Emily Cockey and Nicole J Ullrich*

Department of Neurology, Boston Children’s Hospital, Boston, MA 02115, USA

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder that predisposes patients to develop benign and malignant neoplasms, most often due to a loss of function mutation in the neurofibromatosis type 1 (NF1) gene. Neurofibromin, the protein product of NF1, regulates the inactivation of the Ras pathway, and thus acts as a tumor suppressor. Located in neurons, Schwann cells, and melanocytes, a decrease in neurofibromin predisposes patients with NF1 to tumors in both the central and peripheral nervous systems. Interestingly, brain tumors associated with NF1 often follow a more benign course than their sporadic counterparts and are often found in different locations. Thus, these tumors are often observed without tumor-directed therapy, unless clinical progression is noted, and then they are treated with surgery, chemotherapy or radiation. Current treatment trials seek to create more targeted therapies for specific tumor types associated with NF1 in order to increase efficacy and decrease treatment-related morbidity. This review will examine the most common types of brain tumors associated with NF1, including pilocytic astrocytomas, optic pathway gliomas, brainstem gliomas and glioblastomas, and will provide an overview of the clinical implications, current treatments, and ongoing clinical trials for these tumors.

DOI: 10.29245/2572-9411/2016/2.1017 View / Download Pdf

Sumita Choudhury, William E. Plautz, Cosette Zacarias and Rinku Majumder*

Department of Biochemistry & Molecular Biology, LSU Health Science Center, 1901 Perdido Street, MEB-7114, New Orleans, LA-70112

DOI: 10.29245/2572-9411/2016/2.1031 View / Download Pdf

Tonio Schoenfelder* and Hans-Holger Bleß

IGES Institut GmbH, Friedrichstraße 180, D-10117 Berlin, Germany

DOI: 10.29245/2572-9411/2016/2.1020 View / Download Pdf

Jessica Bauer*, Jonas J Staudacher, Nancy L Krett and Barbara Jung

Department of Medicine, Division of Gastroenterology and Hepatology, University of Illinois at Chicago, Chicago, Illinois, USA

DOI: 10.29245/2572-9411/2016/1.1013 View / Download Pdf

Ilaria Fregno1,2,3*, Maurizio Molinari1,2,4*

1Università della Svizzera italiana, CH-6900 Lugano, Switzerland
2Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland
3Department of Biology, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland
4Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, CH-1015 Lausanne, Switzerland

DOI: 10.29245/2572-9411/2016/1.1016 View / Download Pdf

Maria Favia1 and Anna Atlante2*

1Department of Biosciences, Biotechnology and Biopharmaceutics - University of Bari, Via E. Orabona 4, 70126, Bari, Italy
2Institute of Biomembrane and Bioenergetics - CNR, Via G. Amendola 165/A, 70126, Bari, Italy

 Cystic fibrosis is a progressive, genetic disease that causes persistent lung infections and limits the ability to breathe over time. It results from different possible mutations in the CFTR gene, which encodes the CFTR chloride channel, a protein that controls the movement of salt and water in and out of your body's cells. It follows that the abnormal channel function of the expressed protein on the secretory cell membrane determines the clinical phenotype in its classical form. Novel and more recent studies on mitochondrial bioenergetics - aiming to rediscover a possible role of mitochondria in this disease - provide a springboard for upcoming research to further understand the molecular mechanisms responsible for the involvement of mitochondria in CF and identify the protein/s primarily responsible for the F508del-CFTR-dependent mitochondrial alterations. Here, we review these CFTR-driven mitochondrial defects, thus revealing potential new targets for therapy.

DOI: 10.29245/2572-9411/2016/1.1009 View / Download Pdf

Eunice Mah1 and DeAnn J Liska1*

1Biofortis Innovation Services, 211 E. Lake Street, Addison, IL 60101, USA

 Cranberries have long been associated with the prevention of urinary tract infection (UTI); however, meta-analyses of clinical trials on the effect of cranberry for UTI have provided conflicting results. Liska and colleagues recently examined these meta-analyses to better understand the reasons behind their disparate findings and found several methodological differences. Most notably, the populations influencing conclusions varied. For example, one analysis, which concluded cranberry was not effective for UTI (RR: 0.86; 95% CI: 0.71, 1.04), had the largest contribution of results from studies in patients with complicated UTI. In contrast, another review, which included many of the same studies but weighted the evidence relatively equally across populations with complicated and uncomplicated UTI, concluded cranberry was effective (RR: 0.62; 95% CI: 0.49, 0.80). In both reviews, a significant benefit was noted in healthy women with recurrent UTI, particularly when two or three small trials in this population were analyzed; but, inclusion of a larger study that used a lower bacterial cut-off threshold for UTI outcome definition led to significant heterogeneity and non-significant results. These findings not only impact how we design meta-analyses, but also indicate the importance in considering the patient characteristics when generalizing findings across populations. In addition, the findings suggest additional research on cranberries in healthy women with recurrent UTI may be warranted.

DOI: 10.29245/2572-9411/2016/1.1012 View / Download Pdf

Linda D. Hazlett1,2*, Sharon A. McClellan1 and Sandamali A. Ekanayaka1

1Department of Anatomy and Cell Biology, Wayne State University, School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA
2Department of Ophthalmology, Wayne State University, School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA

 Pseudomonas (P.) aeruginosa is a Gram negative bacterium widely dispersed in the environment which can cause acute and chronic infections in humans. According to the Centers for Disease Control and Prevention (CDC), the overall incidence of P. aeruginosa infections in USA hospitals averages about 0.4% (4/1000 discharges), and the bacterium is the fourth most commonly-isolated nosocomial pathogen accounting for 10.1% of all hospital-acquired infections. P. aeruginosa keratitis is a severe infection of the eye, progresses rapidly and remains a leading cause of corneal ulcers worldwide. Use of contact lenses is the major risk factor in the USA, while in less industrialized countries, trauma from agricultural accidents are of importance. Animal models of bacterial keratitis are of value in the study of this disease and suggest potential alternative therapeutic targets that are needed urgently due to increasing antibiotic resistance. Recently we have shown success and improved disease outcome after down-regulation of one promising target, high mobility group box(HMGB1) using small interfering RNA (siRNA). Testing more clinically relevant approaches are underway to reduce HMGB1 levels in P. aeruginosa keratitis which may hold promise for its treatment.

DOI: 10.29245/2572-9411/2016/1.1015 View / Download Pdf

Khalil Charafeddine and Mohammad-Zouheir Habbal*

Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon

DOI: 10.29245/2572-9411/2016/1.1008 View / Download Pdf

Inmaculada Martinez-Saguer1* and Henriette Farkas2

1Hemophilia Center Rhine Main, Germany
2Hungarian Angioedema Center, 3rd Department of Internal Medicine, Semmelweis University, Hungary

DOI: 10.29245/2572-9411/2016/1.1004 View / Download Pdf

Sally Ann Lynch1,2* & Jillian P Casey2

1National Rare Disease Office, Mater Hospital Dublin 7, Ireland
2UCD Academic Centre of Rare Disease, School of Medicine and Medical Sciences, Belfield, Dublin 4, Ireland

 European Reference Networks are being established across the EU with the aim of improving the care of patients with rare diseases. Recognising that experts are rare, ERNs are tasked with the aim of encouraging collaboration of experts across individual member states. Membership of an ERN is dependent on fulfilling criteria to allow one to be described as a centre of expertise. ERNs will produce guidelines through consensus and the development of EU wide registries should help to facilitate clinical trials. However, the ERN entry requirements are such that some member states will struggle to fulfil the criteria. Investment in trained staff for rare diseases has been poor in some countries risking the possibility that ERN membership may be restricted to a limited number of member states.

DOI: 10.29245/2572-9411/2016/1.1002 View / Download Pdf

Hugh James Freeman*

Department of Medicine (Gastroenterology), University of British Columbia, Vancouver, BC, Canada

 A rarely diagnosed clinical and pathological disorder was historically characterized by multiple benign small intestinal ulcers, involving the mucosa and, occasionally, the submucosa of the small intestine, and histopathologically by non-specific inflammatory changes without granulomas. These early reports also noted that recurrent episodes of abdominal pain often developed due to obstructive events, sometimes associated with localized stricture formation. This usually responded to steroid treatment, intestinal resection, or both. Recent advances owing largely to emerging imaging methods have provided added criteria for separation of this entity from other disorders, including Crohn’s disease and medication-related small bowel ulceration. Most important, recent long-term follow-up studies have suggested a potential for confusion with other functional or motility-based clinical disorders and emphasize the likelihood of a much more benign clinical course.

DOI: 10.29245/2572-9411/2016/1.1001 View / Download Pdf

Michel Lebel*

Centre de recherche du CHU de Québec, Faculty of Medicine, Université Laval, Quebec City Quebec, Canada

 Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a pro-oxidant/pro-inflammatory status, genomic instability, and by the premature onset of several age-associated diseases. The protein defective in WS patients (WRN) is a helicase/exonuclease involved in DNA replication, repair, and transcription. This review focuses on the beneficial impact of vitamin C treatment in mutant mouse and worm models of WS with an emphasis on serum metabolomic and cytokinome profiles in Wrn mutant mice. Vitamin C normalizes the health and life span of these mutant animals. More importantly, our recent results indicate that it will be possible to follow the beneficial impact of vitamin C at a systemic level by monitoring specific serum metabolites and inflammatory cytokines in a longitudinal study involving WS patients.

DOI: 10.29245/2572-9411/2016/1.1003 View / Download Pdf

Paula G. Franco1,2, Ana M. Adamo1,2, Patricia Mathieu1,2, María J. Pérez1,2, Patricia C. Setton-Avruj1,2 and Lucas Silvestroff1,2*

1Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Química Biológica Patológica. Buenos Aires, Argentina
2Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Química y Fisicoquímica

Biológicas (IQUIFIB) Profesor Alejandro C. Paladini, Facultad de Farmacia y Bioquímica, Argentina

 Lysosomal Storage Disorders (LSD) are rare diseases that as a whole have a combined incidence ranging from 1:1500 to 1:7000 live births. One of such diseases is Mucopolysaccharidosis VI (MPS VI), or Maroteaux Lamy Syndrome. MPS VI patients undergo devastating and irreversible skeletal alterations and multisystemic failure as from early childhood due to reduced Arylsulfatse B (ARSB) enzyme activity.

Reaching a final diagnosis is not always a short cut path, but rather a years-long battle against uncertainty and unnecessary medical interventions. Our aim is to contribute from the bench table with different approaches that could serve as alternatives to pre-existing assays for screening and diagnosing MPS VI and other LSD.

The present work is based on our research article authored by Franco et al.1 where we studied the effect of blood-derived hemoglobin, and other blood components, on the fluorescence of 4-Methylumbelliferone when measuring ARSB enzyme activity from dried blood spot (DBS) samples.

Our experience indicates that to date there are plenty of different approaches for measuring ARSB enzyme activity, although the sample type required or the assay in itself often make them more adaptable for either high throughput screening or small scale diagnostics.

As a whole, the fluorometric determinations seem to be the most accessible to low budget laboratories with equally valuable performances as a sophisticated mass spectrometry analysis for this disease. Furthermore, the DBS serves as an attractive sample type for screening the disease in large populations.

DOI: 10.29245/2572-9411/2017/1.1081 View / Download Pdf

Tu-Anh Tran1*, Anne Filleron1, Mathieu Simonin2 and Pierre Corbeau3

1Department of Pediatrics, Nîmes University Hospital, INSERM U 1183, Montpellier-Nîmes University, Nîmes, France
2Institut Gustave Roussy, Department of Pediatric Oncology, 114 Rue Paul Vaillant, 94800 Villejuif, France
3Department of Immunology, Nîmes university hospital, Montpellier-Nîmes university, Nîmes, France

 Systemic capillary leak syndrome (SCLS), is a rare condition characterized by a recurrent stereotypical triad: hypovolemic shock, generalized edema, paradoxical hemoconcentration and hypoalbuminemia. It is caused by massive fluid extravasation into the interstitial space. Mortality may result from hemodynamic failure in the acute phase or cardiac failure due to reflex circulatory overload in the sub-acute phase. To date, twenty-one pediatric cases were reported in the literature. Sex ratio (M/F) was 0.32 with a median age at disease onset of 5.7 years and at diagnosis of 6 years. The disease was recurrent in 81% of patients with a median of three attacks. Severe complications were possible involving central nervous system (n=2) or rhabdomyolysis, with a compartment syndrome needing fasciotomy (n=5). The median time to clinical recovery was five days. Although the clinical manifestations of pediatric and adult SCLS were similar; in the opposite of adult SCLS, none of the children showed evidence of monoclonal gammopathy and three pediatric cases had a family history of SCLS. Seventy five percent of the patients were treated with prophylactic treatment (mainly immunoglobulins, theophylline plus verapamil). Several inflammatory cytokines were suspected to be involved in the pathophysiology of SCLS, especially interleukin-17 and tumor necrosis factor -alpha.

DOI: 10.29245/2572-9411/2017/1.1070 View / Download Pdf