Upregulation of Neurotrophic Factors Selectively in Frontal Cortex in Response to Olfactory Discrimination Learning

We have previously shown that olfactory discrimination learning is accompanied by several forms of long-term enhancement in synaptic connections between layer II pyramidal neurons selectively in the piriform cortex. This study sought to examine whether the previously demonstrated olfactory-learning-task-induced modifications are preceded by suitable changes in the expression of mRNA for neurotrophic factors and in which brain areas this occurs. Rats were trained to discriminate positive cues in pair of odors for a water reward. The relationship between the learning task and local levels of mRNA for brain-derived neurotrophic factor, tyrosine kinase B, nerve growth factor, and neurotrophin-3 in the frontal cortex, hippocampal subregions, and other regions were assessed 24 hours post olfactory learning. The olfactory discrimination learning activated production of endogenous neurotrophic factors and induced their signal transduction in the frontal cortex, but not in other brain areas. These findings suggest that different brain areas may be preferentially involved in different learning/memory tasks

On the Cosmic-Ray Spectra of Three-Body Lepton-Flavor-Violating Dark Matter Decays

We consider possible leptonic three-body decays of spin-1/2, charge-asymmetric dark matter. Assuming a general Dirac structure for the four-fermion contact interactions of interest, we study the cosmic-ray electron and positron spectra and show that good fits to the current data can be obtained for both charged-lepton-flavor-conserving and flavor-violating decay channels. We find that different choices for the Dirac structure of the underlying decay operator can be significantly compensated by different choices for the dark matter mass and lifetime. The decay modes we consider provide differing predictions for the cosmic-ray positron fraction at energies higher than those currently probed at the PAMELA experiment; these predictions might be tested at cosmic-ray detectors like AMS-02.Comment: 14 pages LaTeX, 3 figures (8 eps files). v2 and v3: clarifications and references adde

Amended Classification of the Open Abdomen

Background: In 2009, a classification system for the open abdomen was introduced. The aim of such a classification is to aid the (1) description of the patient's clinical course; (2) standardization of clinical guidelines for guiding open abdomen management; and (3) facilitation of comparisons between studies and heterogeneous patient populations, thus serving as an aid in clinical research. Methods: As part of the revision of the definitions and clinical guidelines performed by the World Society of the Abdominal Compartment Syndrome, this 2009 classification system was amended following a review of experiences in teaching and research and published as part of updated consensus statements and clinical practice guidelines in 2013. Among 29 articles citing the 2009 classification system, nine were cohort studies. They were reviewed as part of the classification revision process. A total of 542 patients (mean: 60, range: 9-160) had been classified. Two problems with the previous classification system were identified: the definition of enteroatmospheric fistulae, and that an enteroatmospheric fistula was graded less severe than a frozen abdomen. Results: The following amended classification was proposed: Grade 1, without adherence between bowel and abdominal wall or fixity of the abdominal wall (lateralization), subdivided as follows: 1A, clean; 1B, contaminated; and 1C, with enteric leak. An enteric leak controlled by closure, exteriorization into a stoma, or a permanent enterocutaneous fistula is considered clean. Grade 2, developing fixation, subdivided as follows: 2A, clean; 2B, contaminated; and 2C, with enteric leak. Grade 3, frozen abdomen, subdivided as follows: 3A clean and 3B contaminated. Grade 4, an established enteroatmospheric fistula, is defined as a permanent enteric leak into the open abdomen, associated with granulation tissue. Conclusions: The authors believe that, with these changes, the requirements on a functional and dynamic classification system, useful in both research and training, will be fulfilled. We encourage future investigators to apply the system and report on its merits and constraints.Peer reviewe

Sharing ICU Patient Data Responsibly Under the Society of Critical Care Medicine/European Society of Intensive Care Medicine Joint Data Science Collaboration: The Amsterdam University Medical Centers Database (AmsterdamUMCdb) Example.

OBJECTIVES: Critical care medicine is a natural environment for machine learning approaches to improve outcomes for critically ill patients as admissions to ICUs generate vast amounts of data. However, technical, legal, ethical, and privacy concerns have so far limited the critical care medicine community from making these data readily available. The Society of Critical Care Medicine and the European Society of Intensive Care Medicine have identified ICU patient data sharing as one of the priorities under their Joint Data Science Collaboration. To encourage ICUs worldwide to share their patient data responsibly, we now describe the development and release of Amsterdam University Medical Centers Database (AmsterdamUMCdb), the first freely available critical care database in full compliance with privacy laws from both the United States and Europe, as an example of the feasibility of sharing complex critical care data. SETTING: University hospital ICU. SUBJECTS: Data from ICU patients admitted between 2003 and 2016. INTERVENTIONS: We used a risk-based deidentification strategy to maintain data utility while preserving privacy. In addition, we implemented contractual and governance processes, and a communication strategy. Patient organizations, supporting hospitals, and experts on ethics and privacy audited these processes and the database. MEASUREMENTS AND MAIN RESULTS: AmsterdamUMCdb contains approximately 1 billion clinical data points from 23,106 admissions of 20,109 patients. The privacy audit concluded that reidentification is not reasonably likely, and AmsterdamUMCdb can therefore be considered as anonymous information, both in the context of the U.S. Health Insurance Portability and Accountability Act and the European General Data Protection Regulation. The ethics audit concluded that responsible data sharing imposes minimal burden, whereas the potential benefit is tremendous. CONCLUSIONS: Technical, legal, ethical, and privacy challenges related to responsible data sharing can be addressed using a multidisciplinary approach. A risk-based deidentification strategy, that complies with both U.S. and European privacy regulations, should be the preferred approach to releasing ICU patient data. This supports the shared Society of Critical Care Medicine and European Society of Intensive Care Medicine vision to improve critical care outcomes through scientific inquiry of vast and combined ICU datasets

The Reversal of Fortunes: Trends in County Mortality and Cross-County Mortality Disparities in the United States

Majid Ezzati and colleagues analyze US county-level mortality data for 1961 to 1999, and find a steady increase in mortality inequality across counties between 1983 and 1999

Comparison between the disease-specific Airways Questionnaire 20 and the generic 15D instruments in COPD

<p>Abstract</p> <p>Background</p> <p>Given that the assessment of health-related quality of life (HRQoL) is an essential outcome measure to optimize chronic obstructive pulmonary disease (COPD) patient management, there is a need for a short and fast, reliable and valid instrument for routine use in clinical practice. The objective of this study was to analyse the relationship between the disease-specific Airways questionnaire (AQ20) and the generic 15D health-related quality of life (HRQoL) instrument simultaneously in a large cohort of patients with COPD. We also compare the HRQoL of COPD patients with that of the general population.</p> <p>Methods</p> <p>The AQ20 and 15D were administered to 739 COPD patients representing an unselected hospital-based COPD population. The completion rates and validity of, and correlations among the questions and dimension scores were examined. A factor analysis with varimax rotation was performed in order to find subsets of highly correlating items of the questionnaires.</p> <p>Results</p> <p>The summary scores of AQ20 and 15D were highly correlated (r = - 0.71, p < 0.01). In AQ20 over 50% of patients reported frequent cough, breathlessness during domestic work, and chest problem limiting their full enjoyment of life. 15D results showed a noteworthy decrease of HRQoL in breathing, mobility, sleeping, usual activities, discomfort and symptoms, vitality, and sexual activity (scores ≤ 0.75). Compared to the age- and gender-standardized Finnish general population, the COPD patients were statistically significantly worse off on 13 of 15 dimensions.</p> <p>Conclusions</p> <p>The AQ20 and 15D summary scores are comparable in terms of measuring HRQoL in COPD patients. The data support the validity of 15D to measure the quality of life in COPD. COPD compromises the HRQoL broadly, as reflected by the generic instrument. Both questionnaires are simple and short, and could easily be used in clinical practice with high completion rates.</p

Antibiotics for the primary prevention of acute rheumatic fever: a meta-analysis

BACKGROUND: Rheumatic fever continues to put a significant burden on the health of low socio-economic populations in low and middle-income countries despite the near disappearance of the disease in the developed world over the past century. Antibiotics have long been thought of as an effective method for preventing the onset of acute rheumatic fever following a Group-A streptococcal (GAS) throat infection; however, their use has not been widely adopted in developing countries for the treatment of sore throats. We have used the tools of systematic review and meta-analysis to quantify the effectiveness of antibiotic treatment for sore throat, with symptoms suggestive of group A streptococcal (GAS) infection, for the primary prevention of acute rheumatic fever. METHODS: Trials were identified through a systematic search of titles and abstracts found in the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 4, 2003), MEDLINE (1966–2003), EMBASE (1966–2003), and the reference lists of identified studies. The selection criteria included randomised or quasi-randomised controlled trials comparing the effectiveness of antibiotics versus no antibiotics for the prevention of rheumatic fever in patients presenting with a sore throat, with or without confirmation of GAS infection, and no history of rheumatic fever. RESULTS: Ten trials (n = 7665) were eligible for inclusion in this review. The methodological quality of the studies, in general, was poor. All of the included trials were conducted during the period of 1950 and 1961 and in 8 of the 10 trials the study population consisted of young adult males living on United States military bases. Fixed effects, meta-analysis revealed an overall protective effect for the use of antibiotics against acute rheumatic fever of 70% (RR = 0.32; 95% CI = 0.21–0.48). The absolute risk reduction was 1.67% with an NNT of 53. When meta-analysis was restricted to include only trials evaluating penicillin, a protective effect of 80% was found (Fixed effect RR = 0.20, 95% CI = 0.11–0.36) with an NNT of 60. The marginal cost of preventing one case of rheumatic fever by a single intramuscular injection of penicillin is approximately US$46 in South Africa. CONCLUSION: Antibiotics appear to be effective in reducing the incidence of acute rheumatic fever following an episode of suspected GAS pharyngitis. This effect may be achieved at relatively low cost if a single intramuscular penicillin injection is administered

Facing Anxiety, Growing Up. Trait Emotional Intelligence as a Mediator of the Relationship Between Self-Esteem and University Anxiety

The current study analyzed how trait emotional intelligence (trait EI) mediates the relationship between self-esteem and state anxiety and trait anxiety. The sample was composed of 153 undergraduate students from the University of Cádiz, Spain (71.9% women and 28.1% men). Students completed measures of self-esteem, state anxiety, trait anxiety, and trait EI. Mediation analyses were completed with three trait EI dimensions (EA, emotional attention; EC, emotional clarity; and MR, mood repair) as mediating variables, self-esteem as the independent variable, and state anxiety and trait anxiety as the dependent ones. Our results confirmed that self-esteem scores explained and predicted both, state and trait anxiety values (13% for state and 21% for trait anxiety). This explanatory capacity is increased by 8% when accounting for all trait EI dimensions. Considering state anxiety, the results of the direct effects showed that a decrease in their levels is predicted through the increases in the levels of both, self-esteem and MR. Regarding trait anxiety, the results of the direct effects showed that a decrease in their levels is predicted, in addition to an increment of self-esteem and MR values, by an increase of EC and a decrease of EA. Conversely, indirect effects revealed that higher levels of self-esteem were associated with worse scores in EA and worse MR, which in turn would enhance both state and trait anxiety levels. Moreover, regarding trait anxiety higher levels of self-esteem were associated with worse scores in EA and worse EC, therefore increasing trait anxiety levels. As shown, the negative association found between self-esteem and EA becomes a key element. The effect of self-esteem on EA and the influence that the latter had on EC and MR exerts an indirect mediated effect with the power to invert the influence that self-esteem wields on both types of anxiety. In this sense, the apparent protective role of self-esteem changed, turning into a risk factor that promotes higher anxiety values

Propofol-Induced Changes in Neurotrophic Signaling in the Developing Nervous System In Vivo

Several studies have revealed a role for neurotrophins in anesthesia-induced neurotoxicity in the developing brain. In this study we monitored the spatial and temporal expression of neurotrophic signaling molecules in the brain of 14-day-old (PND14) Wistar rats after the application of a single propofol dose (25 mg/kg i.p). The structures of interest were the cortex and thalamus as the primary areas of anesthetic actions. Changes of the protein levels of the brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), their activated receptors tropomyosin-related kinase (TrkA and TrkB) and downstream kinases Akt and the extracellular signal regulated kinase (ERK) were assessed by Western immunoblot analysis at different time points during the first 24 h after the treatment, as well as the expression of cleaved caspase-3 fragment. Fluoro-Jade B staining was used to follow the appearance of degenerating neurons. The obtained results show that the treatment caused marked alterations in levels of the examined neurotrophins, their receptors and downstream effector kinases. However, these changes were not associated with increased neurodegeneration in either the cortex or the thalamus. These results indicate that in the brain of PND14 rats, the interaction between Akt/ERK signaling might be one of important part of endogenous defense mechanisms, which the developing brain utilizes to protect itself from potential anesthesia-induced damage. Elucidation of the underlying molecular mechanisms will improve our understanding of the age-dependent component of anesthesia-induced neurotoxicity

G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests

Malaria elimination will be possible only with serious attempts to address asymptomatic infection and chronic infection by both Plasmodium falciparum and Plasmodium vivax. Currently available drugs that can completely clear a human of P. vivax (known as “radical cure”), and that can reduce transmission of malaria parasites, are those in the 8-aminoquinoline drug family, such as primaquine. Unfortunately, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency risk having severe adverse reactions if exposed to these drugs at certain doses. G6PD deficiency is the most common human enzyme defect, affecting approximately 400 million people worldwide. Scaling up radical cure regimens will require testing for G6PD deficiency, at two levels: 1) the individual level to ensure safe case management, and 2) the population level to understand the risk in the local population to guide Plasmodium vivax treatment policy. Several technical and operational knowledge gaps must be addressed to expand access to G6PD deficiency testing and to ensure that a patient’s G6PD status is known before deciding to administer an 8-aminoquinoline-based drug. In this report from a stakeholder meeting held in Thailand on October 4 and 5, 2012, G6PD testing in support of radical cure is discussed in detail. The focus is on challenges to the development and evaluation of G6PD diagnostic tests, and on challenges related to the operational aspects of implementing G6PD testing in support of radical cure. The report also describes recommendations for evaluation of diagnostic tests for G6PD deficiency in support of radical cure