Enough

This collection of short stories follows the themes of trauma and the feeling of not being enough for yourself or others. This includes the pressures we put on ourselves to keep trying to be “right” or what we’re “supposed to be”. The idea is apparent that reaching out instead of self- isolating benefits the characters. What also connects these works is a hint of Southern flair, family, and humor. An irreverent voice connects the work and most of the characters. The inclusion of humor to get through suffering and as a way to talk about tough subjects is a concurrent theme. Body issues, sexual trauma, and aging among other themes are all touched upon and delivered with a side of pole dancing, a GoPro on a fat beagle, a night out with Nana’s ashes and more

Hermeneutic approach to understanding the DNP degree: renewing the charisma of nursing as “caring practice”

This systems change project (SCP) began in ―real-time‖ nursing faculty consultation work in the community setting. It was in the midst of what in academic language is considered service scholarship (or the scholarship of engagement) that I began to reconsider what is meant by a ―practice-focused‖ doctorate degree in nursing. How do doctor of nursing practice (DNP) prepared nursing faculty participate in a socially just manner in health care systems changes? More importantly, what moral tenets and knowledge practices shape participation in societal and community life for DNPs? These questions are essential to the development of the DNP role in academic nursing settings, both in the educational curricular preparation of DNP students and in the actuation of the DNP role by nursing graduates who chose academic life. Questions such as these are being voiced by nursing academics across university settings. The answers to these questions surpass educational preparation. On one hand, the answers to these questions lie between the societal and professional impetus for the development of a non-research doctorate. On the other hand, answers to these sorts of questions originate in nursing‘s rich historical ancestry of women‘s caring practices and ways of knowing and being that unify caring practice and community service (i.e., activist, social reformers, healers, teachers). Ultimately, the present and past weave together to create an emerging understanding of DNP caring practice. This project takes a hermeneutic approach to change. My goal was to open up a space to ask philosophical questions about the scholarly nature of doctoral nursing practice. This SCP revealed that DNP studies unfold as a process of self-actualization as DNP students question their assumptions, values, and beliefs, and gain new understandings of nursing theory and philosophy, political, economic, and social discourses. A framework for DNP self-actualization was revealed and a potential model for DNP charism was shaped

Spt5 Cooperates with Human Immunodeficiency Virus Type 1 Tat by Preventing Premature RNA Release at Terminator Sequences

The human immunodeficiency virus type 1 (HIV-1) Tat protein activates transcription elongation by stimulating the Tat-activated kinase (TAK/p-TEFb), a protein kinase composed of CDK9 and its cyclin partner, cyclin T1. CDK9 is able to hyperphosphorylate the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase during elongation. In addition to TAK, the transcription elongation factor Spt5 is required for the efficient activation of transcriptional elongation by Tat. To study the role of Spt5 in HIV transcription in more detail, we have developed a three-stage Tat-dependent transcription assay that permits the isolation of active preinitiation complexes, early-stage elongation complexes, and Tat-activated elongation complexes. Spt5 is recruited in the transcription complex shortly after initiation. After recruitment of Tat during elongation through the transactivation response element RNA, CDK9 is activated and induces hyperphosphorylation of Spt5 in parallel to the hyperphosphorylation of the CTD of RNA polymerase II. However, immunodepletion experiments demonstrate that Spt5 is not required for Tat-dependent activation of the kinase. Chase experiments using the Spt5-depleted extracts demonstrate that Spt5 is not required for early elongation. However, Spt5 plays an important role in late elongation by preventing the premature dissociation of RNA from the transcription complex at terminator sequences and reducing the amount of polymerase pausing at arrest sites, including bent DNA sequences. This novel biochemical function of Spt5 is analogous to the function of NusG, an elongation factor found in Escherichia coli that enhances RNA polymerase stability on templates and shows sequence similarity to Spt5

Loving-kindness meditation for anxiety and mood disorders: a multiple baseline, single-case experimental evaluation

In recent years, kindness-based meditation practices, including loving-kindness meditation (LKM), have gained empirical support for decreasing depression and anxiety symptoms. LKM is defined as the intentional transmission of unselfish kindness toward all beings. It is practiced by contemplating an object of meditation (e.g., self, difficult person) and offering goodwill by silently repeating phrases (e.g., “May you be happy”). Given LKM’s focus on cultivating positive emotional states, researchers have hypothesized that LKM may work by increasing positive affect (PA), promoting cognitive and behavioral flexibility, and reducing negative affect (NA). This study was the first to employ a multiple baseline, single-case design to evaluate the acceptability and clinical efficacy of a brief, individual LKM intervention for individuals (N = 9) with unipolar depressive disorders, social anxiety disorder, or generalized anxiety disorder and low PA. Participants were randomized to a 2-, 4-, or 6-week baseline and completed weekly assessments during baseline, 7 weeks of treatment, and at 1-, 2- and 4-week follow-up. LKM was hypothesized to be acceptable and effective for reducing depression and anxiety symptoms and increasing PA. Secondary hypotheses were that (1) improvements in PA would precede disorder symptom improvement and (2) LKM would lead to improvements in other treatment variables (e.g., NA, anger, mindfulness, affective regulation styles, quality of life, etc.) Results revealed that the study intervention had good feasibility and acceptability. Per visual inspection, LKM led to improvements in principal disorder symptoms for four participants during treatment and five participants at follow-up (three of whom showed clinically reliable change). Contrary to study hypotheses, only one participant demonstrated reliable improvements in PA during treatment. For this participant, increases in PA occurred simultaneously with reductions in depression. Across participants, LKM exerted moderate to large effects on disorder severity, depression and anxiety symptoms, quality of life, mindful nonreactivity, and tolerating affective style. Overall, individuals with principal unipolar depressive disorders showed the strongest response to the study intervention. In summary, this study provided preliminary evidence for the effectiveness of brief, individual LKM for reducing depression and anxiety in a transdiagnostic outpatient sample with low positive affect

The Effect of Syntax Training on "Adequacy" of Communication in Broca's Aphasia: A Social Validation Study

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Spaced Retrieval Teletherapy for persons with chronic TBI

The effects of Spaced Retrieval (SR) training delivered over the phone on the everyday memory problems of subjects with chronic TBI were investigated in an experimental treatment-control group study. Experimental subjects received SR training on 3 goals; their paired control subject received the same total amount of therapy discussing the use a variety of compensatory memory strategies without SR techniques. Results indicate that SR participants achieved 100% goal mastery, 97% goal maintenance and 63% generalization of mastered goals at 1-month follow-up compared to control subjects who reported 36% use of strategies and 26% generalization of strategies at 1-month

RNA polymerase II stalling promotes nucleosome occlusion and pTEFb recruitment to drive immortalization by Epstein-Barr virus

Epstein-Barr virus (EBV) immortalizes resting B-cells and is a key etiologic agent in the development of numerous cancers. The essential EBV-encoded protein EBNA 2 activates the viral C promoter (Cp) producing a message of ~120 kb that is differentially spliced to encode all EBNAs required for immortalization. We have previously shown that EBNA 2-activated transcription is dependent on the activity of the RNA polymerase II (pol II) C-terminal domain (CTD) kinase pTEFb (CDK9/cyclin T1). We now demonstrate that Cp, in contrast to two shorter EBNA 2-activated viral genes (LMP 1 and 2A), displays high levels of promoter-proximally stalled pol II despite being constitutively active. Consistent with pol II stalling, we detect considerable pausing complex (NELF/DSIF) association with Cp. Significantly, we observe substantial Cp-specific pTEFb recruitment that stimulates high-level pol II CTD serine 2 phosphorylation at distal regions (up to +75 kb), promoting elongation. We reveal that Cp-specific pol II accumulation is directed by DNA sequences unfavourable for nucleosome assembly that increase TBP access and pol II recruitment. Stalled pol II then maintains Cp nucleosome depletion. Our data indicate that pTEFb is recruited to Cp by the bromodomain protein Brd4, with polymerase stalling facilitating stable association of pTEFb. The Brd4 inhibitor JQ1 and the pTEFb inhibitors DRB and Flavopiridol significantly reduce Cp, but not LMP1 transcript production indicating that Brd4 and pTEFb are required for Cp transcription. Taken together our data indicate that pol II stalling at Cp promotes transcription of essential immortalizing genes during EBV infection by (i) preventing promoter-proximal nucleosome assembly and ii) necessitating the recruitment of pTEFb thereby maintaining serine 2 CTD phosphorylation at distal regions

Development of the Precision Link Biobank at Boston Children’s Hospital: Challenges and Opportunities

Increasingly, biobanks are being developed to support organized collections of biological specimens and associated clinical information on broadly consented, diverse patient populations. We describe the implementation of a pediatric biobank, comprised of a fully-informed patient cohort linking specimens to phenotypic data derived from electronic health records (EHR). The Biobank was launched after multiple stakeholders’ input and implemented initially in a pilot phase before hospital-wide expansion in 2016. In-person informed consent is obtained from all participants enrolling in the Biobank and provides permission to: (1) access EHR data for research; (2) collect and use residual specimens produced as by-products of routine care; and (3) share de-identified data and specimens outside of the institution. Participants are recruited throughout the hospital, across diverse clinical settings. We have enrolled 4900 patients to date, and 41% of these have an associated blood sample for DNA processing. Current efforts are focused on aligning the Biobank with other ongoing research efforts at our institution and extending our electronic consenting system to support remote enrollment. A number of pediatric-specific challenges and opportunities is reviewed, including the need to re-consent patients when they reach 18 years of age, the ability to enroll family members accompanying patients and alignment with disease-specific research efforts at our institution and other pediatric centers to increase cohort sizes, particularly for rare diseases