Understanding parents' communication experiences in childhood cancer: a qualitative exploration and model for future research.

PURPOSE: Following their child's cancer diagnosis, parents must rapidly familiarize themselves with cancer-specific information and the health-care setting. Theory-driven research is needed to understand and address parents' difficulties when interacting with health-care professionals (HCPs). We examined parents' health-care experiences during and after the child's cancer treatment. METHODS: We recruited parents of children/adolescents (aged < 18 years) who had recently completed cancer treatment with curative intent from eight Australian hospitals. We conducted in-depth interviews using the psychosocial adjustment to illness scale while recruiting for the "CASCADE" survivorship intervention. We used grounded theory to explore parents' health-care experiences. RESULTS: Fifty-two mothers and six fathers of survivors (mean age at diagnosis = 5.1 years, time since treatment = 1.9 years) participated. Parents' experiences were characterized by (1) positive and negative interactions, (2) attitudes towards health care and HCPs, (3) trust and mistrust in the doctor-parent relationship, and (4) parents' engagement in care. Parents built trust with HCPs, who seemed approachable and personable. Although parents' experience was overall very positive, nearly half of parents reported negative interactions and mistrust. Parents rationalized negative experiences as caused by constraints in the health-care setting. Most parents felt support ended prematurely. We propose a new model accounting for these experiences and identifying potential underlying mechanisms. CONCLUSIONS: Depending on their degree of trust, parents followed recommendations more closely (high trust) or focused on being advocates for their child (low trust). Parents minimized the impact of negative HCP interactions through internal, rationalizing processes. Our findings demonstrate parents' flexibility in acting as a dynamic buffer between HCP-interactions and their child.

Early breast development in overweight girls: does estrogen made by adipose tissue play a role?

BACKGROUND: Girls who are overweight/obese (OB) develop breast tissue but do not undergo menarche (the first menstrual period) significantly earlier than girls of normal weight (NW). It has been proposed that estrogen synthesized by adipose tissue may be contributory, yet OB do not have higher serum estrogen levels than NW matched on breast stage. We hypothesized that estrogen synthesized locally, in mammary fat, may contribute to breast development. This hypothesis would predict that breast development would be more advanced than other estrogen-sensitive tissues as a function of obesity and body fat. METHODS: Eighty premenarchal girls (26 OB, 54 NW), aged 8.2-14.7 years, underwent dual-energy x-ray absorptiometry to calculate percent body fat (%BF), Tanner staging of the breast, breast ultrasound for morphological staging, trans-abdominal pelvic ultrasound, hand x-ray (bone age, BA), a blood test for reproductive hormones, and urine collection to determine the vaginal maturation index (VMI), an index of estrogen exposure in urogenital epithelial cells. RESULTS: When controlling for breast morphological stage determined by ultrasound, %BF was not associated with serum estrogen or gonadotropin (LH and FSH) levels or with indices of systemic estrogen action (uterine volume, endometrial thickness, BA advancement, and VMI). Tanner breast stage did not correlate with breast morphological stage and led to misclassification of chest fatty tissue as breast tissue in some OB. CONCLUSIONS: These studies do not support the hypothesis that estrogen derived from total body fat or local (mammary) fat contributes to breast development in OB girls.

Knowledge of cervical cancer pathology of high school students in San Carlos, Costa Rica.

In Costa Rica, cervical cancer is the second most common female cancer, despite accessibility of screening through the universal health care system. There is little understanding of knowledge levels of the adolescent population on cervical cancer, although this population is the most exposed to risk factors. This study sought to learn about male and female adolescent knowledge of preventative methods, infection acquisition, clinical manifestations and medical services. A total of 533 students from grades 7-12 from five public high schools in the rural San Carlos region participated in the study from March through April 2012. Students were found to lack knowledge, as only 30.8% of students stated that they knew what cervical cancer is. Additionally, a connection was lacking between cervical cancer concepts, as for example 75.2% of students had heard of Human Papiloma Virus, but only 33.9% of those students knew that HPV is related to cervical cancer. Age had a positive relationship with knowledge of main concepts (p < 0.001). More women than men had heard of cervical cancer and the Papanicolaou (p = 0.025, p < 0.0001), but otherwise no significant difference in mean response between genders was found. Students were found to have a limited awareness of the educational cervical cancer campaign (7.7% of the student population) and the ability to go alone to the doctor to receive medical attention (30.6% of students). Additionally, the public education system does not require cervical cancer to be included in the present curriculum. Hence, as students lack education on prevention and risk factors, the majority of prevention responsibility falls only on the universal health care system to regularly perform Papanicolaou exams to detect pre-cancerous or cancerous changes. The findings indicated the importance of including cervical cancer in the sexual education curriculum of the public education system in Costa Rica to educate the at-risk population of preventative methods, infection development, clinical manifestations and medical services in order to lower the presence of cervical cancer.

Facilitated Stories for Change: Digital Storytelling as a Tool for Engagement in Facilitated Discussion for Reduction of Diabetes-Related Health Disparities Among Rural Latino Patients With Diabetes.

INTRODUCTION: Latino populations, particularly those living in rural areas, experience a disproportionately high prevalence and poorer outcomes of type 2 diabetes mellitus (T2DM). The purpose of this study was to test the acceptability and perceived effectiveness of a group-based, facilitated digital storytelling intervention for T2DM self-management among rural Latino patients. METHOD: Twenty Latino adults with T2DM participated in facilitated storytelling discussions at two primary clinics. Participants viewed a 12-minute T2DM self-management digital storytelling intervention, followed by a facilitated group discussion. Surveys, observations, and focus groups were used to assess for acceptability and perceived effectiveness of the intervention through descriptive and qualitative analysis, informed by narrative and social cognitive theory. RESULTS: All participants found the intervention interesting and useful and reported improvement in confidence, motivation, and behavioral intentions for T2DM self-management. Themes mapped closely with narrative theory models, further suggestive of the behavior change potential. DISCUSSION: Facilitated discussions may add value to viewing of digital stories and represent a scalable approach to provide culturally congruent health care for Latino patients with diabetes in rural settings. Within the paradigm of group-based diabetes educational programs, this lends itself well to critical transcultural nursing care.

Longitudinal Investigation of Pubertal Milestones and Hormones as a Function of Body Fat in Girls.

CONTEXT: Epidemiologic studies have demonstrated that overweight/obese girls (OW/OB) undergo thelarche and menarche earlier than normal weight girls (NW). There have been no longitudinal studies to specifically investigate how body weight/fat affects both clinical and biochemical pubertal markers in girls. OBJECTIVE: To investigate the effect of total body fat on reproductive hormones and on the maturation of estrogen-sensitive tissues during puberty in girls. METHODS: Ninety girls (36 OW/OB, 54 NW), aged 8.2 to 14.7 years, completed 2.8 ±â€…1.7 study visits over 4 years. Visits included dual-energy x-ray absorptiometry to calculate total body fat (TBF), Tanner staging, breast ultrasound for morphological staging (BMORPH; A-E), pelvic ultrasound, hormone tests, and assessment of menarchal status. The effect of TBF on pubertal markers was determined using a mixed, multistate, or Cox proportional hazards model, controlling for baseline BMORPH. RESULTS: NW were older than OW/OB (11.3 vs 10.2 years, P < .01) at baseline and had more advanced BMORPH (P < .01). Luteinizing hormone, estradiol, and ovarian and uterine volumes increased with time with no effect of TBF. There was a time × TBF interaction for follicle-stimulating hormone, inhibin B, estrone, total and free testosterone, and androstenedione: Levels were initially similar, but after 1 year, levels increased in girls with higher TBF, plateaued in girls with midrange TBF, and decreased in girls with lower TBF. Girls with higher TBF progressed through BMORPH stage D more slowly but achieved menarche earlier than girls with lower TBF. CONCLUSION: In late puberty, girls with higher TBF demonstrate differences in standard hormonal and clinical markers of puberty. Investigation of the underlying causes and clinical consequences of these differences in girls with higher TBF deserves further study.

Coronary Artery Disease in Young Women After Radiation Therapy for Breast Cancer: The WECARE Study.

BACKGROUND: Radiation therapy (RT) for breast cancer increases risk of coronary artery disease (CAD). Women treated for left- vs right-sided breast cancer receive greater heart radiation exposure, which may further increase this risk. The risk of radiation-associated CAD specifically among younger breast cancer survivors is not well defined. OBJECTIVES: The purpose of this study was to report CAD risk among participants in the Women's Environmental Cancer and Radiation Epidemiology Study. METHODS: A total of 1,583 women who were <55 years of age when diagnosed with breast cancer between 1985 and 2008 completed a cardiovascular health questionnaire. Risk of radiation-associated CAD was evaluated by comparing women treated with left-sided RT with women treated with right-sided RT using multivariable Cox proportional hazards models. Effect modification by treatment and cardiovascular risk factors was examined. RESULTS: In total, 517 women who did not receive RT and 94 women who had a pre-existing cardiovascular disease diagnosis were excluded, leaving 972 women eligible for analysis. Their median follow-up time was 14 years (range 1-29 years). The 27.5-year cumulative incidences of CAD for women receiving left- vs right-sided RT were 10.5% and 5.8%, respectively (P = 0.010). The corresponding HR of CAD for left- vs right-sided RT in the multivariable Cox model was 2.5 (95% CI: 1.3-4.7). There was no statistically significant effect modification by any factor evaluated. CONCLUSIONS: Young women treated with RT for left-sided breast cancer had over twice the risk of CAD compared with women treated with RT for right-sided breast cancer. Laterality of RT is independently associated with an increased risk of CAD and should be considered in survivorship care of younger breast cancer patients.

AMH is Higher Across the Menstrual Cycle in Early Postmenarchal Girls than in Ovulatory Women.

CONTEXT: Adolescents have more small, growing follicles and larger ovaries than normal women and are prone to anovulatory cycles (ANOV). It is unknown if a higher antral follicle count (AFC) per se contributes to ANOV in early postmenarchal girls. OBJECTIVE: To determine the relationship between AMH (an AFC biomarker), other reproductive hormones, and ANOV in postmenarchal girls and to compare AMH in girls and regularly cycling adults. METHODS: A total of 23 girls (1.7 ± 0.2 years postmenarche) and 32 historic adult controls (≤34 years) underwent serial hormone measurements during 1 to 2 menstrual cycles. Girls also had pelvic ultrasounds. AMH was measured 5 times/subject using the Ansh ultrasensitive ELISA. RESULTS: Girls had higher AMH than women (5.2 ± 0.3 vs. 3.3 ± 0.4 ng/mL; P < 0.01) and girls with more ovulatory (OV) cycles tended to have lower AMH than those with ANOV (2 OV 4.5 ± 0.2, 1 OV 5.7 ± 1.1, 0 OV 6.8 ± 1.1 ng/mL; P = 0.1). In girls, AMH correlated with natural-log (ln) transformed LH (r = 0.5, P = 0.01), ln_androstenedione (r = 0.6, P = 0.003), ln_testosterone (r = 0.5, P = 0.02), and ovarian volume (r = 0.7, P < 0.01) but not with FSH, estradiol, P4, or body mass index. In women, AMH correlated with estradiol and P4 (both r = -0.4, P ≤ 0.03) but not with ln_LH or body mass index. CONCLUSIONS: In postmenarchal girls, AMH is higher than in ovulatory women and is associated with LH, androgens, and a propensity for anovulatory cycles. The cause of the transient increase in AMH and AFC during late puberty and the steps underlying the transition to a mature ovary deserve further study.

Development of Ovulatory Menstrual Cycles in Adolescent Girls.

Irregular menstrual cycles due to anovulation are well described in the first few years after menarche, but the normal developmental trajectory from anovulatory to mature ovulatory cycles during adolescence remains undefined. In this article we review the very limited understanding of this final stage of female reproductive axis development and discuss why additional research in this area is critical to the health of women.

Barriers to Cervical Cancer Screening and the Cervical Cancer Care Continuum in Rural Guatemala: A Mixed-Method Analysis.

Purpose Cervical cancer is an important cause of mortality in low- and middle-income countries. Although screening technologies continue to improve, systems of care remain fragmented. It is important to better understand factors that affect use of screening services and loss to follow-up along the care continuum. Methods We conducted a mixed-methods study of a cytology-based screening program in rural Guatemala. A retrospective electronic chart review was performed on data from all patients from 2013 to 2014. We analyzed progression through care and calculated loss-to-follow-up rates. We also analyzed the prior experiences of patients with cervical cancer screening on the basis of self-reported historical data available in the chart review. Structured interviews with a subset of individuals to explore social supports and barriers to screening and engagement in care were conducted at the time of screening. Results The analysis included 515 women (median age, 36 years). Cytologic screening showed concern for neoplastic changes in 0.83%; half resulted in biopsy-proven cervical intraepithelial neoplasia. An additional 9.9% showed severe inflammation. The rate of loss to follow-up was 11.3%. All losses to follow-up occurred for severe inflammation, not for cervical intraepithelial neoplasia. Historical data showed that 73% of the cohort had previously been screened and had high levels of loss to follow-up (57.4%). Qualitative interviews revealed factors that promoted loss to follow-up; these included cost, lack of social supports, transportation, distrust in public facilities, long turn-around times, and failure to return test results or offer follow-up treatments. Conclusions Taken together, these quantitative and qualitative results highlight the need for cervical cancer screening programs in Guatemala to improve uptake of screening services by eligible women and to improve follow-up after a first abnormal screen.

Intermittent treatment with haloperidol or quetiapine does not disrupt motor and cognitive recovery after experimental brain trauma.

Traumatic brain injury (TBI)-induced agitation and aggression pose major obstacles to clinicians in the acute hospital and rehabilitation settings. Thus, management of these symptoms is crucial. Antipsychotic drugs (APDs) are a common treatment approach for alleviating these symptoms. However, previous preclinical TBI studies have indicated that daily and chronic administration of these drugs (e.g., haloperidol; HAL) can exacerbate cognitive and motor deficits. Quetiapine (QUE) is an atypical APD that differs from many typical APDs, such as HAL, in its relatively rapid dissociation from the D2 receptor. The goal of this study was to test the hypotheses that intermittent HAL and QUE would not hinder recovery of cognitive and motor function following TBI and that daily QUE would also not impair functional recovery, which would be in contrast to HAL. Seventy anesthetized male rats received either a controlled cortical impact or sham injury and were then randomly assigned to TBI and sham groups receiving HAL (0.5mg/kg) or QUE (10mg/kg) intraperitoneally once per day or once every other day and compared to each other and vehicle (VEH) controls. Motor function was assessed by beam balance/walk tests on post-operative days 1-5 and cognitive function was evaluated with a Morris water maze task on days 14-19. No differences were revealed among the sham groups in any task, and hence the data were pooled. No overall differences were detected among the TBI groups, regardless of treatment or administration paradigm [p>0.05], but all were impaired vs. SHAM controls [p<0.05]. The SHAM controls also performed significantly better in the cognitive test vs. all TBI groups [p<0.05]. Moreover, the TBI+continuous HAL group performed worse than the TBI+continuous VEH, TBI+continuous QUE, and TBI+intermittent QUE groups [p<0.05], which did not differ from one another. Overall, the data suggest that QUE does not exacerbate TBI-induced cognitive and motor deficits, which supports the hypothesis. QUE may prove useful as an alternative APD treatment for management of agitation and aggression after clinical TBI. HAL may also be safe, but only if used sparingly.

Spontaneous recovery after controlled cortical impact injury is not impeded by intermittent administration of the antipsychotic drug risperidone.

Several preclinical studies have reported that daily administration of the antipsychotic drug (APD) risperidone (RISP) impedes recovery after traumatic brain injury (TBI). However, it is not known whether intermittent dosing would produce similar deleterious effects. The relevance of providing APDs intermittently is that not all patients in rehabilitation require daily treatments to manage TBI-induced agitation. Hence, the goal of the current study was to test the hypothesis that intermittent (vs. daily) administration of RISP would be less disturbing to motor and cognitive recovery after TBI. Anesthetized adult male rats were subjected to either a cortical impact of moderate severity or sham injury and then were randomly assigned to groups receiving intraperitoneal injections of vehicle (VEH; 1.0 mL/kg) or RISP (0.45 mg/kg) 1x, 3x, or 7x per week until the completion of behavioral testing, which consisted of motor and cognitive assessments on post-operative days 1-5 and 14-19, respectively. The group receiving RISP 7x week exhibited greater motor and cognitive impairment compared to those receiving RISP 1x or 3x per week, or VEH [p<0.05]. Moreover, no differences were observed between the intermittent RISP groups vs. VEH [p>0.05], which supports the hypothesis. A potential clinical ramification is that RISP may be safe to manage agitation after TBI, but only when used sparingly.

Albeit nocturnal, rats subjected to traumatic brain injury do not differ in neurobehavioral performance whether tested during the day or night.

Behavioral assessments in rats are overwhelmingly conducted during the day, albeit that is when they are least active. This incongruity may preclude optimal performance. Hence, the goal of this study was to determine if differences in neurobehavior exist in traumatic brain injured (TBI) rats when assessed during the day vs. night. The hypothesis was that the night group would perform better than the day group on all behavioral tasks. Anesthetized adult male rats received either a cortical impact or sham injury and then were randomly assigned to either Day (1:00-3:00p.m.) or Night (7:30-9:30p.m.) testing. Motor function (beam-balance/walk) was conducted on post-operative days 1-5 and cognitive performance (spatial learning) was assessed on days 14-18. Corticosterone (CORT) levels were quantified at 24h and 21days after TBI. No significant differences were revealed between the TBI rats tested during the Day vs. Night for motor or cognition (p's<0.05). CORT levels were higher in the Night-tested TBI and sham groups at 24h (p<0.05), but returned to baseline and were no longer different by day 21 (p>0.05), suggesting an initial, but transient, stress response that did not affect neurobehavioral outcome. These data suggest that the time rats are tested has no noticeable impact on their performance, which does not support the hypothesis. The finding validates the interpretations from numerous studies conducted when rats were tested during the day vs. their natural active period.

The Therapeutic Efficacy of Environmental Enrichment and Methylphenidate Alone and in Combination after Controlled Cortical Impact Injury.

Environmental enrichment (EE) and methylphenidate (MPH) independently confer significant benefit to behavioral recovery after controlled cortical impact (CCI) injury. Given that combinational therapies may be more clinically translatable than monotherapies, the aim of the current study was to test the hypothesis that a combined treatment regimen of EE and MPH would provide greater therapeutic efficacy than either one alone. Anesthetized adult male rats received either a CCI of moderate severity or sham injury and were then randomly assigned to EE or standard (STD) housing where they received either intraperitoneal (ip) MPH (5 mg/kg) or vehicle (VEH; 1.0 mL/kg; ip) beginning 24 h after injury and once daily for 19 days. Motor and cognitive assessments were conducted on post-injury days 1-5 and 14-19, respectively. No differences were observed in sham controls regardless of treatments, and thus their data were pooled. The traumatic brain injury (TBI)+EE+VEH and TBI+EE+MPH groups exhibited enhanced beam balance and beam walk performance relative to the TBI+STD+VEH group (p < 0.05), but did not differ from one another (p > 0.05). No effect of MPH treatment alone was observed in either motor task. In contrast, MPH improved spatial learning and memory when presented alone and also when combined with EE relative to VEH-treated STD controls (p < 0.05). In addition, both EE groups performed significantly better than the TBI+STD+MPH group (p < 0.05), but did not differ from one another (p > 0.05). These data replicate previous findings that both EE and MPH confer cognitive benefits after TBI and extend the findings by revealing that combining EE and MPH does not produce effects greater than either treatment alone, which does not support the hypothesis. The lack of an additive effect may be because of the robustness of the EE.

Abbreviated environmental enrichment confers neurobehavioral, cognitive, and histological benefits in brain-injured female rats.

Environmental enrichment (EE) promotes behavioral recovery after experimental traumatic brain injury (TBI). However, the chronic rehabilitation provided in the laboratory is not analogous to the clinic where physiotherapy is typically limited. Moreover, females make up approximately 40% of the clinical TBI population, yet they are seldom studied in brain trauma. Hence, the goal of this study was to test the hypothesis that abbreviated EE would confer neurobehavioral, cognitive, and histological benefits in brain injured female rats. Anesthetized rats received a cortical impact of moderate-to-severe injury (2.8mm tissue deformation at 4m/s) or sham surgery and then were randomly assigned to groups receiving standard (STD) housing or 4h, 6h, or 24h of EE daily. Motor function (beam-balance/walk and rotarod) was assessed on post-operative days 1-5 and every other day from 1 to 19, respectively. Spatial learning/memory (Morris water maze) was evaluated on days 14-19, and cortical lesion volume was quantified on day 21. No statistical differences were appreciated among the sham controls in any assessment and thus the data were pooled. All EE conditions improved motor function and memory retention, but only 6h and 24h enhanced spatial learning relative to STD (p<0.05). Moreover, EE, regardless of duration reduced cortical lesion volume (p<0.05). These data confirm that abbreviated EE confers robust neurobehavioral, cognitive, and histological benefits in TBI female rats, which supports the hypothesis and strengthens the utility of EE as a pre-clinical model of neurorehabilitation.

Knowledge of cervical cancer pathology of high school students in San Carlos, Costa Rica / Conocimiento sobre cáncer de cérvix entre colegiales de San Carlos, Costa Rica

In Costa Rica, cervical cancer is the second most common female cancer, despite accessibility of screening through the universal health care system. There is little understanding of knowledge levels of the adolescent population on cervical cancer, although this population is the most exposed to risk factors. This study sought to learn about male and female adolescent knowledge of preventative methods, infection acquisition, clinical manifestations and medical services. A total of 533 students from grades 7-12 from five public high schools in the rural San Carlos region participated in the study from March through April 2012. Students were found to lack knowledge, as only 30.8% of students stated that they knew what cervical cancer is. Additionally, a connection was lacking between cervical cancer concepts, as for example 75.2% of students had heard of Human Papiloma Virus, but only 33.9% of those students knew that HPV is related to cervical cancer. Age had a positive relationship with knowledge of main concepts (p≤0.001). More women than men had heard of cervical cancer and the Papanicolaou (p=0.025, p≤0.0001), but otherwise no significant difference in mean response between genders was found. Students were found to have a limited awareness of the educational cervical cancer campaign (7.7% of the student population) and the ability to go alone to the doctor to receive medical attention (30.6% of students). Additionally, the public education system does not require cervical cancer to be included in the present curriculum. Hence, as students lack education on prevention and risk factors, the majority of prevention responsibility falls only on the universal health care system to regularly perform Papanicolaou exams to detect pre-cancerous or cancerous changes. The findings indicated the importance of including cervical cancer in the sexual education curriculum of the public education system in Costa Rica to educate the at-risk population of preventative methods, infection development, clinical manifestations and medical services in order to lower the presence of cervical cancer. Rev. Biol. Trop. 62 (3): 877-886. Epub 2014 September 01.

En Costa Rica, el cáncer de cérvix es el segundo tipo de cáncer femenino más común, a pesar de la accesibilidad del Papanicolaou gracias al sistema de salud universal. No se ha evaluado el nivel de conocimiento de la población adolescente sobre el cáncer de cérvix, aunque este grupo es el más expuesto a los factores de riesgo. Este estudio investigó cuánto sabe el adolescente sobre métodos de prevención, riesgo de infección, manifestaciones clínicas y servicios médicos. En total, 533 estudiantes de séptimo a doceavo año de cinco colegios públicos de la zona rural de San Carlos participaron en esta investigación durante marzo y abril 2012. Se observó que los estudiantes carecen de información, ya que solamente el 30.8% sabían qué es el cáncer de cérvix. Nuestros resultados indican que es importante incluir el cáncer de cérvix en los programas de educación sexual del sistema de educación pública de Costa Rica, para educar a la población en riesgo acerca de los métodos de prevención, desarrollo de la infección y servicios médicos.

Granulocytic differentiation of HL-60 promyelocytic leukemia cells is associated with increased expression of Cul5.

The human HL-60 promyelocytic leukemia cell line has been widely used as a model for studying granulocytic differentiation. All-trans retinoic acid (ATRA) treatment of HL-60 cells promotes granulocytic differentiation and is effective as differentiation therapy for patients with acute promyelocytic leukemia. The identification of genes that are transcriptionally regulated by ATRA has provided insight into granulocytic differentiation and differentiation therapy. The Asb-2 (ankyrin repeat SOCS box 2) gene has previously been identified as a transcriptional target in ATRA-treated HL-60 cells. The ASB-2 protein forms an E3 ubiquitin ligase complex with the proteins, Cul5, regulator of cullin 2 (ROC2), and elongin B and C. The purpose of this study was to determine if there is increased expression of Cul5 during granulocytic differentiation of HL-60 cells. To induce granulocytic differentiation, HL-60 cells were treated for 5 d with ATRA and differentiation was confirmed by examining superoxide anion production, nuclear morphology, and changes in the expression of CD11b, CD13, and CD15. Quantitative real-time RT-PCR was used to measure Cul5 mRNA expression and also the expression of other components of the E3 ubiquitin ligase (ASB-2, ROC2, elongin B and C). Granulocytic differentiation of HL-60 cells was associated with a 1.6-, 1.7-, and 23-fold statistically significant (P

A Stereodivergent Approach for Accessing Both C2,8a-Syn and C2,8a-Anti Relative Stereochemical Manifolds in the Lepadin Family via a TiCL(4)-Promoted Aza-[3 + 3] Annulation.

Details in developing a stereodivergent approach to the lepadin family and establishing an entry to both C2,8a-syn and C2,8a-anti relative stereochemical manifolds through a common intermediate are described here. This works paves a foundation for constructing all members of the lepadin family, which consists of three subsets based on an array of interesting relative configurations. These efforts underline the prominence of aza-[3 + 3] annulation as a unified strategy in alkaloid synthesis.