbing the genome, the phenotypic responses are often genetically determined. Hence, whilst diseases are often defined has having differing degrees of genetic determination, genetic and environmental factors are, with few exceptions, inseparable features of most diseases, not least type 2 diabetes. It follows that to optimize diabetes, prevention and treatment will require that the etiological roles of genetic and environmental risk factors be jointly considered. As we discuss here, studies focused on quantifying gene-environment and gene-treatment interactions are gathering momentum and may eventually yield data that helps guide health-related choices and medical interventions for type 2 diabetes and other complex diseases.

PMID: 27155607 [PubMed - as supplied by publisher]

Polypharmacology in Drug Development: A Minireview of Current Technologies.

ChemMedChem. 2016 May 6;

Authors: Tan Z, Chaudhai R, Zhang S

Abstract
Polypharmacology, the process in which a single drug is able to bind to multiple targets specifically and simultaneously, is an emerging paradigm in drug development. The potency of a given drug can be increased through the engagement of multiple targets involved in a certain disease. Polypharmacology may also help identify novel applications of existing drugs through drug repositioning. However, many problems and challenges remain in this field. Rather than covering all aspects of polypharmacology, this Minireview is focused primarily on recently reported techniques, from bioinformatics technologies to cheminformatics approaches as well as text-mining-based methods, all of which have made significant contributions to the research of polypharmacology.

PMID: 27154144 [PubMed - as supplied by publisher]

Spinal cord ependymoma: a review of the literature and case series of ten patients.

J Neurooncol. 2016 May 6;

Authors: Celano E, Salehani A, Malcolm JG, Reinertsen E, Hadjipanayis CG

Abstract
Spinal cord ependymoma (SCE) is a rare tumor that is most commonly low-grade. Complete surgical resection has been established as first-line treatment and can be curative. However, SCEs tend to recur when complete tumor resection is not possible. Evidence supporting the use of adjuvant radiation and chemotherapy is not definitive. We review the most recent literature on SCE covering a comprehensive range of topics spanning the biology, presentation, clinical management, and outcomes. In addition, we present a case series of ten SCE patients with the goal of contributing to existing knowledge of this rare disease.

PMID: 27154165 [PubMed - as supplied by publisher]

Integrating pharmacogenomics into clinical practice: promise vs reality.

Am J Med. 2016 May 4;

Authors: St Sauver JL, Bielinski SJ, Olson JE, Bell EJ, Mc Gree ME, Jacobson DJ, McCormick JB, Caraballo PJ, Takahashi PY, Roger VL, Rohrer Vitek CR

Abstract
BACKGROUND: Limited information is available regarding primary care clinicians' response to pharmacogenomic Clinical Decision Support (PGx-CDS) alerts integrated in the electronic health record.
METHODS: In February 2015, 159 clinicians in the Mayo Clinic primary care practice were sent e-mail surveys to understand their perspectives on the implementation and use of pharmacogenomic testing in their clinical practice. Surveys assessed how the clinicians felt about pharmacogenomics and whether they thought electronic PGx-CDS alerts were useful. Information was abstracted on the number of CDS alerts the clinicians received between October, 2013 and the date their survey was returned. CDS alerts were grouped into two categories: alert recommended caution using the prescription or the alert recommended an alternate prescription. Finally, data were abstracted regarding whether the clinician changed their prescription in response to the alert recommendation.
RESULTS: The survey response rate was 57% (n=90). Overall, 52% of the clinicians did not expect to use or did not know whether they would use pharmacogenomic information in their future prescribing practices. Additionally, 53% of the clinicians felt that the alerts were confusing, irritating, frustrating, or that it was difficult to find additional information. Finally, only 30% of the clinicians that received a CDS alert changed their prescription to an alternative medication.
CONCLUSIONS: Our results suggest a lack of clinician comfort with integration of pharmacogenomic data into primary care. Further efforts to refine PGx-CDS alerts to make them as useful and user-friendly as possible are needed to improve clinician satisfaction with these new tools.

PMID: 27155109 [PubMed - as supplied by publisher]

Personalized asthma therapy in blacks-the role of genetic ancestry.

J Allergy Clin Immunol. 2016 May;137(5):1370-1372

Authors: Dunn RM, Wechsler ME

PMID: 27155033 [PubMed - as supplied by publisher]

Toward precision medicine and health: Opportunities and challenges in allergic diseases.

J Allergy Clin Immunol. 2016 May;137(5):1289-1300

Authors: Galli SJ

Abstract
Precision medicine (also called personalized, stratified, or P4 medicine) can be defined as the tailoring of preventive measures and medical treatments to the characteristics of each patient to obtain the best clinical outcome for each person while ideally also enhancing the cost-effectiveness of such interventions for patients and society. Clearly, the best clinical outcome for allergic diseases is not to get them in the first place. To emphasize the importance of disease prevention, a critical component of precision medicine can be referred to as precision health, which is defined herein as the use of all available information pertaining to specific subjects (including family history, individual genetic and other biometric information, and exposures to risk factors for developing or exacerbating disease), as well as features of their environments, to sustain and enhance health and prevent the development of disease. In this article I will provide a personal perspective on how the precision health-precision medicine approach can be applied to the related goals of preventing the development of allergic disorders and providing the most effective diagnosis, disease monitoring, and care for those with these prevalent diseases. I will also mention some of the existing and potential challenges to achieving these ambitious goals.

PMID: 27155026 [PubMed - as supplied by publisher]

Identification of line-specific strategies for improving carotenoid production in synthetic maize through data-driven mathematical modelling.

Plant J. 2016 May 7;

Authors: Comas J, Benfeitas R, Vilaprinyo E, Sorribas A, Solsona F, Farré G, Berman J, Zorrilla U, Capell T, Sandmann G, Zhu C, Christou P, Alves R

Abstract
Plant Synthetic Biology is still in its infancy. However, Synthetic Biology approaches have been used to manipulate and improve the nutritional and health value of staple food crops, such as rice, potato, or maize. With current technologies, production yields of the synthetic nutrients are a result of trial and error, and systematic rational strategies to optimize those yields are still lacking. Here, we present a workflow that combines gene expression and quantitative metabolomics with mathematical modeling to identify strategies for increasing production yields of nutritionally important carotenoids in the seed endosperm synthesized through alternative biosynthetic pathways in synthetic lines of white maize, which is normally devoid of carotenoids. Quantitative metabolomics and gene expression data are used to create and fit parameters of mathematical models that are specific for four independent maize lines. Sensitivity analysis and simulation of each model is used to predict which gene activities should be further engineered in order to increase production yields for carotenoid accumulation in each line. Some of these predictions (e.g. increasing Zmlycb/Gllycb will increase accumulated β-carotenes) are valid across the four maize lines and consistent with experimental observations in other systems. Other predictions are line-specific. The workflow is adaptable to any other biological system for which appropriate quantitative information is available. Furthermore, we validate some of the predictions using experimental data from additional synthetic maize lines for which no models were developed. This article is protected by copyright. All rights reserved.

PMID: 27155093 [PubMed - as supplied by publisher]

Modelling tumour cell proliferation from vascular structure using tissue decomposition into avascular elements.

J Theor Biol. 2016 May 4;

Authors: Besenhard MO, Jarzabek M, O'Farrell AC, Callanan JJ, Prehn JH, Byrne AT, Huber HJ

Abstract
Computer models allow the mechanistically detailed study of tumour proliferation and its dependency on nutrients. However, the computational study of large vascular tumours requires detailed information on the 3-dimensional vessel network and rather high computation times due to complex geometries. This study puts forward the idea of partitioning vascularised tissue into connected avascular elements that can exchange cells and nutrients between each other. Our method is able to rapidly calculate the evolution of proliferating as well as dead and quiescent cells, and hence a proliferative index, from a given amount and distribution of vascularisation of arbitrary complexity. Applying our model, we found that a heterogeneous vessel distribution provoked a higher proliferative index, suggesting increased malignancy, and increased the amount of dead cells compared to a more static tumour environment when a homogenous vessel distribution was assumed. We subsequently demonstrated that under certain amounts of vascularisation, cell proliferation may even increase when vessel density decreases, followed by a subsequent decrease of proliferation. This effect was due to a trade-off between an increase in compensatory proliferation for replacing dead cells and a decrease of cell population due to lack of oxygen supply in lowly vascularised tumours. Findings were illustrated by an ectopic colorectal cancer mouse xenograft model. Our presented approach can be in the future applied to study the effect of cytostatic, cytotoxic and anti-angiogenic chemotherapy and is ideally suited for translational systems biology, where rapid interaction between theory and experiment is essential.

PMID: 27155046 [PubMed - as supplied by publisher]

Polypharmacology in Drug Development: A Minireview of Current Technologies.

ChemMedChem. 2016 May 6;

Authors: Tan Z, Chaudhai R, Zhang S

Abstract
Polypharmacology, the process in which a single drug is able to bind to multiple targets specifically and simultaneously, is an emerging paradigm in drug development. The potency of a given drug can be increased through the engagement of multiple targets involved in a certain disease. Polypharmacology may also help identify novel applications of existing drugs through drug repositioning. However, many problems and challenges remain in this field. Rather than covering all aspects of polypharmacology, this Minireview is focused primarily on recently reported techniques, from bioinformatics technologies to cheminformatics approaches as well as text-mining-based methods, all of which have made significant contributions to the research of polypharmacology.

PMID: 27154144 [PubMed - as supplied by publisher]

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