Psychophysiological correlates of peritraumatic dissociative responses in survivors of life-threatening cardiac events

The psychophysiological startle response pattern associated with peritraumatic dissociation (DISS) was studied in 103 survivors of a life-threatening cardiac event (mean age 61.0 years, SD 13.95). Mean time period since the cardiac event was 37 (79 IQD) months. All patients underwent a psychodiagnostic evaluation (including the Peritraumatic Dissociative Experiences Questionnaire) and a psychophysiological startle experience which comprised the delivery of 15 acoustic startle trials. Magnitude and habituation to trials were measured by means of electromyogram (EMG) and skin conductance responses (SCR). Thirty-two (31%) subjects were indexed as patients with a clinically significant level of DISS symptoms. High-level DISS was associated with a higher magnitude of SCR (ANOVA for repeated measures p = 0.017) and EMG (p = 0.055) and an impaired habituation (SCR slope p = 0.064; EMG slope p = 0.005) in comparison to subjects with no or low DISS. In a subgroup analysis, high-level DISS patients with severe post-traumatic stress disorder (PTSD; n = 11) in comparison to high-level DISS patients without subsequent PTSD (n = 19) exhibited higher EMG amplitudes during all trials (repeated measures analysis of variance IF = 5.511, p = 0.026). The results demonstrate exaggerated startle responses in SCR and EMG measures - an abnormal defensive response to high-intensity stimuli which indicates a steady state of increased arousal. DISS patients without PTSD exhibited balanced autonomic responses to the startle trials. DISS may, therefore, unfold malignant properties only in combination with persistent physiological hyperarousability. Copyright (C) 2002 S. Karger AG, Basel

Seismic fragility curves for a concrete bridge using structural health monitoring and digital twins

This paper presents the development of seismic fragility curves for a precast reinforced concrete bridge instrumented with a structural health monitoring (SHM) system. The bridge is located near an active seismic fault in the Dominican Republic (DR) and provides the only access to several local communities in the aftermath of a potential damaging earthquake; moreover, the sample bridge was designed with outdated building codes and uses structural detailing not adequate for structures in seismic regions. The bridge was instrumented with an SHM system to extract information about its state of structural integrity and estimate its seismic performance. The data obtained from the SHM system is integrated with structural models to develop a set of fragility curves to be used as a quantitative measure of the expected damage; the fragility curves provide an estimate of the probability that the structure will exceed different damage limit states as a function of an earthquake intensity measure. To obtain the fragility curves a digital twin of the bridge is developed combining a computational finite element model and the information extracted from the SHM system. The digital twin is used as a response prediction tool that minimizes modeling uncertainty, significantly improving the predicting capability of the model and the accuracy of the fragility curves. The digital twin was used to perform a nonlinear incremental dynamic analysis (IDA) with selected ground motions that are consistent with the seismic fault and site characteristics. The fragility curves show that for the maximum expected acceleration (with a 2% probability of exceedance in 50 years) the structure has a 62% probability of undergoing extensive damage. This is the first study presenting fragility curves for civil infrastructure in the DR and the proposed methodology can be extended to other structures to support disaster mitigation and post-disaster decision-making strategie

Geoenvironmental Analysis of Oil Extraction Activities in Urban and Rural Zones of Santa Elena Province, Ecuador

From an environmental viewpoint, oil wells can be considered a potential source of pollution when improperly managed. The Santa Elena province (Ecuador), located on the Pacific coast, currently has a residual crude oil extraction compared to production generated in the Amazon region of the country. However, this activity in the coastal zone is very near to urban and rural populations. Therefore, a detailed influence analysis of these wells on the environment is necessary. This work aims to analyse, from a geoenvironmental perspective, the oil wells impact located in a pilot zone (urban and rural) of the oil field studied and, complementarily, to describe their incidence on the community and territory. The methodological process includes (i) oil wells compilation and inventory within the study zone and selection of a pilot zone; (ii) contaminating factors identification generated by the wells infrastructure (mechanical and territorial) and their current state of activity (production or abandoned); (iii) environmental impacts analysis generated through the development of a cause-effect matrix and, finally, the evaluation of a method and results found through a focus group technique. The results reflect a negative impact on the land cover and vegetative-animal environment in the vicinity of the wells, caused by the continuous release of gases, metallic oxidation and bituminous exhumation. The overall impacts interpretation compiled indicates that comprehensive action is needed at the wells to control and minimise them. The implementation of new environmental strategies through zoning can help to achieve adequate land-use planning, thus combining the safe and sustainable use of the resource with the development of other community activities (urbanisation, tourism, industry, agriculture and fishing) and environmental protection.This work was carried out in collaboration with the ‘Peninsula Santa Elena Geopark Project’ with code no. 91870000.0000.381017, and ‘Factores Geoambientales de los pozos petroleros y su incidencia en el desarrollo territorial en los cantones Salinas y La Libertad de la provincia de Santa Elena’, with code no: 91870000.0000.385428, by UPSE University. Support for the project was also provided by the ‘Registry of geological and mining heritage and its impact on the defence and preservation of geodiversity in Ecuador’, academic research project by ESPOL University, CIPAT-01-2018

Assessing the Genetic Diversity of Ilex guayusa Loes., a Medicinal Plant from the Ecuadorian Amazon

Ilex guayusa Loes. is a shrub native to the Neotropics, traditionally consumed as an infusion. Despite its cultural value and extensive use, genetic research remains scarce. This study examined the genetic and clonal diversity of guayusa in three different Ecuadorian Amazon regions using 17 species-specific SSR markers. The results obtained suggest a moderately low degree of genetic diversity (He = 0.396). Among the 88 samples studied, 71 unique multilocus genotypes (MLGs) were identified, demonstrating a high genotypic diversity. A Discriminant Analysis of Principal Components (DAPC) revealed the existence of two genetic clusters. We propose that a model of isolation-by-environment (IBE) could explain the genetic differentiation between these clusters, with the main variables shaping the population’s genetic structure being temperature seasonality (SD × 100) (Bio 4) and isothermality ×100 (Bio 3). Nonetheless, we cannot dismiss the possibility that human activities could also impact the genetic diversity and distribution of this species. This study gives a first glance at the genetic diversity of I. guayusa in the Ecuadorian Amazon. It could assist in developing successful conservation and breeding programs, which could promote the economic growth of local communities and reinforce the value of ancestral knowledge

Tribal casinos in California: the last vestige of indoor smoking

Background. High levels of airborne particles from secondhand smoke have been reported in California Indian casinos. Yet, little is known regarding the smoking status of casino patrons, their avoidance of secondhand smoke while visiting, and their views on a hypothetical smoking ban. Methods. Predictors of visiting an Indian casino were assessed among participants of the 2008 California Tobacco Survey (n = 10, 397). Exposure to and avoidance of secondhand smoke were subsequently analyzed among a subset of participants who had visited a casino in the year prior to the survey (n = 3, 361). Results. Ethnic minorities, older individuals, current smokers and residents of sparsely populated regions of California were more likely than other demographic groups to visit a tribal casino. Avoidance of secondhand smoke was more frequent among the never smokers than former and current smokers, particularly those who last visited a casino lacking physical separation between non-smoking and smoking sections. The never smokers versus current smokers disproportionately expressed a willingness to extend their stay and visit again if smoking were prohibited. Conclusions. If casinos became smoke free, then it is anticipated that they would be visited by a significantly larger number of Californians, including both patrons and those who otherwise would not have visited a casino. © 2012 Timberlake et al; licensee BioMed Central Ltd

A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome

Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function. We characterize MYMK-CFZS as a congenital myopathy with marked facial weakness and additional clinical and pathologic features that distinguish it from other congenital neuromuscular syndromes. We show that a heterologous cell fusion assay in vitro and allelic complementation experiments in mymk knockdown and mymk insT/insT zebrafish in vivo can differentiate between MYMK wild type, hypomorphic and null alleles. Collectively, these data establish that MYMK activity is necessary for normal muscle development and maintenance in humans, and expand the spectrum of congenital myopathies to include cell-cell fusion deficits

Evaluation of 22 genetic variants with Crohn's Disease risk in the Ashkenazi Jewish population: a case-control study

<p>Abstract</p> <p>Background</p> <p>Crohn's disease (CD) has the highest prevalence among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Caucasian populations (NJ). We evaluated a set of well-established CD-susceptibility variants to determine if they can explain the increased CD risk in the AJ population.</p> <p>Methods</p> <p>We recruited 369 AJ CD patients and 503 AJ controls, genotyped 22 single nucleotide polymorphisms (SNPs) at or near 10 CD-associated genes, <it>NOD2</it>, <it>IL23R</it>, <it>IRGM</it>, <it>ATG16L1</it>, <it>PTGER4</it>, <it>NKX2-3</it>, <it>IL12B</it>, <it>PTPN2</it>, <it>TNFSF15 </it>and <it>STAT3</it>, and assessed their association with CD status. We generated genetic scores based on the risk allele count alone and the risk allele count weighed by the effect size, and evaluated their predictive value.</p> <p>Results</p> <p>Three <it>NOD2 </it>SNPs, two <it>IL23R </it>SNPs, and one SNP each at <it>IRGM </it>and <it>PTGER4 </it>were independently associated with CD risk. Carriage of 7 or more copies of these risk alleles or the weighted genetic risk score of 7 or greater correctly classified 92% (allelic count score) and 83% (weighted score) of the controls; however, only 29% and 47% of the cases were identified as having the disease, respectively. This cutoff was associated with a >4-fold increased disease risk (p < 10e-16).</p> <p>Conclusions</p> <p>CD-associated genetic risks were similar to those reported in NJ population and are unlikely to explain the excess prevalence of the disease in AJ individuals. These results support the existence of novel, yet unidentified, genetic variants unique to this population. Understanding of ethnic and racial differences in disease susceptibility may help unravel the pathogenesis of CD leading to new personalized diagnostic and therapeutic approaches.</p

Conjugation to the Cell-Penetrating Peptide TAT Potentiates the Photodynamic Effect of Carboxytetramethylrhodamine

Cell-penetrating peptides (CPPs) can transport macromolecular cargos into live cells. However, the cellular delivery efficiency of these reagents is often suboptimal because CPP-cargo conjugates typically remain trapped inside endosomes. Interestingly, irradiation of fluorescently labeled CPPs with light increases the release of the peptide and its cargos into the cytosol. However, the mechanism of this phenomenon is not clear. Here we investigate the molecular basis of the photo-induced endosomolytic activity of the prototypical CPPs TAT labeled to the fluorophore 5(6)-carboxytetramethylrhodamine (TMR).We report that TMR-TAT acts as a photosensitizer that can destroy membranes. TMR-TAT escapes from endosomes after exposure to moderate light doses. However, this is also accompanied by loss of plasma membrane integrity, membrane blebbing, and cell-death. In addition, the peptide causes the destruction of cells when applied extracellularly and also triggers the photohemolysis of red blood cells. These photolytic and photocytotoxic effects were inhibited by hydrophobic singlet oxygen quenchers but not by hydrophilic quenchers.Together, these results suggest that TAT can convert an innocuous fluorophore such as TMR into a potent photolytic agent. This effect involves the targeting of the fluorophore to cellular membranes and the production of singlet oxygen within the hydrophobic environment of the membranes. Our findings may be relevant for the design of reagents with photo-induced endosomolytic activity. The photocytotoxicity exhibited by TMR-TAT also suggests that CPP-chromophore conjugates could aid the development of novel Photodynamic Therapy agents