Defunct brain stem cardiovascular regulation underlies cardiovascular collapse associated with methamphetamine intoxication

<p>Abstract</p> <p>Background</p> <p>Intoxication from the psychostimulant methamphetamine (METH) because of cardiovascular collapse is a common cause of death within the abuse population. For obvious reasons, the heart has been taken as the primary target for this METH-induced toxicity. The demonstration that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse induced by the pesticide mevinphos implicates another potential underlying mechanism. The present study evaluated the hypothesis that METH effects acute cardiovascular depression by dampening the functional integrity of baroreflex via an action on brain stem nuclei that are associated with this homeostatic mechanism.</p> <p>Methods</p> <p>The distribution of METH in brain and heart on intravenous administration in male Sprague-Dawley rats, and the resultant changes in arterial pressure (AP), heart rate (HR) and indices for baroreflex-mediated sympathetic vasomotor tone and cardiac responses were evaluated, alongside survival rate and time.</p> <p>Results</p> <p>Intravenous administration of METH (12 or 24 mg/kg) resulted in a time-dependent and dose-dependent distribution of the psychostimulant in brain and heart. <b/>The distribution of METH to neural substrates associated with brain stem cardiovascular regulation was significantly larger than brain targets for its neurological and psychological effects; the concentration of METH in cardiac tissues was the lowest among all tissues studied. In animals that succumbed to METH, the baroreflex-mediated sympathetic vasomotor tone and cardiac response were defunct, concomitant with cessation of AP and HR. On the other hand, although depressed, those two indices in animals that survived were maintained, alongside sustainable AP and HR. Linear regression analysis further revealed that the degree of dampening of brain stem cardiovascular regulation was positively and significantly correlated with the concentration of METH in key neural substrate involved in this homeostatic mechanism.</p> <p>Conclusions</p> <p>We conclude that on intravenous administration, METH exhibits a preferential distribution to brain stem nuclei that are associated with cardiovascular regulation. We further found that the concentration of METH in those brain stem sites dictates the extent that baroreflex-mediated sympathetic vasomotor tone and cardiac responses are compromised, which in turn determines survival or fatality because of cardiovascular collapse.</p

Flood risk to commercial property: Training and Education Needs of Built Environment Professionals

Improved management of commercial property at risk from flooding may result from well-targeted advice from built environment professionals, such as surveyors, valuers and project managers. However, research indicates that the role of these professionals in providing such advice is currently limited for a variety of reasons. This research aimed to investigate the (perceived and real) barriers and opportunities for providing such advice in a number of international locations. In particular the research sought greater understanding of the link between regulation and guidance; perceived roles and capacity; and training and education needs. In order to cover different international settings an illustrative case study approach was adopted within the selected countries (Australia, UK, US, China and Germany). This involved a qualitative approach using semi-structured interviews of built environment (BE) professionals with experience of advising on commercial properties at risk of flooding. Due to the specific nature of these interviews, a purposive sampling approach was implemented, leading to a sample of 72 interviews across the five international locations. Perceived barriers were linked to regulatory issues, a shortage of suitably experienced professionals, a lack of formal guidance and insurance requirements. BE professionals defined their roles differently in each case study in relation to these factors and stressed the need for closer collaboration among the various disciplines and indeed the other key stakeholders (i.e. insurers, loss adjusters, contractors). A shortage of knowledgeable experts caused by a lack of formal training and education was a common challenge highlighted in all locations. The research is unique in providing an international perspective on issues affecting built environment professionals in providing robust and impartial advice on commercial property at risk of flooding. Whilst acknowledging the existence of local flood conditions, regulatory frameworks and insurance regimes, the results indicate some recurring themes, indicating a lack of general flood risk education and training across all five case study countries. Learning across case studies coupled with appropriate policy development, could contribute towards improved skills development and more consistent integration of BE professionals within future flood risk management practice, policy and strategy

Treatment rates for PTSD and depression in recently hospitalized cardiac patients

Objective Posttraumatic stress disorder (PTSD) and depression are common after evaluation for suspected acute coronary syndrome (ACS), and are associated with poor prognosis. However, it is unclear whether patients discharged after suspected ACS access treatments for subsequent psychological distress. We examined self-reported rates of receiving psychotherapy and/or medication for psychological distress in patients one month after a suspected ACS event. Methods A sample of 448 adults (age 60.4 ± 12.5; 47.8% female; 52.7% Hispanic, 32.1% Black) presenting to the emergency department with suspected ACS were recruited for the REactions to Acute Care and Hospitalization (REACH) study, an ongoing cohort study of medical and psychological outcomes after ACS evaluation. Socio-demographics and depressive symptoms were assessed in-hospital, and PTSD symptoms related to the suspected ACS event were queried via phone one month after enrollment. Participants also indicated whether they received either medication or counseling to deal with their emotions and coping after their heart problem. Results Approximately 15% (n = 68) of the sample reported receiving some form of treatment. Treatment rate did not differ significantly as a function of demographics, ACS status, or insurance coverage, ps > 0.1. Over a quarter of participants (25.3%) who screened positive for PTSD and/or depression reported receiving treatment. Participants with PTSD and depression had a higher treatment rate (47.6%) vs. those with only depression (12.8%) or PTSD (30%) or no psychopathology (10.3%). Conclusion Findings suggest that 1 in 4 patients who screened positive for PTSD and/or depression reported receiving counseling or medication in the first month after a suspected ACS event

How technology-enhanced experiential e-learning can facilitate the development of person-centred communication skills online for health-care students: a qualitative study

Background: The COVID-19 pandemic brought a new challenge to medical education—health-care students had fewer opportunities to interact with and treat real patients in clinical settings. Interpersonal communication skills are often developed through human interaction and communication in person, and few studies have proposed feasible digital solutions to develop learners’ communication skills. Consequently, understanding how medical teachers facilitate and implement online training programmes, with feasible instruments, to enhance students’ learning effectiveness when in-person training is not possible is critical. Methods: By using a convenience sampling method, we recruited 26 health-care students from seven medical schools in Taiwan. Through semistructured interviews and the thematic analysis technique, we analysed the latent learning factors from the experience of implementing the technology-enhanced experiential e-learning tool ‘mPath’. Results: Three themes were generated: A) transferring theory into practice, B) increasing authenticity with analytical features, and C) maintaining autonomy with nondirective learning. The features accessibility, flexibility, intractability, and visualisation with the characteristics of remote accessibility and flexibility, repetition and retrospect, feedback requesting, and visualised analytical reports were considered to enhance learning outcomes. Conclusion: This study indicated how online training using technology could develop the participants’ person-centred communication skills and what features influenced the learning outcomes of social distancing. mPath may be a feasible online learning approach and has provided inspiration for developing health-care students’ communication skills when in-person training is not possible

IRIS3: integrated cell-type-specific regulon inference server from single-cell RNA-Seq

group of genes controlled as a unit, usually by the same repressor or activator gene, is known as a regulon. The ability to identify active regulons within a specific cell type, i.e., cell-type-specific regulons (CTSR), provides an extraordinary opportunity to pinpoint crucial regulators and target genes responsible for complex diseases. However, the identification of CTSRs from single-cell RNA-Seq (scRNA-Seq) data is computationally challenging. We introduce IRIS3, the first-of-its-kind web server for CTSR inference from scRNA-Seq data for human and mouse. IRIS3 is an easy-to-use server empowered by over 20 functionalities to support comprehensive interpretations and graphical visualizations of identified CTSRs. CTSR data can be used to reliably characterize and distinguish the corresponding cell type from others and can be combined with other computational or experimental analyses for biomedical studies. CTSRs can, therefore, aid in the discovery of major regulatory mechanisms and allow reliable constructions of global transcriptional regulation networks encoded in a specific cell type. The broader impact of IRIS3 includes, but is not limited to, investigation of complex diseases hierarchies and heterogeneity, causal gene regulatory network construction, and drug development

Relationship between Obesity and Depression in the Korean Working Population

This study was conducted to investigate potential relationship between obesity and depression in Korean working population. A total of 8,121 workers, aged 21-75 yr, participated in this nationwide cross-section research. The participants asked to complete a questionnaire regarding the socio-demographic factors and health-related behaviors, height, and weight. To measure degree of depression, the Korean version of the Center for Epidemiologic Studies-Depression scale (CES-D) was used. Chi-square test and multivariate logistic regression analyses were performed to examine the degree of association between obesity and depression. Compared to normal-weight women, overweight women had a lower adjusted odds ratio (OR) for depression (OR=0.65, 95% confidence interval 0.46 to 0.97). Underweight (1.42, 0.83 to 2.44) and obese women (BMI ≥30) had higher ORs for depression (1.47, 0.64 to 3.36), but these were insignificant. Compared to normal-weight men, obese men had higher crude ORs (1.94, 1.03 to 3.62) and adjusted ORs (1.77, 0.89 to 3.53) for depression, while underweight and overweight men showed no significant differences. These findings suggest that being overweight may protect Korean female worker against depression

Detection of transcriptional triggers in the dynamics of microbial growth: application to the respiratorily versatile bacterium Shewanella oneidensis

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nucleic Acids Research 40 (2012): 7132-7149, doi:10.1093/nar/gks467.The capacity of microorganisms to respond to variable external conditions requires a coordination of environment-sensing mechanisms and decision-making regulatory circuits. Here, we seek to understand the interplay between these two processes by combining high-throughput measurement of time-dependent mRNA profiles with a novel computational approach that searches for key genetic triggers of transcriptional changes. Our approach helped us understand the regulatory strategies of a respiratorily versatile bacterium with promising bioenergy and bioremediation applications, Shewanella oneidensis, in minimal and rich media. By comparing expression profiles across these two conditions, we unveiled components of the transcriptional program that depend mainly on the growth phase. Conversely, by integrating our time-dependent data with a previously available large compendium of static perturbation responses, we identified transcriptional changes that cannot be explained solely by internal network dynamics, but are rather triggered by specific genes acting as key mediators of an environment-dependent response. These transcriptional triggers include known and novel regulators that respond to carbon, nitrogen and oxygen limitation. Our analysis suggests a sequence of physiological responses, including a coupling between nitrogen depletion and glycogen storage, partially recapitulated through dynamic flux balance analysis, and experimentally confirmed by metabolite measurements. Our approach is broadly applicable to other systems.Office of Science (BER), U.S. Department of Energy [DE-FG02-07ER64388 to D.S. and DE-FG02- 08ER64511 to M.H.S.]; National Aeronautics and Space Administration, NASA Astrobiology Institute [NNA08CN84A to D.S.]

Bioenergetics Failure and Oxidative Stress in Brain Stem Mediates Cardiovascular Collapse Associated with Fatal Methamphetamine Intoxication

Background: Whereas sudden death, most often associated with cardiovascular collapse, occurs in abusers of the psychostimulant methamphetamine (METH), the underlying mechanism is much less understood. The demonstration that successful resuscitation of an arrested heart depends on maintained functionality of the rostral ventrolateral medulla (RVLM), which is responsible for the maintenance of stable blood pressure, suggests that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse. We tested the hypothesis that cessation of brain stem cardiovascular regulation because of a loss of functionality in RVLM mediated by bioenergetics failure and oxidative stress underlies the cardiovascular collapse elicited by lethal doses of METH. Methodology/Principal Findings: Survival rate, cardiovascular responses and biochemical or morphological changes in RVLM induced by intravenous administration of METH in Sprague-Dawley rats were investigated. High doses of METH induced significant mortality within 20 min that paralleled concomitant the collapse of arterial pressure or heart rate and loss of functionality in RVLM. There were concurrent increases in the concentration of METH in serum and ventrolateral medulla, along with tissue anoxia, cessation of microvascular perfusion and necrotic cell death in RVLM. Furthermore, mitochondrial respiratory chain enzyme activity or electron transport capacity and ATP production in RVLM were reduced, and mitochondria-derived superoxide anion level was augmented. All those detrimental physiological and biochemica

Response to Comment on “Plant diversity increases with the strength of negative density dependence at the global scale”

Hülsmann and Hartig suggest that ecological mechanisms other than specialized natural enemies or intraspecific competition contribute to our estimates of conspecific negative density dependence (CNDD). To address their concern, we show that our results are not the result of a methodological artifact and present a null-model analysis that demonstrates that our original findings—(i) stronger CNDD at tropical relative to temperate latitudes and (ii) a latitudinal shift in the relationship between CNDD and species abundance—persist even after controlling for other processes that might influence spatial relationships between adults and recruits

Terrestrial and aquatic responses to climate change and human impact on the southeastern Tibetan Plateau during the past two centuries

Rapid population growth and economic development have led to increased anthropogenic pressures on the Tibetan Plateau, causing significant land cover changes with potentially severe ecological consequences. To assess whether or not these pressures are also affecting the remote montane-boreal lakes on the SE Tibetan Plateau, fossil pollen and diatom data from two lakes were synthesized. The interplay of aquatic and terrestrial ecosystem response was explored in respect to climate variability and human activity over the past 200 years. Nonmetric multidimensional scaling and Procrustes rotation analysis were undertaken to determine whether pollen and diatom responses in each lake were similar and synchronous. Detrended canonical correspondence analysis was used to develop quantitative estimates of compositional species turnover. Despite instrumental evidence of significant climatic warming on the southeastern Plateau, the pollen and diatom records indicate very stable species composition throughout their profiles and show only very subtle responses to environmental changes over the past 200 years. The compositional species turnover (0.36-0.94 SD) is relatively low in comparison to the species reorganizations known from the periods during the mid-and early-Holocene (0.64-1.61 SD) on the SE Plateau, and also in comparison to turnover rates of sediment records from climate-sensitive regions in the circum arctic. Our results indicate that climatically induced ecological thresholds are not yet crossed, but that human activity has an increasing influence, particularly on the terrestrial ecosystem in our study area. Synergistic processes of post-Little Ice Age warming, 20th century climate warming and extensive reforestations since the 19th century have initiated a change from natural oak-pine forests to seminatural, likely less resilient pine-oak forests. Further warming and anthropogenic disturbances would possibly exceed the ecological threshold of these ecosystems and lead to severe ecological consequences