A closer look at ARSA activity in a patient with metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease mainly caused by a deficiency of arylsulfatase A activity. The typical clinical course of patients with the late infantile form includes a regression in motor skills with progression to dysphagia, seizures, hypotonia and death. We present a case of a 4-year-old female with rapidly progressive developmental regression with loss of motor milestones, spasticity and dysphagia. MRI showed volume loss and markedly abnormal deep white matter. Enzymatic testing in one laboratory showed arylsulfatase A activity in their normal range. However, extraction of urine showed a large increase in sulfatide excretion in a second laboratory. Measurement of arylsulfatase A in that laboratory showed a partial decrease in arylsulfatase A activity measured under typical conditions (about 37% of the normal mean). When the concentration of substrate in the assay was lowered to one quarter of that normally used, this individual had activity \u3c10% of controls. The patient was found to be homozygous for an unusual missense mutation in the arylsulfatase A gene confirming the diagnosis of MLD. This case illustrates the importance of careful biochemical and molecular testing for MLD if there is suspicion of this diagnosis

Integrating neuroimaging biomarkers into the multicentre, high-dose erythropoietin for asphyxia and encephalopathy (HEAL) trial: rationale, protocol and harmonisation

Introduction: MRI and MR spectroscopy (MRS) provide early biomarkers of brain injury and treatment response in neonates with hypoxic-ischaemic encephalopathy). Still, there are challenges to incorporating neuroimaging biomarkers into multisite randomised controlled trials. In this paper, we provide the rationale for incorporating MRI and MRS biomarkers into the multisite, phase III high-dose erythropoietin for asphyxia and encephalopathy (HEAL) Trial, the MRI/S protocol and describe the strategies used for harmonisation across multiple MRI platforms. Methods and analysis: Neonates with moderate or severe encephalopathy enrolled in the multisite HEAL trial undergo MRI and MRS between 96 and 144 hours of age using standardised neuroimaging protocols. MRI and MRS data are processed centrally and used to determine a brain injury score and quantitative measures of lactate and n-acetylaspartate. Harmonisation is achieved through standardisation-thereby reducing intrasite and intersite variance, real-time quality assurance monitoring and phantom scans. Ethics and dissemination: IRB approval was obtained at each participating site and written consent obtained from parents prior to participation in HEAL. Additional oversight is provided by an National Institutes of Health-appointed data safety monitoring board and medical monitor

Infantile onset Spinocerebellar ataxia 2 (SCA2): a clinical report with review of previous cases

Autosomal dominant cerebellar ataxia type I is a heterogenous group of spinocerebellar ataxias with variable neurologic presentations, with age of onset varying from infancy to adulthood. Autosomal dominant cerebellar ataxia type I is composed mainly of 3 prevalent spinocerebellar ataxia types with different pathogenic loci, specifically spinocerebellar ataxia 1 (6p24-p23), spinocerebellar ataxia 2 (12q24.1), and spinocerebellar ataxia 3 (14q32.1). The shared pathogenic mutational event is the expansion of the CAG repeat that results in polyglutamine extended stretches in the encoded proteins. CAG repeat disorders generally show the phenomenon of anticipation, which is more often associated with paternal transmission. In this report, we describe a patient with infantile-onset spinocerebellar ataxia type 2 (∼320 CAG repeat) who inherited the disease from his father (47 CAG repeats). We have summarized the clinical, neuroimaging, electroencephalographic (EEG), and molecular data of previous cases and attempt to highlight the most consistent findings. Our intent is to help treating clinicians to suspect this disorder and to offer timely genetic counseling for a currently potentially untreatable disorder

Design, synthesis, molecular docking, and biological studies of novel phytoestrogen-tanaproget hybrids

<p>A diverse range of novel and highly functionalized flavonoid-based tanaproget hybrids were synthesized and evaluated in vitro for their antimicrobial and antiproliferative activities. Novel products were synthesized in good yields (81–95%) under Pd-catalyzed reaction from bromo flavones and tanaproget boronic acids within 18–20 min at 60 °C. Bioassay results exhibited excellent activities against both hormone-dependent and hormone-independent human breast cancer cells (MCF-7, MDA-MB-231, DU-145, PC-3, and HeLa). Among them, compounds <b>4e, 9a, 9c, 9e, 9 g, 9 h, 9 m,</b> and <b>9n</b> displayed excellent activity. Compounds <b>4d, 4o,</b> and <b>9o</b> were found equally potent against <i>C. albicans</i> compared to fluconazole. Compound <b>5c</b> showed better antibacterial activity against <i>S. aureus</i>. Compounds <b>5a, 9i, 9o,</b> and <b>10c</b> have shown admirable antibacterial activity against <i>E. coli</i>.</p

3D printed model aiding in minimally invasive thoracoabdominal ganglioneuroblastoma resection: A case report

The creation of 3D models of tumors and their surrounding structures is becoming a useful tool for preoperative and intraoperative surgical planning. This case details the presentation and oncologic course of a 2.5-year old female patient with a thoracoabdominal ganglioneuroblastoma. Upon initial diagnosis, her tumor was encasing the aorta and abutting the left renal vein and was not a candidate for resection. She underwent alternative therapy for several years that was not standard of care before returning to our institution. A 3D model of the tumor was created based on pre-operative computerized tomography (CT) images, and the physical model demonstrated clear planes and lack of invasion into surrounding structures, making surgical resection an option. The 3D model was then utilized as a guide intraoperatively for the laparoscopic operation during difficult portions of the case. The tumor was successfully removed in entirety, and the patient was discharged following an uneventful post-operative course. The use of 3D printing in a pediatric abdominal oncologic case is novel, and could be a beneficial tool in future cases to complement a minimally invasive surgical approach