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

Роль хемокинов в рекрутировании клеток-предшественников в опухолевую нишу при раке молочной железы

Развитие первичной опухоли сопровождается формированием опухолевой ниши, котораясоздает благоприятные условия для выживания и пролиферации раковых клеток. Одним из ключевых элементов эволюции опухолевой ниши является рекрутирование костномозговых клеток-предшественников, включая клетки-предшественники макрофагов, мезенхимальные столовые клетки, эндотелиальные и гемопоэтические клетки-предшественники. Миграция упомянутых клеток в опухоль регулируется рядом хемокинов, в том числе CCL2, CXCL12, MSP (macrophage stimulating protein) и MIF (macrophage inhibitory factor). Целью настоящего исследования являлось изучение параметров опухолевой ниши при раке молочной железы. Исследование включало 24 больных с инвазивной карциномой неспецифического типа молочной железы. В суспензии опухолевых клеток методом проточной цитофлюориметрии определяли содержание клеток-предшественников. Концентрацию хемокинов CCL2, CXCL12, MSP и MIF в венозной крови больных оценивали с помощью твердофазного иммуноферментного анализа. Достоверных различий в содержании исследованных клеточных популяций, а также концентрации изученных хемокинов между пациентами, разделенными на группы взависимости от наличия или отсутствия лимфогенных метастазов и неоадъювантного лечения, обнаружено не было. В то же время, установлена прямая корреляционная связь между содержанием гемопоэтических клеток-предшественников в опухоли и концентрацией CXCL12 и MIF в крови

Input-Admittance Passivity Compliance for Grid-Connected Converters With an LCL Filter

This work presents a design methodology and its experimental validation for the input-admittance passivity compliance of LCL grid-connected converters. The designs of the LCL filter parameters and discrete controller are addressed systematically, and suitable design guidelines are provided. The controller design is developed in the z-domain, with capacitor voltage based active damping used as degree of freedom to compensate for system delay effects. The role of resistive components in the circuit, which have inherent dissipative properties, is also discussed. As an outcome of the design, a passive input admittance shaping is obtained. The theoretical development is further verified in a low-scale prototype supplied from a controllable grid simulator. For the sake of generality, different combinations of resonant to sampling frequency are tested. Experimental results fully prove the input-admittance passivity compliance

Severe hypoxaemic hypercapnia compounds cerebral oxidative-nitrosative stress during extreme apnoea: implications for cerebral bioenergetic function

We examined to what extent apnoea-induced extremes of oxygen demand/carbon dioxide production impact redox-regulation of cerebral bioenergetic function. Ten ultra-elite apnoeists (6 men, 4 women) performed two maximal dry apnoeas preceded by, [1] normoxic normoventilation resulting in severe end-apnoea hypoxaemic hypercapnia and [2] hyperoxic hyperventilation designed to ablate hypoxaemia resulting in hyperoxaemic hypercapnia. Transcerebral exchange of ascorbate radicals (A·-, electron paramagnetic resonance spectroscopy) and nitric oxide metabolites (NO, tri-iodide chemiluminescence) were calculated as the product of global cerebral blood flow (gCBF, duplex ultrasound) and radial arterial (a) to internal jugular venous (v) concentration gradients. Apnoea duration increased from 306 ± 62 s during hypoxaemic hypercapnia to 959 ± 201 s in hyperoxaemic hypercapnia (P = &lt;0.001). Apnoea generally increased gCBF (all P = &lt;0.001) but was insufficient to prevent a reduction in the cerebral metabolic rates of oxygen and glucose (P = 0.015 to 0.044). This was associated with a general net cerebral output (v&gt;a) of A·- that was greater in hypoxaemic hypercapnia (P = 0.046 vs. hyperoxaemic hypercapnia) and coincided with a selective suppression in plasma nitrite (〖"NO" 〗_"2" ^"-" ) uptake (a&gt;v) and gCBF (P = 0.034 to &lt;0.001 vs. hyperoxaemic hypercapnia), implying reduced consumption and delivery of NO consistent with elevated cerebral oxidative-nitrosative stress (OXNOS). In contrast, we failed to observe equidirectional gradients consistent with S-nitrosohaemoglobin consumption and plasma S-nitrosothiol delivery during apnoea (all P = &gt;0.05). Collectively, these findings highlight a key catalytic role for hypoxaemic hypercapnia in cerebral OXNOS

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

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