Inhibition of mitochondrial translation as a therapeutic strategy for human acute myeloid leukemia

To identify FDA-approved agents targeting leukemic cells, we performed a chemical screen on two human leukemic cell lines and identified the antimicrobial tigecycline. A genome-wide screen in yeast identified mitochondrial translation inhibition as the mechanism of tigecycline-mediated lethality. Tigecycline selectively killed leukemia stem and progenitor cells compared to their normal counterparts and also showed antileukemic activity in mouse models of human leukemia. ShRNA-mediated knockdown of EF-Tu mitochondrial translation factor in leukemic cells reproduced the antileukemia activity of tigecycline. These effects were derivative of mitochondrial biogenesis that, together with an increased basal oxygen consumption, proved to be enhanced in AML versus normal hematopoietic cells and were also important for their difference in tigecycline sensitivity.     

Availability of a Flavored Beverage and Impact on Children’s Hydration Status,Sleep, and Mood

Euhydration remains a challenge in children due to lack of access and unpalatability of water and to other reasons. The purpose of this study was to determine if the availability/access to a beverage (Creative Roots^®) influences hydration in children and, therefore, sleep quality and mood. Using a crossover investigation, 46 participants were randomly assigned to a control group (CON) or an intervention group and received Creative Roots^® (INT) for two-week periods. We recorded daily first morning and afternoon urine color (Ucol), thirst perception, and bodyweight of the two groups. Participants reported to the lab once per week and provided first morning urine samples to assess Ucol, urine specific gravity (USG), and urine osmolality (Uosmo). Participants also completed the questionnaires Profile of Mood States-Adolescents (POMS-a) and Pittsburgh Sleep Quality Index (PSQI). Dependent t-tests were used to assess the effects of the intervention on hydration, mood, and sleep quality. Uosmo was greater and Ucol was darker in the control group (mean ± SD) [Uosmo: INT = 828 ± 177 mOsm·kg⁻¹, CON = 879 ± 184 mOsm·kg⁻¹, (p = 0.037], [Ucol:INT = 5 ± 1, CON = 5 ± 1, p = 0.024]. USG, POMS-a, and PSQI were not significant between the groups. At-home daily afternoon Ucol was darker in the control group [INT = 3 ± 1, CON = 3 ± 1, p = 0.022]. Access to Creative Roots^® provides a small, potentially meaningful hydration benefit in children. However, children still demonstrated consistent mild dehydration based on Uosmo, despite consuming the beverage.     

Relationships between resting heart rate,heart rate variability and sleep characteristics among female collegiate cross‐country athletes

Even though sleep has been shown to be influenced by athletes’ training status, the association with resting heart rate and heart rate variability remains unclear. The purpose of this study was to compare the changes in and relationships between resting heart rate, heart rate variability and sleep characteristics across a female collegiate cross‐country season. Ten NCAA Division I collegiate female cross‐country athletes (mean ± SD; age, 19 ± 1 year; height, 167.6 ± 7.6 cm; body mass, 57.7 ± 10.2 kg; VO_2max, 53.3 ± 5.9 ml kg^?1 min^?1) participated in this study. Resting heart rate, heart rate variability and the percentage of time in slow wave sleep were captured using a wrist‐worn multisensor sleep device throughout the 2016 competitive cross‐country season (12 weeks). Linear mixed‐effects models and magnitude‐based inferences were used to assess differences between each week. Pearson product moment correlations were used to investigate relationships between variables. Resting heart rate at the end of the season, specifically during weeks 10–12 (mean ± SE; week 10, 48 ± 2; week 11, 48 ± 3; week 12, 48 ± 3), showed a practically meaningful increase compared to the beginning of the season, weeks 2–4 (week 2, 44 ± 2; week 3, 45 ± 2; week 4, 44 ± 2). Higher resting heart rate (r = 0.55) and lower heart rate variability (r = ?0.62) were largely associated with an increase in percentage of time spent in slow wave sleep. These data suggest that when physiological state was impaired, meaning the physiological restorative demand was higher, the percentage of time in slow wave sleep was increased to ensure recovery. Thus, it is important to implement sleep hygiene strategies to promote adequate slow wave sleep when the body needs physiological restoration.     

Natural Spillover of a Distinctly Canidae-Associated Biotype of Rabies Virus into an Expanded Wildlife Host Range in Southern Africa

Rabies enzootics in southern Africa are associated with two genetically distinct groups of viruses, thought to be adapted to two different sets of host species. The virus groups are referred to as the canid biotype (infecting carnivores of the family Canidae) and the viverrid biotype (infecting carnivores of the subfamily Viverrinae). Cross- or spillover infections of one biotype into the host range of the other are thought to occur from time to time. However, very little is known about this phenomenon and its role in the epidemiology of rabies in southern Africa. We have investigated spillover by monoclonal antibody and nucleic acid sequence analysis of a wide range of virus isolates. Although the inverse had been documented, this report constitutes the first evidence of spillover of canid biotype viruses into viverrid hosts. Our genetic analysis was focused specifically on the G-L intergenic region of the virus genome, thought to be a remnant or pseudogene and it was indicated that, with respect to this region of the genome, spillover does not influence the phylogeny of virus isolates. This revised version was published online in July 2006 with corrections to the Cover Date.     

Neuroactive steroids and suicidality in posttraumatic stress disorder

OBJECTIVE: Recent studies suggest that neuroactive steroids may be altered in posttraumatic stress disorder (PTSD). Since high rates of suicidality accompany PTSD, the authors investigated neuroactive steroid levels and correlations to suicide attempts in veterans with this disorder. METHOD: Male veterans with PTSD enrolled in a larger study during inpatient hospitalization (N=130) were assessed for suicidal ideation or suicide attempt in the last 6 months. Serum levels of dehydroepiandrosterone (DHEA), androstenedione, testosterone, and estradiol were determined. The authors investigated associations between neuroactive steroids and suicidality. RESULTS: High rates of suicidality were observed. Close to 70% of these patients had suicidal thoughts, and 25% had attempted suicide in the last 6 months. Patients who had attempted suicide demonstrated significantly higher median DHEA levels than those who had not attempted suicide (15.6 versus 8.3 ng/ml), an association that persisted after adjustment for age. CONCLUSIONS: These findings suggest that higher DHEA levels may be linked to suicidality in veterans with PTSD and may be associated with the risk of self-harm.     

Mental Health During Pregnancy: A Study Comparing Asian, Caucasian and Native Hawaiian Women

Objective: This study examines perinatal mental health issues, ethnic differences, and comorbidity among pregnant women in Hawaii. Methods: Eighty-four participants were recruited from women, ages 18–35, seeking prenatal care on Oahu. They were interviewed at their initial prenatal visit about substance use, depression, and anxiety. Results: Sixty-one percent of women screened positive for at least one mental health issue. Thirteen percent of all pregnant women reported drinking during pregnancy with 5% reporting problem drinking, 15% reported smoking cigarettes on a regular basis, 5% of pregnant women had probable depression, and 13% of pregnant women had probable anxiety. Significant ethnic differences were found in cigarette smoking, with the highest rate among Native Hawaiian women (35%). Native Hawaiian women were also more likely to binge drink. Conclusion: Given the high rates of potential mental health issues in our sample, our findings highlight the importance of screening and treatment for mental health issues early in pregnancy in Hawaii.