A comprehensive literature scoping review of infection prevention and control methods for viral-mediated gene therapies.

Objective: This comprehensive literature scoping review outlines available infection prevention and control (IPC) methods for viral-mediated gene therapies and provides one IPC strategy for the healthcare setting based on a single-center recommendation. Methods: A team of experts in pharmacy, healthcare epidemiology, and biosafety with experience in viral-mediated gene therapy was assembled within a pediatric hospital to conduct a comprehensive literature scoping review. The comprehensive review included abstracts and full-text articles published since 2009 and utilized prespecified search terms of the five viral vectors of interest: adenovirus (AV), retrovirus (RV), adeno-associated virus (AAV), lentivirus (LV), and herpes simplex virus (HSV). Case reports, randomized controlled trials, and bench research studies were all included, while systematic reviews were excluded. Results: A total of 4473 case reports, randomized control trials, and benchtop research studies were identified using the defined search criteria. Chlorine compounds were found to inactivate AAV and AV, while alcohol-based disinfectants were ineffective. There was a relative paucity of studies investigating surface-based disinfection for HSV, however, alcohol-based disinfectants were effective in one study. Ultraviolent irradiation was also found to inactivate HSV in numerous studies. No studies investigated disinfection for LV and RV vectors. Conclusions: The need to define IPC methods is high due to the rapid emergence of viral-mediated gene therapies to treat rare diseases, but published clinical guidance remains scarce. In the absence of these data, our center recommends a 1:10 sodium hypochlorite solution in clinical and academic environments to ensure complete germicidal activity of viral-mediated gene therapies.

Factors Influencing the Distribution of Endemic Damselflies in Vanuatu.

Vanuatubasis Ober and Staniczek is a genus of damselfly endemic to Vanuatu. Little is known about the distribution and general natural history of the genus. We present the results of 14 weeks of fieldwork in Vanuatu to provide a better understanding of the biology of this genus. Specifically, we tested ecological niche models to predict the presence of Vanuatubasis throughout the region and explored how water pH may play a role in their distribution and ecology. The results of this fieldwork refined our model and further predicted the presence of this genus on additional islands. We also found stream pH as a strong predictor for the presence of Vanuatubasis, with their presence in alkaline streams significantly higher (p < 0.001). The mean pH for those streams where the genus was collected was 8.44 (n = 53).

The role of maternal elaborative structure and control in children's memory and suggestibility for a past event.

In this investigation, preschool-aged children experienced a staged event about which their mothers received misinformation suggesting that their children witnessed an activity that did not occur. Later, mothers were asked to talk about this event with their children. Consistent with previous research, mothers' provision of structure (defined as elaborative questions and statements) and degree of control (defined in terms of functional control of conversational turns) emerged as separate dimensions of maternal memory sharing style. When later interviewed by an unfamiliar examiner about the event, children whose mothers demonstrated both high structure and high control provided the highest levels of false reports of the activity suggested to mothers and generously embellished their accounts of this activity with nonoccurring details. In contrast, children with mothers who provided low structure, regardless of their degree of control, made few false reports and used sparse narrative detail. The implications of these findings for children's memory and suggestibility are discussed.

Do Individual Differences and Aging Effects in the Estimation of Geographical Slant Reflect Cognitive or Perceptual Effects?

Several individual differences including age have been suggested to affect the perception of slant. A cross-sectional study of outdoor hill estimation (N = 106) was analyzed using individual difference measures of age, experiential knowledge, fitness, personality traits, and sex. Of particular note, it was found that for participants who reported any experiential knowledge about slant, estimates decreased (i.e., became more accurate) as conscientiousness increased, suggesting that more conscientious individuals were more deliberate about taking their experiential knowledge (rather than perception) into account. Effects of fitness were limited to those without experiential knowledge, suggesting that they, too, may be cognitive rather than perceptual. The observed effects of age, which tended to produce lower, more accurate estimates of hill slant, provide more evidence that older adults do not see hills as steeper. The main effect of age was to lower slant estimates; such effects may be due to implicit experiential knowledge acquired over a lifetime. The results indicate the impact of cognitive, rather than perceptual factors on individual differences in slant estimation.

Resistance training improves vasoreactivity in end-stage heart failure patients on inotropic support.

PURPOSE: Peripheral vascular abnormalities contribute to compromised functional status in heart failure (HF) patients. The purpose of the present study was to test whether the intervention of moderate-intensity, resistance training could improve peripheral vascular responsiveness, that is, flow-mediated dilation (FMD) in HF. METHODS: Baseline brachial artery FMD analysis (2 minutes of cuff occlusion and 5 minutes of reperfusion) was measured in HF patients on intravenous inotropic support (n = 9) awaiting cardiac transplantation. Unilateral, upper-body resistance exercises (moderate intensity, combination of isometric and isotonic exercises at 60%-80% of maximum) were performed 3 d/wk for 4 weeks. Follow-up FMD analysis was conducted after training. Central hemodynamics were defined via right-side-heart catheterization. RESULTS: At baseline prior to training, HF patients elicited a significant hyperemic response 10 seconds following cuff occlusion (mean increase in blood flow: 194 ± 44 mL/min, P < .05). Despite this significant hyperemic response, HF patients demonstrated a mild, but paradoxical vasoconstriction of nearly 3% at 1-minute after cuff release. Four weeks of resistance training corrected the paradoxical vasoconstriction observed at baseline and resulted in vasodilatation (a positive increase in brachial artery diameter of 0.04 ± 0.04 mm, at 1 minute after cuff release; P < .05). Conversely, in a subset of 3 HF patients, studies in the untrained contralateral arm revealed no change in the FMD response. CONCLUSION: Moderate-intensity upper-body resistance training improved brachial artery FMD in end-stage HF patients on inotropic support. The reversal of the paradoxical vasoconstrictive response to reactive hyperemia following 4 weeks of training may be secondary to local improvements in vascular endothelial function rather than a quantitative change in the reactive hyperemic stimulus.

Insulin regulates adipocyte lipolysis via an Akt-independent signaling pathway.

After a meal, insulin suppresses lipolysis through the activation of its downstream kinase, Akt, resulting in the inhibition of protein kinase A (PKA), the main positive effector of lipolysis. During insulin resistance, this process is ineffective, leading to a characteristic dyslipidemia and the worsening of impaired insulin action and obesity. Here, we describe a noncanonical Akt-independent, phosphoinositide-3 kinase (PI3K)-dependent pathway that regulates adipocyte lipolysis using restricted subcellular signaling. This pathway selectively alters the PKA phosphorylation of its major lipid droplet-associated substrate, perilipin. In contrast, the phosphorylation of another PKA substrate, hormone-sensitive lipase (HSL), remains Akt dependent. Furthermore, insulin regulates total PKA activity in an Akt-dependent manner. These findings indicate that localized changes in insulin action are responsible for the differential phosphorylation of PKA substrates. Thus, we identify a pathway by which insulin regulates lipolysis through the spatially compartmentalized modulation of PKA.

Impaired vasoreactivity in end-stage heart failure patients on intravenous inotropic support.

BACKGROUND: Vasoreactivity is known to be impaired in heart failure patients; however, it has not been determined whether standard medical therapy for end-stage heart failure patients (ES-HF) ameliorates this impairment. Therefore, we sought to investigate flow-mediated dilation (FMD) responses in ES-HF with normal or near normal cardiac indices from continuous inotropic support. METHODS AND RESULTS: Vascular ultrasound was used to assess FMD responses to isometric exercise and cuff occlusion in 15 ES-HF patients and 5 control subjects (C). ES-HF patients had significant hyperemic response to maximal exercise (P < .05), which was blunted relative to C (ES-HF; 84 +/- 21 mL/min versus C; 299 +/- 85 mL/min, P < .05). ES-HF patients did not show a significant hyperemic response to submaximal exercise. C had a significant increase in arterial diameter that exceeded ES-HF after both maximal (C; 8 +/- 1% versus. ES-HF; -0.9 +/- 0.86%, P < .05) and submaximal exercise (C; 6 +/- 1% versus ES-HF; 0.57 +/- 1%, P < .05). FMD responses at similar absolute workloads showed that both the mean hyperemic response and the change in arterial diameter were significantly greater in C. After cuff occlusion, the mean hyperemic response for ES-HF was again significantly blunted compared with C (ES-HF; 117 +/- 26% versus C; 352 +/- 86%, P < .05). After cuff occlusion, arterial diameter in C significantly increased in response to hyperemia, whereas ES-HF patients had a paradoxical vasoconstrictive response (C; 10.7 +/- 1.1% versus ES-HF; -5.3 +/- 1.5%, P < .05). CONCLUSION: Peripheral vasoreactivity in response to either maximal exercise, submaximal exercise, or hyperemic stimuli is impaired in ES-HF patients with normal resting cardiac outputs.