Stability and mechanism of threose nucleic acid toward acid-mediated degradation.

Xeno-nucleic acids (XNAs) have gained significant interest as synthetic genetic polymers for practical applications in biomedicine, but very little is known about their biophysical properties. Here, we compare the stability and mechanism of acid-mediated degradation of α-l-threose nucleic acid (TNA) to that of natural DNA and RNA. Under acidic conditions and elevated temperature (pH 3.3 at 90°C), TNA was found to be significantly more resistant to acid-mediated degradation than DNA and RNA. Mechanistic insights gained by reverse-phase HPLC and mass spectrometry indicate that the resilience of TNA toward low pH environments is due to a slower rate of depurination caused by induction of the 2'-phosphodiester linkage. Similar results observed for 2',5'-linked DNA and 2'-O-methoxy-RNA implicate the position of the phosphodiester group as a key factor in destabilizing the formation of the oxocarbenium intermediate responsible for depurination and strand cleavage of TNA. Biochemical analysis indicates that strand cleavage occurs by ß-elimination of the 2'-phosphodiester linkage to produce an upstream cleavage product with a 2'-threose sugar and a downstream cleavage product with a 3' terminal phosphate. This work highlights the unique physicochemical properties available to evolvable non-natural genetic polymers currently in development for biomedical applications.

Evaluation of a standardized collection device for exhaled breath sampling onto thermal desorption tubes.

The Respiration Collector for In Vitro Analysis (ReCIVA) sampler, marketed by Owlstone Medical, provides a step forward in exhaled breath sampling through active sampling directly onto thermal desorption (TD) tubes. Although an improvement to the issues surrounding breath bag sampling, the ReCIVA device, first released in 2015, is a relatively new research and clinical tool that requires further exploration. Here, data are presented comparing two distinct ReCIVA devices. The results, comparing ReCIVA serial numbers #33 and #65, demonstrate that overall statistically insignificant results are obtained via targeted isoprene quantitation (p > 0.05). However, when the data are parsed by the TD tube type used to capture breath volatiles, either Tenax TA or the dual bed Tenax/Carbograph 5TD (5TD), a statistical difference (p < 0.05) among the two different TD tubes was present. These data, comparing the two ReCIVA devices with both Tenax TA and 5TD tubes, are further supported by a global metabolomics analysis yielding 85% of z-scores, comparing ReCIVA devices, below the limit for significance. Experiments to determine the effect of breathing rate on ReCIVA function, using guided breathing for low (7.5 breaths min-1) and high (15 breaths min-1) breathing rates, demonstrate the ReCIVA device shows no statistical difference among breathing rates for quantitated isoprene (p > 0.05). Global metabolomics analysis of the guided breathing rate data shows more than 87% of the z-scores, comparing high and low breathing rates using both the Tenax and the 5TD tubes, are below the level for significance. Finally, data are provided from a single participant who displayed background levels of isoprene while illustrating levels of acetone consistent with the remaining participants. Collectively, these data support the use of multiple ReCIVA devices for exhaled breath collection and provide evidence for an instance where exhaled isoprene is consistent with background levels.

Administration of Hypertonic Solutions for Hemorrhagic Shock: A Systematic Review and Meta-analysis of Clinical Trials.

BACKGROUND: Several clinical trials on hypertonic fluid administration have been completed, but the results have been inconclusive. The objective of this study is to summarize current evidence for treating hypovolemic patients with hypertonic solutions by performing a systematic review and meta-analysis. METHODS: Major electronic databases were searched from inception through June 2014. We included only randomized controlled trials involving hemorrhagic shock patients treated with hypertonic solutions. After screening 570 trials, 12 were eligible for the final analysis. Pooled effect estimates were calculated with a random effect model. RESULTS: The 12 studies included 6 trials comparing 7.5% hypertonic saline (HS) with 0.9% saline or Ringer's lactate solution and 11 trials comparing 7.5% hypertonic saline with dextran (HSD) with isotonic saline or Ringer's lactate. Overall, there were no statistically significant survival benefits for patients treated with HS (relative risk [RR], 0.96; 95% confidence interval [CI], 0.82-1.12) or HSD (RR, 0.92; 95% CI, 0.80-1.06). Treatment with hypertonic solutions was also not associated with increased complications (RR, 1.03; 95% CI, 0.78-1.36). Subgroup analysis on trauma patients in the prehospital or emergency department settings did not change these conclusions. There was no evidence of significant publication bias. Meta-regression analysis did not find any significant sources of heterogeneity. CONCLUSIONS: Current evidence does not reveal increased mortality when the administration of isotonic solutions is compared to HS or HSD in trauma patients with hemorrhagic shock. HS or HSD may be a viable alternative resuscitation fluid in the prehospital setting. Further studies are needed to determine the optimum volume and regimen of intravenous fluids for the treatment of trauma patients.

Posttraumatic stress disorder and general psychopathology in children and adolescents following a wildfire disaster.

OBJECTIVE: To report on the use of the Post Traumatic Stress Disorder Reaction Index (PTSD-RI) and the Strengths and Difficulties Questionnaire (SDQ) in identifying children and adolescents who may require psychological interventions following exposure to a wildfire disaster. METHOD: Six months after a wildfire disaster, we conducted a school-based program to screen for wildfire-related events, such as exposure to and perception of threat, posttraumatic stress disorder (PTSD), and general psychopathology. RESULTS: The screening battery was completed by 222 children (mean age 12.5 years, SD 2.48; range 8 to 18 years). Severe or very severe PTSD was reported by 9.0% of students, while 22.6% scored in the abnormal range on the Emotional Symptoms subscale of the SDQ. Younger children and individuals with greater exposure to and perception of threat experienced higher levels of PTSD and general psychopathology. Female students reported a greater perception of threat but did not report higher levels of PTSD or other symptoms. CONCLUSIONS: Screening was well received by students, parents, and staff and proved feasible in the postdisaster environment. The PTSD-RI and SDQ demonstrated different individual risk associations and functioned as complementary measures within the screening battery. The identification of children at greatest risk of mental health morbidity enabled service providers to selectively target limited mental health resources.