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OBJECTIVES/SPECIFIC AIMS: To study the biology of Phosholamban (PLN) in a human relevant model. METHODS/STUDY POPULATION: State of the art stem-cell technologies using iPSC-CMs derived from carriers of a lethal PLN mutation. RESULTS/ANTICIPATED RESULTS: Our preliminary data demonstrate that this particular PLN mutation (L39) results in reduced expression and mis-localization of PLN as well as increased incidence of early after depolarization in isolated iPSC-CMs. DISCUSSION/SIGNIFICANCE OF IMPACT: Phospholamban (PLN) is a critical regulator of Ca++ homeostasis yet many uncertainties still remain regarding its role in humans. Our study will provide unique insights into the pathophysiology of this protein in HF.
Candida auris is an emerging fungal pathogen that is often resistant to major classes of antifungal drugs. It is considered a serious global health threat because it can cause severe infections with frequent mortality in more than a dozen countries. It can survive on healthcare environmental surfaces for at least 7 days and can cause outbreaks in healthcare facilities. Clearly, infection prevention strategies, such as surface disinfection, will be essential to controlling Candida transmission. Unfortunately, data on the activity of antiseptics and disinfectants used in healthcare to inactivate this pathogen are limited.1–5 In this study, we investigated 12 different disinfectants (ie, 8 low- and intermediate-level disinfectants in 2 dilutions of sodium hypochlorite and 5 high-level disinfectants/chemical sterilants) and 9 antiseptics commonly used in healthcare facilities for their antimicrobial activity against C. auris and C. albicans.
Cognitive behavioral therapy (CBT) is an effective treatment for many patients suffering from major depressive disorder (MDD), but predictors of treatment outcome are lacking, and little is known about its neural mechanisms. We recently identified longitudinal changes in neural correlates of conscious emotion regulation that scaled with clinical responses to CBT for MDD, using a negative autobiographical memory-based task.
We now examine the neural correlates of emotional reactivity and emotion regulation during viewing of emotionally salient images as predictors of treatment outcome with CBT for MDD, and the relationship between longitudinal change in functional magnetic resonance imaging (fMRI) responses and clinical outcomes. Thirty-two participants with current MDD underwent baseline MRI scanning followed by 14 sessions of CBT. The fMRI task measured emotional reactivity and emotion regulation on separate trials using standardized images from the International Affective Pictures System. Twenty-one participants completed post-treatment scanning. Last observation carried forward was used to estimate clinical outcome for non-completers.
Pre-treatment emotional reactivity Blood Oxygen Level-Dependent (BOLD) signal within hippocampus including CA1 predicted worse treatment outcome. In contrast, better treatment outcome was associated with increased down-regulation of BOLD activity during emotion regulation from time 1 to time 2 in precuneus, occipital cortex, and middle frontal gyrus.
CBT may modulate the neural circuitry of emotion regulation. The neural correlates of emotional reactivity may be more strongly predictive of CBT outcome. The finding that treatment outcome was predicted by BOLD signal in CA1 may suggest overgeneralized memory as a negative prognostic factor in CBT outcome.
Hospital environmental surfaces are frequently contaminated by microorganisms. However, the causal mechanism of bacterial contamination of the environment as a source of transmission is still debated. This prospective study was performed to characterize the nature of multidrug-resistant organism (MDRO) transmission between the environment and patients using standard microbiological and molecular techniques.
Prospective cohort study at 2 academic medical centers.
A prospective multicenter study to characterize the nature of bacterial transfer events between patients and environmental surfaces in rooms that previously housed patients with 1 of 4 ‘marker’ MDROs: methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Clostridium difficile, and MDR Acinetobacter baumannii. Environmental and patient microbiological samples were obtained on admission into a freshly disinfected inpatient room. Repeat samples from room surfaces and patients were taken on days 3 and 7 and each week the patient stayed in the same room. The bacterial identity, antibiotic susceptibility, and molecular sequences were compared between organisms found in the environment samples and patient sources.
We enrolled 80 patient–room admissions; 9 of these patients (11.3%) were asymptomatically colonized with MDROs at study entry. Hospital room surfaces were contaminated with MDROs despite terminal disinfection in 44 cases (55%). Microbiological Bacterial Transfer events either to the patient, the environment, or both occurred in 12 patient encounters (18.5%) from the microbiologically evaluable cohort.
Microbiological Bacterial Transfer events between patients and the environment were observed in 18.5% of patient encounters and occurred early in the admission. This study suggests that research on prevention methods beyond the standard practice of room disinfection at the end of a patient’s stay is needed to better prevent acquisition of MDROs through the environment.
We evaluated the ability of high-intensity visible violet light with a peak output of 405 nm to kill epidemiologically important pathogens. The high irradiant light significantly reduced both vegetative bacteria and spores at some time points over a 72-hour exposure period.
In this prospective study, we monitored 4 epidemiologically important pathogens (EIPs): methicillin-resistane Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Clostridium difficile, and multidrug-resistant (MDR) Acinetobacter to assess the effectiveness of 3 enhanced disinfection strategies for terminal room disinfection against standard practice. Our data demonstrated that a decrease in room contamination with EIPs of 94% was associated with a 35% decrease in subsequent patient colonization and/or infection.
We measured the disinfection of MRSA and Clostridium difficile spores using an ultraviolet C (UV-C) device, and we correlated those results to measurements and computer simulations of UV-C surface intensity. The results demonstrate both large differences in UV light intensity across various surfaces and how this leads to significant differences in disinfection.
Our understanding of stellar dynamos has largely been driven by the phenomena we have observed of our own Sun. Yet, as we amass longer-term datasets for an increasing number of stars, it is clear that there is a wide variety of stellar behavior. Here we briefly review observed trends that place key constraints on the fundamental dynamo operation of solar-type stars to fully convective M dwarfs, including: starspot and sunspot patterns, various magnetism-rotation correlations, and mean field flows such as differential rotation and meridional circulation. We also comment on the current insight that simulations of dynamo action and flux emergence lend to our working knowledge of stellar dynamo theory. While the growing landscape of both observations and simulations of stellar magnetic activity work in tandem to decipher dynamo action, there are still many puzzles that we have yet to fully understand.
Empirical data on the use of services due to mental health problems in older adults in Europe is lacking. The objective of this study is to identify factors associated with service utilization in the elderly.
As part of the MentDis_ICF65+ study, N = 3,142 people aged 65–84 living in the community in six European and associated countries were interviewed. Based on Andersen's behavioral model predisposing, enabling, and need factors were analyzed with logistic regression analyses.
Overall, 7% of elderly and 11% of those with a mental disorder had used a service due to mental health problems in the last 12 months. Factors significantly associated with underuse were male sex, lower education, living in the London catchment area, higher functional impairment and more comorbid mental disorders. The most frequently reported barrier to service use was personal beliefs, e.g. “I can deal with my problem on my own” (90%).
Underutilization of mental health services among older people in the European community is common and interventions are needed to achieve an adequate use of services.
Except for dementia and depression, little is known about common mental disorders in elderly people.
To estimate current, 12-month and lifetime prevalence rates of mental disorders in different European and associated countries using a standardised diagnostic interview adapted to measure the cognitive needs of elderly people.
The MentDis_ICF65+ study is based on an age-stratified, random sample of 3142 older men and women (65–84 years) living in selected catchment community areas of participating countries.
One in two individuals had experienced a mental disorder in their lifetime, one in three within the past year and nearly one in four currently had a mental disorder. The most prevalent disorders were anxiety disorders, followed by affective and substance-related disorders.
Compared with previous studies we found substantially higher prevalence rates for most mental disorders. These findings underscore the need for improving diagnostic assessments adapted to the cognitive capacity of elderly people. There is a need to raise awareness of psychosocial problems in elderly people and to deliver high-quality mental health services to these individuals.
Evidence of surface magnetism is now observed on an increasing number of cool stars. The detailed manner by which dynamo-generated magnetic fields giving rise to starspots traverse the convection zone still remains unclear. Some insight into this flux emergence mechanism has been gained by assuming bundles of magnetic field can be represented by idealized thin flux tubes (TFTs). Weber & Browning (2016) have recently investigated how individual flux tubes might evolve in a 0.3M⊙ M dwarf by effectively embedding TFTs in time-dependent flows representative of a fully convective star. We expand upon this work by initiating flux tubes at various depths in the upper ~50-75% of the star in order to sample the differing convective flow pattern and differential rotation across this region. Specifically, we comment on the role of differential rotation and time-varying flows in both the suppression and promotion of the magnetic flux emergence process.
The influence of threading dislocations (TDs) on the dry thermal oxidation of c-plane gallium nitride (GaN) is investigated for oxidation temperatures above 800°C. The transformation of GaN to gallium oxide (Ga2O3) is preferably found at TDs and grain boundaries, showing enhanced vertical oxidation, compared to defect free surface sites. Therefore, the increase in surface roughness commonly obtained upon oxidation is explained by an inhomogeneous chemical reactivity associated with those crystal defects. Additionally, annealing in an N2 atmosphere showed that also decomposition is favored at such chemically reactive spots. Comparison between decomposition and oxidation suggests that at temperatures above 950°C, the Ga2O3 formation is supported by the decomposition of GaN and subsequent oxidation of the metallic gallium.
Carbapenem-resistant Enterobacteriaceae (CRE) only contaminated the environmental surfaces of rooms housing CRE colonized/infected patients infrequently (8.4%) and at low levels (average, 5.1 colony-forming units [CFU]/120 cm2 per contaminated surface). Three species of CRE (Klebsiella, Enterobacter, and Escherichia) survived poorly (>85% die-off in 24 hours) when ~2 log10 CFU were inoculated onto 5 different environmental surfaces.
Adult hospitalized patients with cystic fibrosis commonly receive nebulized medications. For single-patient-use nebulizers that are cleaned after each use, there is infrequent nebulizer contamination (0%–11%) with only low numbers of epidemiologically important pathogens (less than 100 colony-forming units), and this contamination is similar after 24, 48, and 72 hours of use.
Infect Control Hosp Epidemiol 2014;35(12):1553–1546