High-altitude exposure in patients with cardiovascular disease: risk assessment and practical recommendations.

Because of the development of modern transportation facilities, an ever rising number of individuals including many patients with preexisting diseases visit high-altitude locations (>2500 m). High-altitude exposure triggers a series of physiologic responses intended to maintain an adequate tissue oxygenation. Even in normal subjects, there is enormous interindividual variability in these responses that may be further amplified by environmental factors such as cold temperature, low humidity, exercise, and stress. These adaptive mechanisms, although generally tolerated by most healthy subjects, may induce major problems in patients with preexisting cardiovascular diseases in which the functional reserves are already limited. Preexposure assessment of patients helps to minimize risk and detect contraindications to high-altitude exposure. Moreover, the great variability and nonpredictability of the adaptive response should encourage physicians counseling such patients to adapt a cautionary approach. Here, we will briefly review how high-altitude adjustments may interfere with and aggravate/decompensate preexisting cardiovascular diseases. Moreover, we will provide practical recommendations on how to investigate and counsel patients with cardiovascular disease desiring to travel to high-altitude locations.

Validation of a wrist monitor for accurate estimation of RR intervals during sleep.

While the incidence of sleep disorders is continuously increasing in western societies, there is a clear demand for technologies to asses sleep-related parameters in ambulatory scenarios. The present study introduces a novel concept of accurate sensor to measure RR intervals via the analysis of photo-plethysmographic signals recorded at the wrist. In a cohort of 26 subjects undergoing full night polysomnography, the wrist device provided RR interval estimates in agreement with RR intervals as measured from standard electrocardiographic time series. The study showed an overall agreement between both approaches of 0.05 ± 18 ms. The novel wrist sensor opens the door towards a new generation of comfortable and easy-to-use sleep monitors.

The 500 Ma-old Thyon metagranite: A new A-type granite occurrence in the western Penninic Alps (Wallis, Switzerland)

The Thyon metagranite is located in the frontal part of the Siviez-Mischabel Nappe, in the western Penninic Alps. It is intrusive in a polymetamorphic banded volcanic complex as leucocratic concordant sills with pseudoaplitic rims. A distinct metamorphic schistosity is defined by dark-green Fe-rich biotite. Abundant mesoperthites, chess-board albite and low microcline are presumably related to magmatic stages and/or greenschist-facies metamorphic retrogression. Major, trace element and REE geochemistry, zircon typology, Y and Nb-bearing accessory minerals such as fergusonite and euxenite, all point to a metaluminous to peraluminous alkaline A-type granite. High-precision U-Pb zircon dating yielded a sub-concordant age of 500 +3/-4 Ma. The Thyon metagranite is the third record of a Cambro-Ordovician alkaline magmatic activity in the Alps. As A-type granitic magmatism is common in post-orogenic to anorogenic extensional tectonic regime, the Thyon intrusion could mark the transition between the Cadomian and the Caledonian orogenies.

Systemic vascular dysfunction in patients with chronic mountain sickness.

ABSTRACT BACKGROUND: Chronic mountain sickness (CMS) is a major public health problem characterized by exaggerated hypoxemia and erythrocytosis. In more advanced stages, these patients often present functional and structural changes of the pulmonary circulation, but there is little information on the systemic circulation. In patients suffering from diseases associated with chronic hypoxemia at low altitude, systemic vascular function is altered. We hypothesized that patients with CMS display systemic vascular dysfunction that may predispose them to increased systemic cardiovascular morbidity. METHODS: To test this hypothesis, we assessed systemic endothelial function (by flow- mediated dilation, FMD), arterial stiffness and carotid intima-media thickness and arterial oxygenation (SaO(2)) in 23 patients with CMS without additional classical cardiovascular risk factors and 27 age-matched healthy mountain dwellers born and permanently living at 3600 m. For some analyses subjects were classified according to baseline SaO(2) quartiles; FMD of the highest quartile subgroup (SaO(2) ≥90%) was used as reference value for post-hoc comparisons. RESULTS: Patients with CMS displayed marked systemic vascular dysfunction, as evidenced by impaired FMD (4.6±1.2 vs. 7.6±1.9%, CMS vs. controls, P<0.0001), greater pulse wave velocity (10.6±2.1 vs. 8.4±1.0 m/s, P<0.001) and carotid intima-media thickness (690±120 vs. 570±110 μm, P=0.001). A positive relationship existed between SaO(2) and FMD (r=0.62, P<0.0001). Oxygen inhalation improved (P<0.001), but did not normalize FMD in patients with CMS; whereas it normalized FMD in hypoxemic controls (SaO(2) <90%) and had no detectable effect in normoxemic (SaO(2) ≥90%) control subjects. CONCLUSIONS: Patients with CMS display marked systemic vascular dysfunction. Structural and functional alterations contribute to this problem that may predispose these patients to premature cardiovascular disease. Clinical Trials Gov Registration # NCT01182792.

Alpine deformation and 40Ar/39Ar geochronology of synkinematic white mica in the Siviez-Mischabel Nappe, western Pennine Alps, Switzerland

We explore the timing of deformation and exhumation of the Siviez-Mischabel Nappe (western Swiss Alps), which has been considered a classic example of a midcrustal crystalline nappe since the studies of Argand [1916]. This study presents Ar-40/Ar-39 ages obtained on both synkinematic white mica from Permo-Triassic cover sediments and more complex white mica populations from basement gneisses of the Siviez-Mischabel and middle Pennine Nappes. Primary foliation developed in cover units by nucleation, growth, and rigid rotation of mica grains during noncoaxial Alpine deformation. Although some samples show a crenulation of this primary foliation, mica growth appears to have occurred only during the development of primary foliation, the main phase of greenschist facies deformation related to imbrication of the Siviez-Mischabel Nappe and other middle Pennine Nappes. Good agreement exists between independent estimates of the timing of deformation and reported Ar-40/Ar-39, white mica ages from cover units of the central and southern Siviez-Mischabel Nappe. In cover units from the central and southern Siviez-Mischabel regions of the study area, Ar-40/Ar-39 ages appear to date synkinematic white mica growth. Results suggest that the Siviez-Mischabel :Nappe was emplaced and developed foliation during a 5 m.y. period from 41 to 36 Ma. In cover units from the eastern Siviez-Mischabel, however, Ar-40/Ar-39 white mica ages appear to date postkinematic thermal events. These thermal events may be related to Oligocene magmatic activity in the lower Pennine Nappes or to Miocene development of the Simplon fault zone. Variations in the relation between Alpine age and grain size for cover samples from the central, eastern, and southern Siviez-Mischabel correlate well with the regional variations in temperature inferred from quartz microfabrics and the pattern of regional metamorphism. When considered in concert with other recent isotopic studies on the timing of major tectonic and thermal events in the western Swiss Alps, these data support arguments that the relative timing of events such as thrusting and back thrusting of crystalline nappes in hinterland units and exhumation of high-pressure units in the suture zone of the western Alps are intimately related and synchronous on the scale of a few million years. Copyright 1998 by the American Geophysical Union.

Vascular dysfunction in offspring of preeclampsia is related to preeclampsia per se rather than genetically determined

Objectives: Epidemiological studies suggest that adverse events in utero may predispose to premature cardiovascular disease in adulthood, but the mechanisms are not known. Recently, we found that young apparently healthy offspring of mothers with preeclampsia (PE) display systemic endothelial dysfunction. This problem could be related to PE per se or to a genetic abnormality that predisposes the mother to PE and the offspring to vascular dysfunction. To distinguish between these two possibilities, we assessed vascular function in offspring of PE, their siblings who were born after a normal pregnancy, and in control subjects.Methods: We measured endothelium-dependent vasodilation (flow-mediated vasodilation, FMD), in 10 pairs of healthy normotensive siblings, one born after PE (age 15±6 y; mean±SD), the other after normal pregnancy (17±6y) and in 17 (16±7y) controls. All subjects were born at term.Results: The vascular function in siblings of PE who were born after normal pregnancy was normal and comparable to the one in controls (8.6±1.5% vs. 8.1±1.3%, P=0.32), whereas offspring of PE displayed a roughly 30% smaller FMD than the two other groups (5.9±1.6%, P<0.005 vs. both siblings and controls, Figure). The endothelial dysfunction in the offspring of PE was not related to a difference in the central arterial blood pressure or arterial oxygen saturation, because they were comparable in the 3 groups. Figure 1. FMD in the three groups.Conclusions: These findings provide the first evidence that vascular dysfunction in offspring of PE is caused by PE itself, rather than by a genetic abnormality that predisposes the mother to PE and the offspring to a vascular defect. Prevention of PE and/or its successful treatment is expected to prevent vascular dysfunction and premature cardiovascular morbidity and mortality in the offspring.

Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase.

BACKGROUND: Insulin resistance and arterial hypertension are related, but the underlying mechanism is unknown. Endothelial nitric oxide synthase (eNOS) is expressed in skeletal muscle, where it may govern metabolic processes, and in the vascular endothelium, where it regulates arterial pressure. METHODS AND RESULTS: To study the role of eNOS in the control of the metabolic action of insulin, we assessed insulin sensitivity in conscious mice with disruption of the gene encoding for eNOS. eNOS(-/-) mice were hypertensive and had fasting hyperinsulinemia, hyperlipidemia, and a 40% lower insulin-stimulated glucose uptake than control mice. Insulin resistance in eNOS(-/-) mice was related specifically to impaired NO synthesis, because in equally hypertensive 1-kidney/1-clip mice (a model of renovascular hypertension), insulin-stimulated glucose uptake was normal. CONCLUSIONS: These results indicate that eNOS is important for the control not only of arterial pressure but also of glucose and lipid homeostasis. A single gene defect, eNOS deficiency, may represent the link between metabolic and cardiovascular disease.

Respostas de tangerineiras 'Montenegrina' à calagem e adubação orgânica e mineral

Esta pesquisa objetivou estudar a influência da calagem e de adubações minerais e orgânicas na produção de tangerineiras (Citrus deliciosa Tenore) cv. Montenegrina, enxertadas em Poncirus trifoliata Raf. O plantio foi realizado em julho de 1988, num solo Podzólico Vermelho-Escuro, de textura franco-argilosa. O delineamento experimental constou de blocos ao acaso, com nove tratamentos e quatro repetições, usando três plantas úteis por parcela. Os tratamentos utilizados foram: testemunha (sem adubação e sem calagem); solo corrigido a pH 6,5 antes do plantio; adubações com esterco de aviário + calagem anualmente; adubações com esterco bovino + calagem anualmente; adubações com N e K + calagem anualmente; adubações com N e K + calagem anualmente + correção com P antes do plantio; adubações com N, P na dose simples e K + calagem anualmente; adubações com N, P na dose dupla e K + calagem anualmente; adubações anuais com N, P na dose simples e K, sem calagem. A adubação corretiva com P, na instalação do pomar, foi suficiente para assegurar uma produção de frutos similar à obtida pelas adubações de reposição anual deste nutriente, até oito anos após o plantio. A elevação dos teores foliares de N foi positivamente relacionada com o aumento da produção de frutos e com a diminuição do peso médio dos mesmos. O uso de sulfato de amônio acidifica o solo e requer maior quantidade de calagem de manutenção.

Níveis de fósforo para caprinos: perda endógena fecal e exigência líquida para mantença

Foram utilizados, no experimento, nove caprinos machos castrados, da raça Alpina, em dois períodos. Os animais permaneceram 28 dias em dieta experimental composta de feno e concentrado, sem suplementação de P, ou com 1g ou 2 g de P, na forma de fosfato bicálcico. No 21º dia os animais receberam injeção de 7,4 MBq de 32P na jugular, e coletaram-se amostras de sangue, fezes e urina, por sete dias, com o objetivo de avaliar o metabolismo do P. O aumento do consumo de P levou a aumento linear significativo do P excretado nas fezes, do P absorvido, do P endógeno fecal, da eficiência de absorção, e dos teores de P nas fezes e no plasma. O aumento do P endógeno fecal (Y) em função do consumo de P (X) pode ser descrito pela equação Y= 10,36 + 0,58X (r=0,94); a perda endógena mínima desses animais foi de 10,36 mg/kg de peso vivo/dia. A eficiência de absorção média foi de 65,76% para os animais suplementados. O teor de P na saliva não apresentou relação linear significativa com o P consumido, e não houve excreção de P pela urina.

Regional deterministic characterization of fracture networks and its application to GIS-based rock fall risk assessment

The study investigates the possibility to incorporate fracture intensity and block geometry as spatially continuous parameters in GIS-based systems. For this purpose, a deterministic method has been implemented to estimate block size (Bloc3D) and joint frequency (COLTOP). In addition to measuring the block size, the Bloc3D Method provides a 3D representation of the shape of individual blocks. These two methods were applied using field measurements (joint set orientation and spacing) performed over a large field area, in the Swiss Alps. This area is characterized by a complex geology, a number of different rock masses and varying degrees of metamorphism. The spatial variability of the parameters was evaluated with regard to lithology and major faults. A model incorporating these measurements and observations into a GIS system to assess the risk associated with rock falls is proposed. The analysis concludes with a discussion on the feasibility of such an application in regularly and irregularly jointed rock masses, with persistent and impersistent discontinuities.

Lung fluid movements in hypoxia.

Pulmonary edema is a problem of major clinical importance resulting from a persistent imbalance between forces that drive water into the airspace of the lung and the biological mechanisms for its removal. Here, we will first review the fundamental mechanisms implicated in the regulation of lung fluid homeostasis, namely, the Starling forces and the respiratory transepithelial sodium transport. Second, we will discuss the contribution of hypoxia to the perturbation of this fine balance and the role of such perturbations in the development of high-altitude pulmonary edema, a disease characterized by a very high morbidity and mortality. Finally, we will review possible interventions aimed to maintain/restore lung fluid homeostasis and their importance for the prevention/treatment of pulmonary edema.

Teste de hipótese sobre o coeficiente de coancestria de populações haplóides

Neste trabalho foram estudadas as distribuições dos quadrados médios na análise de variância com as freqüências alélicas em amostras de indivíduos extraídas em populações haplóides, procurando avaliar o uso do teste F para testar a hipótese de nulidade do coeficiente de coancestria. Foi demonstrado que as expressões da soma de quadrados entre populações e da soma de quadrados entre indivíduos dentro de populações divididas pelas respectivas esperanças de quadrados médios possuem distribuições dechi² aproximadas, indicando que o quociente entre os quadrados médios na análise de variância tem distribuição F aproximada. Um estudo de simulação foi realizado comparando-se os valores experimentais simulados com os da distribuição teórica de F, procurando-se avaliar a validade das aproximações sugeridas. Os resultados mostraram que o teste F pode ser usado para testar a hipótese de nulidade do coeficiente de coancestria quando se trabalha com pelo menos cinco populações apresentando freqüência alélica média entre 0,3 e 0,7 utilizando-se no mínimo 50 indivíduos.

Silagem de grãos úmidos de milho na alimentação de frangos de corte

O objetivo deste trabalho foi avaliar a silagem de grãos úmidos de milho (SGUM) como ingrediente nas rações de frangos de corte, em substituição total aos grãos secos de milho (GSM), no desempenho, no rendimento da carcaça, no peso dos órgãos e na morfologia intestinal. No primeiro experimento, 600 pintainhos machos Ross foram distribuídos em blocos casualizados, com seis tratamentos (A: GSM de 1-42 dias; B: SGUM de 1-42 dias; C: SGUM de 1-7 dias e GSM de 8-42 dias; D: SGUM de 1-14 dias e GSM de 15-42 dias; E: SGUM de 1-21 dias e GSM de 22-42 dias; F: GSM + água de 1-42 dias), com quatro repetições, de 25 aves. No segundo experimento, foram utilizados 24 pintainhos machos Ross, distribuídos ao acaso, em dois tratamentos (com e sem SGUM) e 12 repetições cada. A SGUM até 21 dias de idade não interferiu no desempenho das aves e no rendimento de carcaça aos 42 dias de idade. Frangos alimentados com SGUM apresentaram maior peso relativo do fígado, menor largura das vilosidades do duodeno e íleo, maior altura de vilosidade no jejuno aos 21 dias, e menor profundidade de cripta no duodeno e no íleo aos 42 dias de idade. A SGUM pode ser considerada um ingrediente em dietas de frangos de corte até 21 dias de idade, por não interferir no peso final das aves, no rendimento de carcaça e peso dos órgãos.

Prevalence and time course of acute mountain sickness in older children and adolescents after rapid ascent to 3450 meters

OBJECTIVE: Acute mountain sickness is a frequent and debilitating complication of high-altitude exposure, but there is little information on the prevalence and time course of acute mountain sickness in children and adolescents after rapid ascent by mechanical transportation to 3500 m, an altitude at which major tourist destinations are located throughout the world. METHODS: We performed serial assessments of acute mountain sickness (Lake Louise scores) in 48 healthy nonacclimatized children and adolescents (mean +/- SD age: 13.7 +/- 0.3 years; 20 girls and 28 boys), with no previous high-altitude experience, 6, 18, and 42 hours after arrival at the Jungfraujoch high-altitude research station (3450 m), which was reached through a 2.5-hour train ascent. RESULTS: We found that the overall prevalence of acute mountain sickness during the first 3 days at high altitude was 37.5%. Rates were similar for the 2 genders and decreased progressively during the stay (25% at 6 hours, 21% at 18 hours, and 8% at 42 hours). None of the subjects needed to be evacuated to lower altitude. Five subjects needed symptomatic treatment and responded well. CONCLUSION: After rapid ascent to high altitude, the prevalence of acute mountain sickness in children and adolescents was relatively low; the clinical manifestations were benign and resolved rapidly. These findings suggest that, for the majority of healthy nonacclimatized children and adolescents, travel to 3500 m is safe and pharmacologic prophylaxis for acute mountain sickness is not needed.

Arginase II Promotes Macrophage Inflammatory Responses Through Mitochondrial Reactive Oxygen Species, Contributing to Insulin Resistance and Atherogenesis.

BACKGROUND: Macrophage-mediated chronic inflammation is mechanistically linked to insulin resistance and atherosclerosis. Although arginase I is considered antiinflammatory, the role of arginase II (Arg-II) in macrophage function remains elusive. This study characterizes the role of Arg-II in macrophage inflammatory responses and its impact on obesity-linked type II diabetes mellitus and atherosclerosis. METHODS AND RESULTS: In human monocytes, silencing Arg-II decreases the monocytes' adhesion to endothelial cells and their production of proinflammatory mediators stimulated by oxidized low-density lipoprotein or lipopolysaccharides, as evaluated by real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Macrophages differentiated from bone marrow cells of Arg-II-deficient (Arg-II(-/-)) mice express lower levels of lipopolysaccharide-induced proinflammatory mediators than do macrophages of wild-type mice. Importantly, reintroducing Arg-II cDNA into Arg-II(-/-) macrophages restores the inflammatory responses, with concomitant enhancement of mitochondrial reactive oxygen species. Scavenging of reactive oxygen species by N-acetylcysteine prevents the Arg-II-mediated inflammatory responses. Moreover, high-fat diet-induced infiltration of macrophages in various organs and expression of proinflammatory cytokines in adipose tissue are blunted in Arg-II(-/-) mice. Accordingly, Arg-II(-/-) mice reveal lower fasting blood glucose and improved glucose tolerance and insulin sensitivity. Furthermore, apolipoprotein E (ApoE)-deficient mice with Arg-II deficiency (ApoE(-/-)Arg-II(-/-)) display reduced lesion size with characteristics of stable plaques, such as decreased macrophage inflammation and necrotic core. In vivo adoptive transfer experiments reveal that fewer donor ApoE(-/-)Arg-II(-/-) than ApoE(-/-)Arg-II(+/+) monocytes infiltrate into the plaque of ApoE(-/-)Arg-II(+/+) mice. Conversely, recipient ApoE(-/-)Arg-II(-/-) mice accumulate fewer donor monocytes than do recipient ApoE(-/-)Arg-II(+/+) animals. CONCLUSIONS: Arg-II promotes macrophage proinflammatory responses through mitochondrial reactive oxygen species, contributing to insulin resistance and atherogenesis. Targeting Arg-II represents a potential therapeutic strategy in type II diabetes mellitus and atherosclerosis. (J Am Heart Assoc. 2012;1:e000992 doi: 10.1161/JAHA.112.000992.).