Increased hemorrhagic transformation and altered infarct size and localization after experimental stroke in a rat model type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>Interruption of flow through of cerebral blood vessels results in acute ischemic stroke. Subsequent breakdown of the blood brain barrier increases cerebral injury by the development of vasogenic edema and secondary hemorrhage known as hemorrhagic transformation (HT). Diabetes is a risk factor for stroke as well as poor outcome of stroke. The current study tested the hypothesis that diabetes-induced changes in the cerebral vasculature increase the risk of HT and augment ischemic injury.</p> <p>Methods</p> <p>Diabetic Goto-Kakizaki (GK) or control rats underwent 3 hours of middle cerebral artery occlusion and 21 h reperfusion followed by evaluation of infarct size, hemorrhage and neurological outcome.</p> <p>Results</p> <p>Infarct size was significantly smaller in GK rats (10 ± 2 vs 30 ± 4%, p < 0.001). There was significantly more frequent hematoma formation in the ischemic hemisphere in GK rats as opposed to controls. Cerebrovascular tortuosity index was increased in the GK model (1.13 ± 0.01 vs 1.34 ± 0.06, P < 0.001) indicative of changes in vessel architecture.</p> <p>Conclusion</p> <p>These findings provide evidence that there is cerebrovascular remodeling in diabetes. While diabetes-induced remodeling appears to prevent infarct expansion, these changes in blood vessels increase the risk for HT possibly exacerbating neurovascular damage due to cerebral ischemia/reperfusion in diabetes.</p

Thoracic empyema with scarlatiniform rash and acral desquamation: a case report

A 5 year old girl with thoracic empyema developed a scarlatiniform rash and acral desquamation. Cultures from blood, throat, and pleural fluid all grew Streptococcus pyogenes, a common etiologic agent of pediatric thoracic empyema. The presence of a scarlatiniform rash and acral desquamation in children with a thoracic empyema may help identify the causative organism

An organization‐ and category‐level comparison of diagnostic requirements for mental disorders in ICD‐11 and DSM‐5

In 2013, the American Psychiatric Association (APA) published the 5th edition of its Diagnostic and Statistical Manual of Mental Disorders (DSM‐5). In 2019, the World Health Assembly approved the 11th revision of the International Classification of Diseases (ICD‐11). It has often been suggested that the field would benefit from a single, unified classification of mental disorders, although the priorities and constituencies of the two sponsoring organizations are quite different. During the development of the ICD‐11 and DSM‐5, the World Health Organization (WHO) and the APA made efforts toward harmonizing the two systems, including the appointment of an ICD‐DSM Harmonization Group. This paper evaluates the success of these harmonization efforts and provides a guide for practitioners, researchers and policy makers describing the differences between the two systems at both the organizational and the disorder level. The organization of the two classifications of mental disorders is substantially similar. There are nineteen ICD‐11 disorder categories that do not appear in DSM‐5, and seven DSM‐5 disorder categories that do not appear in the ICD‐11. We compared the Essential Features section of the ICD‐11 Clinical Descriptions and Diagnostic Guidelines (CDDG) with the DSM‐5 criteria sets for 103 diagnostic entities that appear in both systems. We rated 20 disorders (19.4%) as having major differences, 42 disorders (40.8%) as having minor definitional differences, 10 disorders (9.7%) as having minor differences due to greater degree of specification in DSM‐5, and 31 disorders (30.1%) as essentially identical. Detailed descriptions of the major differences and some of the most important minor differences, with their rationale and related evidence, are provided. The ICD and DSM are now closer than at any time since the ICD‐8 and DSM‐II. Differences are largely based on the differing priorities and uses of the two diagnostic systems and on differing interpretations of the evidence. Substantively divergent approaches allow for empirical comparisons of validity and utility and can contribute to advances in the field

Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment

Peer reviewedPublisher PD

Dispelling urban myths about default uncertainty factors in chemical risk assessment - Sufficient protection against mixture effects?

© 2013 Martin et al.; licensee BioMed Central LtdThis article has been made available through the Brunel Open Access Publishing Fund.Assessing the detrimental health effects of chemicals requires the extrapolation of experimental data in animals to human populations. This is achieved by applying a default uncertainty factor of 100 to doses not found to be associated with observable effects in laboratory animals. It is commonly assumed that the toxicokinetic and toxicodynamic sub-components of this default uncertainty factor represent worst-case scenarios and that the multiplication of those components yields conservative estimates of safe levels for humans. It is sometimes claimed that this conservatism also offers adequate protection from mixture effects. By analysing the evolution of uncertainty factors from a historical perspective, we expose that the default factor and its sub-components are intended to represent adequate rather than worst-case scenarios. The intention of using assessment factors for mixture effects was abandoned thirty years ago. It is also often ignored that the conservatism (or otherwise) of uncertainty factors can only be considered in relation to a defined level of protection. A protection equivalent to an effect magnitude of 0.001-0.0001% over background incidence is generally considered acceptable. However, it is impossible to say whether this level of protection is in fact realised with the tolerable doses that are derived by employing uncertainty factors. Accordingly, it is difficult to assess whether uncertainty factors overestimate or underestimate the sensitivity differences in human populations. It is also often not appreciated that the outcome of probabilistic approaches to the multiplication of sub-factors is dependent on the choice of probability distributions. Therefore, the idea that default uncertainty factors are overly conservative worst-case scenarios which can account both for the lack of statistical power in animal experiments and protect against potential mixture effects is ill-founded. We contend that precautionary regulation should provide an incentive to generate better data and recommend adopting a pragmatic, but scientifically better founded approach to mixture risk assessment. © 2013 Martin et al.; licensee BioMed Central Ltd.Oak Foundatio

Water Contamination Reduces the Tolerance of Coral Larvae to Thermal Stress

Coral reefs are highly susceptible to climate change, with elevated sea surface temperatures (SST) posing one of the main threats to coral survival. Successful recruitment of new colonies is important for the recovery of degraded reefs following mortality events. Coral larvae require relatively uncontaminated substratum on which to metamorphose into sessile polyps, and the increasing pollution of coastal waters therefore constitutes an additional threat to reef resilience. Here we develop and analyse a model of larval metamorphosis success for two common coral species to quantify the interactive effects of water pollution (copper contamination) and SST. We identify thresholds of temperature and pollution that prevent larval metamorphosis, and evaluate synergistic interactions between these stressors. Our analyses show that halving the concentration of Cu can protect corals from the negative effects of a 2–3°C increase in SST. These results demonstrate that effective mitigation of local impacts can reduce negative effects of global stressors

Impact of periodic health examination on surgical treatment for uterine fibroids in Beijing: a case-control study

<p>Abstract</p> <p>Background</p> <p>During the past 2 decades, there has been a rapid proliferation of "health examination center (HEC)" across China. The effects of their services on public's health have not been systemically investigated. This study aimed to assess the impact of periodic health examination (PHE) at HEC on surgical treatment for uterine fibroids in Beijing residents.</p> <p>Methods</p> <p>We identified 224 patients with a primary diagnosis of uterine fibroids who had surgical treatment at four Level-1 general hospitals in Beijing, from June 1, 2009 to October 20, 2009. Controls were women who did not have surgery for uterine fibroids, matched (1:1 ratio) for age (within 2 years). A standard questionnaire was used to inquire about whether participants had PHE at HEC during the previous 2 years.</p> <p>Results</p> <p>PHE at HEC within 2 years were associated with surgical treatment for uterine fibroids. Odds ratios was 4.05 (95% CI, 2.61-6.29 P < 0.001), after adjustment for marital status, whether have children, annual family income, health insurance, education level and self-rated uterine fibroids-related symptom severity.</p> <p>Conclusions</p> <p>Our study showed PHE currently provided at HEC in China were associated with significantly increased use of surgical treatment for uterine fibroids in women. Further studies are needed to assess the effects of PHE on clinical as well as on broad societal outcomes in Chinese in contemporary medical settings.</p

Design and mechanistic insight into ultrafast calcium indicators for monitoring intracellular calcium dynamics.

Calmodulin-based genetically encoded fluorescent calcium indicators (GCaMP-s) are powerful tools of imaging calcium dynamics from cells to freely moving animals. High affinity indicators with slow kinetics however distort the temporal profile of calcium transients. Here we report the development of reduced affinity ultrafast variants of GCaMP6s and GCaMP6f. We hypothesized that GCaMP-s have a common kinetic mechanism with a rate-limiting process in the interaction of the RS20 peptide and calcium-calmodulin. Therefore we targeted specific residues in the binding interface by rational design generating improved indicators with GCaMP6fu displaying fluorescence rise and decay times (t1/2) of 1 and 3 ms (37 °C) in vitro, 9 and 22-fold faster than GCaMP6f respectively. In HEK293T cells, GCaMP6fu revealed a 4-fold faster decay of ATP-evoked intracellular calcium transients than GCaMP6f. Stimulation of hippocampal CA1 pyramidal neurons with five action potentials fired at 100 Hz resulted in a single dendritic calcium transient with a 2-fold faster rise and 7-fold faster decay time (t1/2 of 40 ms) than GCaMP6f, indicating that tracking high frequency action potentials may be limited by calcium dynamics. We propose that the design strategy used for generating GCaMP6fu is applicable for the acceleration of the response kinetics of GCaMP-type calcium indicators