Exogenous Nitric Oxide and Bubble Formation in Divers

. Purpose: Prevention of bubble formation is a central goal in standard decompression procedures. Previously we have shown that exercise 20 Y 24 h prior to a dive reduces bubble formation and increases survival in rats exposed to a simulated dive. Furthermore, we have demonstrated that nitric oxide (NO) may be involved in this protection; blocking the production of NO increases bubble formation while giving rats a long-lasting NO donor 20 h and immediately prior to a dive reduces bubble formation. This study determined whether a short-lasting NO donor, nitroglycerine, reduced bubble formation after standard dives and decompression in man. Methods: A total of 16 experienced divers were randomly assigned into two groups. One group performed two dives to 30 m of seawater (msw) for 30 min breathing air, and performed exercise at an intensity corresponding to 30% of maximal oxygen uptake during the bottom time. The second group performed two simulated dives to 18 msw for 80 min breathing air in a hyperbaric chamber, and remained sedentary during the bottom period. The first dive for each diver served as the control dive, whereas the divers received 0.4 mg of nitroglycerine by oral spray 30 min before the second dive. Following the dive, gas bubbles in the pulmonary artery were recorded using ultrasound. Results: The open-water dive resulted in significantly more gas bubbles than the dry dive (0.87 T 1.3 vs 0.12 T 0.23 bubbles per square centimeter). Nitroglycerine reduced bubble formation significantly in both dives from 0.87 T 1.3 to 0.32 T 0.7 in the in-water dive and from 0.12 T 0.23 to 0.03 T 0.03 bubbles per square centimeter in the chamber dive. Conclusion: The present study demonstrates that intake of a short-lasting NO donor reduces bubble formation following decompression after different dives

Venous gas embolism as a predictive tool for improving CNS decompression safety

A key process in the pathophysiological steps leading to decompression sickness (DCS) is the formation of inert gas bubbles. The adverse effects of decompression are still not fully understood, but it seems reasonable to suggest that the formation of venous gas emboli (VGE) and their effects on the endothelium may be the central mechanism leading to central nervous system (CNS) damage. Hence, VGE might also have impact on the long-term health effects of diving. In the present review, we highlight the findings from our laboratory related to the hypothesis that VGE formation is the main mechanism behind serious decompression injuries. In recent studies, we have determined the impact of VGE on endothelial function in both laboratory animals and in humans. We observed that the damage to the endothelium due to VGE was dose dependent, and that the amount of VGE can be affected both by aerobic exercise and exogenous nitric oxide (NO) intervention prior to a dive. We observed that NO reduced VGE during decompression, and pharmacological blocking of NO production increased VGE formation following a dive. The importance of micro-nuclei for the formation of VGE and how it can be possible to manipulate the formation of VGE are discussed together with the effects of VGE on the organism. In the last part of the review we introduce our thoughts for the future, and how the enigma of DCS should be approached

Self-Reported Mental Health Problems Among Adults Born Preterm : A Meta-analysis

CONTEXT: Preterm birth increases the risk for mental disorders in adulthood, yet findings on abstract self-reported or subclinical mental health problems are mixed. OBJECTIVE: To study self-reported mental health problems among adults born preterm at very low birth weight (VLBW; DATA SOURCES: Adults Born Preterm International Collaboration. STUDY SELECTION: Studies that compared self-reported mental health problems using the Achenbach Young Adult Self Report or Adult Self Report between adults born preterm at VLBW (n = 747) and at term (n = 1512). DATA EXTRACTION: We obtained individual participant data from 6 study cohorts and compared preterm and control groups by mixed random coefficient linear and Tobit regression. RESULTS: Adults born preterm reported more internalizing (pooled beta =.06; 95% confidence interval.01 to.11) and avoidant personality problems (.11;.05 to.17), and less externalizing (-.10;-. 15 to-. 06), rule breaking (-.10;-. 15 to-. 05), intrusive behavior (-.14;-. 19 to-.09), and antisocial personality problems (-.09;-. 14 to-.04) than controls. Group differences did not systematically vary by sex, intrauterine growth pattern, neurosensory impairments, or study cohort. LIMITATIONS: Exclusively self-reported data are not confirmed by alternative data sources. CONCLUSIONS: Self-reports of adults born preterm at VLBW reveal a heightened risk for internalizing problems and socially avoidant personality traits together with a lowered risk for externalizing problem types. Our findings support the view that preterm birth constitutes an early vulnerability factor with long-term consequences on the individual into adulthood.Peer reviewe

Wireless transmission of biosignals for hyperbaric chamber applications

[EN] This paper presents a wireless system to send biosignals outside a hyperbaric chamber avoiding wires going through the chamber walls. Hyperbaric chambers are becoming more and more common due to new indications of hyperbaric oxygen treatments. Metallic walls physically isolate patients inside the chamber, where getting a patient's vital signs turns into a painstaking task. The paper proposes using a ZigBee-based network to wirelessly transmit the patient's biosignals to the outside of the chamber. In particular, a wearable battery supported device has been designed, implemented and tested. Although the implementation has been conducted to transmit the electrocardiography signal, the device can be easily adapted to consider other biosignals.The authors would like to thanks the University of Balearic Islands (UIB), the Miguel Hernandez University (UMH), MEDIBAROX unit of the Perpetuo Socorro Hospital and the "Catedra de Medicina Hiperbarica" (UMH) for their support allowing the use of its facilities for this work. The authors would also like to thank Borja Mas Boned for his help designing the LabVIEW application. This research has been carried out with funding and promotion of "Catedra de Medicina Hiperbarica" of the Miguel Hernandez University. http://nbio.umh.es/es/2010/12/01/catedra-de-medicina-hiperbarica-medibarox/.Perez-Vidal, C.; Gracia Calandin, LI.; Carmona, C.; Alorda, B.; Salinas, A. (2017). Wireless transmission of biosignals for hyperbaric chamber applications. PLoS ONE. 12(3):1-19. https://doi.org/10.1371/journal.pone.0172768S119123Sureda, A., Batle, J. M., Martorell, M., Capó, X., Tejada, S., Tur, J. A., & Pons, A. (2016). Antioxidant Response of Chronic Wounds to Hyperbaric Oxygen Therapy. PLOS ONE, 11(9), e0163371. doi:10.1371/journal.pone.0163371Branco, B. H. M., Fukuda, D. H., Andreato, L. V., Santos, J. F. da S., Esteves, J. V. D. C., & Franchini, E. (2016). The Effects of Hyperbaric Oxygen Therapy on Post-Training Recovery in Jiu-Jitsu Athletes. PLOS ONE, 11(3), e0150517. doi:10.1371/journal.pone.0150517Xu, Y., Ji, R., Wei, R., Yin, B., He, F., & Luo, B. (2016). The Efficacy of Hyperbaric Oxygen Therapy on Middle Cerebral Artery Occlusion in Animal Studies: A Meta-Analysis. PLOS ONE, 11(2), e0148324. doi:10.1371/journal.pone.0148324Lin, B.-S., Lin, B.-S., Chou, N.-K., Chong, F.-C., & Chen, S.-J. (2006). RTWPMS: A Real-Time Wireless Physiological Monitoring System. IEEE Transactions on Information Technology in Biomedicine, 10(4), 647-656. doi:10.1109/titb.2006.874194Hu, S., Wei, H., Chen, Y., & Tan, J. (2012). A Real-Time Cardiac Arrhythmia Classification System with Wearable Sensor Networks. Sensors, 12(9), 12844-12869. doi:10.3390/s120912844Burns, A., Greene, B. R., McGrath, M. J., O’Shea, T. J., Kuris, B., Ayer, S. M., … Cionca, V. (2010). SHIMMER™ – A Wireless Sensor Platform for Noninvasive Biomedical Research. IEEE Sensors Journal, 10(9), 1527-1534. doi:10.1109/jsen.2010.2045498Gil, Y., Wu, W., & Lee, J. (2012). A Synchronous Multi-Body Sensor Platform in a Wireless Body Sensor Network: Design and Implementation. Sensors, 12(8), 10381-10394. doi:10.3390/s120810381Chin-Teng Lin, Kuan-Cheng Chang, Chun-Ling Lin, Chia-Cheng Chiang, Shao-Wei Lu, Shih-Sheng Chang, … Li-Wei Ko. (2010). An Intelligent Telecardiology System Using a Wearable and Wireless ECG to Detect Atrial Fibrillation. IEEE Transactions on Information Technology in Biomedicine, 14(3), 726-733. doi:10.1109/titb.2010.2047401W. Y. Chung, Y. D. Lee, and S. J. Jung, 'A Wireless Sensor Network Compatible Wearable U-Healthcare Monitoring System Using Integrated Ecg, Accelerometer and Spo2', Conf Proc IEEE Eng Med Biol Soc, 2008 (2008), 1529–32.ZigBee Alliance; http://www.zigbee.org/Mahmood, A., Javaid, N., & Razzaq, S. (2015). A review of wireless communications for smart grid. Renewable and Sustainable Energy Reviews, 41, 248-260. doi:10.1016/j.rser.2014.08.036J.S. Lee, Y.W. Su, and C.C. Shen, "A comparative study of wireless protocols: Bluetooth, UWB, ZigBee, and Wi-Fi, 33rd Annual Conference of the IEEE Industrial Electronics Society (IECON), 2007, pp. 46–51.P.P. Parikh, M.G. Kanabar, and T.S. Sidhu, "Opportunities and challenges of wireless communication technologies for smart grid applications, IEEE PES General Meeting, 2010, pp. 1–7.Fadlullah, Z. M., Fouda, M. M., Kato, N., Takeuchi, A., Iwasaki, N., & Nozaki, Y. (2011). Toward intelligent machine-to-machine communications in smart grid. IEEE Communications Magazine, 49(4), 60-65. doi:10.1109/mcom.2011.5741147A.C. Olteanu, G.D. Oprina, N. Tapus, and S. Zeisberg, "Enabling mobile devices for home automation using ZigBee, 19th IEEE International Conference on Control Systems and Computer Science, 2013, pp. 189–195.Shang, Y. (2014). Vulnerability of networks: Fractional percolation on random graphs. Physical Review E, 89(1). doi:10.1103/physreve.89.012813R. Barea-Navarro. Biomedical Instrumentation. Chapter 3. University of Alcala

Deadly diving? Physiological and behavioural management of decompression stress in diving mammals

© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Proceedings of the Royal Society B Biological Sciences 279 (2012): 1041-1050, doi:10.1098/rspb.2011.2088.Decompression sickness (DCS; ‘the bends’) is a disease associated with gas uptake at pressure. The basic pathology and cause are relatively well known to human divers. Breath-hold diving marine mammals were thought to be relatively immune to DCS owing to multiple anatomical, physiological and behavioural adaptations that reduce nitrogen gas (N2) loading during dives. However, recent observations have shown that gas bubbles may form and tissue injury may occur in marine mammals under certain circumstances. Gas kinetic models based on measured time-depth profiles further suggest the potential occurrence of high blood and tissue N2 tensions. We review evidence for gas-bubble incidence in marine mammal tissues and discuss the theory behind gas loading and bubble formation. We suggest that diving mammals vary their physiological responses according to multiple stressors, and that the perspective on marine mammal diving physiology should change from simply minimizing N2 loading to management of the N2 load. This suggests several avenues for further study, ranging from the effects of gas bubbles at molecular, cellular and organ function levels, to comparative studies relating the presence/absence of gas bubbles to diving behaviour. Technological advances in imaging and remote instrumentation are likely to advance this field in coming years.This paper and the workshop it stemmed from were funded by the Woods Hole Oceanographic Institution Marine Mammal Centre

Ventilation-perfusion inequality in the human lung is not increased following no-decompression-stop hyperbaric exposure

Venous gas bubbles occur in recreational SCUBA divers in the absence of decompression sickness, forming venous gas emboli (VGE) which are trapped within pulmonary circulation and cleared by the lung without overt pathology. We hypothesized that asymptomatic VGE would transiently increase ventilation-perfusion mismatch due to their occlusive effects within the pulmonary circulation. Two sets of healthy volunteers (n = 11, n = 12) were recruited to test this hypothesis with a single recreational ocean dive or a baro-equivalent dry hyperbaric dive. Pulmonary studies (intrabreath VA/Q (iV/Q), alveolar dead space, and FVC) were conducted at baseline and repeat 1- and 24-h after the exposure. Contrary to our hypothesis VA/Q mismatch was decreased 1-h post-SCUBA dive (iV/Q slope 0.023 ± 0.008 ml−1 at baseline vs. 0.010 ± 0.005 NS), and was significantly reduced 24-h post-SCUBA dive (0.000 ± 0.005, p < 0.05), with improved VA/Q homogeneity inversely correlated to dive severity. No changes in VA/Q mismatch were observed after the chamber dive. Alveolar dead space decreased 24-h post-SCUBA dive (78 ± 10 ml at baseline vs. 56 ± 5, p < 0.05), but not 1-h post dive. FVC rose 1-h post-SCUBA dive (5.01 ± 0.18 l vs. 5.21 ± 0.26, p < 0.05), remained elevated 24-h post SCUBA dive (5.06 ± 0.2, p < 0.05), but was decreased 1-hr after the chamber dive (4.96 ± 0.31 L to 4.87 ± 0.32, p < 0.05). The degree of VA/Q mismatch in the lung was decreased following recreational ocean dives, and was unchanged following an equivalent air chamber dive, arguing against an impact of VGE on the pulmonary circulation

Nutritional considerations during prolonged exposure to a confined, hyperbaric, hyperoxic environment: Recommendations for saturation divers

Saturation diving is an occupation that involves prolonged exposure to a confined, hyperoxic, hyperbaric environment. The unique and extreme environment is thought to result in disruption to physiological and metabolic homeostasis, which may impact human health and performance. Appropriate nutritional intake has the potential to alleviate and/or support many of these physiological and metabolic concerns, whilst enhancing health and performance in saturation divers. Therefore, the purpose of this review is to identify the physiological and practical challenges of saturation diving and consequently provide evidence-based nutritional recommendations for saturation divers to promote health and performance within this challenging environment. Saturation diving has a high-energy demand, with an energy intake of between 44 and 52 kcal/kg body mass per day recommended, dependent on intensity and duration of underwater activity. The macronutrient composition of dietary intake is in accordance with the current Institute of Medicine guidelines at 45-65 % and 20-35 % of total energy intake for carbohydrate and fat intake, respectively. A minimum daily protein intake of 1.3 g/kg body mass is recommended to facilitate body composition maintenance. Macronutrient intake between individuals should, however, be dictated by personal preference to support the attainment of an energy balance. A varied diet high in fruit and vegetables is highly recommended for the provision of sufficient micronutrients to support physiological processes, such as vitamin B12 and folate intake to facilitate red blood cell production. Antioxidants, such as vitamin C and E, are also recommended to reduce oxidised molecules, e.g. free radicals, whilst selenium and zinc intake may be beneficial to reinforce endogenous antioxidant reserves. In addition, tailored hydration and carbohydrate fueling strategies for underwater work are also advised

Does rapid HIV disease progression prior to combination antiretroviral therapy hinder optimal CD4 + T-cell recovery once HIV-1 suppression is achieved?

Objective: This article compares trends in CD4+ T-cell recovery and proportions achieving optimal restoration (>=500 cells/µl) after viral suppression following combination antiretroviral therapy (cART) initiation between rapid and nonrapid progressors. Methods: We included HIV-1 seroconverters achieving viral suppression within 6 months of cART. Rapid progressors were individuals experiencing at least one CD4+ less than 200 cells/µl within 12 months of seroconverters before cART. We used piecewise linear mixed models and logistic regression for optimal restoration. Results: Of 4024 individuals, 294 (7.3%) were classified as rapid progressors. At the same CD4+ T-cell count at cART start (baseline), rapid progressors experienced faster CD4+ T-cell increases than nonrapid progressors in first month [difference (95% confidence interval) in mean increase/month (square root scale): 1.82 (1.61; 2.04)], which reversed to slightly slower increases in months 1–18 [-0.05 (-0.06; -0.03)] and no significant differences in 18–60 months [-0.003 (-0.01; 0.01)]. Percentage achieving optimal restoration was significantly lower for rapid progressors than nonrapid progressors at months 12 (29.2 vs. 62.5%) and 36 (47.1 vs. 72.4%) but not at month 60 (70.4 vs. 71.8%). These differences disappeared after adjusting for baseline CD4+ T-cell count: odds ratio (95% confidence interval) 0.86 (0.61; 1.20), 0.90 (0.38; 2.17) and 1.56 (0.55; 4.46) at months 12, 36 and 60, respectively. Conclusion: Among people on suppressive antiretroviral therapy, rapid progressors experience faster initial increases of CD4+ T-cell counts than nonrapid progressors, but are less likely to achieve optimal restoration during the first 36 months after cART, mainly because of lower CD4+ T-cell counts at cART initiation

Treatment of Inborn Errors of Urea Synthesis — Activation of Alternative Pathways of Waste Nitrogen Synthesis and Excretion

Abstract Children with inborn errors of urea synthesis accumulate ammonium and other nitrogenous precursors of urea, leading to episodic coma and a high mortality rate. We used alternative pathways for the excretion of waste nitrogen as substitutes for the defective ureagenic pathways in 26 infants. These pathways involve synthesis and excretion of hippurate after sodium benzoate administration, and of citrulline and argininosuccinate after arginine supplementation. The children were treated for seven to 62 months; 22 survived. The mean plasma level of ammonium (±S.E.) was 36±2 μmol per liter, and that of benzoate was 1.5±1.0 mg per deciliter. Alternative pathways accounted for between 28 and 59 per cent of the total effective excretion of waste nitrogen. Nineteen infants had normal height, weight, and head circumference, and 13 had normal intellectual development. Activation of alternative pathways of waste nitrogen excretion can prolong survival and improve clinical outcome in children with inborn errors of urea synthesis. (N Engl J Med. 1982; 306:1387–92.

Can antibiotic prescriptions in respiratory tract infections be improved? A cluster-randomized educational intervention in general practice – The Prescription Peer Academic Detailing (Rx-PAD) Study [NCT00272155]

BACKGROUND: More than half of all antibiotic prescriptions in general practice are issued for respiratory tract infections (RTIs), despite convincing evidence that many of these infections are caused by viruses. Frequent misuse of antimicrobial agents is of great global health concern, as we face an emerging worldwide threat of bacterial antibiotic resistance. There is an increasing need to identify determinants and patterns of antibiotic prescribing, in order to identify where clinical practice can be improved. METHODS/DESIGN: Approximately 80 peer continuing medical education (CME) groups in southern Norway will be recruited to a cluster randomized trial. Participating groups will be randomized either to an intervention- or a control group. A multifaceted intervention has been tailored, where key components are educational outreach visits to the CME-groups, work-shops, audit and feedback. Prescription Peer Academic Detailers (Rx-PADs), who are trained GPs, will conduct the educational outreach visits. During these visits, evidence-based recommendations of antibiotic prescriptions for RTIs will be presented and software will be handed out for installation in participants PCs, enabling collection of prescription data. These data will subsequently be linked to corresponding data from the Norwegian Prescription Database (NorPD). Individual feedback reports will be sent all participating GPs during and one year after the intervention. Main outcomes are baseline proportion of inappropriate antibiotic prescriptions for RTIs and change in prescription patterns compared to baseline one year after the initiation of the tailored pedagogic intervention. DISCUSSION: Improvement of prescription patterns in medical practice is a challenging task. A thorough evaluation of guidelines for antibiotic treatment in RTIs may impose important benefits, whereas inappropriate prescribing entails substantial costs, as well as undesirable consequences like development of antibiotic resistance. Our hypothesis is that an educational intervention program will be effective in improving prescription patterns by reducing the total number of antibiotic prescriptions, as well as reducing the amount of broad-spectrum antibiotics, with special emphasis on macrolides