Acute myeloid leukemia with mutated NPM1 mimics acute promyelocytic leukemia presentation.

OBJECTIVES: To investigate clinicopathological and molecular features of NPM1-mutated acute myeloid leukemia that presented with infrequent acute promyelocytic leukemia (APL)-like phenotype and clinical presentation. METHODS: Cases with both de novo or secondary Acute Myeloid Leukemia (AML) were retrieved. Data from flow cytometry immunophenotyping, cytogenetics, molecular studies, and clinical presentation were analyzed. RESULTS: Cases presented with abnormal coagulation parameters and low platelets count; four of them showed a DIC index compatible with overt DIC. Two cases showed Auer rods. In all cases, immunophenotypes mimicked APL: blasts expressed CD33, CD13, and cytoplasmic MPO but did not express CD34, HLA-DR, or CD11b. Notably, CD4 expression was observed in all cases. Neither t(15;17) nor PML/RARα gene rearrangement was detected. NPM1 gene mutation was identified in all cases. In four cases, TET2 or IDH2 co-mutations were identified. CONCLUSIONS: Our findings provide additional evidence of association between NPM1-mutated AML with TET2 or IDH2 co-mutations and the APL-like immunophenotype. This AML subset was found to exist in both de novo and secondary AML. High WBC count and blasts with low to moderate side scatter and significant expression of CD4 are observed features that could assist in the differential diagnosis with APL. The occurrence of significant elevated D-dimer levels, or even overt DIC observed at diagnosis in these cases could be relevant for this AML subtype.

Loss of nuclear receptor SHP impairs but does not eliminate negative feedback regulation of bile acid synthesis.

The in vivo role of the nuclear receptor SHP in feedback regulation of bile acid synthesis was examined. Loss of SHP in mice caused abnormal accumulation and increased synthesis of bile acids due to derepression of rate-limiting CYP7A1 and CYP8B1 hydroxylase enzymes in the biosynthetic pathway. Dietary bile acids induced liver damage and restored feedback regulation. A synthetic agonist of the nuclear receptor FXR was not hepatotoxic and had no regulatory effects. Reduction of the bile acid pool with cholestyramine enhanced CYP7A1 and CYP8B1 expression. We conclude that input from three negative regulatory pathways controls bile acid synthesis. One is mediated by SHP, and two are SHP independent and invoked by liver damage and changes in bile acid pool size.

Assessing the critical thinking skills of faculty: What do the findings mean for nursing education?

The purpose of this study was twofold: to determine the critical thinking skills of nurse faculty and to examine the relationship between epistemological position and critical thinking. Most participants reported having no education on critical thinking. Data were collected using the California Critical Thinking Skills Test (CCTST) and the Learning Environment Preferences (LEP). Findings from the CCTST indicated that faculty varied considerably in their ability to think critically; LEP findings suggested that participants had not reached the intellectual level needed for critical thinking. In addition, 12 faculty participated in one-hour telephone interviews in which they described experiences in which students demonstrated critical thinking. Despite a lack of clarity on the definition of critical thinking, faculty described clinical examples where students engaged in analysis, inference, and evaluation. Based on these findings, it is recommended that faculty transfer their ability to engage students in critical thinking in the clinical setting to the classroom setting. Benchmarks can be established based on the ability of faculty to engage in critical thinking.

Suicidal ideation in a United States jail: Demographic and psychiatric correlates.

Suicidal behavior is a significant problem in United States jails. Suicidal ideation (SI) is an established precursor to suicidal behavior in incarcerated populations. No studies to date have examined the prevalence of SI or its correlates in a mixed gender U.S. jail sample. The purpose of the present study was to document rates of SI in a mixed gender jail sample and examine socio-demographic and psychiatric correlates. This study of 511 jail inmates found that approximately 16% of participants reported clinically significant SI upon incarceration. White participants, suicide attempters, and those with a psychiatric diagnosis history endorsed greater SI. Reported SI did not differ by sex and was not correlated with age. Clinically, results indicate that screening for SI in jail samples is necessary to identify high-risk individuals for intervention to prevent suicidal behavior.

Feasibility and Acceptability of an Impact of Crime Group Intervention with Jail Inmates.

The current study evaluated the feasibility and acceptability of a manualized Impact of Crime (IOC) group intervention implemented with male inmates (N = 108) at a county jail. Facilitator adherence to the intervention and participant attendance, homework completion, and feedback were assessed. On average facilitators covered 93.7% of each manual topic. Victim speaker recruitment was a challenge-43.5% of relevant sessions lacked victim speakers. Findings suggested significant participant engagement-67.3% attended at least 75% of sessions and 93.3% of homework assignments were submitted on time. Overall, participants indicated satisfaction with the intervention. Successful strategies, challenges, and potential enhancements are discussed.

Fus1p interacts with components of the Hog1p mitogen-activated protein kinase and Cdc42p morphogenesis signaling pathways to control cell fusion during yeast mating.

Cell fusion in the budding yeast Saccharomyces cerevisiae is a temporally and spatially regulated process that involves degradation of the septum, which is composed of cell wall material, and occurs between conjugating cells within a prezygote, followed by plasma membrane fusion. The plasma membrane protein Fus1p is known to be required for septum degradation during cell fusion, yet its role at the molecular level is not understood. We identified Sho1p, an osmosensor for the HOG MAPK pathway, as a binding partner for Fus1 in a two-hybrid screen. The Sho1p-Fus1p interaction occurs directly and is mediated through the Sho1p-SH3 domain and a proline-rich peptide ligand on the Fus1p COOH-terminal cytoplasmic region. The cell fusion defect associated with fus1Delta mutants is suppressed by a sho1Delta deletion allele, suggesting that Fus1p negatively regulates Sho1p signaling to ensure efficient cell fusion. A two-hybrid matrix containing fusion proteins and pheromone response pathway signaling molecules reveals that Fus1p may participate in a complex network of interactions. In particular, the Fus1p cytoplasmic domain interacts with Chs5p, a protein required for secretion of specialized Chs3p-containing vesicles during bud development, and chs5Delta mutants were defective in cell surface localization of Fus1p. The Fus1p cytoplasmic domain also interacts with the activated GTP-bound form of Cdc42p and the Fus1p-SH3 domain interacts with Bni1p, a yeast formin that participates in cell fusion and controls the assembly of actin cables to polarize secretion in response to Cdc42p signaling. Taken together, our results suggest that Fus1p acts as a scaffold for the assembly of a cell surface complex involved in polarized secretion of septum-degrading enzymes and inhibition of HOG pathway signaling to promote cell fusion.

Reflections on caring narratives: enhancing patterns of knowing.

The purpose of this study was to provide graduate students with the opportunity to enrich their esthetic knowing and acquire the meaning of caring in their practice by reflecting on their caring narratives. Content analysis examining for context, process, and fulfillment was used to analyze 68 caring encounters written by five classes of graduate nursing students over five semesters of course work. This article focuses on the value of reflection in knowing and the fulfillment identified by the students through the reflective process. Student fulfillment included reflecting on the need to care for self, knowing that emotional attachment can be dangerous, recognizing caring as a moral responsibility, attending to caring teaches one about caring, and reflecting on caring encounters engages one in defining caring. It is concluded that graduate nursing students can enhance multiple ways of knowing and their understanding of caring through the process of reflecting on caring encounters.

Analyzing the teaching style of nursing faculty. Does it promote a student-centered or teacher-centered learning environment?

The purposes of this study were to a) describe the predominant teaching style of a group of nursing faculty members, either as teacher centered or student centered, and b) to compare teaching style to the instructional methods the faculty members used in the courses they taught and to their stated philosophies of teaching/learning. Findings indicate that the participants were more teacher centered than student centered; their written philosophies supported the teacher-centered approach. However, evidence that faculty used student-centered language, often in a teacher-centered context, indicates that participants in the study may recognize the need for a student-centered environment but may have difficulty with implementation. Recommendations for faculty members and administrators are offered.

Breastfeeding in chronic illness: the voices of women with fibromyalgia.

PURPOSE: To describe what it is like for women with fibromyalgia (FM) to breastfeed their infants. STUDY DESIGN AND METHODS: Nine women with FM who chose to breastfeed their infants were the sample for this qualitative study. van Manen's phenomenological method of reflection, writing, and rewriting was used to analyze the data collected through in-depth tape-recorded interviews and written stories. RESULTS: All nine women felt that they were not successful in their attempts to breastfeed, and felt frustrated. Themes included (a) muscle soreness, pain, and stiffness made it difficult to breastfeed the baby; (b) fatigue interfered with the breastfeeding process; (c) the need for medication, perceived insufficient milk supply, and sore nipples led to forced unplanned weaning; and (d) being forced to wean the infant when not ready to do so created sadness and a feeling of depression. CLINICAL IMPLICATIONS: Nurses who work with women with FM who choose to breastfeed need to be proactive in providing informational, emotional, and physical support to facilitate a successful breastfeeding experience for these women. Knowing that the pain, muscle soreness, stiffness, and fatigue of FM may affect breastfeeding can direct nurses to help women with FM plan for support after childbirth and learn techniques to control/reduce the muscle pain and stiffness. Nurses are encouraged to refer breastfeeding women with FM to lactation consultants and support groups for encouragement and validation regarding their concerns about breastfeeding. It is important that nurses continue to serve as advocates for breastfeeding women with FM and keep other healthcare providers informed about the issues related to breastfeeding for women with FM.

Caring behaviors of advanced practice nursing students.

The purpose of this project was to provide advanced practice nursing (APN) students with the opportunity to enrich their aesthetic knowing and acquire the meaning of caring in their practice by reflecting on their caring narratives. Students were asked to write about a caring encounter they experienced in their practice. The instructor analyzed and organized that data from each narrative. The instructor shared the data with the students for reflection and discussion. This report focuses on the caring practices of the APN students. Nine themes that embraced physical care, communication, comfort, presence, knowing, acceptance, touch, collaboration, and encouragement were identified. The APN students demonstrated aesthetic knowing as well as other ways of knowing in their caring narratives. Through reflection on the caring experiences and discussion in class, students were able to identify the meaning of caring in their practice.

Caring for the patient with fibromyalgia: the rehabilitation nurse's role.

Fibromyalgia (FM) is a chronic, potentially disabling, cluster of symptoms that manifests as pain for 3 months or more and pain with pressure on 11 of 18 tender points throughout the body. Because there is no known cause, and therefore, no cure, treatment focuses on the control or relief of symptoms. Many patients are referred to rehabilitation settings for physical or exercise therapy. While exercise is helpful in the control of the pain, stiffness, fatigue, sleep disorders, and mood changes, a holistic approach to treatment is more effective. Rehabilitation nurses provide major support for patients with FM. Validation of the patients' experiences is essential for achieving quality of life. Many patients have a history of being undertreated because of a lack of credibility and invisibility of the illness. This article provides background information about FM, summarizes the FM trajectory, reviews approaches to management, and discusses the role of rehabilitation nurses in a holistic approach to care of clients with FM.

Social support and positive events as suicide resiliency factors: examination of synergistic buffering effects.

This study examines the role of social support and positive events as protective factors in suicide. Participants (n = 379) were administered measures of social support, life events, depressive symptoms, and suicide ideation. Results indicated that (1) social support had a direct protective effect on suicide ideation, (2) social support and positive events acted as individual buffers in the relationship between negative events and suicide ideation, and (3) social support and positive events synergistically buffered the relationship between negative events and suicide ideation. Our results provide evidence that positive events and social support act as protective factors against suicide individually and synergistically when they co-occur.

The brief self-control scale predicts jail inmates' recidivism, substance dependence, and post-release adjustment.

Previous research finds that self-control is positively associated with adaptive and negatively associated with maladaptive behavior. However, most previous studies use cross-sectional designs, low-risk samples, and limited assessments of self-control. This study of 553 jail inmates examined the relationship of a valid measure of self-control (Brief Self-Control Scale) completed on incarceration with behavior before, during, and 1 year after incarceration. After controlling for positive impression management (PIM), self-control was negatively related to substance misuse, suicidality, risky sex, and criminal history prior to incarceration and post-release illegal substance misuse, recidivism, and positive adjustment. Lower self-control predicted increases in substance dependence at post-release compared with pre-incarceration. Self-control was not related to misbehavior during incarceration, nor alcohol use or HIV-risk behavior 1 year post-release. Results were consistent as a function of age, race, and gender. This study supports self-control as an important risk and protective factor in a sample of criminal offenders.

PTSD and marital satisfaction in military service members: examining the simultaneous roles of childhood sexual abuse and combat exposure.

Childhood sexual abuse (CSA) is relatively common and is associated with a multitude of negative outcomes in adulthood, including posttraumatic stress disorder (PTSD) and lower marital satisfaction. However, CSA has been understudied in military samples. The purpose of the present study was to examine the relative contributions of CSA and combat exposure to PTSD and marital satisfaction. Two hundred eighteen National Guard/Reserve veterans who deployed overseas between 2001 and 2008 completed self-report measures of CSA, marital satisfaction, combat exposure, and PTSD symptom severity. Data were analyzed using linear regression and path analysis to evaluate a comprehensive model including all variables. CSA accounted for unique variance in PTSD symptom severity independent of combat exposure. CSA also had a negative direct association with marital satisfaction, independent of combat exposure and PTSD symptom severity. In contrast, combat exposure had only a negative indirect association with marital satisfaction via PTSD when all variables were examined simultaneously. CSA accounted for unique variance in both PTSD symptom severity and marital satisfaction in this sample of combat veterans. Clinically, results suggest that assessment and treatment of CSA is indicated for military veterans suffering from PTSD. Further, treatment of CSA may improve marital satisfaction, which may positively affect psychological functioning in the veteran.

The role of impulsivity in the relationship between anxiety and suicidal ideation.

BACKGROUND: The purpose of the present study was to examine the degree to which trait and cognitive (looming cognitive style) measures of anxiety are associated with suicidal ideation (SI), as well as whether trait and cognitive (time misperception) measures of impulsivity moderate the association between these variables. METHODS: The sample included 100 undergraduate students (72% female) who completed the Spielberger State-Trait Anxiety Inventory, Looming Maladaptive Style Questionnaire, Barratt Impulsiveness Scale, Time Paradigm Version 1.0 Task, Beck Scale for Suicidal Ideation, and the Brief Symptom Inventory. RESULTS: Trait anxiety and looming cognitive style were found to be positively associated with SI. Further, both trait impulsivity and time misperception moderated the association between these variables and SI, but in a different manner. Consistent with study hypotheses, among those high in trait anxiety, greater overestimation of time was associated with a higher likelihood of SI. Contrary to study hypotheses, among those low in trait anxiety, high trait impulsivity was associated with a greater likelihood of SI. The same pattern of results was found when looming cognitive style served as the independent variable. LIMITATIONS: The use of a cross-sectional design limits the ability to determine the temporal relationship of the study variables. Further, the sample included predominantly Caucasian undergraduates and thus study results may not generalize to other populations. CONCLUSIONS: Clinically, results suggest that high trait anxiety, looming cognitive style, time misperception, and trait impulsivity may be important risk factors for SI among college students and thus should be assessed when students present for treatment. Treatments that focus on problem solving, cognitive restructuring, and affect regulation strategies may help decrease anxiety and impulsivity, which in turn may help reduce the likelihood of suicidal thoughts.

The moderating role of social support on the relationship between impulsivity and suicide risk.

BACKGROUND: Suicide is the second leading cause of death among college students. There has been considerable research into risk factors for suicide, such as impulsivity, but considerably less research on protective factors. AIMS: The present study examines the role that social support plays in the relationship between impulsivity and suicide risk. METHODS: Participants were 169 undergraduates who completed self-report measures of impulsivity and social support. Suicide risk was assessed using an interview measure. RESULTS: Social support moderates the relationship between impulsivity and suicide risk, such that those who are highly impulsive are less likely to be at risk for suicide if they also have high levels of social support. CONCLUSIONS: Social support can be a useful buffer to suicide risk for at-risk individuals who are highly impulsive.

SEP-225289 serotonin and dopamine transporter occupancy: a PET study.

UNLABELLED: SEP-225289 is a novel compound that, based on in vitro potencies for transporter function, potentially inhibits reuptake at dopamine, norepinephrine, and serotonin transporters. An open-label PET study was conducted during the development of SEP-225289 to investigate its dopamine and serotonin transporter occupancy. METHODS: Different single doses of SEP-225289 were administered to healthy volunteers in 3 cohorts: 8 mg (n = 7), 12 mg (n = 5), and 16 mg (n = 7). PET was performed before and approximately 24 h after oral administration of SEP-225289, to assess occupancy at trough levels. Dopamine and serotonin transporter occupancies were estimated from PET using (11)C-N-(3-iodoprop-2E-enyl)-2ß-carbomethoxy-3ß-(4-methylphenyl)nortropane ((11)C-PE2I) and (11)C-N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine ((11)C-DASB), respectively. Plasma concentration of SEP-225289 was assessed before ligand injection, and subjects were monitored for adverse events. RESULTS: Average dopamine and serotonin transporter occupancies increased with increasing doses of SEP-225289. Mean dopamine and serotonin transporter occupancies were 33% ± 11% and 2% ± 13%, respectively, for 8 mg; 44% ± 4% and 9% ± 10%, respectively, for 12 mg; and 49% ± 7% and 14% ± 15%, respectively, for 16 mg. On the basis of the relationship between occupancy and plasma concentration, dopamine transporter IC(50) (the plasma concentration of drug at 50% occupancy) was determined (4.5 ng/mL) and maximum dopamine transporter occupancy was extrapolated (85%); however, low serotonin transporter occupancy prevented similar serotonin transporter calculations. No serious adverse events were reported. CONCLUSION: At the doses evaluated, occupancy of the dopamine transporter was significantly higher than that of the serotonin transporter, despite similar in vitro potencies, confirming that, in addition to in vitro assays, PET occupancy studies can be instrumental to the drug development process by informing early decisions about indication, dose, and therapeutic potential.