Meta-analyses of genome-wide association studies for postpartum depression

Objective: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD. Method: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)–based heritability (), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system. Results: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD. Conclusions: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Impact of Nintendo Wii Games on Physical Literacy in Children: Motor Skills, Physical Fitness, Activity Behaviors, and Knowledge

Physical literacy is the degree of fitness, behaviors, knowledge, and fundamental movement skills (agility, balance, and coordination) a child has to confidently participate in physical activity. Active video games (AVG), like the Nintendo Wii, have emerged as alternatives to traditional physical activity by providing a non-threatening environment to develop physical literacy. This study examined the impact of AVGs on children’s (age 6–12, N = 15) physical literacy. For six weeks children played one of four pre-selected AVGs (minimum 20 min, twice per week). Pre and post measures of motivation, enjoyment, and physical literacy were completed. Results indicated a near significant improvement in aiming and catching (p = 0.06). Manual dexterity significantly improved in males (p = 0.001), and females felt significantly less pressured to engage in PA (p = 0.008). Overall, there appears to be some positive impact of an AVG intervention on components of physical literacy

The Effect of Wave Motion Intensities on Performance in a Simulated Search and Rescue Task and the Concurrent Demands of Maintaining Balance

Objective The purpose of this study was to examine how intensity of wave motions affects the performance of a simulated maritime search and rescue (SAR) task. Background Maritime SAR is a critical maritime occupation; however, the effect of wave motion intensity on worker performance is unknown. Methods Twenty-four participants (12 male, 12 female) performed a simulated search and rescue task on a six-degree-of-freedom motion platform in two conditions that differed in motion intensity (low and high). Task performance, electromyography (EMG), and number of compensatory steps taken by the individual were examined. Results As magnitude of simulated motion increased, performance in the SAR task decreased, and was accompanied by increases in lower limb muscle activation and number of steps taken. Conclusions Performance of an SAR task and balance control may be impeded by high-magnitude vessel motions. Application This research has the potential to be used by maritime engineers, occupational health and safety professionals, and ergonomists to improve worker safety and performance for SAR operators

The Effect of Wave Motion Intensities on Performance in a Simulated Search and Rescue Task and the Concurrent Demands of Maintaining Balance

Objective: The purpose of this study was to examine how intensity of wave motions affects the performance of a simulated maritime search and rescue (SAR) task. Background: Maritime SAR is a critical maritime occupation; however, the effect of wave motion intensity on worker performance is unknown. Methods: Twenty-four participants (12 male, 12 female) performed a simulated search and rescue task on a six-degree-of-freedom motion platform in two conditions that differed in motion intensity (low and high). Task performance, electromyography (EMG), and number of compensatory steps taken by the individual were examined. Results: As magnitude of simulated motion increased, performance in the SAR task decreased, and was accompanied by increases in lower limb muscle activation and number of steps taken. Conclusions: Performance of an SAR task and balance control may be impeded by high-magnitude vessel motions. Application: This research has the potential to be used by maritime engineers, occupational health and safety professionals, and ergonomists to improve worker safety and performance for SAR operators

Unilateral Rolling of the Foot did not Affect Non-Local Range of Motion or Balance

Non-local or crossover (contralateral and non-stretched muscles) increases in range-of-motion (ROM) and balance have been reported following rolling of quadriceps, hamstrings and plantar flexors. Since there is limited information regarding plantar sole (foot) rolling effects, the objectives of this study were to determine if unilateral foot rolling would affect ipsilateral and contralateral measures of ROM and balance in young healthy adults. A randomized within-subject design was used to examine non-local effects of unilateral foot rolling on ipsilateral and contralateral limb ankle dorsiflexion ROM and a modified sit-and-reach-test (SRT). Static balance was also tested during a 30 s single leg stance test. Twelve participants performed three bouts of 60 s unilateral plantar sole rolling using a roller on the dominant foot with 60 s rest intervals between sets. ROM and balance measures were assessed in separate sessions at pre-intervention, immediately and 10 minutes post-intervention. To evaluate repeated measures effects, two SRT pre-tests were implemented. Results demonstrated that the second pre-test SRT was 6.6% higher than the first pre-test (p = 0.009, d = 1.91). There were no statistically significant effects of foot rolling on any measures immediately or 10 min post-test. To conclude, unilateral foot rolling did not produce statistically significant increases in ipsilateral or contralateral dorsiflexion or SRT ROM nor did it affect postural sway. Our statistically non-significant findings might be attributed to a lower degree of roller-induced afferent stimulation due to the smaller volume of myofascia and muscle compared to prior studies. Furthermore, ROM results from studies utilizing a single pre-test without a sufficient warm-up should be viewed critically

Barefoot running does not affect simple reaction time: an exploratory study

Background Converging evidence comparing barefoot (BF) and shod (SH) running highlights differences in foot-strike patterns and somatosensory feedback, among others. Anecdotal evidence from SH runners attempting BF running suggests a greater attentional demand may be experienced during BF running. However, little work to date has examined whether there is an attentional cost of BF versus SH running. Objective This exploratory study aimed to examine whether an acute bout of BF running would impact simple reaction time (SRT) compared to SH running, in a sample of runners naïve to BF running. Methods Eight male distance runners completed SRT testing during 10 min of BF or SH treadmill running at 70% maximal aerobic speed (17.9 ± 1.4 km h−1). To test SRT, participants were required to press a hand-held button in response to the flash of a light bulb placed in the center of their visual field. SRT was tested at 1-minute intervals during running. BF and SH conditions were completed in a pseudo-randomized and counterbalanced crossover fashion. SRT was defined as the time elapsed between the light bulb flash and the button press. SRT errors were also recorded and were defined as the number of trials in which a button press was not recorded in response to the light bulb flash. Results Overall, SRT later in the exercise bouts showed a statistically significant increase compared to earlier (p  0.05) or the number of SRT errors (17.6 ± 6.6 trials vs. 17.0 ± 13.0 trials, p > 0.05). Discussion In a sample of distance runners naïve to BF running, there was no statistically significant difference in SRT or SRT errors during acute bouts of BF and SH running. We interpret these results to mean that BF running does not have a greater attentional cost compared to SH running during a SRT task throughout treadmill running. Literature suggests that stride-to-stride gait modulation during running may occur predominately via mechanisms that preclude conscious perception, thus potentially attenuating effects of increased somatosensory feedback experienced during BF running. Future research should explore the present experimental paradigm in a larger sample using over-ground running trials, as well as employing different tests of attention

Population Differences in Postural Response Strategy Associated with Exposure to a Novel Continuous Perturbation Stimuli: Would Dancers Have Better Balance on a Boat?

<div><p>Central or postural set theory suggests that the central nervous system uses short term, trial to trial adaptation associated with repeated exposure to a perturbation in order to improve postural responses and stability. It is not known if longer-term prior experiences requiring challenging balance control carryover as long-term adaptations that influence ability to react in response to novel stimuli. The purpose of this study was to determine if individuals who had long-term exposure to balance instability, such as those who train on specific skills that demand balance control, will have improved ability to adapt to complex continuous multidirectional perturbations. Healthy adults from three groups: 1) experienced maritime workers (n = 14), 2) novice individuals with no experience working in maritime environments (n = 12) and 3) individuals with training in dance (n = 13) participated in the study. All participants performed a stationary standing task while being exposed to five 6 degree of freedom motions designed to mimic the motions of a ship at sea. The balance reactions (change-in-support (CS) event occurrences and characteristics) were compared between groups. Results indicate dancers demonstrated significantly fewer CS events than novices during the first trial, but did not perform as well as those with offshore experience. Linear trend analyses revealed that short-term adaptation across all five trials was dependent on the nature of participant experience, with dancers achieving postural stability earlier than novices, but later than those with offshore experience. These results suggest that long term previous experiences also have a significant influence on the neural control of posture and balance in the development of compensatory responses.</p></div

Total number of steps made per trial.

<p>Data presented as group means with error bars representing standard error.</p

Percentage of trial spent performing change-in-support strategies.

<p>Data presented as group means with error bars representing standard error.</p