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Electroconvulsive therapy (ECT) is the most acutely effective treatment for severe treatment-resistant depression. However, there are concerns about its cognitive side-effects and we cannot yet confidently predict who will experience these. Telomeres are DNA-protein complexes that maintain genomic integrity. In somatic cells, telomeres shorten with each cell division. Telomere length (TL) can thus provide a measure of ‘biological’ aging. TL appears to be reduced in depression, though results are mixed. We sought to test the following hypotheses: (1) that TL would be shorter in patients with depression compared to controls; (2) that TL would be a predictor of response to ECT; and (3) that shorter TL would predict cognitive side-effects following ECT.
We assessed TL in whole blood DNA collected from severely depressed patients (n = 100) recruited as part of the EFFECT-Dep Trial and healthy controls (n = 80) using quantitative real-time polymerase chain reaction. Mood and selected cognitive measures, including global cognition, re-orientation time, and autobiographical memory, were obtained pre-/post-ECT and from controls.
Our results indicate that TL does not differ between patients with depression compared to controls. TL itself was not associated with mood ratings and did not predict the therapeutic response to ECT. Furthermore, shorter baseline TL is not a predictor of cognitive side-effects post-ECT.
Overall, TL assessed by PCR does not represent a useful biomarker for predicting the therapeutic outcomes or risk for selected cognitive deficits following ECT.
OBJECTIVES/SPECIFIC AIMS: Scholars and faculty in the Clinical and Translational Science (CTS) track of our institution’s biomedical science graduate school reported a lack of satisfaction with our learning management system (LMS); specifically, they reported frustration with the amount of time spent locating learning assignment guidelines, course readings, and submission portals. As a result, we created a new master template to address their concerns. METHODS/STUDY POPULATION: A new template was created within the LMS based on scholar and faculty feedback. Surveys and other tools have been used to determine student and faculty satisfaction as well as measure secondary outcomes of time spent in the online learning space. Some key changes include a redesigned menu and submission portal. RESULTS/ANTICIPATED RESULTS: There was an increase in satisfaction with the new LMS template. Next steps include systematically rolling out the new template, with continued solicitation of feedback from all stakeholders. All courses in the CTS track will be converted to the new template by summer quarter 2020. DISCUSSION/SIGNIFICANCE OF IMPACT: The strengths of this project include the multidisciplinary team-based approach to improving course satisfaction and usability, as well as the use of innovative technologies. Additionally, the analytical capabilities of the LMS will be maximized in the new template, which was a shortcoming of the previously available template.
The transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator (PGC-1α), termed the ‘master regulator of mitochondrial biogenesis’, has been implicated in stress and resilience to stress-induced depressive-like behaviours in animal models. However, there has been no study conducted to date to examine PGC-1α levels in patients with depression or in response to antidepressant treatment. Our aim was to assess PGC-1α mRNA levels in blood from healthy controls and patients with depression pre-/post-electroconvulsive therapy (ECT), and to examine the relationship between blood PGC-1α mRNA levels and clinical symptoms and outcomes with ECT.
Whole blood PGC-1α mRNA levels were analysed in samples from 67 patients with a major depressive episode and 70 healthy controls, and in patient samples following a course of ECT using quantitative real-time polymerase chain reaction (qRT-PCR). Exploratory subgroup correlational analyses were carried out to determine the relationship between PGC-1α and mood scores.
PGC-1α levels were lower in patients with depression compared with healthy controls (p = 0.03). This lower level was predominantly accounted for by patients with psychotic unipolar depression (p = 0.004). ECT did not alter PGC-1α levels in the depressed group as a whole, though exploratory analyses revealed a significant increase in PGC-1α in patients with psychotic unipolar depression post-ECT (p = 0.045). We found no relationship between PGC-1α mRNA levels and depression severity or the clinical response to ECT.
PGC-1α may represent a novel therapeutic target for the treatment of depression, and be a common link between various pathophysiological processes implicated in depression.
Children with CHD and acquired heart disease have unique, high-risk physiology. They may have a higher risk of adverse tracheal-intubation-associated events, as compared with children with non-cardiac disease.
Materials and methods
We sought to evaluate the occurrence of adverse tracheal-intubation-associated events in children with cardiac disease compared to children with non-cardiac disease. A retrospective analysis of tracheal intubations from 38 international paediatric ICUs was performed using the National Emergency Airway Registry for Children (NEAR4KIDS) quality improvement registry. The primary outcome was the occurrence of any tracheal-intubation-associated event. Secondary outcomes included the occurrence of severe tracheal-intubation-associated events, multiple intubation attempts, and oxygen desaturation.
A total of 8851 intubations were reported between July, 2012 and March, 2016. Cardiac patients were younger, more likely to have haemodynamic instability, and less likely to have respiratory failure as an indication. The overall frequency of tracheal-intubation-associated events was not different (cardiac: 17% versus non-cardiac: 16%, p=0.13), nor was the rate of severe tracheal-intubation-associated events (cardiac: 7% versus non-cardiac: 6%, p=0.11). Tracheal-intubation-associated cardiac arrest occurred more often in cardiac patients (2.80 versus 1.28%; p<0.001), even after adjusting for patient and provider differences (adjusted odds ratio 1.79; p=0.03). Multiple intubation attempts occurred less often in cardiac patients (p=0.04), and oxygen desaturations occurred more often, even after excluding patients with cyanotic heart disease.
The overall incidence of adverse tracheal-intubation-associated events in cardiac patients was not different from that in non-cardiac patients. However, the presence of a cardiac diagnosis was associated with a higher occurrence of both tracheal-intubation-associated cardiac arrest and oxygen desaturation.
Extremely low birth weight (ELBW; <1000 g) infants have been exposed to stressful intrauterine and early postnatal environments. Even greater early adversity has been experienced by ELBW survivors who were also born small for gestational age (SGA; <10th percentile for GA) compared to those born appropriate for GA (AGA). ELBW survivors, particularly those born SGA, face increased risk for internalizing problems compared to normal BW (NBW; ≥2500 g) controls. Internalizing problems are related to allelic variations in the promoter region of the serotonin transporter linked polymorphic region gene (5-HTTLPR). We followed the oldest longitudinal cohort of ELBW survivors to adulthood. Participants provided buccal cells and reported on internalizing problems, using the Young Adult Self-Report when they were in their mid-20s (ELBW/SGA, N = 28; ELBW/AGA, N = 60; NBW, N = 81) and mid-30s (ELBW/SGA, N = 27; ELBW/AGA, N = 58; NBW, N = 76). The findings indicate that ELBW/SGAs carrying the 5-HTTLPR short allele reported increased internalizing problems, particularly depression, during the third and fourth decades of life. This is the first known report on gene–environment interactions predicting psychopathology among ELBW survivors. Our findings elucidate putative neurobiological pathways that underlie risk for psychopathology.
There are conflicting data on the role of anxiety in predicting mortality.
To evaluate the 10-year mortality risk associated with anxiety in community-dwelling elderly people.
Using data from 718 men and 1046 women aged 65 years and over, gender-stratified associations of anxiety symptoms (Spielberger State–Trait Anxiety Inventory, third tertile) and current DSM-IV anxiety disorder including generalised anxiety disorder (GAD) and phobia with all-cause and cardiovascular mortality were determined.
In women, mortality risk was increased for anxiety disorder and GAD in multivariate Cox models (hazard ratio (HR) = 1.53, 95% Cl 1.02-2.27 and HR = 2.04, 95% Cl 1.08-3.86 respectively), whereas for phobia it was nearly significant (HR= 1.52, 95% Cl 0.94-2.47). Anxiety trait symptoms became non-significant as a result of the confounding effect of depressive symptoms. Anxiety disorder was associated with cardiovascular mortality in univariate analysis (HR = 2.42, 95% Cl 1.16-5.07). No significant associations were found in men.
Our study suggests a gender-specific association of anxiety and mortality.
The diagnosis of smear-positive pulmonary tuberculosis in a medical officer working in a metropolitan Australian neonatal intensive care unit led to a contact investigation involving 125 neonates, 165 relatives, and 122 healthcare workers with varying degrees of exposure. There was no evidence of nosocomial tuberculosis transmission from the index case.
Evidence suggests a role for oestrogen in depression but the involvement
of oestrogen receptor polymorphisms remains unknown.
To determine the association between oestrogen receptor polymorphisms and
late-life depression and the modifying effect of hormone treatment.
Depression was assessed using the Mini-International Neuropsychiatric
Interview, according to DSM-IV criteria and the Centre for Epidemiologic
Studies – Depression Scale. The association between oestrogen receptor α
and β (ER-α and ER-β) polymorphisms with severe depression was examined
in 6017 community-dwelling elderly people using multivariate logistic
In women, the ER-α rs2234693 and rs9340799 polymorphisms were
significantly associated with the risk of late-life depression. The
A allele of ER-β rs1256049 increased the risk of
depression, but only for non-current users of hormone treatment. In men,
only the ER-β rs4986938 polymorphism showed a weak association with
Oestrogen receptor polymorphisms are associated with severe late-life
depression risk in women only.
The general population has been involved in considerable debate about communication and awareness within the context of death and dying. However, there has been little research on how matters of communication on this topic are handled for people with life-limiting illness and intellectual disabilities. This qualitative study explored how staff managed communication about death and dying with people with intellectual disabilities in a Health Service Executive area in Ireland.
Ninety-one individuals took part in 16 focus groups. Interviews were analysed using framework analysis.
Participants infrequently discussed death and dying with people with intellectual disabilities. Participants operated most commonly in suspicious awareness environments with people with mild-to-moderate intellectual disabilities, and closed awareness environments with people with severe intellectual disabilities. The majority of participants did not hold absolute opinions that talking about illness, death, and dying with people with intellectual disabilities was “wrong.” Rather, they were concerned that their lack of skill and experience in the area would cause harm if they engaged in open conversations. Relatives had an influential role on the process of communication. Participants were strongly motivated to provide quality care and were willing to consider alternative approaches to communication if this would benefit people with intellectual disabilities.
Significance of results:
Although there has been a shift toward conditional open awareness of death and dying in Western society, people with intellectual disabilities have not been afforded the same opportunity to engage in open discussion of their mortality. This study points to the urgent need to engage in debate about this issue in order to ensure that people with intellectual disabilities receive high quality palliative care toward the end of life.
The effect of the dietary n-3 long-chain PUFA, DHA (22 : 6n-3), on the growth of pre-term infants is controversial. We tested the effect of higher-dose DHA (approximately 1 % dietary fatty acids) on the growth of pre-term infants to 18 months corrected age compared with standard feeding practice (0·2–0·3 % DHA) in a randomised controlled trial. Infants born < 33 weeks gestation (n 657) were randomly allocated to receive breast milk and/or formula with higher DHA or standard DHA according to a concealed schedule stratified for sex and birth-weight ( < 1250 and ≥ 1250 g). The dietary arachidonic acid content of both diets was constant at approximately 0·4 % total fatty acids. The intervention was from day 2 to 5 of life until the infant's expected date of delivery (EDD). Growth was assessed at EDD, and at 4, 12 and 18 months corrected age. There was no effect of higher DHA on weight or head circumference at any age, but infants fed higher DHA were 0·7 cm (95 % CI 0·1, 1·4 cm; P = 0·02) longer at 18 months corrected age. There was an interaction effect between treatment and birth weight strata for weight (P = 0·01) and length (P = 0·04). Higher DHA resulted in increased length in infants born weighing ≥ 1250 g at 4 months corrected age and in both weight and length at 12 and 18 months corrected age. Our data show that DHA up to 1 % total dietary fatty acids does not adversely affect growth.
Microbatteries and integrated microbattery systems are likely to be the sole power source or a power-source component for the next generation of microelectronic devices. As part of the LEAPS (Laser Engineering of Advanced Power Sources) program, custom-designed microbatteries and ultracapacitors will be integrated in microelectronic circuits for optimum performance. The Naval Research Laboratory's Matrix-Assisted Pulsed-Laser Deposition Direct-Write (MAPLE DW) process is used to rapidly fabricate various primary and secondary (non-rechargeable and chargeable) electrochemical power sources. This laser forward-transfer process can be used to transfer any type of battery material and battery material mixtures, including polymers, hydrated oxides, metals, and corrosive electrolytes. Additional laser micromachining capabilities are used to tailor the battery sizes, interfaces, and configurations. Examples are given for planar RuO2 ultracapacitors and stacked alkaline batteries.
We are using a laser engineering approach to develop and optimize hydrous ruthenium dioxide (RuOxHy or RuO2·0.5 H2O) pseudocapacitors. We employ a novel laser forward transfer process, Matrix Assisted Pulsed Laser Evaporation Direct Write (MAPLE-DW), in combination with UV laser machining, to fabricate mesoscale pseudocapacitors and microbatteries under ambient temperature and atmospheric conditions. Thin films with the desired high surface area morphology are obtained without compromising their electrochemical performance. The highest capacitance structures are achieved by depositing mixtures of sulfuric acid with the RuO2·0.5 H2O electrode material. Our pseudocapacitors exhibit linear discharge behavior and their properties scale proportionately when assembled in parallel and series configurations.