Rose Chami*

Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada

“Pulmonary Interstitial Glycogenosis (PIG) associated with a spectrum of neonatal pulmonary disorders”, reported by Cutz et al represents one of the largest series published to date. The report included twenty-eight cases of lung or cardiac disorders with coincident diffuse, patchy, or focal PIG reviewed in Division of Pathology, The Hospital for Sick Children. The authors focused on reporting a spectrum of disorders associated with PIG and described four clinicopathological subgroups including imaging, ultrastructural findings, and clinical outcome. The present paper highlights the main findings reported by Cutz et al, and a review of literature is also presented.

DOI: 10.29245/2572-9411/2018/1.1170 View / Download Pdf

Núria Pujol-Moix1,2*, Blanca Jimenez2, Eduardo Muñiz-Diaz3, Manel Roca4, Joan Carles Souto2,5

1Medicine Department, Unitat Docent Sant Pau, Universitat Autònoma de Barcelona, Spain

2Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain

3Division of Immunohematology, Banc de Sang i Teixits de Catalunya, Barcelona, Spain

4Nuclear Medicine Department, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Spain

5Unitat d'Hemostàsia i Trombosi, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

Immune thrombocytopenia (ITP) is an acquired disorder that generally occurs in sporadic individuals, but a few patients are grouped in families. The aims of the present study were: 1) to perform a retrospective descriptive study of a series of patients with familial ITP, and 2) to perform a literature review on familial ITP.

We studied 16 ITP patients, from 8 families, selected by using the general established exclusion criteria as well as at least one of the following additional positive criteria: the finding of autoantibodies on the platelet surface, a short platelet survival in the kinetic study, or a clear therapeutic response to immunosupressors or splenectomy. Moreover, we studied 60 patients with familial ITP previously reported in the literature, selected by using the same diagnostic criteria as for our patients.

The patient’s characteristics of familial ITP were not substantially different from those of sporadic ITP patients. The small number of patients reported in the literature suggests that, familial ITP has been underdiagnosed. We recommend considering the possible diagnosis of familial ITP when a familial thrombocytopenia has no demonstrable genetic cause, especially if there are other autoimmune disorders in the family. Moreover, to obtain a true diagnosis in these families we recommend applying the additional positive criteria mentioned above besides the exclusion diagnostic criteria.

ITP = immune thrombocytopenia

Ig = immunoglobuin, immunoglobulins

AD = autoimmune disorder, autoimmune disorders

DOI: 10.29245/2572-9411/2018/4.1167 View / Download Pdf

Natalie M. Bath1*, Daniel H. Williams2, Hans W. Sollinger1, Robert R. Redfield III1

1 Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

2 Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

Loin Pain Hematuria Syndrome (LPHS) remains a rare disease but has a significant impact on those affected by it. Patients diagnosed with LPHS experience severe, constant or intermittent flank pain that radiates to the groin and may be exacerbated even by a gentle touch. These patients often require significant narcotic regimens for pain control and are unable to maintain a functional lifestyle. Previously, diagnosis has been made based on clinical presentation. One treatment for this syndrome is renal autotransplant; however, success rates are varied. Therefore, patient selection for this procedure is important. We have developed the UW-LPHS test as a diagnostic maneuver in order to determine which patients with LPHS would benefit from renal autotransplant. To perform this diagnostic test, bupivacaine is instilled into the ureter on the affected side and left to dwell. Patients who experience pain relief following this test are deemed to benefit from renal autotransplant. Here we describe this novel diagnostic test and initial success rates following renal autotransplant.

DOI: 10.29245/2572-9411/2018/4.1169 View / Download Pdf

Photios Anninos1*, Athanasia Kotini1, Adam Adamopoulos1, Nicolaos Tsagas2

1Labratory of Medical Physics, Department of Medicine, School of Health Sciences, Alexandroupoli, Greece

2Department of Electrical Engineering, Polytechnic School, Democritus University of Thrace, Xanthi, Greece

The purpose of this research is to identify any change in the frequencies of 2-7Hz in the brain state of epilepsy patients after pico-Tesla transcranial magnetic stimulation (pT-TMS). It is a noninvasive technique for treating neurological disorders. We used magneto encephalographic (MEG) recordings of 10 epilepsy patients with a whole-head 122 - channel MEG system in a magnetically shielded room of low magnetic noise. The subjects were 5 male and 5 female epilepsy volunteers between 18-42 years of age. Afterwards, external pT-TMS was applied to the above patients. A software program was developed in our lab in order to detect the primary dominant frequency of the power spectra of the MEG obtained from every patient and channel before and after the application of pT-TMS. We found that 7 out of 10 patients (70%) had increased their 2-7Hz frequencies after the application of pT-TMS. We concluded that frequency analysis is a promising means for the assessment of epilepsy disorders.

DOI: 10.29245/2572-9411/2018/4.1164 View / Download Pdf

Moises Rodriguez-Gonzalez1*, Alvaro Antonio Perez-Reviriego2, Ana Castellano-Martinez2, Helena Maria Cascales-Poyatos2

1Pediatric Cardiology Department, Puerta del Mar Universitary Hospital, Cadiz, Spain

2Pediatrics Department, Puerta del Mar Universitary Hospital, Cadiz, Spain

Propionic acidemia, is an autosomal recessive disorder due to the deficiency of the enzyme propionyl?coenzyme A carboxylase, which is a critical component for the metabolism of certain amino acids and lipids. The clinical complications are varied and may present at any time in the patient's life, mainly the neurological symptoms. Outside the central nerve system, haematological abnormalities including anaemia, neutropenia, thrombocytopenia or pancytopenia, immune defects, osteoporosis and pancreatitis are other rare complications reported. Of note, cardiac diseases have been recognized as increasing and life-threatening manifestations, including cardiomyopathy and electrophysiological changes such as prolongation of the QT interval.

The possible mechanisms of propionic acidemia?associated cardiac disorder, and the importance of appropriate management and early recognition, are discussed.

DOI: 10.29245/2572-9411/2018/3.1162 View / Download Pdf

Dr. Sona B. Nair*

Department of Assisted Reproduction and Genetics, Jaslok Hospital and Research Centre, Mumbai, India

DOI: 10.29245/2572-9411/2018/3.1161 View / Download Pdf

Daniel da Motta Girardi1*, Gabriela Oliveira Mendes2

1Department of Oncology, Hospital Sírio Libanês, Brazil

2Hospital de Base do Distrito Federal, Brasília, Brazil

Curative treatment for localized gastric cancer involves a multidisciplinary approach that includes surgery and chemotherapy with or without radiotherapy. In the past decades several studies have shown survival benefit of postoperative and perioperative treatments in comparison with surgery alone. Only a few trials have compared directly chemotherapy with chemoradiotherapy without a clear benefit favoring one strategy over another. In the absence of a standard approach, the choice of the best treatment is individualized and varies by geographic region and the preference of the institution where the patient is being treated. This review summarizes what is new in the treatment of localized gastric cancer and seeks to deeply analyze chemotherapy and chemoradiotherapy strategies.

DOI: 10.29245/2572-9411/2018/3.1159 View / Download Pdf

Yoichiro Ikeda*, Yoko Yoshida, Yuuka Sugawara, Masaomi Nangaku

Division of Nephrology and Endocrinology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by the dysfunction of the alternative pathway of the complement system, which leads to the spontaneous activation of the complement system in the circulating plasma or cell surface. Recently our group published the cohort analysis of aHUS in Japan (n=118). Through the study, we revealed the followings; 1) the genetic background of aHUS in Japan was different from that in Western countries, 2) the most frequent genetic mutation detected in this study was I1157T in C3 (n=24), which was associated with superior renal outcome in spite of frequent replases, 3) Anti-CFH antibody positive aHUS had an excellent renal outcome, 4) 44% cases presented nephrotic syndrome, 5) only 12 % developed end stage renal disease (ESRD) and 6) there were 13 cases that discontinued eculizumab treatment and were followed up. These findings might help establishing the robust evidence for the optimal treatment of aHUS.

DOI: 10.29245/2572-9411/2018/3.1156 View / Download Pdf

Emma Nally1,2, Robert D. Bunning1*

1MedStar National Rehabilitation Hospital, 102 Irving St., NW, Washington, DC, 20010, USA

2Georgetown University Hospital, Department of Rehabilitation Medicine, Washington, DC, USA

DOI: 10.29245/2572-9411/2018/2.1154 View / Download Pdf

Girish Hiremath1*, Evan S. Dellon2

1Division of Pediatric Gastroenterology, Hepatology and Nutrition, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville TN 37232, USA

2Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA

DOI: 10.29245/2572-9411/2018/2.1155 View / Download Pdf

Sangjucta Barkataki1,2, Madhura Joglekar-Javadekar1,2, Patti Bradfield3, Thomas Murphy1, Diana Dickson-Witmer2,4 and Kenneth L. van Golen1,2*

1The University of Delaware Department of Biological Sciences, Newark, DE, USA

2The Center for Translational Cancer Research, Newark, DE, USA

3The Inflammatory Breast Cancer Foundation, Newark, DE, USA

4The Breast Center at the Helen F. Graham Cancer Center, Christiana Care Health System, Newark, DE 19716-2500, USA

Inflammatory breast cancer (IBC) is a unique breast cancer with a highly virulent course and low 5- and 10-year survival rates. Although IBC only accounts for 1-5% of breast cancers it is estimated to account for 10% of breast cancer deaths annually in the United States. The accuracy of diagnosis and classification of this unique cancer is a major concern within the medical community. Multimodality treatment includes preoperative chemotherapy, mastectomy, and radiation therapy is the therapeutic mainstay and has been shown to improve prognosis. The potential for inaccurate diagnosis and misclassification in cases of IBC is increased by many factors. This includes the misleading initial symptoms of IBC. The early signs of IBC will present in women who have inflammation of the skin of the affected breast, as well as red or purple coloration of the inflamed area. Molecular studies have shown unique signature genes that are hallmarks of IBC. The current article reviews multiple aspects of primary inflammatory breast cancer.

DOI: 10.29245/2572-9411/2018/2.1150 View / Download Pdf

Tan Vu Le1, Hoang Minh Tue Nguyen1, Wayne J.G. Hellstrom1*

1Tulane University School of Medicine, Department of Urology, New Orleans LA, USA

Post-orgasmic illness syndrome (POIS) is rare condition that is characterized by transient flu-like symptoms and cognition disorders that occur shortly after ejaculation and last for 2-7 days. There are about 50 cases of POIS in the literature. The prevalence and incidence of POIS are still unknown due to a paucity of studies. The exact pathogenesis of POIS remains unknown; the most acceptable hypothesis is an autoimmune/allergic process. We made a literature search via PubMed for publications from 2002 to 2018 with the “post orgasmic illness syndrome” medical subject heading term to analyze current data regarding symptoms, burden, pathophysiology, and to discuss potential management options for POIS. POIS is diagnosed by five preliminary diagnostic criteria. It is categorized into two types: primary and secondary. There is the concomitance between POIS and PE. The autoimmune/allergy hypothesis is the most accepted hypothesis explaining POIS pathogenesis. A competing hypothesis involves a disorder of endogenous μ-opioid receptors. Patients with POIS have been symptomatically treated with antihistamines, selective serotonin reuptake inhibitors, and benzodiazepines. A trial of hyposensitization therapy with autologous semen was successful. A trial of nonsteroidal anti-inflammatory medication helped in a single case report but failed to successfully treat other patients with POIS.

DOI: 10.29245/2572-9411/2018/2.1152 View / Download Pdf

Natan Gadoth1*

1The Sackler faculty of medicine, Tel-Aviv University and Maynei Hayeshua Medical Center, Bnei Barak, Israel

Rare genetic disorders are usually a diagnostic challenge mainly due to the complexity of the clinical presentation which is frequently changing with age and progression of the particular disorder. Familial Dysautonomia is a rare and complex multisystem disorder with peculiar but distinct clinical features . Some of those features are unique to this particular syndrome and the one who is familiar with them can quite easily reach the diagnosis without the need for sophisticated laboratory work-up. In this short review those “clinical pearls” will be described in some detail.

DOI: 10.29245/2572-9411/2018/2.1153 View / Download Pdf

Francisco José Guerrero-Márquez1*, José María Cubero-Gómez1, Agustín Guisado-Rasco1, Luis Salvador Díaz-de la-Llera1, Mónica Fernández-Quero1, Manuel Villa-Gil Ortega1

1Haemodynamic and Interventional Cardiology, University Hospital Virgen del Rocío, Seville, Spain

Thrombocytopenia induced by iodinated contrasts is a rare adverse effect but with significant morbidity and mortality. The molecular mechanisms that produce this phenomenon are unknown; however, an idiosyncratic reaction after a previous exposure may be part of its etiopathogenesis. The best alternative to these media is gadolinium medium, although its scarce radiopacity and possible adverse effects secondary to its dose result in limitations to its use. The use of intracoronary diagnostic techniques, such as intravascular ultrasound (IVUS), can provide information and reduce the risks inherent in a higher dose of gadolinium. In the absence of experience in the form of literature in this field, the best alternative that we have to guide a coronary intervention in patients with a contraindication to iodinated contrasts is gadolinium medium supported with IVUS.

DOI: 10.29245/2572-9411/2018/2.1149 View / Download Pdf

Kazuhiko Hashimoto1*, Yutaka Oda1, Shigeshi Mori2, Koutaro Yamagishi1, Tsukamoto Ichiro1, Masao Akagi1

1Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka 589-8511, Japan

2Department of Orthopedic Surgery, Kindai University Nara Hospital, Ikoma City, Nara 630-0293, Japan

The lectin-like, oxidized low-density lipoprotein (ox-LDL) receptor-1 (LOX-1)/ox-LDL system contributes to atherosclerosis and thus may play a role in cartilage degeneration. The purpose of this study was to determine whether the LOX-1/ox-LDL system contributes to the pathogenesis of age-related osteoarthritis (OA) in vivo, using LOX-1 knockout (LOX-1 KO) mice. Knee cartilage samples from 6-, 12-, and 18-month-old (n = 10 per group) C57Bl/6 wild-type (WT) and LOX-1 KO mice were compared for OA-related changes with Safranin-O staining. At 12 and 18 months, the OA changes were significantly reduced in LOX-1 KO mice compared to those in WT mice. Moreover, an immunohistological analysis showed that the expression levels of Runt-related transcription factor-2, type-X collagen, and matrix metalloproteinase-13 in the articular chondrocytes were significantly decreased in LOX-1 KO mice compared with those in WT mice. Overall, this study indicates that the LOX-1/ox-LDL system in chondrocytes plays a role in the pathogenesis of age-related knee OA, highlighting a novel potential target for preventing OA progression.

DOI: 10.29245/2572-9411/2018/2.1151 View / Download Pdf

Chi Yun Yu1, Syed Wasim2, Dominick Amato3*

1University of Toronto, Medical Sciences Building, 1 King's College Cir #3172, Toronto, ON M5S 1A8, Canada

260 Murray Street, Box 34, 3rd Floor, Room 400, Toronto, ON M5T 3L9, Canada

3Mark Freedman and Judy Jacobs Program for Gaucher Disease, Mount Sinai Hospital, 60 Murray Street, Room L3-415, Toronto, Ontario M5T 3L9, Canada

Gaucher disease (GD) is characterized by a deficiency in lysosomal glucocerebrosidase, resulting in a multisystemic disease with substantial variability in clinical manifestations, disease progression, and treatment response. This is the first study in Canada that examines the epidemiological profile of Gaucher patients, mapping out the GD clinical spectrum in the ethnically diverse province of Ontario.

Study found a prevalence of 1:155,367 (1: 9,853 for Ashkenazi-Jews) type 1 GD adults in Ontario. Splenectomy was associated with improved thrombocytopenia, worsened hyperferritinemia and bone pain, but no effects on anemia, bone mineral density or bone crises. Compared to the non-treatment group, a higher proportion of patients who received enzyme replacement/ substrate reduction therapy (ERT/SRT) presented with anemia, hepatomegaly, bone pain, and bone crises at baseline, suggesting that these presentations may be predictive of subsequent need for treatment. ERT/SRT were effective in improving all hematological, visceral, and skeletal manifestations (except bone mineral density), whereas the non-treatment group remained clinically stable over time (10.88 years) without significant disease progression – thus early use of ERT/SRT may not be necessary in all patients.

This comprehensive analysis summarizes the genotypic and phenotypic heterogeneity of GD, serving as a comparative resource for optimization of care for adult patients.

DOI: 10.29245/2572-9411/2018/2.1148 View / Download Pdf

Josivan Gomes Lima1*, Marcel Catão Ferreira dos Santos1, Julliane Tamara Araújo de Melo Campos2

1Departamento de medicina clínica, disciplina de endocrinologia e metabologia. Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN, Brazil

2Faculty of Health Sciences of Trairi, Federal University of Rio Grande do North (UFRN), Natal, RN, Brazil

Congenital Generalized Lipodystrophy (CGL) is a rare and severe autosomal recessive disease. Patients are defective in the storage of body fat and, consequently, they deposit fat in ectopic tissues, mainly liver, and can develop cirrhosis. Insulin resistance is a typical finding, causing diabetes that require high daily doses of insulin. In the state of Rio Grande do Norte, Brazil, we have one of the largest cohorts of patients with CGL. In this article, we review pathophysiology, clinical picture and treatment of this disease.

DOI: 10.29245/2572-9411/2018/2.1147 View / Download Pdf

Peter Dambach1*

1Institute of Public Health, University of Heidelberg, Germany

In most parts of sub-Saharan Africa, malaria is still the most important vector borne disease, severely affecting people´s lives and causing economic loss. Malaria vector control to date almost exclusively relies on long lasting insecticide treated nets (LLINs) and indoor residual spraying (IRS), while other approaches such as larviciding are less implemented. Rising resistances against commonly used insecticides and changes in vector behavior and genetics slow down further reductions in malaria transmission. There is an urgent need for the implementation of additional approaches to appropriately react to vector adaptations. One promising option is the targeting of vector larvae with biological larvicides. During a three-year field trial (EMIRA – Ecologic Malaria Reduction for Africa), evidence was generated on the feasibility, effectiveness, acceptability, and cost of biological larviciding in North-Western Burkina Faso. Here, possible ways on how to further increase cost effectiveness and community support for future programs are presented. Reducing the need for frequent retreatment of vector larvae habitats is a major cost saver for material and workforce. Additional expenditure reductions could be achieved through targeting multiple disease vectors, which in some cases share vector breeding and resting sites. Due to limited overlap in mosquito breeding preference, major cost savings are expected to originate in infrastructural synergy effects. The development of new approaches to further cut down program costs could be a powerful contributor to promote vector larvae control and techniques that target several diseases at once.

DOI: 10.29245/2572-9411/2018/1.1144 View / Download Pdf

Thet Tun Aung1, Roger W Beuerman1,2,3*

1Singapore Eye Research Institute, Singapore 169856

2SRP Neuroscience and Behavioral Disorders, Duke-NUS, Singapore 169857

3Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228

Atypical mycobacteria are wide spread in the environment; they are now known to be a cause of a variety of infections including corneal infections especially after refractive surgery. The diagnosis and clinical management are often unsatisfactory due to misdiagnosis and requirement of prolonged combination of antibiotics. Evolving drug resistance is known to be a unique feature in managing atypical mycobacterial keratitis due to the propensity for the development of biofilms. In this article, we provide an etiology of atypical mycobacterial keratitis, mycobacterial biofilm pathogenesis, and the importance of mycobacterial biofilm matrix component (extracellular DNA) in maintaining mycobacterial biofilm matrix maintenance. Current treatment options for atypical mycobacterial keratitis are summarized and suggestions are made for the new treatment strategies targeting on the mycobacterial biofilm pathogenesis pathway.

DOI: 10.29245/2572-9411/2018/1.1143 View / Download Pdf

Bartholomew Dicky Akanmori1, Joseph Okeibunor1*, and Matshidiso Rebecca Moeti2

1WHO Regional Office for Africa, Brazzaville, Congo

2WHO Regional Director for Africa, Brazzaville, Congo

The WHO Regional Office for Africa is systematically taking steps to realize the goals of malaria control in the Region. One of such steps is the pursuit for the development of malaria vaccine, which is being tested in three countries in the Region, namely Ghana, Kenya and Malawi. This paper reviews the potential contributions of a vaccine against malaria in endemic regions like sub-Saharan Africa beyond just coming as another intervention for malaria control. The injectable vaccine, RTS,S, was developed to protect young children from the most deadly form of malaria, Plasmodium falciparum, which is endemic in the Region. However, sceptics argued that this could be unlikely outside of rigorously controlled clinical trials, as well as waning efficacy over time. There has been calls for cautious optimism and emphasized that “the vaccine is just an additional tool in the current limited armamentarium for making progress against malaria”. This review demonstrates the benefits of having the malaria vaccine are numerous, including strengthening national immunization and malaria control programmes; stimulating and boosting the scale-up of the existing interventions which have so far made significant reductions in malaria burden across several countries of the region.

DOI: 10.29245/2572-9411/2018/1.1141 View / Download Pdf

Alexandra Prufer de Queiroz Campos Araujo1*, Igor Prufer de Queiroz Campos Araujo2, Abelardo de Queiroz Campos Araujo3

1Institute of Pediatrics, Federal University of Rio de Janeiro (UFRJ). Rua Bruno Lobo 50, Cidade Universitária, Rio de Janeiro, RJ 21941-912, Brazil

2School of Medicine, Federal University of Rio de Janeiro (UFRJ) Rua Bruno Lobo 50, Cidade Universitária, Rio de Janeiro, RJ 21044-020, Brazil

3The Institute of Neurology, Federal University of Rio de Janeiro (UFRJ). Av Venceslau Braz, 215, Botafogo, Rio de Janeiro, RJ 22290-160, Brazil

Background: Motor neuron disorders predominately result in progressive weakness. Nevertheless a wider expression of symptoms and signs point to a more multisystemic involvement. Autonomic nervous system findings have been reported in animal models, adult and child motor neuron diseases.

Objective: Review the literature on autonomic findings in motor neuron diseases.

Method: A PubMed literature search.

Results: In the present review, we will discuss the neuropathological and clinical features of dysautonomia reported in motor neuron disease in humans and animal models.

Conclusion: The literature points to considering careful autonomic evaluation and management in patients with motor neuron disorders.

DOI: 10.29245/2572-9411/2018/1.1136 View / Download Pdf

Monika Bekiesinska-Figatowska1*

1Department of Diagnostic Imaging, Institute of Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland

Neurofibromatosis type one (NF1) belongs to the most frequent rare diseases, requiring various methods of diagnostic imaging at different stages of diagnostics and follow-up. Magnetic resonance imaging (MRI) is a method of choice in diagnostics of brain: unidentified neurofibromatosis objects, optic pathway gliomas and other tumours which can spontaneously regress. NF1 patients suffer from vascular abnormalities with a predominance of aortic, renal, mesenteric, and carotid-vertebral stenoses or aneurysms. These are evaluated by ultrasound, computed tomography- or MRI-angiography and by digital subtraction angiography. In our material we described twofold higher occurrence of arterial variants in brain in NF1 than in the control group. Characteristic skeletal changes include tibial pseudarthrosis, scoliosis, sphenoid wing dysplasia, rib penciling, and gracile bones, usually diagnosed with plain radiographs. Outside CNS we deal with neurofibromas and plexiform neurofibromas in any location in the body. Their malignant transformation leads to development of malignant peripheral nerve sheath tumour, or malignant triton tumour. Rhabdomyosarcoma, juvenile myelomonocytic leukemia and phaeochromocytoma are also encountered in NF1 patients with increased frequency. Regular imaging follow-up studies should not be routinely performed in NF1 patients. MRI is recommended for follow-up of clinically suspected tumours, single whole-body MR is recommended at transition to adulthood. Positron emission tomography/computed tomography is useful for the detection of malignant transformation of tumours in NF1 patients.

DOI: 10.29245/2572-9411/2017/6.1140 View / Download Pdf

Myeshia V. Shelby*

Department of Genetics and Human Genetics, Howard University Graduate School, Howard University, USA

Through a combination of in silico research and reviews of previous work, mechanisms by which nonsense-mediated mRNA decay (NMD) affects the inheritance and expressivity of Waardenburg syndrome is realized. While expressivity and inheritance both relate to biochemical processes underlying a gene’s function, this research explores how alternative splicing and premature termination codons (PTC’s) within mRNAs mutated in the disease are either translated into deleterious proteins or decayed to minimize expression of altered proteins. Elucidation of splice variants coupled with NMD perpetuating the various symptoms and inheritance patterns of this disease represent novel findings. By investigating nonsense mutations that lie within and outside the NMD boundary of these transcripts we can evaluate the effects of protein truncation versus minimized protein expression on the variable expressivity found between Type I and Type III Waardenburg syndrome, PAX3, while comparatively evaluating EDN3 and SOX10’s role in inheritance of Type IV subtypes of the disease. This review will demonstrate how alternative splicing perpetuates or limits NMD activity by way of PTC positioning, thereby affecting the presentation of Waardenburg syndrome.

DOI: 10.29245/2572-9411/2017/6.1118 View / Download Pdf

Kenneth L. van Golen*

The laboratory for cytoskeletal physiology, Department of biological sciences, The university of delaware, The center for translational cancer research, The Helen F. Graham Cancer Center, Newark, DE, USA

DOI: 10.29245/2572-9411/2017/6.1142 View / Download Pdf

Yijie Hu1,2, Wolfgang M. Kuebler1,3,4

1Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada
2Department of Cardiovascular Surgery, Institute of Surgical Research, Daping Hospital, Third Military Medical University, Chongqing, China
3Departments of Surgery and Physiology, University of Toronto, Toronto, ON, Canada
4Institute of Physiology, Charité Universitätsmedizin Berlin, Berlin, Germany

Of recent, inflammatory responses, formation of ectopic lymphoid tissue and autoantibodies have been increasingly implicated in the pathophysiology of pulmonary hypertension (PH). One of the earliest immune cells detected in PH and implicated in its pathogenesis were mast cells based on their demonstrated abundance in the vicinity of vascular lesions in PH patients, as well as in lungs of animal models of PH. Experimental studies using mast cell stabilizers or mast cell deficient rats in classic PH models provided proof-of-principle for the functional relevance of mast cells in the initiation and/or progression of PH and lung vascular remodeling. Yet, the cellular mechanisms by which mast cells contribute to the development of PH and pulmonary vascular remodeling has so far remained largely unclear. Importantly, understanding the downstream effectors by which activated mast cells and their secretome trigger or promote vascular remodeling may lead to the development of novel therapies for PH. Notably, recent work has unveiled a novel interplay between mast cells and the adaptive immune system in PH, in that mast cell-targeted interventions attenuate the formation of tertiary lymphoid tissue in the lung and the formation of autoantibodies. This minireview will focus on the role of mast cells in PH and their possible downstream mechanism.

DOI: 10.29245/2572-9411/2017/6.1137 View / Download Pdf