Mindfulness meditation training alters stress-related amygdala resting state functional connectivity: a randomized controlled trial

Recent studies indicate that mindfulness meditation training interventions reduce stress and improve stress-related health outcomes, but the neural pathways for these effects are unknown. The present research evaluates whether mindfulness meditation training alters resting state functional connectivity (rsFC) of the amygdala, a region known to coordinate stress processing and physiological stress responses. We show in an initial discovery study that higher perceived stress over the past month is associated with greater bilateral amygdala-subgenual anterior cingulate cortex (sgACC) rsFC in a sample of community adults (n = 130). A follow-up, single-blind randomized controlled trial shows that a 3-day intensive mindfulness meditation training intervention (relative to a well-matched 3-day relaxation training intervention without a mindfulness component) reduced right amygdala-sgACC rsFC in a sample of stressed unemployed community adults (n = 35). Although stress may increase amygdala-sgACC rsFC, brief training in mindfulness meditation could reverse these effects. This work provides an initial indication that mindfulness meditation training promotes functional neuroplastic changes, suggesting an amygdala-sgACC pathway for stress reduction effects.     

Variation in estrogen-related genes associated with cardiovascular phenotypes and circulating estradiol, testosterone, and dehydroepiandrosterone sulfate levels

BACKGROUND: Younger age at the onset of menopause and lower circulating levels of estrogen are risk factors for cardiovascular disease. Several studies have detected associations between variations in genes encoding estrogen receptors alpha (ESR1) and beta (ESR2), and enzyme aromatase (CYP19A1), which regulates the estrogen to testosterone ratio, and cardiovascular phenotypes in the Framingham Heart Study. To explore potential mechanisms by which these gene variants may contribute to cardiovascular disease, we tested the hypothesis that the polymorphisms were associated with endogenous steroid hormone levels. METHODS: Multiple regression analysis was used to assess the relation between reported polymorphisms and total serum estradiol, testosterone, and dehydroepiandrosterone sulfate levels in 834 men and 687 women who attended the third and fourth Framingham Heart Study examination cycles. RESULTS: In men, significant associations were detected between CYP19A1 polymorphisms and estradiol and testosterone levels, and the estradiol to testosterone ratio (P ranges 0.0005-0.01). Specifically, carriers of common haplotype rs700518[G]-(TTTA)(n) [L]-rs726547[C] had higher estradiol levels (5% per copy; P = 0.0004), lower testosterone levels (17% per copy; P = 0.036), and a higher estradiol to testosterone ratio (24% per copy; P < 0.0001) compared with the rs700518[A]-(TTTA)(n) [S]-rs726547[C] carriers. In addition, postmenopausal carriers of the ESR2 (CA)(n) long allele and rs1256031 [C] allele had moderately higher estradiol levels (P < or = 0.03). No significant associations with the ESR1 variants were detected. CONCLUSIONS: Our findings suggest that variations in CYP19A1 correlate with steroid hormone levels in men. Knowledge that a specific carrier status may predispose to altered steroid hormone levels may lead to targeted intervention strategies to reduce health risks in genetically susceptible individuals.     

Problematic Alcohol Use Among Individuals with HIV: Relations with Everyday Memory Functioning and HIV Symptom Severity

Problematic alcohol use has been shown to negatively impact cognitive functions germane to achieving optimal HIV health outcomes. The present study, a secondary data analysis, examined the impact of problematic alcohol use on aspects of everyday memory functioning in a sample of 172 HIV-infected individuals (22 % female; M _age = 48.37 years, SD = 8.64; 39 % Black/non-Hispanic). Additionally, we tested whether self-reported memory functioning explained the relation between problematic alcohol use and HIV symptom severity. Results indicated that problematic patterns of alcohol use were associated with lower total memory functioning, retrieval (e.g., recall-difficulty) and memory for activity (e.g., what you did yesterday) and greater HIV symptom severity. Memory functioning mediated the relation between problematic alcohol use and HIV symptom severity. However, the direction of this relation was unclear as HIV symptom severity also mediated the relation between problematic alcohol use and memory functioning. Findings highlight the importance of integrated care for HIV and alcohol use disorders and suggest that routine alcohol and cognitive screenings may bolster health outcomes among this vulnerable population.     

Rac2-MRC-cIII-generated ROS cause genomic instability in chronic myeloid leukemia stem cells and primitive progenitors

Chronic myeloid leukemia in chronic phase (CML-CP) is induced by BCR-ABL1 oncogenic tyrosine kinase. Tyrosine kinase inhibitors eliminate the bulk of CML-CP cells, but fail to eradicate leukemia stem cells (LSCs) and leukemia progenitor cells (LPCs) displaying innate and acquired resistance, respectively. These cells may accumulate genomic instability, leading to disease relapse and/or malignant progression to a fatal blast phase. In the present study, we show that Rac2 GTPase alters mitochondrial membrane potential and electron flow through the mitochondrial respiratory chain complex III (MRC-cIII), thereby generating high levels of reactive oxygen species (ROS) in CML-CP LSCs and primitive LPCs. MRC-cIII-generated ROS promote oxidative DNA damage to trigger genomic instability, resulting in an accumulation of chromosomal aberrations and tyrosine kinase inhibitor-resistant BCR-ABL1 mutants. JAK2(V617F) and FLT3(ITD)-positive polycythemia vera cells and acute myeloid leukemia cells also produce ROS via MRC-cIII. In the present study, inhibition of Rac2 by genetic deletion or a small-molecule inhibitor and down-regulation of mitochondrial ROS by disruption of MRC-cIII, expression of mitochondria-targeted catalase, or addition of ROS-scavenging mitochondria-targeted peptide aptamer reduced genomic instability. We postulate that the Rac2-MRC-cIII pathway triggers ROS-mediated genomic instability in LSCs and primitive LPCs, which could be targeted to prevent the relapse and malignant progression of CML.     

Pregnancy among residents enrolled in general surgery: a nationwide survey of attitudes and experiences

Background

Medical student interest in general surgery has declined, and the lack of adequate accommodation for pregnancy and parenting during residency training may be a deterrent. We explored resident and program director experiences with these issues in general surgery programs across Canada.

Methods

Using a web-based tool, residents and program directors from 16 Canadian general surgery programs were surveyed regarding their attitudes toward and experiences with pregnancy during residency.

Results

One hundred seventy-six of 600 residents and 8 of 16 program directors completed the survey (30% and 50% response rate, respectively). Multiple issues pertaining to pregnancy during surgical residency were reported including the lack of adequate policies for maternity/parenting, the major obstacles to breast-feeding, and the increased workload for fellow resident colleagues. All program directors reported the lack of a program-specific maternity/parenting policy.

Conclusions

General surgery programs lack program-specific maternity/parenting policies. Several issues have been highlighted in this study emphasizing the importance of creating and implementing such a policy.