Biologic Therapies for the Management of Cutaneous Findings in Genodermatoses: A Review.

Genodermatoses are genetically inherited dermatologic conditions. The management of cutaneous findings in genodermatoses is challenging, and first-line therapies, such as steroids and/or retinoids, are often inadequate. In recent years, research on the molecular basis of genodermatoses has led to the use of biologic therapies for intractable disease.

Baroclinic waves in the northern hemisphere of Mars as observed by the MRO Mars Climate Sounder and the MGS Thermal Emission Spectrometer.

The climatology of baroclinic waves in the northern hemisphere of Mars is investigated through analysis of observations by the infrared sounders on Mars Reconnaissance Orbiter (MRO) and Mars Global Surveyor (MGS). We focus on the lowest scale height above the surface, where the waves have a large impact on the Martian dust cycle. Profiles retrieved by the MRO Mars Climate Sounder (MCS) rarely reach the lower atmosphere at the season and location of interest.

Evaluation of Effectiveness and Safety of Transcatheter Mitral Valve Repair Under Moderate Conscious Sedation.

Background: Transcatheter mitral valve repair (TMVR) using the MitraClip system (Abbott Vascular) has become a world-wide, well-established therapeutic alternative to symptomatic patients with severe mitral regurgitation (MR) and prohibitive surgical risk. Currently, TMVRs are performed under general anesthesia. Herein, we aimed to present the effectiveness and safety of TMVR under moderate conscious sedation (MCS).

The atmosphere of Pluto as observed by New Horizons.

Observations made during the New Horizons flyby provide a detailed snapshot of the current state of Pluto's atmosphere. Whereas the lower atmosphere (at altitudes of less than 200 kilometers) is consistent with ground-based stellar occultations, the upper atmosphere is much colder and more compact than indicated by pre-encounter models. Molecular nitrogen (N2) dominates the atmosphere (at altitudes of less than 1800 kilometers or so), whereas methane (CH4), acetylene (C2H2), ethylene (C2H4), and ethane (C2H6) are abundant minor species and likely feed the production of an extensive haze that encompasses Pluto.

The Pluto system: Initial results from its exploration by New Horizons.

The Pluto system was recently explored by NASA's New Horizons spacecraft, making closest approach on 14 July 2015. Pluto's surface displays diverse landforms, terrain ages, albedos, colors, and composition gradients. Evidence is found for a water-ice crust, geologically young surface units, surface ice convection, wind streaks, volatile transport, and glacial flow.

Physiological and behavioural indices of hostility: an extension of the capacity model to include exposure to affective stress and right lateralized motor stress.

Right hemisphere functional cerebral systems have reliably been associated with sympathetic nervous system arousal and the perception of negative affective events. The goal of the current research was to provide additional support for the capacity model of hostility by examining changes attributable to functional cerebral systems within the right hemisphere using a dual concurrent task paradigm. To incorporate exposure to negative affective and right-lateralized motor stress using this approach, high and low hostile individuals completed a series of grip-strength tasks before and after hearing a recording of angry infant vocalizations.

Duplicated facial nerve trunk with a first branchial cleft cyst.

First branchial cleft anomalies are rare and their various anatomical relationships to the facial nerve have been described. We encountered a 15-year-old female with a type II first branchial cleft cyst presenting as a right neck mass that we found during surgical excision to transverse two main facial nerve trunks. To our knowledge, this is the first reported case of a first branchial cleft anomaly in conjunction with a duplicated facial nerve trunk.

Effects of solar flares on the ionosphere of Mars.

All planetary atmospheres respond to the enhanced x-rays and ultraviolet (UV) light emitted from the Sun during a flare. Yet only on Earth are observations so continuous that the consequences of these essentially unpredictable events can be measured reliably. Here, we report observations of solar flares, causing up to 200% enhancements to the ionosphere of Mars, as recorded by the Mars Global Surveyor in April 2001.

A sporadic third layer in the ionosphere of Mars.

The daytime martian ionosphere has been observed as a two-layer structure with electron densities that peak at altitudes between about 110 and 130 kilometers. The Mars Express Orbiter Radio Science Experiment on the European Mars Express spacecraft observed, in 10 out of 120 electron density profiles, a third ionospheric layer at altitude ranges of 65 to 110 kilometers, where electron densities, on average, peaked at 0.8 x 10(10) per cubic meter.

Using the Veterans Administration National Surgical Quality Improvement Program to improve patient outcomes.

Background: The primary goal of collecting quality assurance data is to ultimately improve patient care. The VA National Surgical Quality Improvement Program (NSQIP) provides each station with risk-adjusted morbidity and mortality data on a regular basis. This report of one medical center's use of the risk-adjusted data shows how it can be used to improve patient care.

Performance standards: piece of cake or pie in the sky?

Background: Centrally mandated levels of performance are now common in the Veterans Health Administration. Performance standards for ambulatory procedures were developed based on HCFA data. The 11 procedures to be measured were arthroscopy, breast biopsy, eyelid procedures, lens/cataracts, bronchoscopy, endoscopy, colonoscopy, hernia repair, cystoscopy, laparoscopy, and cardiac catheterization.

Identification of a mutation cluster in mevalonate kinase deficiency, including a new mutation in a patient of Mennonite ancestry.

Mevalonate kinase (MKase) deficiency (MKD) is a rare autosomal recessive disorder in the pathway of cholesterol and nonsterol isoprenoid biosynthesis. Thus far, two disease-causing missense alleles have been identified, N301T and A334T. We report four additional mutations associated with MKD: L264F, T243I, L265P, and I268T, the last found in a patient of Mennonite ancestry.

Hematological abnormalities and cholestatic liver disease in two patients with mevalonate kinase deficiency.

We describe two patients with mevalonate kinase deficiency and prominent hematologic abnormalities and cholestatic liver disease. Patient R.B.

Two exon-skipping mutations as the molecular basis of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria).

Succinic semialdehyde dehydrogenase (SSADH) deficiency, a rare metabolic disorder of 4-aminobutyric acid degradation, has been identified in approximately 150 patients. Affected individuals accumulate large quantities of 4-hydroxybutyric acid, a compound with a wide range of neuropharmacological activities, in physiological fluids. As a first step in beginning an investigation of the molecular genetics of SSADH deficiency, we have utilized SSADH cDNA and genomic sequences to identify two point mutations in the SSADH genes derived from four patients.

Inhaled nitric oxide versus conventional therapy: effect on oxygenation in ARDS.

A randomized, controlled clinical trial was performed with patients with acute respiratory distress syndrome (ARDS) to compare the effect of conventional therapy or inhaled nitric oxide (iNO) on oxygenation. Patients were randomized to either conventional therapy or conventional therapy plus iNO for 72 h. We tested the following hypotheses: (1) that iNO would improve oxygenation during the 72 h after randomization, as compared with conventional therapy; and (2) that iNO would increase the likelihood that patients would improve to the extent that the FI(O2) could be decreased by > or = 0.

Post-translational regulation of mevalonate kinase by intermediates of the cholesterol and nonsterol isoprene biosynthetic pathways.

To assess the potential for feedback inhibition by isoprene intermediates in the cholesterol and nonsterol isoprene biosynthetic pathway, we expressed human cDNAs encoding mevalonate kinase (MKase), phosphomevalonate kinase (PMKase), and mevalonate diphosphate decarboxylase (MDDase) as fusion proteins in Escherichia coli DH5alpha, and purified these proteins by affinity chromatography. Several phosphorylated and non-phosphorylated isoprenes were analyzed as inhibitors of the enzymes using a standard spectrophotometric assay. Of the three proteins, only MKase was inhibited through competitive interaction at the ATP-binding site.

Identification of an active site alanine in mevalonate kinase through characterization of a novel mutation in mevalonate kinase deficiency.

Sequencing of polymerase chain reaction-amplified cDNAs from cultured cells of three patients with mevalonate kinase deficiency revealed a G --> A transversion at nucleotide 1000 of the coding region, converting alanine to threonine at position 334 (A334T). To characterize this defect, we expressed wild-type and mutant cDNAs in Escherichia coli as the glutathione S-transferase fusion proteins, with purification by affinity chromatography. SDS-polyacrylamide gel electrophoresis analysis for wild-type and mutant fusion proteins indicated an expected molecular mass of 42-43 kDa.

The ionosphere of Europa from Galileo radio occultations.

The Galileo spacecraft performed six radio occultation observations of Jupiter's Galilean satellite Europa during its tour of the jovian system. In five of the six instances, these occultations revealed the presence of a tenuous ionosphere on Europa, with an average maximum electron density of nearly 10(4) per cubic centimeter near the surface and a plasma scale height of about 240 +/- 40 kilometers from the surface to 300 kilometers and of 440 +/- 60 kilometers above 300 kilometers. Such an ionosphere could be produced by solar photoionization and jovian magnetospheric particle impact in an atmosphere having a surface density of about 10(8) electrons per cubic centimeter.

Melatonin and a 21-aminosteroid attenuate shock after hemorrhage but differentially affect serum cytokines.

Unlabelled: Melatonin and 21-aminosteroids (lazaroids) are potent antioxidants and may attenuate the increased membrane permeability associated with profound shock. Our purpose was to test the effect of melatonin and a lazaroid (U74389-G) on cytokine production and fluid requirements after shock.

Methods: Male C3H/HeN mice, 20-25 g, were hemorrhaged via a femoral artery catheter to a mean arterial pressure of 35 +/- 5 mm Hg, which was maintained for 1 hr, and then resuscitated with shed blood and crystalloid (2x vol of shed blood).

Molecular cloning of the mature NAD(+)-dependent succinic semialdehyde dehydrogenase from rat and human. cDNA isolation, evolutionary homology, and tissue expression.

Three rat brain cDNA clones approximately 3500, 1465, and 1135 base pairs in length encoding succinic semialdehyde dehydrogenase (SSADH; EC 1.2.1.