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.

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.

Diagnóstico e intervención temprana de insuficiencia velofaringea posterior a palatoplastia primaria en pacientes atendidos interdisciplinariamente en fisulab (Bogotá, Colombia) / Diagnosis and early intervention of velofaringeal insufficiency posterior to primary palatoplasty in patients attended interdisciplinarily in fisulab (Bogotá, Colombia)

Introducción y Objetivo: El tratamiento integral e interdisciplinario de los pacientes con paladar hendido es fundamental para garantizar resultados a largo plazo. El habla es una de las metas principales en el tratamiento ya que permitirá un adecuado aprendizaje escolar y socialización. La insuficiencia velofaríngea (IVF) se debe a alteraciones anatómicas del esfínter velofaringeo y el manejo temprano y adecuado de los pacientes con paladar hendido es clave para evitarla. El objetivo de este estudio es determinar el porcentaje de IVF detectado y manejado antes de los primeros 5 años de vida en pacientes con paladar hendido tratados interdisciplinariamente en el Centro de Rehabilitación para Niños con Labio y Paladar Fisurado (FISULAB) en Bogotá, Colombia, evidenciando la efectividad del abordaje temprano. Material y Método: Estudio descriptivo tipo serie de casos en el que presentamos los resultados funcionales del tratamiento continuo en pacientes con paladar hendido, diagnosticados y tratados de forma exclusiva en FISULAB de acuerdo a su guía integral. Del total de 972 pacientes atendidos en la institución, 118 cumplían con los criterios de inclusión. Resultados: Estudiamos 118 pacientes con paladar hendido con o sin labio hendido atendidos bajo la guía integral desde el nacimiento hasta los 5 años de edad: 67 varones y 51 mujeres. Del total, 17 (14.4%) presentaron IVF (8 varones y 9 mujeres). De los que presentaron IVF, 4 (23.5%) tenían diagnóstico sindrómico asociado. La incidencia de IVF en nuestra población de pacientes, excluyendo los pacientes sindromáticos, fue del 11%, con una resolución del 100% de la IVF en los pacientes que fueron llevados a uno o múltiples procedimientos quirúrgicos. Conclusiones: El diagnóstico temprano y el manejo interdisciplinario de la IVF son esenciales para asegurar el éxito en la rehabilitación del lenguaje de los pacientes con paladar hendido. Un tratamiento conservador y por etapas de la IVF puede asegurar buenos resultados minimizando complicaciones

Background and Objective: A comprehensive and interdisciplinary treatment of patients with cleft palate is essential to ensure satisfactory long-term results. Adequate speech is one of the main goals because it allows each patient a proper adjustment to their educational and social environment. Velo- pharyngeal insufficiency (VPI) occurs due to anatomic changes of the velo- pharyngeal sphincter. Early and appropriate management of patients with cleft palate is crucial to prevent velopharyngeal insufficiency. The aim of this study is to determine the incidence of patients with VPI that were detected and received treatment during their first 5 years of age at FISULAB (Rehabilitation Center for Children with Cleft lip and Palate), Bogota, Colombia, and to evaluate the effectiveness early treatment. Methods: Descriptive study of case series. Patients included were diagnosed with cleft palate and treated exclusively in FISULAB, following the treatment protocol of this institution. A total of 972 patients were treated and 118 patients met the inclusion criteria. Results: A total of 118 patients with cleft palate, with or without associated cleft lip, were treated following the institutional protocol: 17 (14.4%) had VPI (8 male and 9 female). Of the patients who had VPI, 4 (23.5%) had a syndromic diagnosis. The incidence of VPI in our patient population was 11% with a resolution of 100% of VPI after surgical treatment. Conclusions: Early diagnosis and interdisciplinary management of VPI are essential to ensure the success in speech rehabilitation in patients with cleft palate. A conservative and stepwise treatment of VPI has shown good results, minimizing complications

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.

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.

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.

The genetic landscape of Equatorial Guinea and the origin and migration routes of the Y chromosome haplogroup R-V88.

Human Y chromosomes belonging to the haplogroup R1b1-P25, although very common in Europe, are usually rare in Africa. However, recently published studies have reported high frequencies of this haplogroup in the central-western region of the African continent and proposed that this represents a 'back-to-Africa' migration during prehistoric times. To obtain a deeper insight into the history of these lineages, we characterised the paternal genetic background of a population in Equatorial Guinea, a Central-West African country located near the region in which the highest frequencies of the R1b1 haplogroup in Africa have been found to date. In our sample, the large majority (78.6%) of the sequences belong to subclades in haplogroup E, which are the most frequent in Bantu groups. However, the frequency of the R1b1 haplogroup in our sample (17.0%) was higher than that previously observed for the majority of the African continent. Of these R1b1 samples, nine are defined by the V88 marker, which was recently discovered in Africa. As high microsatellite variance was found inside this haplogroup in Central-West Africa and a decrease in this variance was observed towards Northeast Africa, our findings do not support the previously hypothesised movement of Chadic-speaking people from the North across the Sahara as the explanation for these R1b1 lineages in Central-West Africa. The present findings are also compatible with an origin of the V88-derived allele in the Central-West Africa, and its presence in North Africa may be better explained as the result of a migration from the south during the mid-Holocene.

Genetic polymorphism of 15 STR loci in Chinese Han population from Shanghai municipality in East China.

The aim of this study was to estimate the allelic frequencies of the fifteen STRs included in AmpFlSTR(®) Identifiler(®) PCR Amplification Kit (Applied Biosystems, USA) in a sample of 186 unrelated individuals resident in Shanghai. Allelic frequencies and forensic parameters were calculated. All loci showed no departure from Hardy-Weinberg equilibrium. The obtained frequencies were compared with other previously reported population data.

Genotipos de resistencia antimicrobiana y su expresión fenotípica en cepas de Staphylococcus aureus / Genotypes for antimicrobial resistance and their phenotypic expression in Staphylococcus aureus strains

Se determinó la resistencia antimicrobiana mediante métodos fenotípicos y genotípicos a 106 cepas de S. aureus aisladas de pacientes atendidos en el Centro de Referencia Bacteriológica del Servicio Autónomo Hospital Universitario de Maracaibo durante el primer trimestre del 2009. El cultivo, aislamiento e identificación se realizó siguiendo la metodología convencional. Fenotípicamente, 103 cepas (97,17%) resultaron resistentes a penicilina G; 54 (50,94%) a meticilina; 43,39% a eritromicina (46) y 34,91% (37) a gentamicina. Además, 13 (12,26%) se mostraron intermedias a eritromicina. Genotípicamente, 90 cepas (84,91%) portaban el gen blaZ mediante la reacción en cadena de la polimerasa (PCR); 53 (50%) acarreaban el gen mecA; sólo 10 (9,43%) albergaban el gen aac(6’)/aph(2’’); el gen ermA se detectó en 41 aislados (38,68%) y msrA en 17 (16,04%). Los resultados discordantes fueron: (1) Una cepa mecA-negativa; pero resistente a meticilina, la cual resultó blaZ-positiva e hiperproductora de b-lactamasas; (2) Una cepa resistente a eritromicina y negativa para los genes ermA, B, C y msr y; (3) veintiséis cepas gentamicina-resistentes; pero negativas para aac(6’)/aph(2’’). Los fenotipos y genotipos de resistencia antimicrobiana están relacionados; sin embargo, existe una marcada variabilidad en los determinantes genéticos de la resistencia lo que repercute, indudablemente en su expresión fenotípica. Para oxacilina y en menor proporción para eritromicina, existe una buena concordancia entre los fenotipos y genotipos de resistencia encontrados; observándose la mayor discrepancia en los aminoglicósidos, y penicilina G.

Antimicrobial resistance was determined for 106 S. aureus strain isolates from patients treated in the Bacteriological Reference Center at the University Hospital Autonomous Service, Maracaibo, during the first trimester of 2009, using phenotypic and genotypic methods. Culture, isolation and identification were performed following conventional methodology. Phenotypically, 103 strains (97.17%) were resistant to penicillin G; 54 (50.94%) to methicillin; 43.39% to erythromycin (46) and 34.91% (37) to gentamicin. In addition, 13 (12.26%) were intermediate to erythromycin. Genotypically, 90 strains (84.91%) carried the blaZ gene through the polymerase chain reaction (PCR); 53 (50%) carried the mecA gene; only 10 (9.43%) harbored the gene aac(6’)/aph(2’’); the gene ermA was detected in 41 isolates (38.68%) and msrA in 17 (16.04%). The discordant results were: (1) A mecA-negative, but methicillin-resistant strain, which proved blaZ-positive and hyper-productive of b-lactamases; (2) An erythromycin-resistant strain, negative for ermA, B, C and msrA genes, and; (3)Twenty-six gentamicin-resistant strains, negative for aac(6’)/aph(2’’). The phenotypes and genotypes of antimicrobial resistance are related; however, there is a marked variability in the genetic determinants for resistance, which undoubtedly affects phenotypic expression. For oxacillin and, to a lesser degree erythromycin, there is a good match between the resistance phenotypes and genotypes found, noting the greatest discrepancy in the aminoglycosides and penicillin G.

A novel SNaPshot assay to detect genetic mutations related to iron metabolism.

The minisequencing method is a cost-effective tool to study single-nucleotide polymorphisms in human disease. For this reason, a novel polymerase chain reaction multiplex SNaPshot reaction has been developed that targets 10 autosomal mutations in genes, or regions near to them, reported to be involved in iron metabolism: TMPRSS6, TF, and HFE. To validate this multiplex, 284 samples from unrelated women from the Spanish population were tested at a fertile age. The novel polymerase chain reaction multiplex SNaPshot reaction developed is a very simple, sensitive, and low-cost approach, and therefore will be useful as a tool of clinic diagnosis in iron metabolism alterations and to replicate results obtained from genome-wide linkage analysis.

CYP2C9 polymorphism in five autochthonous population of the same geographic area (Spanish Pyrenees).

OBJECTIVE: To evaluate the frequency of CYP2C9 polymorphisms in a cohort of Caucasians (Spanish Pyrenees), previously classified in autochthonous populations. METHODS: Blood samples from 154 anonymous volunteer donors were collected. All the individuals were autochthonous to their respective populations (four grandparents born in the region): 23 from Valle de Arán (Lérida), 29 from Alto Urgel (Lérida), 32 from La Cerdaña (Gerona), 30 from Jacetania (Huesca) and 40 from Cinco Villas (Navarra). The analyses for allelic mutation, CYP2C9*2 and CYP2C9*3, were identified with Taqman Allelic Discrimination kits. RESULTS: No statistical differences were found when allelic frequencies in the five autochthonous populations were compared. Frequency distribution of genotypic classes (wt/wt, wt/mut and mut/mut) in Alto Urgel was different from that in La Cerdaña, Cinco Villas and Jacetania samples. Comparison of Pyrenean and other European populations through exact test revealed significant differences in the distribution of genotypic classes: Alto Urgel, Barcelona, and Croatia yielded the highest significant differences. According to the exact test these populations were pooled in four groups. This classification produced a statistically significant percentage of variation explained by differences among groups (1.94%, P= 0.036), but not by differences among populations within groups (P=0.914), although most of the percentage of variance is explained by differences within populations (97.46%, P<0.001). CONCLUSION: This study increases the evidence of intra-population genotypic variability and highlights the significant genotypic heterogeneity when different autochthonous populations are considered, despite no clear differences in allelic frequencies do exist.

Y-chromosome haplotypes defined by 17 STRs included in AmpFlSTR Yfiler PCR Amplification Kit in a multi ethnical population from El Beni Department (North Bolivia).

Seventeen Y-STRs included in AmpFlSTR Yfiler PCR Amplification Kit (Applied Biosystems, USA) were studied in males from a multi ethnical population from El Beni Department (North Bolivia). Haplotypic and allelic frequencies were reported. Comparison of El Beni population with other samples from the region was carried out through Multidimensional Scalling over Rst distances matrix.

Identifying genetic traces of historical expansions: Phoenician footprints in the Mediterranean.

The Phoenicians were the dominant traders in the Mediterranean Sea two thousand to three thousand years ago and expanded from their homeland in the Levant to establish colonies and trading posts throughout the Mediterranean, but then they disappeared from history. We wished to identify their male genetic traces in modern populations. Therefore, we chose Phoenician-influenced sites on the basis of well-documented historical records and collected new Y-chromosomal data from 1330 men from six such sites, as well as comparative data from the literature. We then developed an analytical strategy to distinguish between lineages specifically associated with the Phoenicians and those spread by geographically similar but historically distinct events, such as the Neolithic, Greek, and Jewish expansions. This involved comparing historically documented Phoenician sites with neighboring non-Phoenician sites for the identification of weak but systematic signatures shared by the Phoenician sites that could not readily be explained by chance or by other expansions. From these comparisons, we found that haplogroup J2, in general, and six Y-STR haplotypes, in particular, exhibited a Phoenician signature that contributed > 6% to the modern Phoenician-influenced populations examined. Our methodology can be applied to any historically documented expansion in which contact and noncontact sites can be identified.

Population data for 15 Y-chromosome STRs in a population sample from Quito (Ecuador).

Population frequencies for the 9 Y-STR loci included in the "minimal haplotype" from Y-STR Haplotype Reference Database (YHRD), plus other 6 Y-STRs (DYS437, DYS438, DYS439, GATA A7.2, GATA H4 and GATA A10) were obtained for a sample of 120 males from Quito (Ecuador). One hundred and sixteen unique haplotypes were identified within the sample. Haplotype diversity (0.9994) was among the highest in comparison to other populations from Iberia and South-America. Genetic distances were calculated and our sample presented significative differences with all other samples, the lowest values being with a Guinean sample.

Genetic variability of 16 Y-chromosome STRs in a sample from Equatorial Guinea (Central Africa).

Nine Y-STR loci from the "minimal haplotype" included in Y-STR Haplotype Reference Databases (YHRD) together with eight additional Y-STRs (DYS437, DYS438, DYS439, DYS460, DYS461, GATA C4, GATA H4 and GATA A10) were analyzed in a sample of 101 males from Equatorial Guinea living in Madrid. Haplotype and allelic frequencies were calculated and genetic diversities were estimated for each genetic system as well as for the whole haplotype. An unexpected high frequency (6%) of intermediate alleles (13.2 and 14.2) was found in DYS385. For DYS19, two alleles were found in one sample. Another sample failed to amplify with DYS393 primers using either PowerPlex Y System (Promega Corporation) or the Y-PLEXtrade mark 12 (Reliagene, New Orleans, LA) commercial kits. Comparison between Equatorial Guinea and another African population (Mozambique; South East Coast) revealed a significant pairwise Phi(st) value between them (Phi(st)=0.03309; P=0.00000).

Early population differentiation in extinct aborigines from Tierra del Fuego-Patagonia: ancient mtDNA sequences and Y-chromosome STR characterization.

Ancient mtDNA was successfully recovered from 24 skeletal samples of a total of 60 ancient individuals from Patagonia-Tierra del Fuego, dated to 100-400 years BP, for which consistent amplifications and two-strand sequences were obtained. Y-chromosome STRs (DYS434, DYS437, DYS439, DYS393, DYS391, DYS390, DYS19, DYS389I, DYS389II, and DYS388) and the biallelic system DYS199 were also amplified, Y-STR alleles could be characterized in nine cases, with an average of 4.1 loci per sample correctly typed. In two samples of the same ethnic group (Aonikenk), an identical and complete eight-loci haplotype was recovered. The DYS199 biallelic system was used as a control of contamination by modern DNA and, along with DYS19, as a marker of American origin. The analysis of both mtDNA and Y-STRs revealed DNA from Amerindian ancestry. The observed polymorphisms are consistent with the hypothesis that the ancient Fuegians are close to populations from south-central Chile and Argentina, but their high nucleotide diversity and the frequency of single lineages strongly support early genetic differentiation of the Fuegians through combined processes of population bottleneck, isolation, and/or migration, followed by strong genetic drift. This suggests an early genetic diversification of the Fuegians right after their arrival at the southernmost extreme of South America.

Seroepidemiología de la toxoplasmosis en una comunidad marginal del Municipio Maracaibo, Estado Zulia, Venezuela / Seroepidemiology of toxoplasmosis in a marginal community of Maracaibo, Venezuela

El propósito de la investigación fue determinar la prevalencia de anticuerpos anti-toxoplasma gondii en una comunidad marginal del Municipio Maracaibo, Estado Zulia, Venezuela y si existía asociación entre los factores de riesgo e infección. Se realizó una encuesta epidemiológica que incluyó datos personales, condiciones sanitarias de la vivienda y convivencia con gatos. Se examinaron 254 muestras de suero de individuos de ambos sexos, con un rango de edad de 8 meses a 76 años. La determinación de anticuerpos anti-toxoplasma gondii se realizó a través de la técnica de hemaglutinación indirecta, utilizando un kit disponible comercialmente. Se consideró como reacción positiva diluciones>=1:64. El análisis estadístico se realizó a través de chi cuadrado. La prevalencia de infección fue de 36,6 por ciento observándose que el 21,5 por ciento de los sueros positivos presentaron títulos los considerados no significativos (<=1:64), 51,6 por ciento títulos intermedios (1:128 a 1:512), 24,8 por ciento títulos altos (1:1024 a 1:4096) y 2,1 por ciento títulos muy altos (>=1:8192). El mayor porcentaje de seropositivos (50 por ciento) se observó en el grupo >= de 46 años. No se observaron diferencias estadísticamente significativas en relación al sexo. El chi cuadrado reveló que no existe asociación estadísticamente significativa entre los factores de riesgo (conviviencia con gatos, condiciones sanitarias de la vivienda) y la presencia de infección, sin embargo la toxoplasmosis es frecuente en la comunidad de Puerto Caballo, desempeñando los gatos y las condiciones sanitarias de la vivienda un papel importante en la transmisión de la infección