Pulmonary Hypertension in Latin America Pulmonary Vascular Disease: The Global Perspective

Latin America is here defined as all of the Americas south of the United States. In the setting of pulmonary hypertension, there are social inequalities and geophysical aspects in this region that account for a high prevalence of certain etiologies. This review aimed to analyze some of these factors. Data were collected from the existing literature. Information also was obtained from local tertiary-care centers to where patients with pulmonary hypertension generally are referred. Further, local experience and expertise was taken into consideration. Three etiologies of pulmonary hypertension were found to be the most prevalent: schistosomiasis (similar to 1 million affected people in Brazil), high altitude (particularly in the Andes), and congenital heart disease (late diagnosis of congenital left-to-right shunts leading to development of pulmonary vasculopathy). The diversity in terms of ancestries and races probably accounts for the differences in phenotype expression of pulmonary hypertension when a given region is considered (eg, schistosomiasis-, high-altitude-, or congenital heart disease-associated pulmonary hypertension). Governmental measures are needed to improve social and economic inequalities with an obvious impact on certain etiologies, such as schistosomiasis and congenital heart disease. Early diagnosis of pulmonary hypertension and access to medication remain important challenges all over Latin America. CHEST 2010; 137(6)(Suppl):78S-84S

Reciprocal interactions of obstructive sleep apnea and hypertension associated with ACE I/D polymorphism in males

Background: The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism gene contributes to the genesis of hypertension (HTN) and may help explain the relationship between obstructive sleep apnea (OSA) and HTN. However, ACE is a pleiotropic gene that has several influences, including skeletal muscle and control of ventilation. We therefore tested the hypothesis that ACE polymorphism influences OSA severity. Methods: Male OSA patients (apnea-hypopnea index [AHI] > 5 events/h) from 2 university sleep centers were evaluated by polysomnography and ACE I/D polymorphism genotyping. Results: We studied 266 males with OSA (age = 48 +/- 13y, body mass index = 29 5kg/m(2), AHI = 34 +/- 25events/h). HTN was present in 114 patients (43%) who were older (p < 0.01), heavier (p < 0.05) and had more severe OSA (p < 0.01). The I allele was associated with HTN in patients with mild to moderate OSA (p < 0.01), but not in those with severe OSA. ACE I/D polymorphism was not associated with apnea severity among normotensive patients. In contrast. the only variables independently associated with OSA severity among patients with hypertension in multivariate analysis were BMI (OR = 1.12) and 11 genotype (OR = 0.27). Conclusions: Our results indicate reciprocal interactions between OSA and HTN with ACE I/D polymorphism, suggesting that among hypertensive OSA males, the homozygous ACE I allele protects from severe OSA. (C) 2009 Elsevier B.V. All rights reserved.

Cell cycle and apoptosis in normal and cloned bovine near-term placentae

The bovine maternal epithelium is composed of cuboidal cells interspersed with low columnar cells having centrally located nuclei. Bovine trophoblast is composed of two cell types: mononuclear trophoblastic and giant trophoblastic cells that can have two or more nuclei. Number of apoptotic cells and proliferative cells are variable in both cell populations. This study compared tissue growth and apoptosis by flow cytometry in the cell population found at distinct placental regions (central region of placentomes, <= 1-cm microplacentomes and the interplacentomal region) between normal and cloned near-term bovine pregnancies. After a morphological comparison between regions and groups (controls vs. clones), a lesser proportion of diploid to tetraploid cells was observed in the central region of placentomes and in microplacentomes from cloned-derived pregnancies. In addition, cloned animals had a fewer apoptotic cells in the central region of the placentome and in interplacentomal region and a greater proliferative capacity in all regions (cells in G(2)/M) near term as opposed to control animals. These results may reveal the existence of a relationship between such changes in the proportions of uterine and trophoblastic epithelial cells at the end of pregnancy and normal placental function. This could be related to faulty placentation in early pregnancy, placental insufficiency during pregnancy or lack of placental and/or fetal maturation in late pregnancy, which may contribute to someof the abnormalities after in vitro embryo manipulations, such as poor preparation and initiation of parturition, prolonged gestation and lesser post-natal survival in some cloned animals. (C) 2008 Elsevier B.V. All rights reserved.

The validity of self-reported energy intake as determined using the doubly labelled water technique

In the 1980s the development of the doubly labelled water (DLW) technique made it possible to determine the validity of dietary assessment methods using external, independent markers of intake in free-living populations. Since then, the accuracy of self-reported energy intake (EI) has been questioned on a number of occasions as under-reporting has been found to be prevalent in many different populations. This paper is a review of investigations using the DLW technique in conjunction with self-reported EI measures in groups including adults, children and adolescents, obese persons, athletes, military personnel and trekking explorers. In studies where a person other than the subject is responsible for recording dietary intake, such as parents of young children, EI generally corresponds to DLW determined energy expenditure. However, in instances where the subjects themselves report their intake, EI is generally under-reported when compared with energy expenditure. It was originally believed that this phenomenon of under-reporting was linked to increased adiposity and body size, however, it is now apparent that other factors, such as dietary restraint and socio-economic status, are also involved. This paper therefore aims to present a more comprehensive picture of under-reporting by tying in the findings of many DLW studies with other studies focusing particularly on the characteristics and mechanisms for under-reporting. Awareness of these characteristics and mechanisms will enable researchers to obtain more accurate self-reports of EI using all dietary recording techniques.

Qualidade fisiológica de sementes e diversidade genética de maracujazeiros cultivados em diferentes altitudes no Espírito Santo

O maracujazeiro pertence à família Passifloraceae e ao gênero Passiflora que é o mais importante economicamente. Altitudes entre 100 a 900 m são indicadas para o plantio do maracujazeiro e estudos sobre localizações geográficas distintas possibilitam expressões do genótipo, influenciadas pelas condições ambientais. O gradiente altitudinal influencia a distribuição da variação genética dentro e entre populações de plantas e a diversidade genética muda com a altitude. O presente trabalho teve como objetivo avaliar a qualidade fisiológica de sementes e a diversidade genética de maracujazeiros cultivados em diferentes altitudes do Espírito Santo. Para avaliação da qualidade fisiológica das sementes, os frutos de Passiflora spp. maduros foram colhidos em pomares localizados em altitudes baixa (0-100 m), média (>100 até 600 m) e alta (>600 m) de diferentes municípios do Espírito Santo. Os tratamentos pré-germinativos nas sementes foram: T1- escarificação física, feita manualmente com lixa d´água nº 120; T2- tratamento com ácido giberélico (GA3) na concentração de 500 mg L-1 com embebição por 24 horas e T3- sementes sem escarificação realizados nas sementes em laboratório e em casa de vegetação. Foi avaliado o envelhecimento acelerado tradicional, envelhecimento acelerado com saturação salina e deterioração controlada em sementes de maracujá amarelo sem escarificação localizado em alta altitude e as condições que apresentaram menor deterioração das sementes para aplicação às demais espécies e altitudes com os respectivos tratamentos pré-germinativos que apresentaram maiores valores de germinação e vigor em laboratório e em casa de vegetação. Assim, para as sementes do maracujá amarelo utilizou-se o tratamento sem escarificação, para sementes de maracujá roxo, a escarificação física e para as sementes de maracujá doce, o tratamento com ácido giberélico. O teste de envelhecimento acelerado com saturação salina a 43 ºC por 72 horas e deterioração controlada a 25% de umidade expostas por 24 horas diferencia as espécies nas diferentes altitudes. Sementes de maracujá amarelo e sementes localizadas em alta altitude apresentam qualidade fisiológica superior. Para a avaliação da diversidade genética foram utilizadas folhas jovens de cinco plantas matrizes de Passiflora edulis Sims f. flavicarpa Degener, P. edulis Sims e P. alata Curtis cultivadas em três altitudes (baixa, média e alta) do Espírito Santo. Para SSR foi encontrado baixo número de alelos, alta heterozigosidade esperada e altos valores de PIC e para a análise ISSR detectou um elevado número de bandas por primer e alto polimorfismo. Há maior similaridade genética entre P. edulis f. flavicarpa Deg. e P. edulis. Passiflora alata apresenta maior distância genética em relação às espécies. As populações de baixa altitude se diferenciam das demais independente da espécie e do marcador utilizado.

New mitochondrial and nuclear evidences support recent demographic expansion and an atypical phylogeographic pattern in the Spittlebug Philaenus spumarius (Hemiptera, Aphrophoridae)

Copyright: © 2014 Rodrigues et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Proboscideans and other vertebrates from Anchrif, Morocco

The paleontological richness of Morocco has been scientifically known since at least the early 20th century. The region of the Middle Atlas, more specifically the Boulemane area, has been however only sparsely studied since the 60’s when it supplied various vertebrate fossils from the Middle Jurassic.In the beginning of the 2000’s some fossil bones were discovered in a new fossil-site near the village of Taghrout, in the Boulemane area and in September 2013 a Moroccan-Portuguese expedition made excavations in the site with the help locals from the village of Taghrout. The site is Pleistocene in age and is located on a rare bone bearing small high-altitude sedimentary basin, non-charted in previous geological maps. The excavations yielded new bone material from large mammals. The most common findings are elephants ascribed to the genus Elephas, but artiodactyls, turtles, and in-situ hominid Acheulean tools were also collected. During the excavation campaign the Jurassic sites were revisited and new dinosaur trails and possible crocodilomorph bones were discovered. Surface collection of in a cave near Taghrout with Holocene mammal material, including the genera Canis, Capra, Bos, Panthera and Hystrix was also conducted and its fossils elements identified.

Restriction site-associated DNA sequencing, genotyping error estimation and de novo assembly optimization for population genetic inference.

Restriction site-associated DNA sequencing (RADseq) provides researchers with the ability to record genetic polymorphism across thousands of loci for nonmodel organisms, potentially revolutionizing the field of molecular ecology. However, as with other genotyping methods, RADseq is prone to a number of sources of error that may have consequential effects for population genetic inferences, and these have received only limited attention in terms of the estimation and reporting of genotyping error rates. Here we use individual sample replicates, under the expectation of identical genotypes, to quantify genotyping error in the absence of a reference genome. We then use sample replicates to (i) optimize de novo assembly parameters within the program Stacks, by minimizing error and maximizing the retrieval of informative loci; and (ii) quantify error rates for loci, alleles and single-nucleotide polymorphisms. As an empirical example, we use a double-digest RAD data set of a nonmodel plant species, Berberis alpina, collected from high-altitude mountains in Mexico.

Discordances between phylogenetic and morphological patterns in alpine leaf beetles attest to an intricate biogeographic history of lineages in postglacial Europe.

Pleistocene glacial and interglacial periods have moulded the evolutionary history of European cold-adapted organisms. The role of the different mountain massifs has, however, not been accurately investigated in the case of high-altitude insect species. Here, we focus on three closely related species of non-flying leaf beetles of the genus Oreina (Coleoptera, Chrysomelidae), which are often found in sympatry within the mountain ranges of Europe. After showing that the species concept as currently applied does not match barcoding results, we show, based on more than 700 sequences from one nuclear and three mitochondrial genes, the role of biogeography in shaping the phylogenetic hypothesis. Dating the phylogeny using an insect molecular clock, we show that the earliest lineages diverged more than 1 Mya and that the main shift in diversification rate occurred between 0.36 and 0.18 Mya. By using a probabilistic approach on the parsimony-based dispersal/vicariance framework (MP-DIVA) as well as a direct likelihood method of state change optimization, we show that the Alps acted as a cross-roads with multiple events of dispersal to and reinvasion from neighbouring mountains. However, the relative importance of vicariance vs. dispersal events on the process of rapid diversification remains difficult to evaluate because of a bias towards overestimation of vicariance in the DIVA algorithm. Parallels are drawn with recent studies of cold-adapted species, although our study reveals novel patterns in diversity and genetic links between European mountains, and highlights the importance of neglected regions, such as the Jura and the Balkanic range.

Increasing respiratory dead space improves sleep disordered breathing and hypoxemia in patients with chronic mountain sickness

Background: Chronic mountain sickness (CMS), which is characterised by hypoxemia, erythrocytosis and pulmonary hypertension, is a major public health problem in high-altitude dwellers. The only existing treatment is descent to low altitude, an option that for social reasons almost never exists. Sleep disordered breathing may represent an underlying mechanism. We recently found that in mountaineers increasing the respiratory dead space markedly improves sleep disordered breathing. The aim of the present study was to assess the effects of this procedure on sleep disordered breathing in patients with CMS. Methods: In 10 male Bolivian high-altitude dwellers (mean ± SD age, 59 ± 9 y) suffering from CMS (haemoglobin >20 g/L) full night sleep recordings (Embletta, RespMed) were obtained in La Paz (3600 m). In random order, one night was spent with a 500 ml increase in dead space through a custom designed full face mask and the other night without it. Exclusion criteria were: secondary erythrocytosis, smoking, drug intake, acute infection, cardio- pulmonary or neurologic disease and travelling to low altitude in the preceding 6 months. Results: The major new finding was that added dead space dramatically improved sleep disordered breathing in patients suffering from CMS. The apnea/hypopnea index decreased by >50% (from 34.5 ± 25.0 to 16.8 ± 14.9, P = 0.003), the oxygen desaturation index decreased from 46.2 ± 23.0 to 27.2 ± 20.0 (P = 0.0004) and hypopnea index from 28.8 ± 20.9 to 16.3 ± 14.0 (P = 0.01), whereas nocturnal oxygen saturation increased from 79.8 ± 3.6 to 80.9 ± 3.0% (P = 0.009). The procedure was easily accepted and well tolerated. Conclusion: Here, we show for the very first time that an increase in respiratory dead space through a fitted mask dramatically improves nocturnal breathing in high-altitude dwellers suffering from CMS. We speculate that when used in the long-term, this procedure will improve erythrocytosis and pulmonary hypertension and offer an inexpensive and easily implementable treatment for this major public health problem.

Repeated Pre-Syncope from Increased Inspired CO2 in a Background of Severe Hypoxia.

We describe a case of experimentally induced pre-syncope in a healthy young man when exposed to increased inspired CO2 in a background of hypoxia. Acute severe hypoxia (FIO2=0.10) was tolerated, but adding CO2 to the inspirate caused pre-syncope symptoms accompanied by hypotension and large reductions in both mean and diastolic middle cerebral artery velocity, while systolic flow velocity was maintained. The mismatch of cerebral perfusion pressure and vascular tone caused unique retrograde cerebral blood flow at the end of systole and a reduction in cerebral tissue oxygenation. We speculate that this occurrence of pre-syncope was due to hypoxia-induced inhibition of brain regions responsible for compensatory sympathetic activity to relative hypercapnia.

Exercise induces rapid interstitial lung water accumulation in patients with chronic mountain sickness.

BACKGROUND: Chronic mountain sickness (CMS) is a major public health problem in mountainous regions of the world. In its more advanced stages, exercise intolerance is often found, but the underlying mechanism is not known. Recent evidence indicates that exercise-induced pulmonary hypertension is markedly exaggerated in CMS. We speculated that this problem may cause pulmonary fluid accumulation and aggravate hypoxemia during exercise. METHODS: We assessed extravascular lung water (chest ultrasonography), pulmonary artery pressure, and left ventricular function in 15 patients with CMS and 20 control subjects at rest and during exercise at 3,600 m. RESULTS: Exercise at high altitude rapidly induced pulmonary interstitial fluid accumulation in all patients but one (14 of 15) with CMS and further aggravated the preexisting hypoxemia. In contrast, in healthy high-altitude dwellers exercise did not induce fluid accumulation in the majority of subjects (16 of 20) (P = .002 vs CMS) and did not alter arterial oxygenation. Exercise-induced pulmonary interstitial fluid accumulation and hypoxemia in patients with CMS was accompanied by a more than two times larger increase of pulmonary artery pressure than in control subjects (P < .001), but no evidence of left ventricular dysfunction. Oxygen inhalation markedly attenuated the exercise-induced pulmonary hypertension (P < .01) and interstitial fluid accumulation (P < .05) in patients with CMS but had no detectable effects in control subjects. CONCLUSIONS: To our knowledge, these findings provide the first direct evidence that exercise induces rapid interstitial lung fluid accumulation and hypoxemia in patients with CMS that appear to be related to exaggerated pulmonary hypertension. We suggest that this problem contributes to exercise intolerance in patients with CMS. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov.

Restriction site-associated DNA sequencing, genotyping error estimation and de novo assembly optimization for population genetic inference.

Restriction site-associated DNA sequencing (RADseq) provides researchers with the ability to record genetic polymorphism across thousands of loci for nonmodel organisms, potentially revolutionizing the field of molecular ecology. However, as with other genotyping methods, RADseq is prone to a number of sources of error that may have consequential effects for population genetic inferences, and these have received only limited attention in terms of the estimation and reporting of genotyping error rates. Here we use individual sample replicates, under the expectation of identical genotypes, to quantify genotyping error in the absence of a reference genome. We then use sample replicates to (i) optimize de novo assembly parameters within the program Stacks, by minimizing error and maximizing the retrieval of informative loci; and (ii) quantify error rates for loci, alleles and single-nucleotide polymorphisms. As an empirical example, we use a double-digest RAD data set of a nonmodel plant species, Berberis alpina, collected from high-altitude mountains in Mexico.

Exogenous selection shapes germination behaviour and seedling traits of populations at different altitudes in a Senecio hybrid zone.

BACKGROUND AND AIMS: The Senecio hybrid zone on Mt Etna, Sicily, is characterized by steep altitudinal clines in quantitative traits and genetic variation. Such clines are thought to be maintained by a combination of 'endogenous' selection arising from genetic incompatibilities and environment-dependent 'exogenous' selection leading to local adaptation. Here, the hypothesis was tested that local adaptation to the altitudinal temperature gradient contributes to maintaining divergence between the parental species, S. chrysanthemifolius and S. aethnensis. METHODS: Intra- and inter-population crosses were performed between five populations from across the hybrid zone and the germination and early seedling growth of the progeny were assessed. KEY RESULTS: Seedlings from higher-altitude populations germinated better under low temperatures (9-13 °C) than those from lower altitude populations. Seedlings from higher-altitude populations had lower survival rates under warm conditions (25/15 °C) than those from lower altitude populations, but also attained greater biomass. There was no altitudinal variation in growth or survival under cold conditions (15/5 °C). Population-level plasticity increased with altitude. Germination, growth and survival of natural hybrids and experimentally generated F(1)s generally exceeded the worse-performing parent. CONCLUSIONS: Limited evidence was found for endogenous selection against hybrids but relatively clear evidence was found for divergence in seed and seedling traits, which is probably adaptive. The combination of low-temperature germination and faster growth in warm conditions might enable high-altitude S. aethnensis to maximize its growth during a shorter growing season, while the slower growth of S. chrysanthemifolius may be an adaptation to drought stress at low altitudes. This study indicates that temperature gradients are likely to be an important environmental factor generating and maintaining adaptive divergence across the Senecio hybrid zone on Mt Etna.

Lymnaea cousini Jousseaume, 1887 (Gastropoda: Lymnaeidae): first record for Venezuela

Lymnaea cousini Jousseaume, 1887 was collected in Mucubaji, Merida State, Venezuela, from a permanent pond located at a very high altitude (3760 m). Identification of the collected specimens was made by comparison with the original description of the shell by Jousseaume and the description of the renal organ and reproductive system of topotypic specimens by Paraense.