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A specific mutation (Arg179) of the ACTA2 gene has previously been described to cause a syndrome of multisystemic smooth muscle dysfunction with an extremely characteristic cerebrovascular appearance.1 Accurate neuroimaging diagnosis of this entity is important as this syndrome predisposes to complications such as early-onset ischemic stroke and ascending thoracic aortic aneurysm.2,3 The following case demonstrates a previously undescribed ACTA2 mutation (Met46) with an identical cerebrovascular imaging appearance to that of Arg179 mutations, but a less severe overall phenotype.
Zn plays an important role in maintaining the anti-oxidant status within the heart and helps to counter the acute redox stress that occurs during myocardial ischaemia and reperfusion. Individuals with low Zn levels are at greater risk of developing an acute myocardial infarction; however, the impact of this on the extent of myocardial injury is unknown. The present study aimed to compare the effects of dietary Zn depletion with in vitro removal of Zn (N,N,N′,N′-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN)) on the outcome of acute myocardial infarction and vascular function. Male Sprague–Dawley rats were fed either a Zn-adequate (35 mg Zn/kg diet) or Zn-deficient (<1 mg Zn/kg diet) diet for 2 weeks before heart isolation. Perfused hearts were subjected to a 30 min ischaemia/2 h reperfusion (I/R) protocol, during which time ventricular arrhythmias were recorded and after which infarct size was measured, along with markers of anti-oxidant status. In separate experiments, hearts were challenged with the Zn chelator TPEN (10 µm) before ischaemia onset. Both dietary and TPEN-induced Zn depletion significantly extended infarct size; dietary Zn depletion was associated with reduced total cardiac glutathione (GSH) levels, while TPEN decreased cardiac superoxide dismutase 1 levels. TPEN, but not dietary Zn depletion, also suppressed ventricular arrhythmias and depressed vascular responses to nitric oxide. These findings demonstrate that both modes of Zn depletion worsen the outcome from I/R but through different mechanisms. Dietary Zn deficiency, resulting in reduced cardiac GSH, is the most appropriate model for determining the role of endogenous Zn in I/R injury.
OBJECTIVES/SPECIFIC AIMS: Hepatitis C virus (HCV) has a high prevalence among individuals in jail and prisons. Access to HCV treatment has been restricted in jails and prisons. We hypothesized that HCV infection in inmates would be associated with increased mortality in people who were hospitalized while incarcerated. METHODS/STUDY POPULATION: We created and then linked a database of people who were incarcerated and admitted at Lemuel Shattuck Hospital (2004, 2008, 2011) to the Massachusetts Vital Statistic Registry (updated through end of 2015). Death was classified using the Automatic Classification of Medical Entry Death Code. The primary outcome of interest was mortality within 1 year of hospitalization, and the secondary outcome was mortality at any time. The primary indicator of interest was HCV, defined as the presence of the ICD-9 code for HCV on discharge. Covariates included in univariate and multivariate modeling included age, year of admission, and race/ethnicity classified as: White, Black, Hispanic or Other (i.e., Asian, Native American, Multi-Racial, or No answer). RESULTS/ANTICIPATED RESULTS: Of the 1,541 hospital admissions, 21% had HCV, and 57% were white, 22% black, 8% Hispanic and 12% other. Of the 273 total deaths (18% of cohort), 82 deaths occurred within 1 year of hospitalization (5.3% of the entire cohort, 30% of all deaths). The primary cause of death was vascular (21%), followed by chronic liver disease (18%), cancer (17%), overdose/suicide/trauma (19%), pulmonary (7%) and infection (6%). People with HCV were more likely to die of chronic liver disease (40% vs 7%, p<0.001). In the multivariable adjusted model, people with HCV were more likely to die within 1 year of hospitalization (HR 1.59, 95% CI 1.02, 2.49) and more likely to die at any time (HR 1.38, 95% CI 1.06, 1.79). Age, race and gender were not associated with risk of death. Compared to 2004, people admitted in 2008 (HR 2.05, 95% CI, 1.50-2.80) and 2011 (HR 4.02, 95% CI 2.77, 5.83) were more likely to die within 1 year. DISCUSSION/SIGNIFICANCE OF IMPACT: Despite advances in HCV treatment in the community, HCV in inmates is associated with increased mortality.
OBJECTIVES/SPECIFIC AIMS: The clinical and translational research workforce is in jeopardy due to investigator attrition and competing demands upon researchers. Resilience and wisdom are measurable traits that can be acquired. The aim of this study was to examine a pilot curricular intervention promoting resilience and wisdom formation in early-career translational researchers. METHODS/STUDY POPULATION: We conducted a prospective, mixed-methods evaluation of a curricular intervention promoting the development of wisdom and resilience among junior faculty in a career development program. Six 90 minute sessions were delivered between September 2017 and January 2018. Pre- and post- resilience and wisdom were measured using the Connor Davidson Resilience Scale and 3D-Wisdom Scale. Individual semi-structured interviews were conducted before and after the intervention RESULTS/ANTICIPATED RESULTS: Five scholars participated. Median resilience and wisdom scores revealed moderate levels of each trait; pre- and post-scores were not significantly different. Four themes emerged from the analysis of interview transcripts: 1. “Success” broadly defined; 2. Adversity threatens success; 3. Community breeds resilience; and 4. Wisdom formation parallels growth towards independence. DISCUSSION/SIGNIFICANCE OF IMPACT: An intervention aimed at developing capacities of resilience and wisdom is feasibly delivered to early career researchers. The relationship between these capacities and the sustainability of a research career warrants additional study.
OBJECTIVES/SPECIFIC AIMS: (1) To evaluate the association of patient and clinical factors with adherence to adjuvant hormone therapy (HT). (2) To examine the association of HT-related symptoms and the extent of remediation with early discontinuation of hormone therapy. METHODS/STUDY POPULATION: Retrospective cohort study of risk factors for interruption and early discontinuation of adjuvant hormone therapy in hormone receptor-positive nonmetastatic breast cancer patients diagnosed between 2009 and 2015. This study will include incident hormone receptor-positive breast cancer patients who initiated their HT and were followed at Tufts MC until Dec 31, 2016. Primary data source is electronic medical records (EMRs) RESULTS/ANTICIPATED RESULTS: The primary outcome of this study is early discontinuation to HT, defined as the first treatment gap of greater than or equal to 180 days following the initiation of HT. Treatment interruption, defined as any patient- or provider-initiated treatment gap of ≥ 2 weeks, will be examined as the secondary endpoint. Any HT-related symptoms occurred during a follow-up interval will be captured and categorized into five major types (i.e., vasomotor, neuropsychological, gastrointestinal, gynecological, and musculoskeletal symptoms). Onset and duration of a HT-related symptom will be recorded. Severity of the symptoms will also be rated by clinical oncologists. Remediations in response to HT- related symptoms will be collected and categorized into to two groups (pharmacological or non-pharmacological) and whether they were patient- or provider-initiated. Response to a remediation is defined as complete relief, partial relied, no relief, or with worsening symptoms. Response to a treatment change (i.e., HT switch or hold) was collected separately but using the same criteria. Analyses will be performed on the association between patient and clinical factors with rates of nonadherence (unplanned treatment interruption and/or early discontinuation) of hormone therapy, respectively. We also will explore whether patients with elevated symptoms and/or incomplete remediation will have earlier discontinuation of hormone therapy. DISCUSSION/SIGNIFICANCE OF IMPACT: Through formal chart review, we will establish a dataset that contains highly detailed information about treatment-emergent symptoms and remediations, which will enable us to quantitatively assess the impact of these treatment factors on adherence to hormone therapy for breast cancer. The in-depth analysis of risk factors associated with nonadherence to hormone therapy will inform development of interventions to improve cancer outcomes.
This study examined effects of risk factors in multiple domains measured in preschool and kindergarten on age 6 depression symptoms, and on changes in symptom levels between ages 4 and 6. Two models were examined in a large, diverse (N = 796) community sample of children and parents. Risk variables included SES, stress, conflict, parental depression, parental hostility, support, scaffolding, child negative affect (NA), effortful control (EC), sensory regulation (SR), and attachment security. Model 1 included effects of risk factors at ages 4 and 5 on child depression symptoms at age 6. Model 2 also included depression symptoms at all three ages to examine changes in these symptoms. Model 1 revealed that age 4 and 5 parental depression, NA, EC, and SR predicted age 6 child depression levels, Several age 4 variables had indirect pathways to age 6 depression via age 5 EC. Model 2 revealed that preschool depression was the only age 4 variable, and EC and SR were the only age 5 variables that significantly predicted increases in age 6 depression. These findings highlight the role of self-regulation in child depression and suggest that targeting self-regulation may be an effective prevention and intervention strategy.
Dignity therapy (DT) is designed to address psychological and existential challenges that terminally ill individuals face. DT guides patients in developing a written legacy project in which they record and share important memories and messages with those they will leave behind. DT has been demonstrated to ease existential concerns for adults with advanced-stage cancer; however, lack of institutional resources limits wide implementation of DT in clinical practice. This study explores qualitative outcomes of an abbreviated, less resource-intensive version of DT among participants with advanced-stage cancer and their legacy project recipients.
Qualitative methods were used to analyze postintervention interviews with 11 participants and their legacy recipients as well as the created legacy projects. Direct content analysis was used to assess feedback from the interviews about benefits, barriers, and recommendations regarding abbreviated DT. The legacy projects were coded for expression of core values.
Findings suggest that abbreviated DT effectively promotes (1) self-expression, (2) connection with loved ones, (3) sense of purpose, and (4) continuity of self. Participants observed that leading the development of their legacy projects promoted independent reflection, autonomy, and opportunities for family interaction when reviewing and discussing the projects. Consistent with traditional DT, participants expressed “family” as the most common core value in their legacy projects. Expression of “autonomy” was also a notable finding.
Significance of results
Abbreviated DT reduces resource barriers to conducting traditional DT while promoting similar benefits for participants and recipients, making it a promising adaptation warranting further research. The importance that patients place on family and autonomy should be honored as much as possible by those caring for adults with advanced-stage cancer.
Advance care planning (ACP) increases quality of life and satisfaction with care for those with cancer and their families, yet these important conversations often do not occur. Barriers include patients’ and families’ emotional responses to cancer, such as anxiety and sadness, which can lead to avoidance of discussing illness-related topics such as ACP. Interventions that address psychological barriers to ACP are needed. The purpose of this study was to explore the effects of a mindfulness intervention designed to cultivate patient and caregiver emotional and relational capacity to respond to the challenges of cancer with greater ease, potentially decreasing psychological barriers to ACP and enhancing ACP engagement.
The Mindfully Optimizing Delivery of End-of-Life (MODEL) Care intervention provided 12 hours of experiential training to two cohorts of six to seven adults with advanced-stage cancer and their family caregivers (n = 13 dyads). Training included mindfulness practices, mindful communication skills development, and information about ACP. Patient and caregiver experiences of the MODEL Care program were assessed using semistructured interviews administered immediately postintervention and open-ended survey questions delivered immediately and at 4 weeks postintervention. Responses were analyzed using qualitative methods.
Four salient themes were identified. Patients and caregivers reported the intervention (1) enhanced adaptive coping practices, (2) lowered emotional reactivity, (3) strengthened relationships, and (4) improved communication, including communication about their disease.
Significance of results
The MODEL Care intervention enhanced patient and caregiver capacity to respond to the emotional challenges that often accompany advanced cancer and decreased patient and caregiver psychological barriers to ACP.
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.
This Companion provides a broad, historically informed introduction to the study of the US constitutional system. In place of the usual laundry lists of cases, doctrines, and theories, it presents a picture of the constitutional system in action, with separate sections devoted to constitutional principles, organizational structures, and the various legal and extra-legal 'actions' through which litigators and average citizens have attempted to bring about constitutional change. Finally, the volume covers a number of subjects that are rarely discussed in works aimed at a general audience, but which are critical to ensuring that constitutional rights are honored in the day-to-day lives of citizens. These include standing and causes of action, suits against officeholders, and the inner workings of the Foreign Intelligence Surveillance Court (FISC). This Companion places present-day constitutional controversies in historical context, and offers insights from a range of disciplines, including history, political science, and law.