Jasmin Barman-Aksoezen1, Xiaoye Schneider-Yin1, Elisabeth I. Minder2*

1Stadtspital Triemli, Institute of Laboratory medicine, Zurich, Switzerland
2Stadtspital Triemli, Porphyria outpatient clinics, Zurich, Switzerland

Erythropoietic protoporphyria consists of two different genetic diseases, erythropoietic protoporphyria (EPP) and X-linked erythropoietic protoporphyria (XLEPP). Both of them are often accompanied by iron deficiency. Iron supplementation appears to be beneficial in XLEPP, although the clinical experience until to date is limited. In EPP, iron supplementation is discussed ambiguously and may cause harm in the majority of cases.

This minireview summarizes the limited knowledge on the connections of iron metabolism to regulation of porphyrin and heme synthesis and the influence these regulations may have on disease severity in the protoporphyrias. Further, we propose clinical guidelines, how to manage iron deficiency in both XLEPP and EPP.

DOI: 10.29245/2572-9411/2017/4.1110 View / Download Pdf

Mara Sanches Guaragna1*, Anna Cristina GB Lutaif2, Vera MS Belangero2 Andréa T. Maciel-Guerra3,4, Gil Guerra-Junior4,5 and Maricilda P. De Mello1

1Center for molecular biology and Genetic engineering – CBMEG, State university of campinas, UNICAMP, Campinas, Brazil
2Integrated center of pediatric nephrology – CIN - School of medical sciences – FCM, State university of campinas, UNICAMP, Campinas, Brazil
3Department of medical genetics - School of medical sciences – FCM, State university of campinas, UNICAMP, Campinas, Brazil
4Interdisciplinary group for the Study of sex determination and differentiation – GIEDDS - State university of campinas, UNICAMP, Campinas, Brazil
5Pediatrics endocrinology, Department of pediatrics, School of medical sciences – FCM, State university of campinas, UNICAMP, Campinas, Brazil

DOI: 10.29245/2572-9411/2017/3.1115 View / Download Pdf

Kristen Whitworth*, Nicholas Graff, and Christopher Trigger

Lakeland Health Emergency Medicine Residency Program, 1234 Napier Avenue, St. Joseph, MI 49085, USA

DOI: 10.29245/2572-9411/2017/3.1112 View / Download Pdf

Sarah Plucinsky1, and Kerney J. Glover1*

1Department of chemistry, Lehigh university, 6 E. Packer ave., Bethlehem, Pennsylvania, 18015, USA

Pulmonary Arterial Hypertension (PAH) is a rare disease that affects the vasculature in the lungs. Currently, there is no cure for PAH, and there appears to be no clear causal factors for the disease. Recently, through whole exome sequencing, caveolin-1, a critical component of cell surface invaginations called caveolae, has been identified as a key protein in the progression of PAH. Specifically, the mutations associated with PAH have been localized to the C-terminal domain of the protein. Since it is known that the C-terminus of caveolin-1 directly interacts with endothelial nitric oxide synthase (eNOS), the link between caveolin-1 and PAH may reside in disrupted nitric oxide (NO) levels, which ultimately triggers the disease state. Recent biophysical studies have now allowed for this relationship to be viewed in a structural context. In this mini-review, we will put the recent structural insights into the C-terminal domain of caveolin-1 into the context of PAH disease progression.

DOI: 10.29245/2572-9411/2017/3.1116 View / Download Pdf

Laura Manelyte

Biochemistry Center Regensburg, Laboratory of Chromatin Dynamics and Nuclear Architecture, University of Regensburg, Universitätstraße 31, Regensburg DE-93053, Germany

The chromatin remodeling complexes alter chromatin structures. They remodel nucleosomes in ATP-dependent manner and have essential roles in DNA damage repair, recombination, replication and transcriptional control. Increasing evidences indicate that subunits of chromatin remodelers are mutated and/or deregulated in a number of human cancers, and how they influence the cancer gene expression program during cancer initiation and progression is becomming clearer. Therefore, chromatin remodeling complexes arose as promising new targets for the treatment of human cancers. In this review, chromatin remodeling complexes, their epigenetic reader domains and available inhibitors are described. The insights into the misregulated chromatin remodelers pathways in human malignancies and the novel approach targeting deregulated chromatin remodelers to improve chemotherapy efficiency are discussed.

DOI: 10.29245/2572-9411/2017/3.1108 View / Download Pdf

Takuhiro Sonoyama1, Masakatsu Sone2*

1Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan

2Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan

 Primary aldosteronism (PA), one of the most frequent causes of secondary hypertension, is mainly composed of two major subtypes: aldosterone-producing adenoma (APA) and bilateral hyperaldosteronism (BHA). In APA, ACTH plays a dominant role in the regulation of circulating aldosterone level, while in physiological condition and BHA angiotensin II has a stronger effect. This pronounced regulation of aldosterone by ACTH in APA causes a differential response of aldosterone to either ACTH stimulation or ACTH suppression in APA from that in physiological condition and BHA, and therefore, ACTH stimulation test can be informative in differentiating APA among patients with PA and essential hypertension. Histologic studies have suggested a possibility that the origin of APA especially consisting of clear, lipid rich cells could be zona fasticulata, rather than zona glomerulosa. Recent studies have been focusing on molecular classification among APA, which could lead to a better understanding of ACTH responsiveness in APA.

DOI: 10.29245/2572-9411/2017/3.1101 View / Download Pdf

Ercole L. Cavalieri1,2* and Eleanor G. Rogan1,2

1Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA
2Department of Environmental, Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198-4388, USA

Endogenous estrogens become carcinogens when excessive catechol estrogen quinone metabolites are formed. Specifically, the catechol estrogen-3,4-quinones can react with DNA to produce a large amount of specific depurinating estrogen-DNA adducts, formed at the N-3 of Ade and N-7 of Gua. Loss of these adducts leaves apurinic sites in the DNA, which can generate subsequent cancer-initiating mutations. Unbalanced estrogen metabolism yields excessive catechol estrogen-3,4-quinones, increasing formation of the depurinating estrogen-DNA adducts and the risk of initiating cancer. Evidence for this mechanism of cancer initiation comes from studies in vitro, in cell culture, in animal models and in human subjects. High levels of estrogen-DNA adducts have been observed in women with breast, ovarian or thyroid cancer, and in men with prostate cancer or non-Hodgkin lymphoma. Observation of high levels of depurinating estrogen-DNA adducts in high risk women before the presence of breast cancer indicates that adduct formation is a critical factor in breast cancer initiation. Two dietary supplements, N-acetylcysteine and resveratrol, complement each other in reducing formation of catechol estrogen-3,4-quinones and inhibiting formation of estrogen-DNA adducts in cultured human and mouse breast epithelial cells. They also inhibit malignant transformation of these epithelial cells. In addition, formation of adducts was reduced in women who followed a Healthy Breast Protocol that includes N-acetylcysteine and resveratrol. Blocking initiation of cancer prevents promotion, progression and development of the disease. These results suggest that reducing formation of depurinating estrogen-DNA adducts can reduce the risk of developing a variety of types of human cancer.

DOI: 10.29245/2572-9411/2017/3.1093 View / Download Pdf

Yasuhiro Nakagami1,2

1Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan

2Asubio Pharma Co., Ltd., 6-4-3 Minatojima-minamimachi, Chuo-ku, Kobe-shi, Hyogo 650-0047, Japan

 Radiation therapy is a common treatment for cancer, often in combination with other approaches such as surgery and chemotherapy. High doses of radiation basically kill cancer cells; however, one of the common adverse effects of this treatment is acute radiation dermatitis. This leads to itching, pain, and diminished appearance, and can also interrupt the therapy itself. Reactive oxygen species are generated in the injured tissues, especially in keratinocytes, and cause inflammation, mitochondrial dysfunction, and DNA damage. Current drugs such as topical steroid creams and dressings are not sufficient to alleviate these detrimental events. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that binds to antioxidant response elements located in the promoter region of genes that encode antioxidant enzymes. Synthesized chemical Nrf2 activators have been shown to be effective in many pathological models, including acute radiation dermatitis models. Preclinical data identified RTA 402 as one of the most promising compounds for reducing or preventing acute radiation dermatitis, and this was recently tested in patients with breast cancer. This review discusses current links between Nrf2 activators and acute radiation dermatitis, and explores the possibility that symptoms can be alleviated by upregulating the Nrf2 signaling pathway.

DOI: 10.29245/2572-9411/2017/3.1109 View / Download Pdf

Yasuhiro Nakagami1,2

1Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan

2Asubio Pharma Co., Ltd., 6-4-3 Minatojima-minamimachi, Chuo-ku, Kobe-shi, Hyogo 650-0047, Japan

 Radiation therapy is a common treatment for cancer, often in combination with other approaches such as surgery and chemotherapy. High doses of radiation basically kill cancer cells; however, one of the common adverse effects of this treatment is acute radiation dermatitis. This leads to itching, pain, and diminished appearance, and can also interrupt the therapy itself. Reactive oxygen species are generated in the injured tissues, especially in keratinocytes, and cause inflammation, mitochondrial dysfunction, and DNA damage. Current drugs such as topical steroid creams and dressings are not sufficient to alleviate these detrimental events. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that binds to antioxidant response elements located in the promoter region of genes that encode antioxidant enzymes. Synthesized chemical Nrf2 activators have been shown to be effective in many pathological models, including acute radiation dermatitis models. Preclinical data identified RTA 402 as one of the most promising compounds for reducing or preventing acute radiation dermatitis, and this was recently tested in patients with breast cancer. This review discusses current links between Nrf2 activators and acute radiation dermatitis, and explores the possibility that symptoms can be alleviated by upregulating the Nrf2 signaling pathway.

DOI: 10.29245/2572-9411/2017/3.1109 View / Download Pdf

Eiji Ohashi*

Department of Biology, Faculty of Science, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan

DNA damage response (DDR) pathways play crucial roles in the maintenance of genome integrity, and defects in DDR proteins lead to genome instability and eventually cancer. Rad9-Hus1-Rad1 (9-1-1) is a ring-shaped heterotrimeric complex involved in multiple DDR pathways, especially the DNA damage checkpoint. Rad9 has an intrinsically disordered C-terminal region, called C-tail. The C-tail projects from the ring and has multiple phosphorylation sites and several protein-protein interaction sites, some of which are crucial for checkpoint activation. In addition, it was recently shown that C-tail binds to the 9-1-1 ring structure and is released from it upon binding to TopBP1, an activator of the DNA damage checkpoint. This review focuses on the regulatory roles of the Rad9 C-tail and discusses DNA damage checkpoint activation and the regulation of several DNA repair pathways via this region.

DOI: 10.29245/2572-9411/2017/3.1110 View / Download Pdf

Yuji Saitoh1,2 and Yoshitaka Nagai1,3*

1Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan
2Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8551, Japan
3Department of Neurotherapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan

DOI: 10.29245/2572-9411/2017/3.1106 View / Download Pdf

Ellis J Powell1, Joan E Cunnick2, and Christopher K Tuggle1*

1Genetics and Genomics Graduate Program, Department of Animal Science, Iowa State University, Ames, IA 50011, USA
2Interdepartmental Microbiology Program, Department of Animal Science, Iowa State University, Ames, IA 50011, USA

Severe Combined ImmunoDeficiency (SCID) is defined as the lack or impairment of an adaptive immune system. Although SCID phenotypes are characteristically absent of T and B cells, many such SCID cellular profiles include the presence of NK cells. In human SCID patients, functional NK cells may impact the engraftment success of life saving procedures such as bone marrow transplantation. However, in animal models, a T cell-, B cell-, NK cell+ environment provides a valuable tool for asking specific questions about the extent of the innate immune system function as well as emerging NK targeted therapies against cancer. Physiologically and immunologically the pig is more similar to the human than common rodent research animals. This review discusses why the T- B- NK+ SCID pig may offer a more relevant model for development of human SCID patient therapies as well as provide an opportunity for systematic exploration of the role of NK cells in artiodactyl immunity.

DOI: 10.29245/2572-9411/2017/3.1103 View / Download Pdf

Caitlin Doherty1, Francyne Kubaski2,3, Shunji Tomatsu3,4,5*, and Thomas H. Shaffer3,6*

1University of Delaware, Newark, DE, USA
2Department of Biological Sciences, University of Delaware, Newark, DE, USA
3Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA
4Department of Pediatrics, Gifu University, Gifu, Japan
5Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA, USA
6Center for Pediatric Lung Research, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA

 Morquio patients, in many cases, present with severe tracheal narrowing and restrictive lung problems making them susceptible to high mortality arising from sleep apnea and related complications. Tracheal obstruction with growth imbalance, short neck, adeno and tonsillar hypertrophy, large mandible, and/or pectus carinatum also contributes to the challenges in managing the airway with intubation and extubation due to factors intrinsic to Morquio syndrome. Taken together, these issues lead to serious respiratory distress and life-threatening complications during anesthetic procedures. Furthermore, patients with Morquio syndrome frequently cannot perform standard pulmonary function tests as a result of their distinctive skeletal dysplasia and chest deformity, thus making diagnosis of incipient pulmonary disease difficult. In many cases, conventional spirometry is too difficult for patients to complete, deriving from issues with cooperation or clinical circumstance. Therefore, it is an unmet challenge to assess pulmonary insufficiency with standard pulmonary function test (PFT) with minimal effort. Non-invasive PFT such as respiratory inductance plethysmography, impulse oscillometry system, and pneumotachography were described in Morquio patients as compared with spirometry. Findings from our previous study indicate that these non-invasive tests are a reliable approach to evaluate lung function in a larger range of patients, and provide valuable clinical information otherwise unobtainable from invasive tests. In conclusion, the present study describes the utility of non-invasive (PFT) to accommodate a broad range of patients including intolerance to effort-dependent PFT.

DOI: 10.29245/2572-9411/2017/2.1097 View / Download Pdf

Vaishnavi Raja, Christian A. Reynolds, and Miriam L. Greenberg

Department of Biological Sciences, Wayne State University, USA

Barth syndrome (BTHS) is a rare X-linked genetic disorder characterized by cardiomyopathy, skeletal myopathy, neutropenia, and organic aciduria. The presence and severity of clinical manifestations are highly variable in BTHS, even among patients with identical gene mutations. Currently, less than 200 patients are diagnosed worldwide, but it is estimated that the disorder may be substantially under-diagnosed due to the variable spectrum of clinical manifestations. BTHS is caused by mutations in the gene tafazzin (TAZ), resulting in defective remodeling of cardiolipin (CL), the signature phospholipid of the mitochondrial membranes. Many of the clinical sequela associated with BTHS can be directly attributed to mitochondria defects. In 2008, a definitive biochemical test was described based on detection of the abnormal CL profile characteristic of BTHS. This mini-review provides an overview of the etiology of BTHS, as well as a description of common clinical phenotypes associated with the disorder.

DOI: 10.29245/2572-9411/2017/2.1087 View / Download Pdf

Mitsunori Higuchi1*, Tetsutaro Nemoto2, Hajime Matsuida2, Ikuro Oshibe2, Nobutoshi Soeta2, Toshiyuki Takeshige2, Takuro Saito2, and Hiroyuki Suzuki3

1Department of Thoracic Surgery, Aizu Medical Center, Fukushima Medical University, Fukushima, 969-3492, Japan
2Department of Surgery, Aizu Medical Center, Fukushima Medical University, Fukushima, 969-3492, Japan
3Department of Chest Surgery, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan

 Immune checkpoint inhibitors play crucial roles in the treatment of advanced and recurrent non-small cell lung caner (NSCLC). As yet, there are no biomarkers to help select patients that would benefit from this treatment. Currently, evaluation of the efficacy of immune checkpoint inhibitors is performed using Response Evaluation Criteria In Solid Tumors (RECIST) or immune-related response criteria on the basis of computed tomography (CT) scans, which are based only on anatomical changes and exclude a metabolic assessment. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) can add metabolic information, but is also subject to false-positive and false-negative findings in the presence of inflammation. In this review, we briefly discuss the optimal use of FDG-PET for the evaluation of checkpoint-based cancer immunotherapy and also discuss the relationship between immune checkpoint inhibitors and FDG-PET in NSCLC. We also introduce ongoing clinical studies and pre-clinical experiments involved in the development of diagnostic imaging and treatments for NSCLC.

DOI: 10.29245/2572-9411/2017/2.1098 View / Download Pdf

H.S. Natraj Setty*, J.R. Vijaykumar, C.M Nagesh, Shivanand S Patil, Santhosh Jadav, T.R. Raghu, C.N. Manjunath

Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India

Takayasu’s arteritis (TA) is a chronic inflammatory disease of unknown aetiology. The mechanism of this disease is not exactly defined. The inflammatory process is generally (but not exclusively) initiated in the second or third decade of life through the actions of non-specific inflammatory cells. As the disease progresses, fibrotic stenosis occurs in aorta and its main branches. The consequence of this inflammatory process can be stenosis, thrombosis, dilatation or aneurysm formation in aorta and/ or its branches. Majority of cases have been observed in Asia, Africa, and Latin America. In Asia, its incidence (2.69 in a million per year) has been reported to be 100 times higher than in Europe and North America. Because of the delay in diagnosing the disease, patients often experience claudication, absence of pulses, hypertension, myocardial infarction (MI), and cerebrovascular accidents (CVAs). Accurate and early diagnosis of TA can reduce the economic, social, and psychological burdens. Considering the fact that classical TA has mainly been described in Asia.

DOI: 10.29245/2572-9411/2017/2.1048 View / Download Pdf

Aintzane Urbizu1, Tahir N. Khan2, Allison E. Ashley-Koch1*

1Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA
2Duke Center for Human Disease Modeling, Duke University Medical Center, Durham, NC, USA

 Chiari malformation type 1 is a heterogeneous disease characterized by cerebellar tonsillar herniation through the foramen magnum. Symptomatology is diverse, and diagnosis and treatment are controversial. Some evidence suggests the presence of a genetic component to the disease. However, the specific genetic factors involved remain relatively unknown. Previous reviews have broadly addressed different aspects (clinical manifestations, anatomical trails, treatment) of CM-1 by itself or compared it with other types of Chiari malformation. In this mini-review, we focus our attention on the heterogeneity of this disease and its impact on the study of the genetic etiology of classic CM-1. Patient stratification strategies and endophenotypes definitions are offered to help overcome the heterogeneity.

DOI: 10.29245/2572-9411/2017/2.1082 View / Download Pdf

Marina G. Yefimova1,2 and Nicolas Bourmeyster1*

1Université de Poitiers/CNRS, Laboratoire Signalisation et Transports Ioniques Membranaires, 1 rue Georges Bonnet, F-86022 Poitiers, France
2Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Maurice Thorez Prospekt, 194233 Saint Petersburg, Russia

 Myelinosomes are pleomorphic structures with huge diversity of form, specific hallmark of “lysosomal storage diseases”, but also present in other inborn errors of metabolism such as aggregation diseases HD and CF. In the original work “Myelinosomes act as natural secretory organelles to prevent accumulation of aggregate-prone mutant Huntingtin and CFTR” Yefimova et al., describe an unexpected role of myelinosomes as key regulators of proteostasis in the somatic Sertoli cells from the testis. By releasing myelinosomes loaded with undegraded misfolded proteins, Sertoli cells demonstrate a new aspect of protein quality control mechanism unrelated to catabolic degradation.

DOI: 10.29245/2572-9411/2017/2.1085 View / Download Pdf

Alfred Said Sife1, Tumaini Jonas Wapalila2 and Maulilio John Kipanyula3*

1Sokoine National Agricultural Library (SNAL), Sokoine University of Agriculture, P.O. Box 3022 Chuo Kikuu, Morogoro, Tanzania
2Morogoro Regional Commisioner's Office, Boma Road, P.O. Box 650 Boma Road, Morogoro, Tanzania
3Department of Anatomy Histology and Cell Biology, College of Veterinary and Medical Sciences, Sokoine University of Agriculture, P.O.Box 3016, Morogoro – Tanzania

 The CD4 T-cell count is an important laboratory indicator of the immune status in patients with HIV/AIDS. It is used in decision making to determine when antiretroviral therapy and a need of prophylaxis for opportunistic infections should be initiated. This study was carried out to assess the contribution of donor funded projects to the wellbeing of people living with HIV/AIDS as measured by improvement of CD4 count. A total of 120 respondents were randomly selected from Morogoro urban and Kilombero district, Tanzania. Based on panel data, individual observations were made four times across time and there were a total of 480 observations. The home based care TUNAJALI project provided various interventions including medical care and psychological support with the purpose of improving the health status of people living with HIV/AIDS. The effect of home based care TUNAJALI services was the only predictor of health status of people living with HIV/AIDS that was measured as an improvement of CD4 count over time. The average CD4 count before, one year, two years of home based care, and during the study were: 193.86; 258.83 (25.1%); 375.72 (31.2%); 487.57 respectively. A positive relationship was observed between home based care services and well-being. The findings from the present study show that the home based care positively improved the well-being of HIV/AIDS patients in the studied population. Improved wellbeing also improved CD4 count in patients.

DOI: 10.29245/2572-9411/2017/2.1091 View / Download Pdf

Ramy Sedhom1*, Daniel Sedhom1 and Roger Strair2

1Department of Internal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
2Division of Hematology and Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA

 IgG4-related disease is a fibroinflammatory condition that mimics many malignant, infectious, and inflammatory disorders. Histopathology is key to diagnosis and is hallmarked by tumor like infiltration of IgG4 positive plasma cells in tissues, with dense lymphoplasmacytic infiltrate, storiform fibrosis and oblierative phlebitis. Disease has been reported in virtually every organ system1-4. Though the underlying pathophysiology is still unclear, untreated disease ultimately leads to irreversible fibrosis. We describe the pathogenesis, diagnosis, and relevant features of IgG4-related disease and discuss current evidence regarding treatment.

DOI: 10.29245/2572-9411/2017/2.1089 View / Download Pdf

Breanna R Campbell, David Reynoso, and A Clinton White Jr*

Infectious Disease Division, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA

 Neurocysticercosis, caused by Taenia solium, is a common cause of neurologic disease worldwide. Approximately 2,000 cases per year are diagnosed in the United States. Intraventricular neurocysticercosis is a severe form of the disease, in which cysticerci within the cerebral ventricles cause obstructive hydrocephalus. Symptoms of hydrocephalus include headache, nausea, vomiting, altered mental status, dizziness, and decreased visual acuity. In some cases, sudden onset of symptoms are associated with changes in head position leading to acute obstruction (Bruns’ syndrome). Diagnosis depends on neuroimaging studies, especially 3 dimensional MRI sequences. Optimal treatment involves relief of hydrocephalus by removal of the cysticerci. For cysticerci in the lateral and third ventricles, this can usually be accomplished via minimally invasive surgery (neuroendoscopy). However, this is not possible with adherent cysticerci. In some cases of cysticerci in the 4th ventricle, open surgical microdissection via an occipital approach may be safer. Mortality is rare with appropriate management.

DOI: 10.29245/2572-9411/2017/2.1084 View / Download Pdf

Bryan A. Wilson1,2 and Monte S. Willis1,3*

1McAllister Heart Institute, University of North Carolina, Chapel Hill, NC USA
2Department of Psychology and Neuroscience, University of North Carolina, Chapel Hill, NC USA
3Department of Pharmacology, Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, NC USA

 The 8th annual Rare Disease Scientific Workshop featured presentations on the topic of “Evaluating Models to Provide Early Access for Rare Disease Patients”. The workshop included presentations from and participation by experts in Industry, the Food and Drug Administration, and academia focused on case study examples of successful mechanisms for those seeking to provide early access to experimental therapies for patients. Current regulatory frameworks were discussed and evaluated, with an emphasis on rare and serious diseases with the goal of identifying best practices and useful ideas for a set of standard approaches to early access.

Date: Tuesday, September 13, 2016, Washington, DC

Location: Willard Intercontinental Hotel, Washington DC

Sponsor: The EveryLife Foundation for Rare Diseases

AAV, adeno-associated virus; ALS, Amyotrophic Lateral Sclerosis; CURES, Compassionate Use Reform and Enhancements; DMD, Duchenne Muscular Dystrophy; ERT, enzyme replacement therapy; FDA, US Food and Drug Administration; GLPs, good laboratory practices; ICU, intensive care unit; IND, FDA’s Investigational New Drug program; H.R., House of Representatives; IRB, institutional review boards; J&J, Johnson and Johnson; JAMA, Journal of the American Medical Association; MCT, Medium-chain triglyceride; MPS I, mucopolysaccharidosis I; MPS7, Mucopolysaccharidosis type 7; NYU, New York University; OHOP, Office of Hematology and Oncology Products; rhGUS, recombinant human beta-glucuronidase; RUF, Reagan-Udall Foundation; WT, WideTrial

DOI: 10.29245/2572-9411/2017/2.1095 View / Download Pdf

Matshidiso Moeti*

WHO regional office for Africa, Brazzaville, Congo

 This mini review on my previous article entitled, ‘Winning the battle against the scourge of poliomyelitis in the African Region’ published in Vaccine 34 (2016) 5142–5143 takes another look at the optimism expressed in that article about the success in eradicating poliomyelitis (Polio) from the African Region. Polio is a deadly and painful disease that afflicts mostly children less than 5 years. The struggle to eradicate it and get the African Region polio-free has been tortuous. The struggle has been protracted with a series of public health emergencies and political strife compromising the efforts of global partnership comprising of WHO and its key partners such as the United Nations Children’s Fund, the United States Centres for Disease Control and Prevention, Rotary International, and Bill and Melinda Gates Foundation, among others, as well as other stakeholders and national governments in the African Region. In a renewed effort, the partnership generated a huge amount of resources and skills deployed to interrupt polio transmission in the Region. For the first time since the struggle began in the early 80s, the Region reported no wild polio virus for two years. However, the recent success of the military campaign in Northeast Nigeria brought to the open the realities of reservoirs of transmission isolated in security compromised areas. Thus, after two years new cases of wild polio virus were reported in previously unreachable areas. The lesson here is in understanding the impact of political activities on the realization of health for all in our Region.

DOI: 10.29245/2572-9411/2017/1.1090 View / Download Pdf

Mira Sohn and Tamas Balla*

Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA

 Lenz-Majewski syndrome (LMS) is a rare disease presenting with complex physical and mental abnormalities. Whole exome sequencing performed on five LMS-affected individuals has identified gain-of-function mutations in the PTDSS1 gene encoding phosphatidylserine synthase 1 (PSS1) enzyme. These mutations all rendered PSS1 insensitive to PS-mediated product inhibition. In a recent study we showed that uncontrolled PS production by these mutant PSS1 enzymes lead to the accumulation of PS in the ER where it is not detected in normal cells. This increased PS in the ER in turn, activated the Sac1 phosphatase, which is responsible for the dephosphorylation of the minor lipid, phosphatidylinositol 4-phosphate (PI4P) in the ER. Increased Sac1 activity decreased PI4P levels both in the Golgi and the plasma membrane thereby dissipating the PI4P gradients set up by PI 4-kinase enzymes (PI4Ks) between these membranes and the ER. Such PI4P gradients at membrane contact sites have been shown to support the transports of structural lipids such as cholesterol and PS out of the ER by non-vesicular lipid transfer. Therefore, uncontrolled production of PS not only affects the PS status of cells but also initiates an avalanche of changes in the metabolism of other membrane lipids via affecting PI4P gradients throughout the cell. Recognition of the close metabolic interaction between PS synthesis and PI4P metabolism provided a new clue to better understand the molecular underpinning of this rare and severe disease.

DOI: 10.29245/2572-9411/2017/1.1080 View / Download Pdf

Ryuichi Mashima1* and Torayuki Okuyama1,2

1Department of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan
2Center for Lysosomal Storage Disorders, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan

DOI: 10.29245/2572-9411/2017/1.1079 View / Download Pdf