Therapeutic targeting of EP300/CBP by bromodomain inhibition in hematologic malignancies.

CCS1477 (inobrodib) is a potent, selective EP300/CBP bromodomain inhibitor which induces cell-cycle arrest and differentiation in hematologic malignancy model systems. In myeloid leukemia cells, it promotes rapid eviction of EP300/CBP from an enhancer subset marked by strong MYB occupancy and high H3K27 acetylation, with downregulation of the subordinate oncogenic network and redistribution to sites close to differentiation genes. In myeloma cells, CCS1477 induces eviction of EP300/CBP from FGFR3, the target of the common (4; 14) translocation, with redistribution away from IRF4-occupied sites to TCF3/E2A-occupied sites.

Translating Evidence-based Approaches into optimal Care for individuals at High-risk of ASCVD: Pilot testing of case-based e-learning modules and design of the TEACH-ASCVD study.

Background: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death in the United States. Case-based learning using electronic delivery of the modules can educate clinicians and improve translation of evidence-based guidelines into practice for high-risk ASCVD patients.

Objective: To develop and optimize module design, content, and usability of e-learning modules to teach clinicians evidence-based management in accordance with multi-society guidelines for high-risk ASCVD patients that will be implemented and evaluated in U.

Statin Intolerance: an Overview of US and International Guidance.

Purpose Of Review: To review recent international and domestic definitions, considerations, and treatment algorithms for statin intolerance, and specifically, statin-associated muscle symptoms (SAMS).

Recent Findings: Multiple organizations around the world have produced guidance documents to aid clinicians on managing statin intolerance. A common theme resides among all the guidance documents that most patients can tolerate statins.

General Anesthesia for Pediatric Radiation Therapy in the Era of COVID-19.

Purpose: Managing pediatric patients requiring daily general anesthesia (GA) for radiation therapy (RT) in the setting of COVID-19 is complex, owing to the aerosolizing nature of GA procedures, the risk of cardiopulmonary complications for infected patients, and the treatment of immunocompromised oncology patients in a busy, densely populated radiation oncology clinic.

Methods And Materials: We developed an institutional protocol to define procedures for COVID-19 testing and protection of patients, caregivers, and staff, hypothesizing that this protocol would allow patients requiring GA to be safely treated, minimizing COVID-19 transmission risk to both patients and staff, and at the same time maintaining pre-COVID-19 patient volumes. All patients underwent COVID-19 testing before their first treatment and thrice weekly during treatment.

From the Good Life to Good Living: A Longitudinal Study Investigating the Relationship Between Good-Life Coherence and Motivation, Goal Progress and Subjective Well-Being.

Although considerable research has examined the traits and features involved in living a good life (Baumeister et al. in J Posit Psychol 8(6):505-516, 2013; Ryan et al. in Self-determination theory: Basic psychological needs in motivation, development, and wellness, Guilford Press, 2006; Wong in Can Psychol/Psychol Can 52(2):69-81, 2011), little research has examined personal philosophies of the good life and the motivational outcomes associated with these views.

Integrating primary care into a community mental health center.

Our initiation of a reverse-integration practice model revealed numerous advantages and rewards, as well as many challenges, for which we found solutions.

Interpersonal perception and interpersonal spin.

Introduction: Interpersonal spin is an indicator of intraindividual variability in social behavior. Spin is positively related to Neuroticism and is maladaptive, with well-documented deleterious effects on social functioning. The perceptual processes associated with spin and how spin emerges are less well-understood.

A Visual Analytics Dashboard to Summarize Serial Anesthesia Records in Pediatric Radiation Treatment.

Background: Young children who undergo radiation therapy may require general anesthesia to remain still during weeks of radiation sessions. On a typical day at our hospital, an anesthesia team will care for 10 patients in the radiation therapy suite, and each patient will have multiple prior anesthetic records. Daily review of prior anesthesia records is important to maintain anesthetic consistency and to identify potential improvement, yet our electronic health record (EHR) made such review time-consuming and cumbersome.

Characteristics and Red Flag Correlates of Psychiatric Outpatients in a Mandated-Use Prescription Drug Monitoring Program State: A PBRN Card Study.

Objectives: All 50 states have implemented a Prescription Drug Monitoring Program (PDMP) in efforts to control prescription drug abuse. Many now mandate PDMP checks before clinicians prescribe controlled substances. The aim of this study was to characterize the associations between patient characteristics, red flags found on PDMP reports, and prescriber behavior at community mental health agencies.

Asenapine in the treatment of older adults with bipolar disorder.

Objective: In spite of growing numbers of older people, there are few treatment studies on late-life bipolar disorder (BD). This was a 12-week prospective, open-label trial to assess efficacy and tolerability of adjunct asenapine in non-demented older adults (≥ 60 years) with sub-optimal previous response to BD treatments.

Methods: Asenapine was initiated at 5 mg/day and titrated as tolerated.

Long-lasting effects of maternal condition in free-ranging cervids.

Causes of phenotypic variation are fundamental to evolutionary ecology because they influence the traits acted upon by natural selection. One such cause of phenotypic variation is a maternal effect, which is the influence of the environment experienced by a female (and her corresponding phenotype) on the phenotype of her offspring (independent of the offspring's genotype). While maternal effects are well documented, the longevity and fitness impact of these effects remains unclear because it is difficult to follow free-living individuals through their reproductive lifetimes.

Some gestalt contributions to psychiatry.

Gestalt theory and methods support significant behavioral change and personal growth, yet they have not been widely incorporated into modern psychiatric practice. Challenges to employing Gestalt principles in psychiatric practice exist, such as focus on diagnosis to guide treatment planning, key elements of psychiatric training, primacy of medication management in psychiatric practice, and financial pressures. However, the concepts of the co-created relational field in the here and now, the paradoxical theory of change, the cycle of experience, and the use of experiment are Gestalt concepts and methods that can be effectively applied in the modern practice of clinical psychiatry and psychiatric education.

Usage of the National Board of Medical Examiners Subject Test in Psychiatry by U.S. and Canadian clerkships.

Objective: The authors explored psychiatry clerkship usage of the National Board of Medical Examiners (NBME) Subject Test.

Methods: U.S.

The "shrinking" clerkship: characteristics and length of clerkships in psychiatry undergraduate education.

Objective: The authors explored the time that is currently devoted to psychiatry clerkships to determine whether "shortened" clerkships differ in course director satisfaction and evaluation strategies.

Method: An 18-item questionnaire was sent to 150 U.S.

Standards for Psychiatry Clerkship Directors.

The authors review the literature relevant to the position of Psychiatry Clerkship Director (PCD) and propose standards regarding the expectations for this position. The standards address qualifications, duties, and competencies in the areas of leadership, administration, education, mentoring, and scholarship, as well as the resources of time, administrative assistance, budget, and compensation required to carry out these duties. This paper has been endorsed by the Council of the Association of Directors of Medical Student Education in Psychiatry (ADMSEP), by the American Psychiatric Association's Committee on Medical Student Education, and by the Executive Committee of the American Association of Chairmen of Departments of Psychiatry.

Collectivising the Kulaks? General practitioners and primary care groups in England.

It has previously been suggested that the English Department of Health seems, wittingly or not, to have drawn on the experiences of Stalinist Russia in devising policies for the National Health Service. The development of general practitioner fundholding during the 1990s could be compared to the Soviet support for the Kulaks (rich peasants with capital and entrepreneurship) in 1923. Both initiatives aimed to propel innovation and enhance productivity by giving increased market freedom to an elite group of entrepeneurial workers.

Hepatic angiotensin II nuclear receptors and transcription of growth-related factors.

Objectives: To investigate the influence of angiotensin II (All) receptors in isolated hepatic nuclei on other genes regulated by All and to determine whether the function of these intracellular receptors is influenced by alterations in the endocrine renin system.

Methods: Nuclei were isolated from hepatic tissue of normal and bilaterally nephrectomized or adrenalectomized Wistar rats. Following nuclear run-off, in the presence of varying All concentrations, specific messenger RNAs (mRNA) were determined by slot blot hybridization.

Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y.

Neuropeptide Y (NPY), a 36-amino-acid transmitter distributed throughout the nervous system, is thought to function as a central stimulator of feeding behaviour. NPY has also been implicated in the modulation of mood, cerebrocortical excitability, hypothalamic-pituitary signalling, cardiovascular physiology and sympathetic function. However, the biological significance of NPY has been difficult to establish owing to a lack of pharmacological antagonists.

Nuclear angiotensin receptors induce transcription of renin and angiotensinogen mRNA.

The observation that nuclei from hepatic tissue exhibit specific angiotensin II (Ang II) binding led us to explore whether Ang II modulates mRNA in general, mRNA specific for renin system components, or both. Nuclei from hepatic tissue exhibited a single high-affinity (Kd = 0.4 nmol/L) Ang II-specific binding site, which was associated with increased RNA transcription.

Improved techniques for successful neonatal rat surgery.

Problems encountered in neonatal rat surgery include mortality due to anesthesia and postoperative mortality due to cannibalism or neglect by the dam. We required a method of anesthesia which would enable us to perform complicated, lengthy, recovery eye surgery on day-old rat pups. Because ethical concerns have been raised regarding hypothermia, the currently recommended procedure for anesthesia of newborn rats, we adapted two effective techniques for anesthetizing adult rats for use in neonates.

Characterization of the major 68 kDa heat shock protein in a rat transformed astroglial cell line.

The heat shock response in a transformed astrocyte line was compared with nontransformed astrocytes. The synthesis of HSP 68, the major inducible heat shock protein (HSP 68) was induced by a non-lethal 45 degrees C, 10 min heat shock. Although the incorporation of [35S]methionine into HSP 68 suggested that similar amounts of protein were being synthesized after heat shock, Western immunoblotting demonstrated striking differences in the HSP immunostaining between the two cell types.