The role of enzyme replacement therapy in severe Hunter syndrome—an expert panel consensus

Intravenous enzyme replacement therapy (ERT) with idursulfase for Hunter syndrome has not been demonstrated to and is not predicted to cross the blood–brain barrier. Nearly all published experience with ERT with idursulfase has therefore been in patients without cognitive impairment (attenuated phenotype). Little formal guidance is available on the issues surrounding ERT in cognitively impaired patients with the severe phenotype. An expert panel was therefore convened to provide guidance on these issues. The clinical experience of the panel with 66 patients suggests that somatic improvements (e.g., reduction in liver volume, increased mobility, and reduction in frequency of respiratory infections) may occur in most severe patients. Cognitive benefits have not been seen. It was agreed that, in general, severe patients are candidates for at least a 6–12-month trial of ERT, excluding patients who are severely neurologically impaired, those in a vegetative state, or those who have a condition that may lead to near-term death. It is imperative that the treating physician discuss the goals of treatment, methods of assessment of response, and criteria for discontinuation of treatment with the family before ERT is initiated. Conclusion: The decision to initiate ERT in severe Hunter syndrome should be made by the physician and parents and must be based on realistic expectations of benefits and risks, with the understanding that ERT may be withdrawn in the absence of demonstrable benefits

Mucopolysaccharidosis VI

Mucopolysaccharidosis VI (MPS VI) is a lysosomal storage disease with progressive multisystem involvement, associated with a deficiency of arylsulfatase B leading to the accumulation of dermatan sulfate. Birth prevalence is between 1 in 43,261 and 1 in 1,505,160 live births. The disorder shows a wide spectrum of symptoms from slowly to rapidly progressing forms. The characteristic skeletal dysplasia includes short stature, dysostosis multiplex and degenerative joint disease. Rapidly progressing forms may have onset from birth, elevated urinary glycosaminoglycans (generally >100 μg/mg creatinine), severe dysostosis multiplex, short stature, and death before the 2nd or 3rd decades. A more slowly progressing form has been described as having later onset, mildly elevated glycosaminoglycans (generally <100 μg/mg creatinine), mild dysostosis multiplex, with death in the 4th or 5th decades. Other clinical findings may include cardiac valve disease, reduced pulmonary function, hepatosplenomegaly, sinusitis, otitis media, hearing loss, sleep apnea, corneal clouding, carpal tunnel disease, and inguinal or umbilical hernia. Although intellectual deficit is generally absent in MPS VI, central nervous system findings may include cervical cord compression caused by cervical spinal instability, meningeal thickening and/or bony stenosis, communicating hydrocephalus, optic nerve atrophy and blindness. The disorder is transmitted in an autosomal recessive manner and is caused by mutations in the ARSB gene, located in chromosome 5 (5q13-5q14). Over 130 ARSB mutations have been reported, causing absent or reduced arylsulfatase B (N-acetylgalactosamine 4-sulfatase) activity and interrupted dermatan sulfate and chondroitin sulfate degradation. Diagnosis generally requires evidence of clinical phenotype, arylsulfatase B enzyme activity <10% of the lower limit of normal in cultured fibroblasts or isolated leukocytes, and demonstration of a normal activity of a different sulfatase enzyme (to exclude multiple sulfatase deficiency). The finding of elevated urinary dermatan sulfate with the absence of heparan sulfate is supportive. In addition to multiple sulfatase deficiency, the differential diagnosis should also include other forms of MPS (MPS I, II IVA, VII), sialidosis and mucolipidosis. Before enzyme replacement therapy (ERT) with galsulfase (Naglazyme®), clinical management was limited to supportive care and hematopoietic stem cell transplantation. Galsulfase is now widely available and is a specific therapy providing improved endurance with an acceptable safety profile. Prognosis is variable depending on the age of onset, rate of disease progression, age at initiation of ERT and on the quality of the medical care provided

Invariant submanifolds of Sasakian manifolds admitting semi-symmetric non-metric connection, communicated

The object of this paper is to study invariant submanifolds M of Sasakian manifolds M admitting a semisymmetric nonmetric connection, and it is shown that M admits semisymmetric nonmetric connection. Further it is proved that the second fundamental forms σ and σ with respect to Levi-Civita connection and semi-symmetric nonmetric connection coincide. It is shown that if the second fundamental form σ is recurrent, 2-recurrent, generalized 2-recurrent, semiparallel, pseudoparallel, and Ricci-generalized pseudoparallel and M has parallel third fundamental form with respect to semisymmetric nonmetric connection, then M is totally geodesic with respect to Levi-Civita connection. Semisymmetric Nonmetric Connection The geometry of invariant submanifolds M of Sasakian manifolds M is carried out from 1970&apos;s by M. Kon 1 , D. Chinea 2 , K. Yano and M. Kon 3 and B.S. Anitha and C.S. Bagewadi 4 . The aurthor 1 has proved that invariant submanifold of Sasakian structure also carries Sasakian structure. In this paper we extend the results to invariant submanifolds M of Sasakian manifolds admitting Semisymmetric Nonmetric connection. We know that a connection ∇ on a manifold M is called a metric connection if there is a Riemannian metric g on M if ∇g 0; otherwise it is Nonmetric. Further it is said to be Semisymmetric if its torsion tensor T X, Y 0; thatis, T X, Y w Y X − w X Y , where w is a 1-form. A study of Semisymmetric connection on a Riemannian manifold was initiated by Yano 5 . In 1992, Agashe and Chafle 6 introduced the notion of Semisymmetric Nonmetric connection. If ∇ denotes Semisymmetric Nonmetric connection on a contact metric manifold

A study to correlate dental caries experience with total antioxidant levels of saliva among adolescents in Mangalore

Introduction: The changes in salivary composition could have some role in controlling and/or maintaining oxidative damage in the oral cavity. Many adolescents and children have inadequate oral and general health because of active and uncontrolled dental caries. Materials and Methods: Oral examination to assess the dental caries experience was carried out using decayed, missing and filled teeth (DMFT) index. The salivary total antioxidant capacity (TAC) was measured by using "ammonium molybdate method." Data were analyzed using Pearsons correlation and one-way ANOVA with Bonferroni multiple comparison test. A P value of 0.05 was taken as the level of significance. Results: With increasing DMFT scores, TAC of saliva also increased correspondingly. When the TAC of saliva was correlated against DMFT scores, there was a correlation of 0.981 (P < 0.0005). Conclusion: With increasing dental caries experience, the TAC of saliva was found to increase. TAC of saliva could be a marker for dental caries activity among children

Detecting miRNA mentions and relations in biomedical literature

Introduction: MicroRNAs (miRNAs) have demonstrated their potential as post-transcriptional gene expression regulators, participating in a wide spectrum of regulatory events such as apoptosis, differentiation, and stress response. Apart from the role of miRNAs in normal physiology, their dysregulation is implicated in a vast array of diseases. Dissection of miRNA-related associations are valuable for contemplating their mechanism in diseases, leading to the discovery of novel miRNAs for disease prognosis, diagnosis, and therapy. Motivation: Apart from databases and prediction tools, miRNA-related information is largely available as unstructured text. Manual retrieval of these associations can be labor-intensive due to steadily growing number of publications. Additionally, most of the published miRNA entity recognition methods are keyword based, further subjected to manual inspection for retrieval of relations. Despite the fact that several databases host miRNA-associations derived from text, lower sensitivity and lack of published details for miRNA entity recognition and associated relations identification has motivated the need for developing comprehensive methods that are freely available for the scientific community. Additionally, the lack of a standard corpus for miRNA-relations has caused difficulty in evaluating the available systems. We propose methods to automatically extract mentions of miRNAs, species, genes/proteins, disease, and relations from scientific literature. Our generated corpora, along with dictionaries, and miRNA regular expression are freely available for academic purposes. To our knowledge, these resources are the most comprehensive developed so far. Results: The identification of specific miRNA mentions reaches a recall of 0.94 and precision of 0.93. Extraction of miRNA-disease and miRNA-gene relations lead to an F1 score of up to 0.76. A comparison of the information extracted by our approach to the databases miR2Disease and miRSel for the extraction of Alzheimer's disease related relations shows the capability of our proposed methods in identifying correct relations with improved sensitivity. The published resources and described methods can help the researchers for maximal retrieval of miRNA-relations and generation of miRNA-regulatory networks

Surgical management of intertrochanteric fractures of femur with Proximal Fixation Nail Anti-Rotation-II

Background: Intertrochanteric Femur Fractures are usually complicated withassociated co-morbidities like osteoporosis, diabetes, hypertension, renal failure. In suchcircumstances, nonoperative treatment is mainly reserved for poor medical candidates and non-ambulantpatients with minimal discomfort after fracture. Objective: To study the management of intertrochanteric fractures with proximal femoral nail anti-rotation-II. Material and Methods: Present study was conducted on the patients admitted in at BTGH attached to MR medical college, Kalburgi &amp;Shri B M Patil Medical College Hospital and Research Centre, Vijayapura,with diagnosis of intertrochanteric fractures from October 2017 to April 2019. A total of 21 cases were taken in our study. Results: Majority of the cases i.e., 12(60%) were in the age group of 61- 80 years, followed by 3 cases in the age group 41-60 years. The mean age was 69years. Majority of the patients were males 13 (65%) and 7 (35%) were females. We took less number of exposures time in case of comminuted fractures where reduction was not a problem. Blood loss was more in open reductions. The HARRIS HIP SCORE grading was done and 2 patients were graded excellent, 16 as good, 2 as fair and none as poor

Evaluation of mirror image biopsy for incidence of multiple premalignant and malignant lesions in oral cancer: A clinical study

Introduction: To histologically evaluate the mirror image biopsy obtained from the apparently normal looking mucosa at corresponding contralateral anatomical sites to determine the incidence of multiple premalignant and malignant lesions in oral cancer. Materials and methods: Fifty patients with unilateral, single, untreated, histologically confirmed oral squamous cell carcinoma underwent mirror image biopsy from apparently normal looking mucosa at corresponding contralateral anatomical site. The mirror image biopsy specimens were subjected to histopathological examination Results: The age group of the patients ranged from 42 to 70 years with male to female ratio of 12:1. Of 50 patients, 38 (76%) revealed abnormal epithelial changes ranging in the degree from hyperkeratosis (12%), dysplasia (48%) and premalignant changes like leukoplakia, erythroplakia, submucous fibrosis, etc. (16%) in the mirror image sites. The incidence was high in males, with increasing age of the patient and duration of exposure to habits. Conclusion: Mirror image biopsies should be considered as useful diagnostic tool for early detection of premalignant changes so as to prevent further progression of these changes to oral cancer