The geographical ancestry affects normal hemoglobin values in high-altitude residents

Increasing the hemoglobin (Hb) concentration is a major mechanism adjusting arterial oxygen content to decreased oxygen partial pressure of inspired air at high altitude. Approximately 5% of the world's population living at altitudes higher than 1500 m shows this adaptive mechanism. Notably, there is a wide variation in the extent of increase in Hb concentration among different populations. This short review summarizes available information on Hb concentrations of high-altitude residents living at comparable altitudes (3500-4500 m) in different regions of the world. An increased Hb concentration is found in all high-altitude populations. The highest mean Hb concentration was found in adult male Andean residents and in Han-Chinese living at high altitude, whereas it was lowest in Ethiopians, Tibetans, and Sherpas. A lower plasma volume in Andean high altitude natives may offer a partial explanation. Indeed, male Andean high-altitude natives have a lower plasma volume than Tibetans and Ethiopians. Moreover, Hb values were lower in adult, non-pregnant females than in males; differences between populations of different ancestry were less pronounced. Various genetic polymorphisms were detected in high altitude residents thought to favor life in a hypoxic environment, some of which correlate with the relatively low Hb concentration in the Tibetans and Ethiopians, whereas differences in angiotensin-converting enzyme allele-distribution may be related to elevated Hb in the Andeans. Taken together these results indicate different sensitivity of oxygen dependent control of erythropoiesis or plasma volume among populations of different geographical ancestry, offering explanations for differences in the Hb concentration at high altitude

The Increase in Hemoglobin Concentration With Altitude Differs Between World Regions and Is Less in Children Than in Adults

To compensate for decreased oxygen partial pressure, high-altitude residents increase hemoglobin concentrations [Hb]. The elevation varies between world regions, posing problems in defining cutoff values for anemia or polycythemia. The currently used altitude adjustments (World Health Organization [WHO]), however, do not account for regional differences. Data from The Demographic and Health Survey (DHS) Program were analyzed from 32 countries harboring >4% of residents at altitudes above 1000 m. [Hb]-increase, (ΔHb/km altitude) was calculated by linear regression analysis. Tables show 95% reference intervals (RIs) for different altitude ranges, world regions, and age groups. The prevalence of anemia and polycythemia was calculated using regressions in comparison to WHO adjustments. The most pronounced Δ[Hb]/km was found in East Africans and South Americans while [Hb] increased least in South/South-East Asia. In African regions and Middle East, [Hb] was decreased in some altitude regions showing inconsistent changes in different age groups. Of note, in all regions, the Δ[Hb]/km was lower in children than in adults, and in the Middle East, it was even negative. Overall, the Δ[Hb]/km from our analysis differed from the region-independent adjustments currently suggested by the WHO resulting in a lower anemia prevalence at very high altitudes. The distinct patterns of Δ[Hb] with altitude in residents from different world regions imply that one single, region-independent correction factor for altitude is not be applicable for diagnosing abnormal [Hb]. Therefore, we provide regression coefficients and reference-tables that are specific for world regions and altitude ranges to improve diagnosing abnormal [Hb]

Post-acute delivery of erythropoietin induces stroke recovery by promoting perilesional tissue remodelling and contralesional pyramidal tract plasticity

The promotion of post-ischaemic motor recovery remains a major challenge in clinical neurology. Recently, plasticity-promoting effects have been described for the growth factor erythropoietin in animal models of neurodegenerative diseases. To elucidate erythropoietin's effects in the post-acute ischaemic brain, we examined how this growth factor influences functional neurological recovery, perilesional tissue remodelling and axonal sprouting of the corticorubral and corticobulbar tracts, when administered intra-cerebroventricularly starting 3 days after 30 min of middle cerebral artery occlusion. Erythropoietin administered at 10 IU/day (but not at 1 IU/day), increased grip strength of the contralesional paretic forelimb and improved motor coordination without influencing spontaneous locomotor activity and exploration behaviour. Neurological recovery by erythropoietin was associated with structural remodelling of ischaemic brain tissue, reflected by enhanced neuronal survival, increased angiogenesis and decreased reactive astrogliosis that resulted in reduced scar formation. Enhanced axonal sprouting from the ipsilesional pyramidal tract into the brainstem was observed in vehicle-treated ischaemic compared with non-ischaemic animals, as shown by injection of dextran amines into both motor cortices. Despite successful remodelling of the perilesional tissue, erythropoietin enhanced axonal sprouting of the contralesional, but not ipsilesional pyramidal tract at the level of the red and facial nuclei. Moreover, molecular biological and histochemical studies revealed broad anti-inflammatory effects of erythropoietin in both hemispheres together with expression changes of plasticity-related molecules that facilitated contralesional axonal growth. Our study establishes a plasticity-promoting effect of erythropoietin after stroke, indicating that erythropoietin acts via recruitment of contralesional rather than of ipsilesional pyramidal tract projection

Structured environments in solid state systems: crossover from Gaussian to non-Gaussian behavior

The variety of noise sources typical of the solid state represents the main limitation toward the realization of controllable and reliable quantum nanocircuits, as those allowing quantum computation. Such ``structured environments'' are characterized by a non-monotonous noise spectrum sometimes showing resonances at selected frequencies. Here we focus on a prototype structured environment model: a two-state impurity linearly coupled to a dissipative harmonic bath. We identify the time scale separating Gaussian and non-Gaussian dynamical regimes of the Spin-Boson impurity. By using a path-integral approach we show that a qubit interacting with such a structured bath may probe the variety of environmental dynamical regimes.Comment: 8 pages, 9 figures. Proceedings of the DECONS '06 Conferenc

Ethnic differences in adverse iron status in early pregnancy: a cross-sectional population-based study

We studied ethnic differences in terms of iron status during pregnancy between Dutch women and other ethnicities and explore to what extent these differences can be explained by environmental factors. This cross-sectional population-based study (2002–2006) was embedded in the Generation R study and included a total of 4737 pregnant women from seven ethnic groups (Dutch, Turkish, Moroccan, Cape Verdean, Surinamese-Hindustani, Surinamese-Creole and Antillean). Ethnicity was defined according to the Dutch classification of ethnic background. Ferritin, iron and transferrin were measured in early pregnancy. The overall prevalence of iron deficiency was 7 %, ranging from 4 % in both Dutch and Surinamese-Creoles, to 18 % in Turkish, Moroccan and Surinamese-Hindustani women. Iron overload was most prevalent in Surinamese-Creole (11 %) and Dutch (9 %) women. Socioeconomic factors accounted for 5–36 % of the differences. Income was the strongest socioeconomic factor in the Cape Verdean and Surinamese-Hindustani groups and parity for the Turkish and Moroccan groups. Lifestyle determinants accounted for 8–14 % of the differences. In all groups, the strongest lifestyle factor was folic acid use, being associated with higher iron status. In conclusion, in our population, both iron deficiency and iron overload were common in early pregnancy. Our data suggest that ethnic differences in terms of socioeconomic and lifestyle factors only partly drive the large ethnic differences in iron status. Our data support the development of more specific prevention programmes based on further exploration of socioeconomic inequities, modifiable risk and genetic factors in specific ethnic subgroups, as well as the need for individual screening of iron status before supplementation

Prevalence and predictors of falls and dizziness in people younger and older than 80 years of age-A longitudinal cohort study.

The objectives were to investigate the prevalence and predictors for falls and dizziness among people younger and older than 80 years of age. The sample was drawn from the Swedish National study on Aging and Care (SNAC) and comprised 973 and 1273 subjects with data on the occurrence of falls and dizziness respectively at baseline. Follow-ups were made after 3- and 6-years. Data included socio-demographics, physical function, health complaints, cognition, quality of life and medications. The prevalence of falls was 16.5% in those under aged 80 and 31.7% in those 80+ years while dizziness was reported by 17.8% and 31.0% respectively. Predictors for falls in those under aged 80 were neuroleptics, dependency in personal activities of daily living (PADL), a history of falling, vision impairment and higher age, and in those 80+ years a history of falling, dependency in instrumental activities of daily living (IADL), fatigue and higher age. Factors predicting dizziness in those under aged 80 were a history of dizziness, feeling nervous and reduced grip strength and in those 80+ years a history of dizziness and of falling. Predictors for falls and dizziness differed according to age. Specific factors were identified in those under aged 80. In those 80+ years more general factors were identified implying the need for a comprehensive investigation to prevent falls. This longitudinal study also showed that falling and dizziness in many older people are persistent and therefore should be treated as chronic conditions

Iron- and erythropoietin-resistant anemia in a spontaneous breast cancer mouse model

Anemia of cancer (AoC) with its multifactorial etiology and complex pathology is a poor prognostic indicator for cancer patients. One of the main causes of AoC is cancer-associated inflammation that activates mechanisms, commonly observed in anemia of inflammation, where functional iron deficiency and iron-restricted erythropoiesis is induced by increased hepcidin levels in response to IL-6 elevation. So far only a few AoC mouse models have been described, and most of them did not fully recapitulate the interplay of anemia, increased hepcidin levels and functional iron deficiency in human patients. To test if the selection and the complexity of AoC mouse models dictates the pathology or if AoC in mice per se develops independently of iron deficiency, we characterized AoC in Trp53floxWapCre mice that spontaneously develop breast cancer. These mice developed AoC associated with high IL-6 levels and iron deficiency. However, hepcidin levels were not increased and hypoferremia coincided with anemia rather than causing it. Instead, an early shift in the commitment of common myeloid progenitors from the erythroid to the myeloid lineage resulted in increased myelopoiesis and in the excessive production of neutrophils that accumulate in necrotic tumor regions. This process could neither be prevented by iron nor erythropoietin (EPO) treatment. Trp53floxWapCre mice are the first mouse model where EPO-resistant anemia is described and may serve as a disease model to test therapeutic approaches for a subpopulation of human cancer patients with normal or corrected iron levels that do not respond to EPO

Elevated hepcidin serum level in response to inflammatory and iron signals in exercising athletes is independent of moderate supplementation with vitamin C and E

Iron deficiency among endurance athletes is of major concern for coaches, physicians, and nutritionists. Recently, it has been observed that hepcidin, the master regulator of iron metabolism, was upregulated after exercise and was found to be related to interleukin-6 (IL-6) elevation. In this study performed on noniron deficient and well-trained runners, we observed that hepcidin concentrations remain elevated in response to inflammatory and iron signals despite a 28-days supplementation period with vitamins C (500 mg/day) and E (400 IU/day)