Alpha-synuclein regulates nucleolar DNA double-strand break repair in melanoma.

Although an increased risk of the skin cancer melanoma in people with Parkinson's Disease (PD) has been shown in multiple studies, the mechanisms involved are poorly understood, but increased expression of the PD-associated protein alpha-synuclein (αSyn) in melanoma cells may be important. Our previous work suggests that αSyn can facilitate DNA double-strand break (DSB) repair, promoting genomic stability. We now show that αSyn is preferentially enriched within the nucleolus in the SK-MEL28 melanoma cell line, where it colocalizes with DNA damage markers and DSBs.

A Comparison of Wearable Tonometry, Photoplethysmography, and Electrocardiography for Cuffless Measurement of Blood Pressure in an Ambulatory Setting.

Objective: While non-invasive, cuffless blood pressure (BP) measurement has demonstrated relevancy in controlled environments, ambulatory measurement is important for hypertension diagnosis and control. We present both in-lab and ambulatory BP estimation results from a diverse cohort of participants.

Methods: Participants (N=1125, aged 21-85, 49.

PIN1 Provides Dynamic Control of MYC in Response to Extrinsic Signals.

PIN1 is a phosphorylation-directed member of the peptidyl-prolyl / isomerase (PPIase) family that facilitates conformational changes in phosphorylated targets such as c-MYC (MYC). Following signaling events that mediate phosphorylation of MYC at Serine 62, PIN1 establishes structurally distinct pools of MYC through its and isomerization activity at Proline 63. Through these isomerization steps, PIN1 functionally regulates MYC's stability, the molecular timing of its DNA binding and transcriptional activity, and its subnuclear localization.

The role of cell adhesion in hematopoiesis and leukemogenesis.

The cells of the bone marrow microenvironment are emerging as important contributors and regulators of normal hematopoiesis. This microenvironment is perturbed during leukemogenesis, and evidence points toward a bidirectional communication between leukemia cells and the normal cells of the bone marrow, mediated by direct cell-cell contact as well as soluble factors. These interactions are increasingly appreciated to play a role in leukemogenesis and possibly in resistance to chemotherapy.

Randomized, Controlled, Double-Masked, Multicenter, Pilot Study Evaluating Safety and Efficacy of Intranasal Neurostimulation for Dry Eye Disease.

Purpose: We assess the safety and effectiveness of intranasal neurostimulation to promote tear production via the nasolacrimal pathway in subjects with dry eye disease.

Methods: A multicenter, randomized, controlled, double-masked pilot study was conducted in adults with dry eye diagnosis and at least one eye with corneal fluorescein staining ≥2 in at least one region or a sum of all regions ≥5 (National Eye Institute grading), basal Schirmer test score ≤10 mm, a cotton-swab stimulated Schirmer score ≥7 mm higher, and an Ocular Surface Disease Index score ≥23. Subjects were randomized to receive active intranasal neurostimulation or sham control intranasal stimulation 4 to 8 times per day.

Enhanced Li-S Batteries Using Amine-Functionalized Carbon Nanotubes in the Cathode.

The rechargeable lithium-sulfur (Li-S) battery is an attractive platform for high-energy, low-cost electrochemical energy storage. Practical Li-S cells are limited by several fundamental issues, including the low conductivity of sulfur and its reduction compounds with Li and the dissolution of long-chain lithium polysulfides (LiPS) into the electrolyte. We report on an approach that allows high-performance sulfur-carbon cathodes to be designed based on tethering polyethylenimine (PEI) polymers bearing large numbers of amine groups in every molecular unit to hydroxyl- and carboxyl-functionalized multiwall carbon nanotubes.

Seven-year safety and efficacy with velaglucerase alfa for treatment-naïve adult patients with type 1 Gaucher disease.

Velaglucerase alfa is a human β-glucocerebrosidase approved for Gaucher disease type 1 (GD1) treatment. This report summarizes the 7-year experience of the now-completed phase I/II and extension studies of adult GD1 patients who received velaglucerase alfa. Ten patients who completed the 9-month, phase I/II study entered the extension trial TKT025EXT, of which eight completed this study.

Model Membrane-Free Li-S Batteries for Enhanced Performance and Cycle Life.

is limited in part by the dissolution of lithium-polysulfide in the electrolyte. Remarkably, it is found that removal of the conventional membrane separator in a Li-S cell improves sulfur utilization and cycling performance, whether the sulfur is initially contained in the cathode or electrolyte. An optimized cell design yields discharge capacities as high as 980 mA h g after 100 cycles.

Western spruce budworm outbreaks did not increase fire risk over the last three centuries: a dendrochronological analysis of inter-disturbance synergism.

Insect outbreaks are often assumed to increase the severity or probability of fire occurrence through increased fuel availability, while fires may in turn alter susceptibility of forests to subsequent insect outbreaks through changes in the spatial distribution of suitable host trees. However, little is actually known about the potential synergisms between these natural disturbances. Assessing inter-disturbance synergism is challenging due to the short length of historical records and the confounding influences of land use and climate changes on natural disturbance dynamics.

Impact of velaglucerase alfa on bone marrow burden score in adult patients with type 1 Gaucher disease: 7-year follow-up.

Background: Bone marrow infiltration by substrate-engorged "Gaucher" cells manifests early in Gaucher disease (GD). The impact of velaglucerase alfa on bone marrow burden (BMB) was evaluated as an exploratory assessment.

Methods: BMB scores were assessed using T1- and T2-weighted magnetic resonance images of the lumbar spine (LS) and femora among symptomatic GD patients who participated in the 9-month Phase I/II trial and long-term extension study for velaglucerase alfa.

A multicenter open-label treatment protocol (HGT-GCB-058) of velaglucerase alfa enzyme replacement therapy in patients with Gaucher disease type 1: safety and tolerability.

Purpose: To evaluate the safety of velaglucerase alfa in patients with type 1 Gaucher disease who received velaglucerase alfa in the US treatment protocol HGT-GCB-058 (ClinicalTrials.gov identifier NCT00954460) during a global supply shortage of imiglucerase.

Methods: This multicenter open-label treatment protocol enrolled patients who were either treatment naïve or had been receiving imiglucerase.

Reference electrode assembly and its use in the study of fluorohydrogenate ionic liquid silicon electrochemistry.

Silicon electrochemistry in fluorohydrogenate ionic liquids is partly hampered owing to the incapability of producing an accurate and reproducible potential measurement due to a lack of appropriate reference electrodes. This research work describes a simple assembly of a stable external reference electrode enabling accurate studies of silicon electrochemistry in fluorohydrogenate ionic liquids. The electrode configuration is based on the ferrocene/ferrocenium (Fc|Fc(+)) couple dissolved in the EMIm(HF)(2.

Development of a mnemonic screening tool for identifying subjects with Hunter syndrome.

Unlabelled: The Hunter Outcome Survey (HOS), an international, long-term observational registry of patients with Hunter syndrome, was used to develop a simple mnemonic screening tool (HUNTER) to aid in the diagnosis of Hunter syndrome. Data regarding the prediagnosis prevalence of ten specific signs and symptoms present in individual patients enrolled in the HOS were used to develop the HUNTER mnemonic screening tool. A total score of 6 or greater using a weighting scheme in which certain manifestations were assigned a weight of 2 (facial dysmorphism, nasal obstruction or rhinorrhea, enlarged tongue, enlarged liver, enlarged spleen, joint stiffness) and others assigned a weight of 1 (hernia, hearing impairment, enlarged tonsils, airway obstruction or sleep apnea) correctly identified 95 % of patients who had no family history of Hunter syndrome or who were not diagnosed prenatally.

New insight into the discharge mechanism of silicon-air batteries using electrochemical impedance spectroscopy.

The mechanism of discharge termination in silicon-air batteries, employing a silicon wafer anode, a room-temperature fluorohydrogenate ionic liquid electrolyte and an air cathode membrane, is investigated using a wide range of tools. EIS studies indicate that the interfacial impedance between the electrolyte and the silicon wafer increases upon continuous discharge. In addition, it is shown that the impedance of the air cathode-electrolyte interface is several orders of magnitude lower than that of the anode.

Limitation of discharge capacity and mechanisms of air-electrode deactivation in silicon-air batteries.

The electrocatalytical process at the air cathode in novel silicon-air batteries using the room-temperature ionic liquid hydrophilic 1-ethyl-3-methylimidazolium oligofluorohydrogenate [EMI⋅2.3 HF⋅F] as electrolyte and highly doped silicon wafers as anodes is investigated by electrochemical means, X-ray photoelectron spectroscopy (XPS), and electron paramagnetic resonance (EPR) spectroscopy. The results obtained by XPS and EPR provide a model to describe the limited discharge capacity by means of a mechanism of air-electrode deactivation.

Remarkable impact of water on the discharge performance of a silicon-air battery.

Here, we report on a Si-air/ionic liquid electrolyte battery whose performance improves with small amounts of water in the electrolyte. The shift of the generation zone of the SiO(2) discharge product from the air cathode surface into the bulk region of the liquid electrolyte, caused by water addition, is demonstrated through various means. Addition of 15 vol% water leads to an increase of 40% in the discharge capacity as compared to the capacity obtained using a pure ionic liquid electrolyte.

Significant and continuous improvement in bone mineral density among type 1 Gaucher disease patients treated with velaglucerase alfa: 69-month experience, including dose reduction.

Since bone pathology is a major concern in type 1 Gaucher disease (GD1), we evaluated bone mineral density (BMD) in adults receiving velaglucerase alfa in the seminal Phase I/II and extension trial. Ten treatment-naïve symptomatic patients with GD1 (four men, six women; median age 35years, range 18-62years) were included; of these, four patients were receiving bisphosphonates at enrollment. Using WHO criteria to classify the lumbar spine (LS) and femoral neck (FN) BMD T-scores, respectively, one (10%) and four (40%) patients had osteoporosis; eight (80%) and five (50%) had osteopenia; and one each (10%) was in the normal range, at baseline.

Early achievement and maintenance of the therapeutic goals using velaglucerase alfa in type 1 Gaucher disease.

Introduction: Therapeutic goals have been described to monitor achievement, maintenance and continuity of therapeutic response in patients with type 1 Gaucher disease receiving enzyme replacement therapy.

Aim: To benchmark the impact of velaglucerase alfa treatment against therapeutic goals for 5 key clinical parameters of type 1 Gaucher disease (anemia, thrombocytopenia, hepatomegaly, splenomegaly and skeletal pathology).

Methods: In an open-label Phase I/II study, twelve adults with symptomatic type 1 Gaucher disease and intact spleens received velaglucerase alfa for 9 months (60 U/kg infusion every other week [EOW]).

Phase 1/2 and extension study of velaglucerase alfa replacement therapy in adults with type 1 Gaucher disease: 48-month experience.

Enzyme replacement therapy is the standard of care for symptomatic Gaucher disease. Velaglucerase alfa is a human beta-glucocerebrosidase produced in a well-characterized human cell line. A 9-month phase 1/2 open-label, single-center trial and ongoing extension study were conducted to evaluate safety and efficacy of velaglucerase alfa.

Causes of blindness in rural Myanmar (Burma): Mount Popa Taung-Kalat Blindness Prevention Project.

Purpose: This study is a review of the major causes of visual impairment (VI) and severe visual impairment/blindness (SVI/BL) in Mount Popa Taung-Kalat, a rural region in Myanmar (Burma).

Methods: A review of our clinical records of consecutive patients attending clinics was conducted. Participants of all ages (n = 650) of the population of Mount Popa Taung-Kalat and villages in its vicinity underwent ophthalmic interview and a detailed dilated ocular evaluation by trained Australian ophthalmologists and ophthalmic nurses.

Efficacy of rectal misoprostol as second-line therapy for the treatment of primary postpartum hemorrhage.

Objective: To assess the efficacy of rectal misoprostol as second-line therapy in the management of primary postpartum hemorrhage (PPH) as compared to methylergonovine maleate.

Study Design: This was a retrospective cohort study. Charts from July 2000 to February 2005 were reviewed.

Toward an improved diagnosis of the metabolic syndrome other clues to the presence of insulin resistance.

A substantial portion of the population of the United States has the Metabolic Syndrome, a condition that greatly increases risk for cardiovascular disease and diabetes. Insulin resistance, and the resulting compensatory hyperinsulinemia, is the principal pathophysiologic abnormality underlying the majority of these cases. Based on the most recent recommendations of the National Cholesterol Education Panel, such patients can be identified by the presence of three or more of the following traits: impaired fasting glucose, abdominal obesity, hypertension, elevated levels of triglycerides, and low concentrations of HDL-cholesterol.

Singing seizures.

Automatisms are commonly seen in epilepsy, either ictally or postictally. However, most automatisms are simple, with hand movements, mouth smacking, nose-rubbing, repetition of a single word, or coughing, grunting, or screeching. Complex automatisms are less common and striking.