Loneliness, Depression, and Genetics in the Elderly: Prognostic Factors of a Worse Health Condition?

Loneliness is considered a prognostic factor for poorer health status in the elderly. It is proposed to analyze the role of loneliness in health status in terms of various factors. A total of 1747 individuals from the pilot survey of the Aging in Spain Longitudinal Study (ELES-PS) were reviewed. ELES is a cross-sectional study for collecting health variables, food habits, socioeconomic data, and cognitive and functional capacities, which was carried out on a Spanish representative sample of noninstitutionalized persons of 50 years of age or older. Moreover, since telomere shortening is associated with cellular senescence, 35 telomere-related SNPs and cognitive impairments were analyzed. The results characterize the "solos" as males of 50-60 years, who were overweight and had lower levels of hemoglobin and neutrophils. There is also an association between five SNPs related to telomere length and BDNF. A group of people with loneliness and depression was identified with poorer health and cognitive status, poorer perception of their quality of life, poorer quality of sleep, and lower physical activity. Therefore, it follows that telomeres and BDNF play a role as intermediaries between loneliness and depression and their relationship with a worse state of health.

Small static radiosurgery field dosimetry with small volume ionization chambers.

PURPOSE: To evaluate the response of the four smallest active volume thimble type ionization chambers commercially available (IBA-dosimetry RAZOR Nano Chamber, Standard Imaging Exradin A16, IBA-dosimetry CC01 and PTW T31022) when measuring SRS cone collimated Flattening Filter Free (FFF) fields. METHODS: We employed Monte Carlo simulation for calculating correction factors as defined in IAEA TRS-483. Monte Carlo simulation beam model and ion chamber geometry definitions were supported by an extensive set of measurements. Type A and B uncertainty components were evaluated. RESULTS: Commissioning of Monte Carlo 6 MV and 10 MV FFF beam models yielded relative differences between measured and simulated dose distributions lower than 1.5%. Monte Carlo simulated output factors for 5 mm SRS field agree with experimental values within 1% local relative difference for all chambers. Smallest active volume ion chamber (IBA-dosimetry RAZOR Nano Chamber) exhibits smallest correction, being compatible with unity. Correction factor combined uncertainties range between 0.7% and 0.9%. Smallest uncertainties were recorded for smallest and largest active volume ion chambers, although the latter exhibited largest correction factor. Highest contribution to combined uncertainty was type B component associated with beam model initial electron spatial Full Width Half Maximum (FWHM) uncertainty. CONCLUSIONS: Among the investigated chambers, the IBA RAZOR Nano Chamber was found to be an excellent choice for narrow beam output factor measurement since it requires minimum correction (in line with IAEA TRS-483 recommendations). This is caused by its tiny size and tissue equivalence materials which produce minimum volume averaging and fluence perturbation.

Acenocoumarol Pharmacogenetic Dosing Algorithm versus Usual Care in Patients with Venous Thromboembolism: A Randomised Clinical Trial.

Patients with venous thromboembolism (VTE) require immediate treatment with anticoagulants such as acenocoumarol. This multicentre randomised clinical trial evaluated the effectiveness of a dosing pharmacogenetic algorithm versus a standard-of-care dose adjustment at the beginning of acenocoumarol treatment. We included 144 patients with VTE. On the day of recruitment, a blood sample was obtained for genotyping (CYP2C9*2, CYP2C9*3, VKORC1, CYP4F2, APOE). Dose adjustment was performed on day 3 or 4 after the start of treatment according to the assigned group and the follow-up was at 12 weeks. The principal variable was the percentage of patients with an international normalised ratio (INR) within the therapeutic range on day 7. Thirty-four (47.2%) patients had an INR within the therapeutic range at day 7 after the start of treatment in the genotype-guided group compared with 14 (21.9%) in the control group (p = 0.0023). There were no significant differences in the time to achieve a stable INR, the number of INRs within the range in the first 6 weeks and at the end of study. Our results suggest the use of a pharmacogenetic algorithm for patients with VTE could be useful in achieving target INR control in the first days of treatment.

Spanish allele and haplotype database for 32 X-chromosome Insertion-Deletion polymorphisms.

X-chromosome markers have been proved to be decisive both complementing and solving kinship analysis, particularly when autosomal markers are not able to produce adequate likelihood ratios between different hypothesis. On the other hand, Pereira et al., (2012) have demonstrated that 32 Insertion/Deletion (InDel) markers located on the X-Chromosome have a very important power of discrimination in human populations, being a novel tool in the forensic and population fields. So, the aim of the present work was testing the forensic and population genetic efficiency of the 32 X-InDel polymorphisms in the Spanish population, and subsequently build an allele/haplotype frequencies database. To accomplish this objective, a total of 555 samples comprising male individuals from 13 Spanish regions were analysed for the above mentioned 32 X-InDels in two independent laboratories. A pairwise FST analysis was performed in order to understand if the studied Spanish sub-populations present significant differences among them, detecting possible population substructure. Also, linkage disequilibrium analyses were computed to investigate the presence of association between markers in the Spanish population. After Bonferroni correction, the absence of significant differences among the studied regions supports a global Spanish population database. Concerning LD, besides previously reported linked markers MID356-MID357 and MID3690-MID3719-MID2089, we also detected significant association between MID3703-MID3774, even after Bonferroni correction. Finally, after computing allele and haplotype frequencies, forensic efficiency parameters were calculated (PDmales = 99.999976 %; PDfemales = 99.99999999998 %). Mean exclusion chance values for duos were 0.999 and trios 0.99999. These results reinforce the suitability of the 32 X-InDels marker set both in identification and kinship studies.

Multiparametric magnetic resonance imaging-guided salvage radiotherapy in prostate cancer.

AIM: To analyse the efficacy and toxicity of postprostatectomy SRT in patients with a BCR evaluated with mpMRI. BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) has the ability to detect the site of pelvic recurrence in patients with biochemical recurrence (BCR) after radical prostatectomy (RP). However, we do not know the oncological outcomes of mpMRI-guided savage radiotherapy (SRT). RESULTS: Local, lymph node, and pelvic bone recurrence was observed in 13, 4 and 2 patients, respectively. PSA levels were significantly lower in patients with negative mpMRI (0.4 ng/mL [0.4]) vs. positive mpMRI (2.2 ng/mL [4.1], p = 0.003). Median planning target volume doses in patients with visible vs. non-visible recurrences were 76 Gy vs. 70 Gy. Overall, mean follow-up was 41 months (6-81). Biochemical relapse-free survival (bRFS) at 3 years was 82.3% and 82.5%, respectively, for the negative and positive mpMRI groups (p = 0.800). Three-year rates of late grade ≥2 urinary and rectal toxicity were 14.8% and 1.9%, respectively; all but one patient recovered without sequelae. CONCLUSION: SRT to the macroscopic recurrence identified by mpMRI is a feasible and well-tolerated option. In this study, there were no differences in bRFS between MRI-positive and MRI-negative patients, indicating effective targeting of MRI-positive lesions.

Diseño de un registro de parálisis cerebral de ámbito poblacional: aplicación y análisis en Andorra y Navarra / The design of a population register on cerebral palsy: its application and analysis in Andorra and Navarre

Introducción. La parálisis cerebral describe un grupo de trastornos del desarrollo y la postura que causan una limitación de la actividad debido a alteraciones no progresivas ocurridas en el cerebro en desarrollo. El registro poblacional facilita la identificación de los casos de parálisis cerebral dentro de una población geográfica específica. Está reconocida su utilidad en la bibliografía, pero en España, las bases de datos publicadas se centran en el tratamiento o las complicaciones de la parálisis cerebral. Objetivos. Proponer un registro poblacional que pueda ser útil en diferentes áreas de nuestro entorno y evaluar su validez mediante su aplicación en dos áreas de salud diferenciadas y geográficamente delimitadas. Sujetos y métodos. El registro elaborado constaba de 124 ítems divididos en siete apartados: datos de filiación del niño, historia materna e información de los padres, datos del embarazo y período neonatal, diagnósticos y clasificación, pruebas de neuroimagen, intervenciones terapéuticas y otros. Se incluyó a los pacientes atendidos en consultas externas en Navarra y Andorra. Resultados. En el registro se evaluó a 53 pacientes (52,8% mujeres). El 56,5% fueron prematuros. La parálisis cerebral espástica es la presentación más frecuente. Un 42% asociaba epilepsia. Conclusiones. El uso de registros poblacionales permite un mejor conocimiento de la parálisis cerebral, así como la evaluación y el desarrollo de estrategias de prevención y optimización de los recursos asistenciales con datos objetivos. Es necesaria la generalización del uso de este tipo de registros en nuestro entorno

Introduction. Cerebral palsy describes a group of developmental and posture disorders, which cause a limitation of activity due to non-progressive damage occurring in the developing brain. A population register facilitates the identification of cerebral palsy cases within a specific geographic population. Its usefulness is recognized in the world literature but in Spain, published databases focus on the treatment or complications of cerebral palsy. Aims. To propose a population register that can be useful in different areas of our environment and to evaluate its validity through its application in two differentiated and geographically delimited health areas. Subjects and methods. The registry consists of 124 items divided into seven sections: data on the child filiations, maternal history and parents’ information, pregnancy and neonatal period data, diagnoses and classification, neuroimaging tests, therapeutic interventions and others. Patients attended in external consultations in Navarre and Andorra were included. Results. In the register, 53 patients (52.8% females) were evaluated. 56.5% were premature. Spastic cerebral palsy is the most frequent presentation. 42% have associated epilepsy. Conclusions. The use of population registers allows a better knowledge of cerebral palsy as well as the evaluation and development of prevention strategies and optimization of care resources with objective data. It is necessary to generalize the use of this type of records in our environment

Características clínicas, epidemiológicas y metabólicas en diabéticos tipo 2 recién diagnosticados con insulina como terapéutica transitoria / Clinical, epidemiological and metabolic characteristics in type 2 diabetics newly diagnosed with insulin as transitory therapy

Introducción: en los enfermos con diabetes mellitus tipo 2 el tratamiento inicial con insulina es una modalidad terapéutica utilizada.Objetivo: caracterizar clínica, epidemiológica y metabólicamente los enfermos de diabetes mellitus tipo 2 con uso transitorio de insulina luego del diagnóstico.Método: se realizó un estudio observacional descriptivo prospectivo en el Hospital General Provincial Docente de Ciego de Ávila durante el período de mayo 2015 a julio 2016. De una población de 131 enfermos de diabetes mellitus tipo 2 se tomó una muestra intencional de 67, a los cuales se les indicó insulina de forma transitoria luego del diagnóstico.Resultados: la edad media fue 48,90 años. Predominaron las mujeres (56,71 por ciento) y el antecedente familiar (94,02 por ciento). La dosis media de insulina fue de 29,60 ± 6,20 Ud/día en 42,90 ± 9,3 días. Se produjo mejoría significativa entre el inicio y seis meses: índice de masa corporal (30,80 ± 2,3-28,60 ± 2,06); circunferencia de la cintura abdominal (hombres 108,3 ± 7,8-103,30 ± 6,20 cm y mujeres 103,60 ± 7,10-100,10 ± 5,70 cm); glucemia en ayunas (13,60 ± 1,30 mmol/L y PP2h: 22,10 ± 2,80-10 ± 0,70 mmol/L y 7,90 ± 1,10 mmol/L) y hemoglobina glucocilada (8,70 ± 1,10-6,90 ± 0,60 por ciento). Las hipoglucemias fueron pocas: 2,90 por ciento moderadas y 5,90 por ciento ligeras. La casi totalidad se mantenía controlada con metformina a los seis meses (92,54 por ciento).Conclusiones: los resultados confirman que con el uso inicial transitorio de insulina se logra un control glucémico adecuado, mantenido posteriormente con monoterapia de metformina(AU)

Introduction: in patients with type 2 diabetes mellitus, initial treatment with insulin is a therapeutic modality used.Objective: to characterize clinically, epidemiologically and metabolically patients with type 2 diabetes mellitus with transient use of insulin after diagnosis.Method: a prospective descriptive observational study was carried out in the General Provincial Teaching Hospital of Ciego de Ávila during the period from May 2015 to July 2016. From a population of 131 patients with diabetes mellitus type 2, an intentional sample of 67 was taken, which insulin was indicated transiently after diagnosis. Results: the average age was 48,90 years. Women predominated (56,71 percent) and family history (94,02 percent). The mean insulin dose was 29,60 ± 6,20 Ud/day in 42,90 ± 9,3 days. There was significant improvement between the onset and six months: body mass index (30,80 ± 2,3-28,60 ± 2,06); circumference of the abdominal waist (men 108,3 ± 7,8-103,30 ± 6,20 cm and women 103,60 ± 7,10-100,10 ± 5,70 cm); fasting blood glucose (13,60 ± 1,30 mmol/L y PP2h: 22,10 ± 2,80-10 ± 0,70 mmol/L and 7,90 ± 1,10 mmol/L) and glucocylated hemoglobin (8,70 ± 1,10-6,90 ± 0,60 percent). Hypoglycaemias were few: 2,90 percent moderate and 5,90 percent light. The almost totality was controlled with metformin at six months (92,54 percent).Conclusions: the results confirm that with the initial transient use of insulin an adequate glycemic control is achieved, subsequently maintained with metformin monotherapy(AU)

Kinship analysis and allelic dropout: a forensic approach on an archaeological case.

BACKGROUND: This study relies on the discovery of two pit burials (LTA and LTB) of the Bronze Age Cogotas I archaeological culture (circa 3600-2950 BP) in Spain. LTA was a single burial and LTB contained three skeletal remains of two adults and a newborn or foetus at term. AIM: The central question posed by this find was whether the LTB tomb constituted a traditional nuclear family (father, mother and son or daughter). METHODS: Ancient and forensic DNA protocols were employed to obtain reliable results. Autosomal, X-STR markers and mitochondrial DNA were amplified. Subsequently, different kinship probabilities were estimated by means of LR values calculated using the Familias 3 software. Furthermore, an allelic dropout sensitivity test was developed in order to evaluate the influence of allelic dropout phenomena on the results. RESULTS: It was possible to determine the molecular sex of all individuals and to establish a maternal relationship between the perinatal individual and one of the adults. CONCLUSION: The remains in the LTB tomb were not a traditional nuclear family (father, mother and son/daughter) and it was probably a tomb where two women, one of them pregnant, were buried.

On flattening filter-free portal dosimetry.

Varian introduced (in 2010) the option of removing the flattening filter (FF) in their C-Arm linacs for intensity-modulated treatments. This mode, called flattening filter-free (FFF), offers the advantage of a greater dose rate. Varian's "Portal Dosimetry" is an electronic portal imager device (EPID)-based tool for IMRT verification. This tool lacks the capability of verifying flattening filter-free (FFF) modes due to saturation and lack of an image prediction algorithm. (Note: the latest versions of this software and EPID correct these issues.) The objective of the present study is to research the feasibility of said verifications (with the older versions of the software and EPID). By placing the EPID at a greater distance, the images can be acquired without saturation, yielding a linearity similar to the flattened mode. For the image prediction, a method was optimized based on the clinically used algorithm (analytical anisotropic algorithm (AAA)) over a homogeneous phantom. The depth inside the phantom and its electronic density were tailored. An application was developed to allow the conversion of a dose plane (in DICOM format) to Varian's custom format for Portal Dosimetry. The proposed method was used for the verification of test and clinical fields for the three qualities used in our institution for IMRT: 6X, 6FFF and 10FFF. The method developed yielded a positive verification (more than 95% of the points pass a 2%/2 mm gamma) for both the clinical and test fields. This method was also capable of "predicting" static and wedged fields. A workflow for the verification of FFF fields was developed. This method relies on the clinical algorithm used for dose calculation and is able to verify the FFF modes, as well as being useful for machine quality assurance. The procedure described does not require new hardware. This method could be used as a verification of Varian's Portal Dose Image Prediction.

Genetic contribution to iron status: SNPs related to iron deficiency anaemia and fine mapping of CACNA2D3 calcium channel subunit.

Numerous studies associate genetic markers with iron- and erythrocyte-related parameters, but few relate them to iron-clinical phenotypes. Novel SNP rs1375515, located in a subunit of the calcium channel gene CACNA2D3, is associated with a higher risk of anaemia. The aim of this study is to further investigate the association of this SNP with iron-related parameters and iron-clinical phenotypes, and to explore the potential role of calcium channel subunit region in iron regulation. Furthermore, we aim to replicate the association of other SNPs reported previously in our population. We tested 45 SNPs selected via systematic review and fine mapping of CACNA2D3 region, with haematological and biochemical traits in 358 women of reproductive age. Multivariate analyses include back-step logistic regression and decision trees. The results replicate the association of SNPs with iron-related traits, and also confirm the protective effect of both A allele of rs1800562 (HFE) and G allele of rs4895441 (HBS1L-MYB). The risk of developing anaemia is increased in reproductive age women carriers of A allele of rs1868505 (CACNA2D3) and/or T allele of rs13194491 (HIST1H2BJ). Association of SNPs from fine mapping with ferritin and serum iron suggests that calcium channels could be a potential pathway for iron uptake in physiological conditions.

La técnica en la escalada deportiva: una revisión / The technique in the sport climbing: a review

La escalada puede ser definida como una serie de movimientos acíclicos que buscan un desplazamiento del centro de gravedad, manteniendo el equilibrio tanto de forma estática como dinámica. Considerando esta premisa, la técnica deportiva se vuelve fundamental para el logro de este objetivo. La siguiente revisión busca mostrar los avances en los últimos diez años respecto a la técnica y la escalada deportiva. Fueron consultadas cinco bases de datos online considerando los términos “Escalda deportiva”, “Técnica” y “Biomecánica”.Como resultados de la búsqueda fueron encontrados tan solo nueve artículos originales, los cuales a pesar de incluir la técnica de escalada como una variable a considerar en relación a otros parámetros de diversa índole, no logran entregar una descripción adecuada de técnica en escalada deportiva, limitándose a posicionamientos corporales o formas de tomar agarres específicos, sin describir fases u objetivos de las mismas. Queda como tarea hacia el futuro, establecer bases en cuanto a la técnica en la escalada deportiva, considerando comenzar por definir un modelo técnico a nivel nacional que entregue la posibilidad de avanzar de forma estructurada y secuencial en el desarrollo de la técnica deportiva para la escalada y todas las variables implicadas para la mejora de los rendimientos en nuestros deportistas de la mano de la ciencia y la experiencia.

Climbing may be defined as a series of acyclic movements reaching for displacement of the center of gravity, keeping the balance when being both, static and dynamic. Given this premise, sport technique becomes critical to achieving this goal. The following review seeks to show the progress in the last ten regard the sport climbing. Five online databases were consulted including on the words “Sport climbing”, “Technique” and “Biomechanics”. As search results were found only nine original articles, which despite consider climbing technique as a variable to be considered in relation to other parameters of many types, fail to provide an adequate description of technique in sport climbing, limiting just to body positions or ways of taking specific grips, regardless stages or targets. It is the task ahead, to establish bases in terms of technique in sport climbing, considering to start by defining a national technical model that gives the chance to develop in a structured and sequentially way in the sport climbing technique and all the variables involved for improving yields in our athletes with the science and experience as guides.

Exploring the relationship between lifestyles, diets and genetic adaptations in humans.

BACKGROUND: One of the most important dietary shifts underwent by human populations began to occur in the Neolithic, during which new modes of subsistence emerged and new nutrients were introduced in diets. This change might have worked as a selective pressure over the metabolic pathways involved in the breakdown of substances extracted from food. Here we applied a candidate gene approach to investigate whether in populations with different modes of subsistence, diet-related genetic adaptations could be identified in the genes AGXT, PLRP2, MTRR, NAT2 and CYP3A5. RESULTS: At CYP3A5, strong signatures of positive selection were detected, though not connected to any dietary variable, but instead to an environmental factor associated with the Tropic of Cancer. Suggestive signals of adaptions that could indeed be connected with differences in dietary habits of populations were only found for PLRP2 and NAT2. Contrarily, the demographic history of human populations seemed enough to explain patterns of diversity at AGXT and MTRR, once both conformed the evolutionary expectations under selective neutrality. CONCLUSIONS: Accumulated evidence indicates that CYP3A5 has been under adaptive evolution during the history of human populations. PLRP2 and NAT2 also appear to have been modelled by some selective constrains, although clear support for that did not resist to a genome wide perspective. It is still necessary to clarify which were the biological mechanisms and the environmental factors involved as well as their interactions, to understand the nature and strength of the selective pressures that contributed to shape current patterns of genetic diversity at those loci.

Large-scale recent expansion of European patrilineages shown by population resequencing.

The proportion of Europeans descending from Neolithic farmers ∼ 10 thousand years ago (KYA) or Palaeolithic hunter-gatherers has been much debated. The male-specific region of the Y chromosome (MSY) has been widely applied to this question, but unbiased estimates of diversity and time depth have been lacking. Here we show that European patrilineages underwent a recent continent-wide expansion. Resequencing of 3.7 Mb of MSY DNA in 334 males, comprising 17 European and Middle Eastern populations, defines a phylogeny containing 5,996 single-nucleotide polymorphisms. Dating indicates that three major lineages (I1, R1a and R1b), accounting for 64% of our sample, have very recent coalescent times, ranging between 3.5 and 7.3 KYA. A continuous swathe of 13/17 populations share similar histories featuring a demographic expansion starting ∼ 2.1-4.2 KYA. Our results are compatible with ancient MSY DNA data, and contrast with data on mitochondrial DNA, indicating a widespread male-specific phenomenon that focuses interest on the social structure of Bronze Age Europe.

Genetic polymorphism of 15 STR loci in El Salvador.

The aim of this study was to estimate the allelic frequencies of the 15 short tandem repeat (STR) loci included in AmpFlSTRIdentifiler PCR Amplification Kit. Biological samples were obtained from 109 unrelated individuals from El Salvador. Allelic frequencies and forensic parameters were calculated. All loci showed no departure from Hardy-Weinberg equilibrium after Bonferroni correction. The obtained frequencies were compared with other previously reported population data. The multidimensional scaling plot and the neighbor-joining phylogeny supported a high native Mesoamerican contribution.

The Y-chromosome tree bursts into leaf: 13,000 high-confidence SNPs covering the majority of known clades.

Many studies of human populations have used the male-specific region of the Y chromosome (MSY) as a marker, but MSY sequence variants have traditionally been subject to ascertainment bias. Also, dating of haplogroups has relied on Y-specific short tandem repeats (STRs), involving problems of mutation rate choice, and possible long-term mutation saturation. Next-generation sequencing can ascertain single nucleotide polymorphisms (SNPs) in an unbiased way, leading to phylogenies in which branch-lengths are proportional to time, and allowing the times-to-most-recent-common-ancestor (TMRCAs) of nodes to be estimated directly. Here we describe the sequencing of 3.7 Mb of MSY in each of 448 human males at a mean coverage of 51×, yielding 13,261 high-confidence SNPs, 65.9% of which are previously unreported. The resulting phylogeny covers the majority of the known clades, provides date estimates of nodes, and constitutes a robust evolutionary framework for analyzing the history of other classes of mutation. Different clades within the tree show subtle but significant differences in branch lengths to the root. We also apply a set of 23 Y-STRs to the same samples, allowing SNP- and STR-based diversity and TMRCA estimates to be systematically compared. Ongoing purifying selection is suggested by our analysis of the phylogenetic distribution of nonsynonymous variants in 15 MSY single-copy genes.

Ancient DNA analysis of 8000 B.C. near eastern farmers supports an early neolithic pioneer maritime colonization of Mainland Europe through Cyprus and the Aegean Islands.

The genetic impact associated to the Neolithic spread in Europe has been widely debated over the last 20 years. Within this context, ancient DNA studies have provided a more reliable picture by directly analyzing the protagonist populations at different regions in Europe. However, the lack of available data from the original Near Eastern farmers has limited the achieved conclusions, preventing the formulation of continental models of Neolithic expansion. Here we address this issue by presenting mitochondrial DNA data of the original Near-Eastern Neolithic communities with the aim of providing the adequate background for the interpretation of Neolithic genetic data from European samples. Sixty-three skeletons from the Pre Pottery Neolithic B (PPNB) sites of Tell Halula, Tell Ramad and Dja'de El Mughara dating between 8,700-6,600 cal. B.C. were analyzed, and 15 validated mitochondrial DNA profiles were recovered. In order to estimate the demographic contribution of the first farmers to both Central European and Western Mediterranean Neolithic cultures, haplotype and haplogroup diversities in the PPNB sample were compared using phylogeographic and population genetic analyses to available ancient DNA data from human remains belonging to the Linearbandkeramik-Alföldi Vonaldiszes Kerámia and Cardial/Epicardial cultures. We also searched for possible signatures of the original Neolithic expansion over the modern Near Eastern and South European genetic pools, and tried to infer possible routes of expansion by comparing the obtained results to a database of 60 modern populations from both regions. Comparisons performed among the 3 ancient datasets allowed us to identify K and N-derived mitochondrial DNA haplogroups as potential markers of the Neolithic expansion, whose genetic signature would have reached both the Iberian coasts and the Central European plain. Moreover, the observed genetic affinities between the PPNB samples and the modern populations of Cyprus and Crete seem to suggest that the Neolithic was first introduced into Europe through pioneer seafaring colonization.

Influence of diet, menstruation and genetic factors on iron status: a cross-sectional study in Spanish women of childbearing age.

The aim of this study was to investigate the combined influence of diet, menstruation and genetic factors on iron status in Spanish menstruating women (n = 142). Dietary intake was assessed by a 72-h detailed dietary report and menstrual blood loss by a questionnaire, to determine a Menstrual Blood Loss Coefficient (MBLC). Five selected SNPs were genotyped: rs3811647, rs1799852 (Tf gene); rs1375515 (CACNA2D3 gene); and rs1800562 and rs1799945 (HFE gene, mutations C282Y and H63D, respectively). Iron biomarkers were determined and cluster analysis was performed. Differences among clusters in dietary intake, menstrual blood loss parameters and genotype frequencies distribution were studied. A categorical regression was performed to identify factors associated with cluster belonging. Three clusters were identified: women with poor iron status close to developing iron deficiency anemia (Cluster 1, n = 26); women with mild iron deficiency (Cluster 2, n = 59) and women with normal iron status (Cluster 3, n = 57). Three independent factors, red meat consumption, MBLC and mutation C282Y, were included in the model that better explained cluster belonging (R2 = 0.142, p < 0.001). In conclusion, the combination of high red meat consumption, low menstrual blood loss and the HFE C282Y mutation may protect from iron deficiency in women of childbearing age. These findings could be useful to implement adequate strategies to prevent iron deficiency anemia.

Continent-wide decoupling of Y-chromosomal genetic variation from language and geography in native South Americans.

Numerous studies of human populations in Europe and Asia have revealed a concordance between their extant genetic structure and the prevailing regional pattern of geography and language. For native South Americans, however, such evidence has been lacking so far. Therefore, we examined the relationship between Y-chromosomal genotype on the one hand, and male geographic origin and linguistic affiliation on the other, in the largest study of South American natives to date in terms of sampled individuals and populations. A total of 1,011 individuals, representing 50 tribal populations from 81 settlements, were genotyped for up to 17 short tandem repeat (STR) markers and 16 single nucleotide polymorphisms (Y-SNPs), the latter resolving phylogenetic lineages Q and C. Virtually no structure became apparent for the extant Y-chromosomal genetic variation of South American males that could sensibly be related to their inter-tribal geographic and linguistic relationships. This continent-wide decoupling is consistent with a rapid peopling of the continent followed by long periods of isolation in small groups. Furthermore, for the first time, we identified a distinct geographical cluster of Y-SNP lineages C-M217 (C3*) in South America. Such haplotypes are virtually absent from North and Central America, but occur at high frequency in Asia. Together with the locally confined Y-STR autocorrelation observed in our study as a whole, the available data therefore suggest a late introduction of C3* into South America no more than 6,000 years ago, perhaps via coastal or trans-Pacific routes. Extensive simulations revealed that the observed lack of haplogroup C3* among extant North and Central American natives is only compatible with low levels of migration between the ancestor populations of C3* carriers and non-carriers. In summary, our data highlight the fact that a pronounced correlation between genetic and geographic/cultural structure can only be expected under very specific conditions, most of which are likely not to have been met by the ancestors of native South Americans.

Identification of a novel quantitative trait nucleotype related to iron status in a calcium channel gene.

Several iron-related parameters have been reported to show significant heritability, and thus, seemed to be genetically regulated. A genome wide family-based study revealed two regions that showed a linkage signal with transferrin receptor levels. The aim of the study was to identify genetic markers associated with iron status biomarkers. Ten SNPs selected from the literature were tested, and parameters related to iron metabolism were analysed, in a group (n=284) of Spanish women. Data were analyzed using Bayesian Model Averaging (BMA) test and decision trees. The rs1375515, located in an intronic region of the calcium channel gene CACNA2D3, showed strong associations with levels of mean corpuscular volume according to BMA test, and with levels of haemoglobin and ferritin according to decision trees. The allele G was associated to low levels of these parameters which suggests higher iron deficiency anaemia risk. This SNP along with the C282Y mutation explained significant differences in the distribution of individuals in three iron-related clinical phenotypes (normal, iron deficient and iron deficiency anaemic). In conclusion, the rs1375515, or other genetic polymorphisms in linkage, may play important roles in iron status, probably by affecting the function of a calcium channel. These findings may be useful for further investigation in the etiology of iron diseases.