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1.
Mol Biol Evol ; 39(4)2022 04 11.
Article in English | MEDLINE | ID: mdl-35460423

ABSTRACT

Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. Although classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations, we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ∼4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico, and Peru. Our approach replicates previous reports of selection in the human leukocyte antigen region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas.


Subject(s)
Genetics, Population , Genome, Human , Genomics/methods , Hispanic or Latino/genetics , Humans , Polymorphism, Single Nucleotide/genetics , White People/genetics
2.
Gastroenterol Hepatol ; 44(5): 346-354, 2021 May.
Article in English, Spanish | MEDLINE | ID: mdl-33199128

ABSTRACT

INTRODUCTION: The small bowel capsule endoscopy (SBCE) has revolutionised the study of small bowel diseases. The objective of this study is to determine the indications, findings and diagnostic yield of SBCE in a national registry. PATIENTS AND METHODS: An observational, analytical cross-sectional study was carried out, analysing the SBCE records at seven centres in the country, where different variables were collected. RESULTS: 1,883 SBCEs were evaluated. The average age was 55.4 years (5.6-94.2). The most frequent indications were suspicion of small bowel bleeding (SBB) (64.4%), study of Crohn's disease (15.2%) and chronic diarrhoea (11.2%). 54.3% were prepared with laxatives. The most frequent lesions found were erosions/ulcers (31.6%), angioectasias (25.7%) and parasitosis (2.7%). The diagnostic yield (P1+P2, Saurin classification) of SBCE in SBB was 60.6%, being higher in overt SBB (66.0%) compared to occult SBB (56.0%) (P=.003). The studies with better preparation showed higher detection of lesions (93.8% vs. 89.4%) (OR=1.8, CI: 95%: 1.2-2.6; P=.004). The SBCE complication rate was 3.1%, with complete SB visualisation at 96.6% and SB retention rate of 0.7%. 81.5% of SBCEs were performed on an outpatient basis, and presented a greater complete SB visualisation than hospital ones (97.1% vs. 94.3%) (OR=2.1, CI: 95%, 1.2-3.5; P=.008). CONCLUSIONS: The indications, findings and diagnostic performance of SBCEs in Colombia are similar to those reported in the literature, with a high percentage of complete studies and a low rate of complications.


Subject(s)
Capsule Endoscopy , Intestinal Diseases/pathology , Intestine, Small/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Colombia , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Registries , Young Adult
3.
Chron Respir Dis ; 16: 1479972318769771, 2019.
Article in English | MEDLINE | ID: mdl-29669432

ABSTRACT

The objective of the article was to establish the prevalence, underdiagnosis, and risk factors of chronic bronchitis (CB) in a general population in five Colombian cities. Cross-sectional study using a probabilistic sampling technique in five Colombian cities was adopted. The CB definition was "cough and expectoration for three or more months per year for at least two consecutive years." Underdiagnosis was considered in subjects with clinical definition without previous medical diagnosis. Univariate χ2 or Student's t-test and logistic regression analysis were used. The study included 5539 subjects. The prevalence was 5.5%, the underdiagnosis 50.3%, and 33.7% of the cases were in nonsmokers (53.6% in women vs. 16.9% in men, p < 0.001). The adjusted risk factors were living in Bogota, current smoking, male, age ≥ 64 years, low education, indoor wood smoke exposure, and occupational exposure to vapors, gases, dust, and fumes. CB is a common disease among adults in Colombia. The underdiagnosis was high and there were a large proportion of cases in nonsmokers, particularly in women. Our findings support the association of CB with indoor wood smoke and occupational exposures.


Subject(s)
Air Pollution, Indoor/statistics & numerical data , Bronchitis, Chronic/epidemiology , Non-Smokers/statistics & numerical data , Occupational Exposure/statistics & numerical data , Urban Population/statistics & numerical data , Aged , Bronchitis, Chronic/complications , Bronchitis, Chronic/diagnosis , Cities/epidemiology , Colombia/epidemiology , Cough/etiology , Cross-Sectional Studies , Dust , Educational Status , Female , Gases , Humans , Male , Middle Aged , Prevalence , Risk Factors , Smoke , Smoking/epidemiology
4.
PLoS Genet ; 10(9): e1004572, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25254375

ABSTRACT

The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry.


Subject(s)
Ethnicity/genetics , Genetic Variation , Genetics, Population , Phenotype , Biological Evolution , Female , Geography , Humans , Latin America , Male , Quantitative Trait, Heritable , Self Concept
5.
J Asthma ; 52(8): 823-30, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25996179

ABSTRACT

OBJECTIVE: There are differences in the prevalence and risk factors of asthma around the world. The epidemiological situation of adults 40 years and older is not well established. Our aim was to determine the prevalence, underdiagnosis and risk factors of asthma and wheezing in adults in Colombia. METHODS: A cross-sectional, population-based study including 5539 subjects from 40 to 93 years selected by a probabilistic sampling technique in five cities was conducted. MEASUREMENTS: respiratory symptoms and risk factors questionnaire and spirometry. DEFINITIONS: (a) Wheezing: Affirmative answer to the question "have you ever had two or more attacks of "wheezes" causing you to feel short of breath?" (b) Asthma: Wheezing definition and FEV1/FVC post-bronchodilator ≥ 70%. (c) Underdiagnosis: Asthma definition without a physician-diagnosis. Logistic regression was used for exploring risk factors. RESULTS: Prevalence of asthma was 9.0% (95% CI: 8.3-9.8) and wheezing 11.9% (95% CI: 11.0-12.8). Asthma underdiagnosis was 69.9% and increased to 79.0% in subjects 64 years or older. The risk factors related to asthma and/or wheezing were: living in Bogota or Medellin, female gender, first degree relative with asthma, respiratory disease before 16 years of age, obesity, no education, indoor wood smoke exposure and occupational exposure to dust particles, gases or fumes. CONCLUSION: We described the epidemiologic situation of asthma in adults 40 years and older in Colombia. In addition to some recognized risk factors, our data supports the association of indoor wood smoke and occupational exposures with asthma and wheezing. Underdiagnosis of asthma in adults was high, particularly in older subjects.


Subject(s)
Asthma/epidemiology , Respiratory Sounds , Adult , Aged , Aged, 80 and over , Air Pollution, Indoor , Asthma/diagnosis , Asthma/physiopathology , Colombia/epidemiology , Cooking , Environmental Exposure , Female , Humans , Male , Middle Aged , Prevalence , Risk Factors , Smoke , Smoking/epidemiology , Wood
6.
Am J Phys Anthropol ; 157(1): 58-70, 2015 May.
Article in English | MEDLINE | ID: mdl-25582401

ABSTRACT

Fluctuating and directional asymmetry are aspects of morphological variation widely used to infer environmental and genetic factors affecting facial phenotypes. However, the genetic basis and environmental determinants of both asymmetry types is far from being completely known. The analysis of facial asymmetries in admixed individuals can be of help to characterize the impact of a genome's heterozygosity on the developmental basis of both fluctuating and directional asymmetries. Here we characterize the association between genetic ancestry and individual asymmetry on a sample of Latin-American admixed populations. To do so, three-dimensional (3D) facial shape attributes were explored on a sample of 4,104 volunteers aged between 18 and 85 years. Individual ancestry and heterozygosity was estimated using more than 730,000 genome-wide markers. Multivariate techniques applied to geometric morphometric data were used to evaluate the magnitude and significance of directional and fluctuating asymmetry (FA), as well as correlations and multiple regressions aimed to estimate the relationship between facial FA scores and heterozygosity and a set of covariates. Results indicate that directional and FA are both significant, the former being the strongest expression of asymmetry in this sample. In addition, our analyses suggest that there are some specific patterns of facial asymmetries characterizing the different ancestry groups. Finally, we find that more heterozygous individuals exhibit lower levels of asymmetry. Our results highlight the importance of including ancestry-admixture estimators, especially when the analyses are aimed to compare levels of asymmetries on groups differing on socioeconomic levels, as a proxy to estimate developmental noise.


Subject(s)
Facial Asymmetry/genetics , Hispanic or Latino/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Analysis of Variance , Anthropometry , Face/anatomy & histology , Face/pathology , Humans , Middle Aged , Principal Component Analysis , Young Adult
7.
COPD ; 11(4): 401-6, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24111929

ABSTRACT

BACKGROUND: At Bogota's altitude (2640 m), the lower barometric pressure (560 mmHg) causes severe hypoxemia in COPD patients, limiting their exercise capacity. The aim was to compare the effects of breathing oxygen on exercise tolerance. METHODS: In a blind, crossover clinical study, 29 COPD patients (FEV1 42.9 ± 11.9%) breathed room air (RA) or oxygen (FIO2 28% and 35%) during three treadmill exercise tests at 70% of their maximal capacity in a randomized order. Endurance time (ET), inspiratory capacity (IC), arterial blood gases and lactate were compared. RESULTS: At the end of the exercise breathing RA, the ET was 9.7 ± 4.2 min, the PaO2 46.5 ± 8.2 mmHg, the lactate increased and the IC decreased. The oxygen significantly increased the ET (p < 0.001), without differences between 28% (16.4 ± 6.8 min) and 35% (17.6 ± 7.0 min) (p = 0.22). Breathing oxygen, there was an increase in the PaO2 and SaO2, higher with FIO2 35%, and a decrease in the lactate level. At "isotime" (ET at RA), with oxygen, the SpO2, the oxygen pulse and the IC were higher and the heart rate lower than breathing RA (p < 0.05). CONCLUSION: Oxygen administration for COPD patients in Bogotá significantly increased ET by decreased respiratory load, improved cardiovascular performance and oxygen transport. The higher increases of the PaO2 and SaO2 with 35% FIO2 did not represent a significant advantage in the ET. This finding has important logistic and economic implications for oxygen use in rehabilitation programs of COPD patients at the altitude of Bogotá and similar altitudes.


Subject(s)
Air , Altitude , Exercise Tolerance/physiology , Oxygen/administration & dosage , Pulmonary Disease, Chronic Obstructive/physiopathology , Aged , Colombia , Cross-Over Studies , Exercise Test , Female , Heart Rate , Humans , Inspiratory Capacity , Lactic Acid/blood , Male , Middle Aged , Oxygen/blood , Partial Pressure , Single-Blind Method , Time Factors
8.
J Sci Food Agric ; 94(14): 3030-7, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24623548

ABSTRACT

BACKGROUND: Environmentally friendly agriculture needs to reduce the use of synthetic fertilizers and to reclaim nutrients from organic wastes. In this study the effect of five doses (0, 12, 24, 48 and 96 t ha(-1) ) of two two-phase olive mill waste (TPOMW)-based composts on the bioactivity and chemical characteristics of an agricultural soil and their potential to fertilize alfalfa (Medicago sativa) and stimulate nodulation were assessed during a two-year incubation experiment. The two composts were prepared either with the olive mill waste alone (compost A), which served as control, or mixed with a liquid fatty-proteinaceous hydrolyzate waste (FPH) from the pharmaceutical industry (compost AH). RESULTS: Compost AH resulted in greater N immobilization than compost A because the former supplied the soil with easily degradable C and N, which increased microbial biomass and activity. Both compost mineralizations during the first year of incubation supplied the soil with more nutrients (mainly N), more so with A than with AH. Nevertheless, plant growth was similar in soils amended with either A or AH. Both composts induced nodulation similarly and the highest dose (96 t ha(-1) ) increased the formation of nodules by a factor of 11 compared with the four lower doses. CONCLUSION: TPOMW serves as an effective ground material for co-composting with liquid wastes such as FPH. TPOMW supplies key nutrients and stimulates nodulation in alfalfa.


Subject(s)
Industrial Waste/analysis , Medicago sativa/microbiology , Medicago sativa/physiology , Plant Root Nodulation/drug effects , Refuse Disposal/methods , Soil , Agriculture , Bacteria/drug effects , Bacteria/metabolism , Biomass , Drug Industry , Food Industry , Nitrogen/chemistry , Nitrogen/metabolism , Root Nodules, Plant , Soil Microbiology
9.
J Clin Med ; 13(8)2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38673671

ABSTRACT

Background: climate change is a reality, and more and more people are becoming aware of this global problem, which has generated anxiety in some populations. To validate a short survey to assess eco-anxiety in adults in South America. Methods: It is an instrumental study, and the validation was based on a previous survey, which had six questions and was generated by 217 respondents in the USA in 2021. These questions were subjected to a validation process with expert judgment, pilot and application, and then statistics were obtained. It was validated with 1907 people in six countries in South America, where the mean, standard deviation, skewness and kurtosis were adequate. Results: The initial confirmatory factorial model obtained unsatisfactory goodness-of-fit indices, so the indices were modified through a re-specification, where two items were eliminated, after which adequate values were obtained (χ2 = 22.34, df = 2, p = 0.00; RMR = 0.020; GFI = 0.990; CFI = 0.990; TLI = 0.990; and RMSEA = 0.070). Finally, the overall Cronbach's α was calculated to be 0.88 (95% CI = 0.86-0.89). Conclusions: The test was validated in a large South American population and found that only four questions can efficiently measure anxiety about the effects of climate change. The instrument can be used with other tests to screen different age groups, ethnicities and realities.

10.
Microorganisms ; 11(5)2023 Apr 28.
Article in English | MEDLINE | ID: mdl-37317132

ABSTRACT

Macrofungi are among the most promising sources of biologically active natural products with nutritional qualities and therapeutic values. In this work, the nutritional value of nine species of wild macrofungi from Ibague-Tolima (Colombia) was evaluated. In addition the antioxidant, antimicrobial and cytotoxic activities of an ethanol:water (70:30) extract of wild basidiomata were evaluated. The wild mushrooms' nutritional potential showed that the genus Pleurotus and Lentinus have the best protein percentages, with 18.4% and 18.5%. The nine extracts evaluated managed to stabilize the two radicals evaluated; however, lower IC50 was found for Phellinus gilvus and Ganoderma australe extracts. The results showed that Trametes coccinea, Pleurotus floridanus and Ganoderma australe extracts were the most effective as antimicrobials, with high inhibition percentages against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae. Antifungal activity results against Rhizopus oryzae, Penicillium sp. and Aspergillus niger showed that the nine extracts were effective at the concentrations tested. Considering cell viability against isolated leukocytes, seven of the nine extracts showed percentages higher than 50% of cell viability. This research describes the nutritional value of nine wild macrofungi in Colombia and their potential for antimicrobial, cytotoxic and antioxidant activity.

11.
J Med Chem ; 66(10): 6782-6797, 2023 05 25.
Article in English | MEDLINE | ID: mdl-37154765

ABSTRACT

Breast cancer resistance protein (BCRP, ABCG2) is an efflux transporter that plays a crucial role in multidrug resistance to antineoplastic drugs. Ko143, an analogue of the natural product fumitremorgin C, is a potent inhibitor of ABCG2 but is rapidly hydrolyzed to an inactive metabolite in vivo. To identify ABCG2 inhibitors with improved metabolic stability, we have assessed a series of Ko143 analogues for their ability to inhibit ABCG2-mediated transport in ABCG2-transduced MDCK II cells and determined the stability of the most potent compounds in liver microsomes. The most promising analogues were evaluated in vivo by positron emission tomography. In vitro, three of the tested analogues were potent ABCG2 inhibitors and stable in microsomes. In vivo, they increased the distribution of the ABCG2/ABCB1 substrate [11C]tariquidar to the brain both in wild-type (with Abcb1a/b transport blocked by tariquidar) and Abcb1a/b(-/-) mice. One analogue was more potent than Ko143 in both animal models.


Subject(s)
ATP-Binding Cassette Transporters , Antineoplastic Agents , Mice , Animals , ATP-Binding Cassette Transporters/metabolism , ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism , Neoplasm Proteins/metabolism , Brain/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/metabolism
12.
Commun Biol ; 6(1): 958, 2023 10 10.
Article in English | MEDLINE | ID: mdl-37816865

ABSTRACT

The Nav1.7 voltage-gated sodium channel plays a key role in nociception. Three functional variants in the SCN9A gene (encoding M932L, V991L, and D1908G in Nav1.7), have recently been identified as stemming from Neanderthal introgression and to associate with pain symptomatology in UK BioBank data. In 1000 genomes data, these variants are absent in Europeans but common in Latin Americans. Analysing high-density genotype data from 7594 Latin Americans, we characterized Neanderthal introgression in SCN9A. We find that tracts of introgression occur on a Native American genomic background, have an average length of ~123 kb and overlap the M932L, V991L, and D1908G coding positions. Furthermore, we measured experimentally six pain thresholds in 1623 healthy Colombians. We found that Neanderthal ancestry in SCN9A is significantly associated with a lower mechanical pain threshold after sensitization with mustard oil and evidence of additivity of effects across Nav1.7 variants. Our findings support the reported association of Neanderthal Nav1.7 variants with clinical pain, define a specific sensory modality affected by archaic introgression in SCN9A and are consistent with independent effects of the Neanderthal variants on Nav1.7 function.


Subject(s)
Neanderthals , Pain Threshold , Humans , Animals , Neanderthals/genetics , Pain/genetics , NAV1.7 Voltage-Gated Sodium Channel/genetics , Nociception
13.
Commun Biol ; 6(1): 481, 2023 05 08.
Article in English | MEDLINE | ID: mdl-37156940

ABSTRACT

We report a genome-wide association study of facial features in >6000 Latin Americans based on automatic landmarking of 2D portraits and testing for association with inter-landmark distances. We detected significant associations (P-value <5 × 10-8) at 42 genome regions, nine of which have been previously reported. In follow-up analyses, 26 of the 33 novel regions replicate in East Asians, Europeans, or Africans, and one mouse homologous region influences craniofacial morphology in mice. The novel region in 1q32.3 shows introgression from Neanderthals and we find that the introgressed tract increases nasal height (consistent with the differentiation between Neanderthals and modern humans). Novel regions include candidate genes and genome regulatory elements previously implicated in craniofacial development, and show preferential transcription in cranial neural crest cells. The automated approach used here should simplify the collection of large study samples from across the world, facilitating a cosmopolitan characterization of the genetics of facial features.


Subject(s)
Neanderthals , Humans , Animals , Mice , Neanderthals/genetics , Genome-Wide Association Study , Nose , Cell Differentiation
14.
Mol Imaging Biol ; 23(2): 196-207, 2021 04.
Article in English | MEDLINE | ID: mdl-32989622

ABSTRACT

PURPOSE: The co-stimulatory molecules CD80 and CD86 are upregulated on activated antigen-presenting cells (APC). We investigated whether local APC activation, induced by subcutaneous (s.c.) inoculation of lipopolysaccharides (LPS), can be imaged by positron emission tomography (PET) with CD80/CD86-targeting 64Cu-labelled abatacept. PROCEDURES: Mice were inoculated s.c. with extracellular-matrix gel containing either LPS or vehicle (PBS). Immune cell populations were analysed by flow cytometry and marker expression by RT-qPCR. 64Cu-NODAGA-abatacept distribution was analysed using PET/CT and ex vivo biodistribution. RESULTS: The number of CD80+ and CD86+ immune cells at the LPS inoculation site significantly increased a few days after inoculation. CD68 and CD86 expression were higher at the LPS than the PBS inoculation site, and CD80 was only increased at the LPS inoculation site. CTLA-4 was highest 10 days after LPS inoculation, when CD80/CD86 decreased again. A few days after inoculation, 64Cu-NODAGA-abatacept distribution to the inoculation site was significantly higher for LPS than PBS (4.2-fold). Co-administration of unlabelled abatacept or human immunoglobulin reduced tracer uptake. The latter reduced the number of CD86+ immune cells at the LPS inoculation site. CONCLUSIONS: CD80 and CD86 are upregulated in an LPS-induced local inflammation, indicating invasion of activated APCs. 64Cu-NODAGA-abatacept PET allowed following APC activation over time.


Subject(s)
B7-1 Antigen/metabolism , B7-2 Antigen/metabolism , Inflammation/diagnostic imaging , Inflammation/metabolism , Abatacept/administration & dosage , Abatacept/pharmacokinetics , Animals , Copper Radioisotopes/pharmacokinetics , Immune Checkpoint Inhibitors/administration & dosage , Immune Checkpoint Inhibitors/pharmacokinetics , Inflammation/drug therapy , Inflammation/pathology , Lipopolysaccharides/administration & dosage , Male , Mice , Mice, Inbred C57BL , Models, Animal , Molecular Imaging/methods , Positron Emission Tomography Computed Tomography/methods , Radiopharmaceuticals/administration & dosage , Radiopharmaceuticals/pharmacokinetics , Tissue Distribution , Up-Regulation/drug effects
15.
Forensic Sci Int Genet ; 53: 102517, 2021 07.
Article in English | MEDLINE | ID: mdl-33865096

ABSTRACT

Here we evaluate the accuracy of prediction for eye, hair and skin pigmentation in a dataset of > 6500 individuals from Mexico, Colombia, Peru, Chile and Brazil (including genome-wide SNP data and quantitative/categorical pigmentation phenotypes - the CANDELA dataset CAN). We evaluated accuracy in relation to different analytical methods and various phenotypic predictors. As expected from statistical principles, we observe that quantitative traits are more sensitive to changes in the prediction models than categorical traits. We find that Random Forest or Linear Regression are generally the best performing methods. We also compare the prediction accuracy of SNP sets defined in the CAN dataset (including 56, 101 and 120 SNPs for eye, hair and skin colour prediction, respectively) to the well-established HIrisPlex-S SNP set (including 6, 22 and 36 SNPs for eye, hair and skin colour prediction respectively). When training prediction models on the CAN data, we observe remarkably similar performances for HIrisPlex-S and the larger CAN SNP sets for the prediction of hair (categorical) and eye (both categorical and quantitative), while the CAN sets outperform HIrisPlex-S for quantitative, but not for categorical skin pigmentation prediction. The performance of HIrisPlex-S, when models are trained in a world-wide sample (although consisting of 80% Europeans, https://hirisplex.erasmusmc.nl), is lower relative to training in the CAN data (particularly for hair and skin colour). Altogether, our observations are consistent with common variation of eye and hair colour having a relatively simple genetic architecture, which is well captured by HIrisPlex-S, even in admixed Latin Americans (with partial European ancestry). By contrast, since skin pigmentation is a more polygenic trait, accuracy is more sensitive to prediction SNP set size, although here this effect was only apparent for a quantitative measure of skin pigmentation. Our results support the use of HIrisPlex-S in the prediction of categorical pigmentation traits for forensic purposes in Latin America, while illustrating the impact of training datasets on its accuracy.


Subject(s)
Eye Color/genetics , Hair Color/genetics , Polymorphism, Single Nucleotide , Skin Pigmentation/genetics , Datasets as Topic , Genetics, Population , Genotype , Humans , Latin America , Logistic Models , Phenotype
16.
Sci Adv ; 7(6)2021 02.
Article in English | MEDLINE | ID: mdl-33547071

ABSTRACT

To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wide association study (GWAS) of more than 6000 individuals using 59 landmark-based measurements from two-dimensional profile photographs and ~9,000,000 genotyped or imputed single-nucleotide polymorphisms. We detected significant association of 32 traits with at least 1 (and up to 6) of 32 different genomic regions, more than doubling the number of robustly associated face morphology loci reported until now (from 11 to 23). These GWAS hits are strongly enriched in regulatory sequences active specifically during craniofacial development. The associated region in 1p12 includes a tract of archaic adaptive introgression, with a Denisovan haplotype common in Native Americans affecting particularly lip thickness. Among the nine previously unidentified face morphology loci we identified is the VPS13B gene region, and we show that variants in this region also affect midfacial morphology in mice.


Subject(s)
Face , Polymorphism, Single Nucleotide , Vesicular Transport Proteins , Animals , Face/anatomy & histology , Genome-Wide Association Study , Genotype , Hispanic or Latino/genetics , Humans , Mice , Phenotype , Vesicular Transport Proteins/genetics
17.
J Med Chem ; 62(17): 8090-8100, 2019 09 12.
Article in English | MEDLINE | ID: mdl-31430137

ABSTRACT

The costimulatory molecule CD80 is an early marker for immune activation. It is upregulated on activated antigen-presenting cells. We aimed at developing a tracer for imaging CD80 by positron emission tomography (PET). Novel CD80 ligands were synthesized and tested by SPR for affinity to human CD80 (hCD80) and displacement of endogenous ligands. Several compounds bound with one-digit nanomolar affinity to hCD80 and displaced CTLA-4 and CD28 at nanomolar concentrations. A structure-affinity relationship study revealed relevant moieties for strong affinity to hCD80 and positions for further modifications. Lead compound MT107 (7f) was radiolabeled with carbon-11. In vitro, [11C]MT107 showed specific binding to hCD80-positive tissue and high plasma protein binding. In vivo, [11C]MT107 accumulated in liver, gall bladder, and intestines but only scarcely in hCD80-positive xenografts. The unfavorable in vivo performance may result from high plasma protein binding and extensive biliary excretion.


Subject(s)
B7-1 Antigen/analysis , Positron Emission Tomography Computed Tomography , Small Molecule Libraries/chemistry , Animals , Binding Sites , Humans , Mice , Mice, SCID , Molecular Structure , Neoplasms, Experimental/diagnostic imaging , Small Molecule Libraries/chemical synthesis
18.
Nat Commun ; 10(1): 358, 2019 01 21.
Article in English | MEDLINE | ID: mdl-30664655

ABSTRACT

We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans.


Subject(s)
Epistasis, Genetic , Eye Color/genetics , Genome, Human , Quantitative Trait Loci , Skin Pigmentation/genetics , Alleles , Asian People , Biological Evolution , Ethnicity , Female , Gene Expression , Gene Frequency , Genetics, Population , Genome-Wide Association Study , Guanine Nucleotide Exchange Factors/genetics , Humans , Latin America , Male , Membrane Proteins/genetics , Membrane Transport Proteins/genetics , Polymorphism, Single Nucleotide , Receptor, Metabotropic Glutamate 5/genetics , Ubiquitin-Protein Ligases , White People
19.
Chest ; 133(2): 343-9, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17951621

ABSTRACT

BACKGROUND: The prevalence of COPD in Colombia is unknown. This study aimed to investigate COPD prevalence in five Colombian cities and measure the association between COPD and altitude. METHODS: A cross-sectional design and a random, multistage, cluster-sampling strategy were used to provide representative samples of adults aged >or= 40 years. Each participant was interviewed (validated Spanish version of the Ferris Respiratory Questionnaire) and performed spirometry before and after 200 microg of inhaled salbutamol, using a portable spirometer according to American Thoracic Society recommendations. COPD definitions were as follows: (1) spirometric: fixed ratio (primary definition): FEV1/FVC < 70% after bronchodilator; (2) medical: a diagnosis of chronic bronchitis, emphysema, or COPD made by a physician; (3) clinical: cough and phlegm >or= 3 months every year during >or= 2 consecutive years (chronic bronchitis). Analysis was performed using statistical software. RESULTS: A total of 5,539 orsubjects were included. The overall COPD prevalence using the primary definition (spirometric) was 8.9%, ranging from 6.2% in Barranquilla to 13.5% in Medellín. The prevalence measured by the spirometric definition was higher than medical (2.8%) and clinical (3.2%) definitions. After the logistic regression analysis, the factors related with COPD were age >or= 60 years, male gender, history of tuberculosis, smoking, wood smoke exposure >or= 10 years, and very low education level. There was a nonsignificant tendency toward larger prevalence with higher altitude. CONCLUSION: COPD is an important health burden in Colombia. Additional studies are needed to establish the real influence of altitude on COPD prevalence.


Subject(s)
Altitude , Pulmonary Disease, Chronic Obstructive/epidemiology , Adult , Aged , Colombia/epidemiology , Cross-Sectional Studies , Female , Humans , Logistic Models , Male , Middle Aged , Prevalence , Risk Factors , Smoking/epidemiology , Spirometry , Tuberculosis, Pulmonary/epidemiology
20.
Respirar (Ciudad Autón. B. Aires) ; 15(2): [128-133], jun2023.
Article in Spanish | LILACS | ID: biblio-1437565

ABSTRACT

Introducción: la mayoría de los pacientes que se someten a cirugía torácica pueden ser clasificados en el grupo de alto riesgo para hipoxia, especialmente cuando se decide por una ventilación unipulmonar, debido al desequilibrio V/Q; por lo tanto, se han desa-rrollado nuevas estrategias ventilatorias y maniobras de rescate para hipoxia. Curso clínico: presentamos una paciente de 85 años de edad sin comorbilidades programada para toracotomía abierta y manejada con ventilación unipulmonar. Durante el mane-jo anestésico, se presenta hipoxia secundaria a desequilibrio V/Q y choque hipovolémi-co hemorrágico, con respuesta positiva a las maniobras de rescate para hipoxia. Con-clusión: es importante prevenir en la medida de lo posible la hipoxia en la ventilación unipulmonar, siguiendo las nuevas estrategias ventilatorias. Sin embargo, cuando se presenta una crisis, no debemos retrasar las maniobras de rescate de forma moderna. (AU)


Introduction: most of the patients undergoing thoracic surgery fit in the high risk group for hypoxia, especially when deciding to use one-lung ventilation due to the V/Q mis-match; therefore, new ventilation strategies and hypoxia rescue manoeuvres have been developed. Clinical course: we present an 85-year old female with no major co-morbidities scheduled for open thoracotomy and managed with one-lung ventilation. During the course of the anaesthetic management, hypoxia presents secondary to V/Q mismatch and haemorrhagic hypovolemic shock, with a positive response to hypoxia rescue manoeuvres. Conclusion: it is important to prevent as much as we can the hy-poxia in a one-lung ventilation following the new ventilation strategies. Although when facing a crisis, proper hypoxia management with a modern approach should not be de-layed. (AU)


Subject(s)
Humans , Female , Aged, 80 and over , Abscess/surgery , One-Lung Ventilation/instrumentation , Mediastinitis/pathology , Hypoxia/surgery , Thoracotomy , Oxygenation , Anesthesia
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