Estimation of current density distribution under electrodes for external defibrillation

BACKGROUND: Transthoracic defibrillation is the most common life-saving technique for the restoration of the heart rhythm of cardiac arrest victims. The procedure requires adequate application of large electrodes on the patient chest, to ensure low-resistance electrical contact. The current density distribution under the electrodes is non-uniform, leading to muscle contraction and pain, or risks of burning. The recent introduction of automatic external defibrillators and even wearable defibrillators, presents new demanding requirements for the structure of electrodes. METHOD AND RESULTS: Using the pseudo-elliptic differential equation of Laplace type with appropriate boundary conditions and applying finite element method modeling, electrodes of various shapes and structure were studied. The non-uniformity of the current density distribution was shown to be moderately improved by adding a low resistivity layer between the metal and tissue and by a ring around the electrode perimeter. The inclusion of openings in long-term wearable electrodes additionally disturbs the current density profile. However, a number of small-size perforations may result in acceptable current density distribution. CONCLUSION: The current density distribution non-uniformity of circular electrodes is about 30% less than that of square-shaped electrodes. The use of an interface layer of intermediate resistivity, comparable to that of the underlying tissues, and a high-resistivity perimeter ring, can further improve the distribution. The inclusion of skin aeration openings disturbs the current paths, but an appropriate selection of number and size provides a reasonable compromise

Inhibition of dual-specificity tyrosine phosphorylation-regulated kinase 2 perturbs 26S proteasome-addicted neoplastic progression

Dependence on the 26S proteasome is an Achilles' heel for triple-negative breast cancer (TNBC) and multiple myeloma (MM). The therapeutic proteasome inhibitor, bortezomib, successfully targets MM but often leads to drug-resistant disease relapse and fails in breast cancer. Here we show that a 26S proteasome-regulating kinase, DYRK2, is a therapeutic target for both MM and TNBC. Genome editing or small-molecule mediated inhibition of DYRK2 significantly reduces 26S proteasome activity, bypasses bortezomib resistance, and dramatically delays in vivo tumor growth in MM and TNBC thereby promoting survival. We further characterized the ability of LDN192960, a potent and selective DYRK2-inhibitor, to alleviate tumor burden in vivo. The drug docks into the active site of DYRK2 and partially inhibits all 3 core peptidase activities of the proteasome. Our results suggest that targeting 26S proteasome regulators will pave the way for therapeutic strategies in MM and TNBC

Differentiation syndrome in patients with acute promyelocytic leukemia treated with all- trans retinoic acid and anthracycline chemotherapy: Characteristics, outcome, and prognostic factors

Differentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all- trans retinoic acid (ATRA). Detailed knowl- edge about DS has remained limited. We present an analysis of the incidence, char- acteristics, prognostic factors, and out- come of 739 APL patients treated with ATRA plus idarubicin in 2 consecutive trials (Programa Espanol de Tratamientos en Hematologíc [PETHEMA] LPA96 and LPA99). Overall, 183 patients (24.8%) ex- perienced DS, 93 with a severe form (12.6%) and 90 with a moderate form (12.2%). Severe but not moderate DS was associated with an increase in mortality. A bimodal incidence of DS was observed, with peaks occurring in the first and third weeks after the start of ATRA therapy. A multivariate analysis indicated that a WBC count greater than 5 x 109/L and an abnor- mal serum creatinine level correlated with an increased risk of developing severe DS. Patients receiving systematic pred- nisone prophylaxis (LPA99 trial) in con- trast to those receiving selective prophy- laxis with dexamethasone (LPA96 trial) had a lower incidence of severe DS. Pa- tients developing severe DS showed a reduced 7-year relapse-free survival in the LPA96 trial (60% vs 85%, P = .003), but this difference was not apparent in the LPA99 trial

Subcortical brain atrophy persists even in HAART-regulated HIV disease

The purpose of this study was to determine the pattern and extent of caudate nucleus and putamen atrophy in HIV-infected men with well-controlled immune status and viral replication. 155 men underwent structural brain magnetic resonance imaging; 84 were HIV-infected and 71 were uninfected controls. MRI data were processed using the Fully Deformable Segmentation routine, producing volumes for the right and left caudate nucleus and putamen, and 3-D maps of spatial patterns of thickness. There was significant atrophy in the HIV-infected men in both the caudate and putamen, principally in the anterior regions. The volume of the basal ganglia was inversely associated with the time since first seropositivity, suggesting that either there is a chronic, subclinical process that continues in spite of therapy, or that the extent of the initial insult caused the extent of atrophy

Serum Response Factor Regulates Immediate Early Host Gene Expression in Toxoplasma gondii-Infected Host Cells

Toxoplasma gondii is a wide spread pathogen that can cause severe and even fatal disease in fetuses and immune-compromised hosts. As an obligate intracellular parasite, Toxoplasma must alter the environment of its host cell in order to establish its replicative niche. This is accomplished, in part, by secretion of factors into the host cell that act to modulate processes such as transcription. Previous studies demonstrated that genes encoding transcription factors such as c-jun, junB, EGR1, and EGR2 were amongst the host genes that were the most rapidly upregulated following infection. In cells stimulated with growth factors, these genes are regulated by a transcription factor named Serum Response Factor. Serum Response Factor is a ubiquitously expressed DNA binding protein that regulates growth and actin cytoskeleton genes via MAP kinase or actin cytoskeletal signaling, respectively. Here, we report that Toxoplasma infection leads to the rapid activation of Serum Response Factor. Serum Response Factor activation is a Toxoplasma-specific event since the transcription factor is not activated by the closely related protozoan parasite, Neospora caninum. We further demonstrate that Serum Response Factor activation requires a parasite-derived secreted factor that signals via host MAP kinases but independently of the host actin cytoskeleton. Together, these data define Serum Response Factor as a host cell transcription factor that regulates immediate early gene expression in Toxoplasma-infected cells

Longitudinal variability of time-location/activity patterns of population at different ages: a longitudinal study in California

<p>Abstract</p> <p>Background</p> <p>Longitudinal time-activity data are important for exposure modeling, since the extent to which short-term time-activity data represent long-term activity patterns is not well understood. This study was designed to evaluate longitudinal variations in human time-activity patterns.</p> <p>Method</p> <p>We report on 24-hour recall diaries and questionnaires collected via the internet from 151 parents of young children (mostly under age 55), and from 55 older adults of ages 55 and older, for both a weekday and a weekend day every three months over an 18-month period. Parents also provided data for their children. The self-administrated diary and questionnaire distinguished ~30 frequently visited microenvironments and ~20 activities which we selected to represent opportunities for exposure to toxic environmental compounds. Due to the non-normal distribution of time-location/activity data, we employed generalized linear mixed-distribution mixed-effect models to examine intra- and inter-individual variations. Here we describe variation in the likelihood of and time spent engaging in an activity or being in a microenvironment by age group, day-type (weekday/weekend), season (warm/cool), sex, employment status, and over the follow-up period.</p> <p>Results</p> <p>As expected, day-type and season influence time spent in many location and activity categories. Longitudinal changes were also observed, e.g., young children slept less with increasing follow-up, transit time increased, and time spent on working and shopping decreased during the study, possibly related to human physiological changes with age and changes in macro-economic factors such as gas prices and the economic recession.</p> <p>Conclusions</p> <p>This study provides valuable new information about time-activity assessed longitudinally in three major age groups and greatly expands our knowledge about intra- and inter-individual variations in time-location/activity patterns. Longitudinal variations beyond weekly and seasonal patterns should be taken into account in simulating long-term time-activity patterns in exposure modeling.</p

Communication in the Third Dimension: Song Perch Height of Rivals Affects Singing Response in Nightingales

Many animals use long-range signals to compete over mates and resources. Optimal transmission can be achieved by choosing efficient signals, or by choosing adequate signalling perches and song posts. High signalling perches benefit sound transmission and reception, but may be more risky due to exposure to airborne predators. Perch height could thus reflect male quality, with individuals signalling at higher perches appearing as more threatening to rivals. Using playbacks on nightingales (Luscinia megarhynchos), we simulated rivals singing at the same height as residents, or singing three metres higher. Surprisingly, residents increased song output stronger, and, varying with future pairing success, overlapped more songs of the playback when rivals were singing at the same height than when they were singing higher. Other than expected, rivals singing at the same height may thus be experienced as more threatening than rivals singing at higher perches. Our study provides new evidence that territorial animals integrate information on signalling height and thus on vertical cues in their assessment of rivals

Phylotyping and Functional Analysis of Two Ancient Human Microbiomes

Background: The Human Microbiome Project (HMP) is one of the U.S. National Institutes of Health Roadmap for Medical Research. Primary interests of the HMP include the distinctiveness of different gut microbiomes, the factors influencing microbiome diversity, and the functional redundancies of the members of human microbiotas. In this present work, we contribute to these interests by characterizing two extinct human microbiotas. Methodology/Principal Findings: We examine two paleofecal samples originating from cave deposits in Durango Mexico and dating to approximately 1300 years ago. Contamination control is a serious issue in ancient DNA research; we use a novel approach to control contamination. After we determined that each sample originated from a different human, we generated 45 thousand shotgun DNA sequencing reads. The phylotyping and functional analysis of these reads reveals a signature consistent with the modern gut ecology. Interestingly, inter-individual variability for phenotypes but not functional pathways was observed. The two ancient samples have more similar functional profiles to each other than to a recently published profile for modern humans. This similarity could not be explained by a chance sampling of the databases. Conclusions/Significance: We conduct a phylotyping and functional analysis of ancient human microbiomes, while providing novel methods to control for DNA contamination and novel hypotheses about past microbiome biogeography. We postulate that natural selection has more of an influence on microbiome functional profiles than it does on the species represented in the microbial ecology. We propose that human microbiomes were more geographically structured during pre-Columbian times than today

Rubinstein-Taybi syndrome with scoliosis

<p>Abstract</p> <p>Study Design</p> <p>Case report.</p> <p>Objective</p> <p>The authors present the case of a 14-year-old boy with Rubinstein-Taybi syndrome (RSTS) presenting scoliosis.</p> <p>Summary of Background Data</p> <p>There have been no reports on surgery for RSTS presenting scoliosis.</p> <p>Methods</p> <p>The patient was referred to our hospital for evaluation of a progressive spinal curvature. A standing anteroposterior spine radiograph at presentation to our hospital revealed an 84-degree right thoracic curve from T6 to T12, along with a 63-degree left lumbar compensatory curve from T12 to L4. We planned a two-staged surgery and decided to fuse from T4 to L4. The first operation was front-back surgery because of the rigidity of the right thoracic curve. The second operation of lumbar anterior discectomy and fusion was arranged 9 months after the first surgery to prevent the crankshaft phenomenon due to his natural course of adolescent growth. To avoid respiratory complications, the patient was put on a respirator in the ICU for several days after both surgeries.</p> <p>Results</p> <p>Full-length spine radiographs after the first surgery revealed no instrumentation failure and showed that the right thoracic curve was corrected to 31 degrees and the left lumbar curve was corrected to 34 degrees. No postoperative complications occurred after both surgeries.</p> <p>Conclusions</p> <p>We succeeded in treating the patient without complications. Full-length spine standing radiographs at one year after the second operation demonstrated a stable bony arthrodesis with no loss of initial correction.</p