Structure and function of the hippocampal CA3 module.

The hippocampal formation is crucial for learning and memory, with submodule CA3 thought to be the substrate of pattern completion. However, the underlying synaptic and computational mechanisms of this network are not well understood. Here, we perform circuit reconstruction of a CA3 module using three dimensional (3D) electron microscopy data and combine this with functional connectivity recordings and computational simulations to determine possible CA3 network mechanisms. Direct measurements of connectivity schemes with both physiological measurements and structural 3D EM revealed a high connectivity rate, multi-fold higher than previously assumed. Mathematical modelling indicated that such CA3 networks can robustly generate pattern completion and replay memory sequences. In conclusion, our data demonstrate that the connectivity scheme of the hippocampal submodule is well suited for efficient memory storage and retrieval.

A CRISPR-Cas9-engineered mouse model for GPI-anchor deficiency mirrors human phenotypes and exhibits hippocampal synaptic dysfunctions.

Pathogenic germline mutations in PIGV lead to glycosylphosphatidylinositol biosynthesis deficiency (GPIBD). Individuals with pathogenic biallelic mutations in genes of the glycosylphosphatidylinositol (GPI)-anchor pathway exhibit cognitive impairments, motor delay, and often epilepsy. Thus far, the pathophysiology underlying the disease remains unclear, and suitable rodent models that mirror all symptoms observed in human patients have not been available. Therefore, we used CRISPR-Cas9 to introduce the most prevalent hypomorphic missense mutation in European patients, Pigv:c.1022C > A (p.A341E), at a site that is conserved in mice. Mirroring the human pathology, mutant Pigv341E mice exhibited deficits in motor coordination, cognitive impairments, and alterations in sociability and sleep patterns, as well as increased seizure susceptibility. Furthermore, immunohistochemistry revealed reduced synaptophysin immunoreactivity in Pigv341E mice, and electrophysiology recordings showed decreased hippocampal synaptic transmission that could underlie impaired memory formation. In single-cell RNA sequencing, Pigv341E-hippocampal cells exhibited changes in gene expression, most prominently in a subtype of microglia and subicular neurons. A significant reduction in Abl1 transcript levels in several cell clusters suggested a link to the signaling pathway of GPI-anchored ephrins. We also observed elevated levels of Hdc transcripts, which might affect histamine metabolism with consequences for circadian rhythm. This mouse model will not only open the doors to further investigation into the pathophysiology of GPIBD, but will also deepen our understanding of the role of GPI-anchor-related pathways in brain development.

SynaptoPAC, an optogenetic tool for induction of presynaptic plasticity.

Optogenetic manipulations have transformed neuroscience in recent years. While sophisticated tools now exist for controlling the firing patterns of neurons, it remains challenging to optogenetically define the plasticity state of individual synapses. A variety of synapses in the mammalian brain express presynaptic long-term potentiation (LTP) upon elevation of presynaptic cyclic adenosine monophosphate (cAMP), but the molecular expression mechanisms as well as the impact of presynaptic LTP on network activity and behavior are not fully understood. In order to establish optogenetic control of presynaptic cAMP levels and thereby presynaptic potentiation, we developed synaptoPAC, a presynaptically targeted version of the photoactivated adenylyl cyclase bPAC. In cultures of hippocampal granule cells of Wistar rats, activation of synaptoPAC with blue light increased action potential-evoked transmission, an effect not seen in hippocampal cultures of non-granule cells. In acute brain slices of C57BL/6N mice, synaptoPAC activation immediately triggered a strong presynaptic potentiation at mossy fiber synapses in CA3, but not at Schaffer collateral synapses in CA1. Following light-triggered potentiation, mossy fiber transmission decreased within 20 min, but remained enhanced still after 30 min. The optogenetic potentiation altered the short-term plasticity dynamics of release, reminiscent of presynaptic LTP. Our work establishes synaptoPAC as an optogenetic tool that enables acute light-controlled potentiation of transmitter release at specific synapses in the brain, facilitating studies of the role of presynaptic potentiation in network function and animal behavior in an unprecedented manner. Read the Editorial Highlight for this article on page 270.

The "Who Do You Tell?"™ Child Sexual Abuse Education Program: Eight Years of Monitoring.

School-based programs have been the central strategy to educate children about the serious nature of child sexual abuse (CSA) in the hope of prevention or early intervention. While program evaluations consistently show significant improvement in children's knowledge and skills, it behooves programs to monitor their impacts. Monitoring, or on-going assessments, can take several forms but in the current study refers to monitoring the outcome of knowledge of CSA prevention concepts. The "Who Do You Tell?"™ child sexual abuse education program has been offered for 35 years in Calgary, Canada and was previously evaluated in a randomized pre-test-post-test comparison study with strong positive findings. This article presents the results of subsequently monitoring program outcomes over an eight-year period (2010-2017), examining knowledge/attitudes in 6198 students in 50 schools in a Western Canadian city. All students significantly increased their CSA knowledge/attitudes with large effect sizes. Practice and policy implications are discussed.

Clinical and immunological characteristics of a pediatric population with food protein-induced enterocolitis syndrome (FPIES) to fish.

BACKGROUND: Food protein-induced enterocolitis (FPIES) is an uncommon, non-IgE-mediated food allergy that usually debuts in infancy with profuse vomiting, lethargy, and pallor 2-4 h following ingestion of the offending food. Its immune mechanism is not known. We aimed to describe the clinical features and outcome of children with fish-FPIES as well as to investigate on cellular immune response implicated. METHODS: Prospective and follow-up clinical study of children with FPIES by fish over a period between 2004 and 2013 was conducted. Measurement in vitro of both cytokine production in peripheral blood mononuclear cells (PBMCs) and expression of HLA-DR in monocyte-derived dendritic cells stimulated with fish extracts. RESULTS: Sixteen children (seven male and nine female) were included, with a mean age of onset at 10 months. Diagnosis was established after a median of 4 reactions. Twelve patients were treated in emergency room, and two were admitted in intensive care. Patch tests were positive in six patients. Skin prick tests (SPTs) and specific IgE to all fish tested were negative. Only three children reached tolerance at a mean age of 4.5 years. Eight children avoided fish because of positive oral food challenge (OFC) after 6 years of age. Other patients have not been challenged because of parent refusal to OFC or a recent diagnosis. TNF-α was increased in patients, and a significant elevation of the HLA-DR marker was also observed in these patients vs. control donors. CONCLUSIONS: FPIES caused by fish in many cases presents with severe clinical manifestations. Patch test has poor diagnostic value, and OFC is the gold standard to test tolerance. The cytokine TNF-α may be implicated in the clinical symptoms. Higher expression of HLA-DR in dendritic cells has also been detected in our patients.

Ancestral association between HLA and HFE H63D and C282Y gene mutations from northwest Colombia.

A significant association between HFE gene mutations and the HLA-A*03-B*07 and HLA-A*29-B*44 haplotypes has been reported in the Spanish population. It has been proposed that these mutations are probably connected with Celtic and North African ancestry, respectively. We aimed to find the possible ancestral association between HLA alleles and haplotypes associated with the HFE gene (C282Y and H63D) mutations in 214 subjects from Antioquia, Colombia. These were 18 individuals with presumed hereditary hemochromatosis ("HH") and 196 controls. The HLA-B*07 allele was in linkage disequilibrium (LD) with C282Y, while HLA-A*23, A*29, HLA-B*44, and B*49 were in LD with H63D. Altogether, our results show that, although the H63D mutation is more common in the Antioquia population, it is not associated with any particular HLA haplotype, whereas the C282Y mutation is associated with HLA-A*03-B*07, this supporting a northern Spaniard ancestry.

Physical pretreatment of three biowastes to improve black soldier fly larvae bioconversion efficiency.

Black soldier fly larvae (BSFL, Hermetia illucens (L.)) are recognized for efficient biowaste reduction while yielding valuable proteins and fats for animals. However, lignocellulosic fibers in biowastes are difficult to digest by biowaste and larval digestive tract microorganisms as well as the larvae themselves. This study investigated two biowaste physical pretreatments (thermal, mechanical) for improving BSFL processing of fibrous biowastes. Cow manure, spent grain, and grass clippings were thermally pretreated at 90 °C for three durations (0.5, 1 and 4 h). Contrary to expectations, thermal pretreatment resulted in either no improvement or decreased larval performance on all substrates, regardless of treatment duration. In contrast, mechanical pretreatment of spent grain and grass clippings, involving milling with three screen sizes (0.5, 1 and 2 mm) showed promising results. Specifically, bioconversion rates on 0.5 mm-milled spent grain and grass clippings increased by 0-53 % and 25-44 % dry mass, respectively compared to untreated. Additionally, larval protein conversion increased by 41 % and 23 % on spent grain and grass clippings, respectively. However, mechanical pretreatment did not affect fiber degradation by larval conversion, as hemicellulose decreased by 25 % and 75 % for spent grain and grass clippings, respectively, regardless of particle size. Particle size reduction influenced substrate microbial respiration (CO2 mg/min), with 0.5-mm milled grass clippings exhibiting higher respiration compared to untreated, although this effect was not observed for spent grain. This study highlights mechanical pretreatment's potential in enhancing BSFL bioconversion of fibrous biowastes and the importance of understanding substrate physical properties influencing substrate microorganisms and BSFL.

The Lack of Synapsin Alters Presynaptic Plasticity at Hippocampal Mossy Fibers in Male Mice.

Synapsins are highly abundant presynaptic proteins that play a crucial role in neurotransmission and plasticity via the clustering of synaptic vesicles. The synapsin III isoform is usually downregulated after development, but in hippocampal mossy fiber boutons, it persists in adulthood. Mossy fiber boutons express presynaptic forms of short- and long-term plasticity, which are thought to underlie different forms of learning. Previous research on synapsins at this synapse focused on synapsin isoforms I and II. Thus, a complete picture regarding the role of synapsins in mossy fiber plasticity is still missing. Here, we investigated presynaptic plasticity at hippocampal mossy fiber boutons by combining electrophysiological field recordings and transmission electron microscopy in a mouse model lacking all synapsin isoforms. We found decreased short-term plasticity, i.e., decreased facilitation and post-tetanic potentiation, but increased long-term potentiation in male synapsin triple knock-out (KO) mice. At the ultrastructural level, we observed more dispersed vesicles and a higher density of active zones in mossy fiber boutons from KO animals. Our results indicate that all synapsin isoforms are required for fine regulation of short- and long-term presynaptic plasticity at the mossy fiber synapse.

Eosinophilic enterocolitis in duodenum, ileum, and colon: A case report.

Eosinophilic gastroenteritis (EGE) is a rare disease which mainly consists of an abnormal eosinophile infiltration of the gastrointestinal tract. It's classified according to its location: eosinophilic esophagitis, eosinophilic gastritis, eosinophilic enteritis (including duodenum, jejunum and/or ileum) and eosinophilic colitis and degree of infiltration (mucosal, muscular, serosal). Depending on eosinophile concentration, type of EGE and the patient's condition it may manifest with different clinical presentations such as functional dyspepsia, abdominal pain, irritability, hypoproteinemia, diarrhea, anemia, among others. Few research has been done on such an uncommon pathology to the extent that treatment evidence is mostly limited to small case series. This case study reports an infrequent presentation of EGE in the small and large intestine as an undifferentiated gastrointestinal disease and successful corticoid management given to the patient in order to further broaden knowledge on this subject and facilitate an established clinical conduct for the treating physician.

Branch point strength controls species-specific CAMK2B alternative splicing and regulates LTP.

Regulation and functionality of species-specific alternative splicing has remained enigmatic to the present date. Calcium/calmodulin-dependent protein kinase IIß (CaMKIIß) is expressed in several splice variants and plays a key role in learning and memory. Here, we identify and characterize several primate-specific CAMK2B splice isoforms, which show altered kinetic properties and changes in substrate specificity. Furthermore, we demonstrate that primate-specific CAMK2B alternative splicing is achieved through branch point weakening during evolution. We show that reducing branch point and splice site strengths during evolution globally renders constitutive exons alternative, thus providing novel mechanistic insight into cis-directed species-specific alternative splicing regulation. Using CRISPR/Cas9, we introduce a weaker, human branch point sequence into the mouse genome, resulting in strongly altered Camk2b splicing in the brains of mutant mice. We observe a strong impairment of long-term potentiation in CA3-CA1 synapses of mutant mice, thus connecting branch point-controlled CAMK2B alternative splicing with a fundamental function in learning and memory.

Microplastic pollution in water, sediments and commercial fish species from Ciénaga Grande de Santa Marta lagoon complex, Colombian Caribbean.

Microplastics are emerging pollutants that have been found in different environmental matrices of marine and coastal ecosystems, where they can generate harmful ecological impacts. Little is known about the current state of microplastic pollution in fragile tropical lagoon ecosystems, such as Ciénaga Grande de Santa Marta (CGSM) in the Caribbean coast of Colombia. This study assesses microplastic pollution in surface waters and sediments, and the occurrence of microplastic ingestion in commercially important fish species from CGSM. In waters, microplastic abundances ranged from 0.0 to 0.3 items L-1 while in sediments they varied from 0.0 to 3.1 items kg-1. The most abundant types of microplastics are fibers and fragments, with polypropylene, polyethylene and high-density polyethylene as the most abundant polymers. Also, 100 (i.e. 21.1%) out of 474 individuals from nine fish species had microplastics in their digestive tracts. Microplastics present in water and sediments and in the digestive tract of the analyzed fish species have similar characteristics, also showing a moderate and statistically significant association. Microplastic abundances are higher near river mouths and in urban areas with a high density of fishing activities and aquaculture infrastructures, which are important sources of contaminants. Microplastic pollution in CGSM represents a threat to the lagoon ecosystem and to local people depending on artisanal fishing. Consequently, effective actions to reduce pollution and its socio-environmental impacts are urgently required.

The abbreviation "PWE" may carry a negative connotation compared with the labels "person with epilepsy" and "epileptic".

PURPOSE: Ways of labeling a person with epilepsy (PWE) may have an impact on public position towards affected persons. This study analyzed college students position changes, influenced by three different labels of PWE. METHODS: Observational, descriptive, cross-sectional study. Students of three schools answered one of three questionnaires whose content changed in the labeling form: person with epilepsy, epileptic or PWE. Proportions were compared with Chi square test or Fisher's exact test to explore considering age, gender, religion practicing, socioeconomic status, knowing an affected person and by faculty. RESULTS: A total of 273 questionnaires were included were distributed in medicine 133 (48.7 %), engineering 108 (39.6 %) and law 32 (11.7 %) schools. Labeling type distribution was person with epilepsy 94 (34.4 %), epileptic 93 (34.1 %) and PWE 86 (31.5 %. No statistical differences were found according the labels person with epilepsy and epileptic. The abbreviation PWE had statistical significant connotation in aspects of academic achievement p = 0,007, selecting a PWE in your work team p = 0,009, self control p < 0,000, being dangerous p < 0,000 and having any disturbance in thought or behavior p = 0,05. Religion practicing, socioeconomic status and knowing a person with epilepsy did not impact in attitude related to labeling. Engineering and law students expressed their concern in employability. CONCLUSION: The abbreviation PWE may have negative connotations when used in written questionnaires. No differences were found with the labels person with epilepsy and epileptic in college students. More studies are needed to explore the stigmatizing or destigmatizing effects of labeling a person with epilepsy on different populations.

Species-specific differences in synaptic transmission and plasticity.

Synaptic transmission and plasticity in the hippocampus are integral factors in learning and memory. While there has been intense investigation of these critical mechanisms in the brain of rodents, we lack a broader understanding of the generality of these processes across species. We investigated one of the smallest animals with conserved hippocampal macroanatomy-the Etruscan shrew, and found that while synaptic properties and plasticity in CA1 Schaffer collateral synapses were similar to mice, CA3 mossy fiber synapses showed striking differences in synaptic plasticity between shrews and mice. Shrew mossy fibers have lower long term plasticity compared to mice. Short term plasticity and the expression of a key protein involved in it, synaptotagmin 7 were also markedly lower at the mossy fibers in shrews than in mice. We also observed similar lower expression of synaptotagmin 7 in the mossy fibers of bats that are evolutionarily closer to shrews than mice. Species specific differences in synaptic plasticity and the key molecules regulating it, highlight the evolutionary divergence of neuronal circuit functions.

Circuit-Specific Dendritic Development in the Piriform Cortex.

Dendritic geometry is largely determined during postnatal development and has a substantial impact on neural function. In sensory processing, postnatal development of the dendritic tree is affected by two dominant circuit motifs, ascending sensory feedforward inputs and descending and local recurrent connections. In the three-layered anterior piriform cortex (aPCx), neurons in the sublayers 2a and 2b display vertical segregation of these two circuit motifs. Here, we combined electrophysiology, detailed morphometry, and Ca2+ imaging in acute mouse brain slices and modeling to study circuit-specific aspects of dendritic development. We observed that determination of branching complexity, dendritic length increases, and pruning occurred in distinct developmental phases. Layer 2a and layer 2b neurons displayed developmental phase-specific differences between their apical and basal dendritic trees related to differences in circuit incorporation. We further identified functional candidate mechanisms for circuit-specific differences in postnatal dendritic growth in sublayers 2a and 2b at the mesoscale and microscale levels. Already in the first postnatal week, functional connectivity of layer 2a and layer 2b neurons during early spontaneous network activity scales with differences in basal dendritic growth. During the early critical period of sensory plasticity in the piriform cortex, our data are consistent with a model that proposes a role for dendritic NMDA-spikes in selecting branches for survival during developmental pruning in apical dendrites. The different stages of the morphologic and functional developmental pattern differences between layer 2a and layer 2b neurons demonstrate the complex interplay between dendritic development and circuit specificity.

Emotion Regulation and Attitudes Toward Conflict in Colombia: Effects of Reappraisal Training on Negative Emotions and Support for Conciliatory and Aggressive Statements.

Control of negative emotions (e.g., anger and fear) by political cues perpetuate intractable conflict by mobilizing public support for aggressive actions. Halperin et al. (2013) found that reappraisal - an adaptive form of emotion regulation - decreased negative emotions triggered by anger-inducing information related to the Israeli-Palestinian conflict, and increased support for conciliatory statements. We tested these effects in the context of the conflict between the Colombian government and the Fuerzas Armadas Revolucionarias de Colombia-Ejército del Pueblo (FARC-EP). Reappraisal training reduced negative emotions produced by a presentation that illustrated FARC's violent actions, and increased support for conciliatory statements (with overall moderate effect magnitudes). We also found that negative emotions mediated the effects of reappraisal on the support for aggressive and conciliatory statements. These findings indicate a high degree of generality of the phenomena, especially considering the differences between the Israeli-Palestinian conflict and the Colombian conflict. Our findings also show promise for replicating these effects on other types of intergroup conflicts and guiding effective public policy.

Does public attitude change by labeling a person as epileptic, person with epilepsy or the acronym PWE? A systematic review.

PURPOSE: It is still unknown if attitudinal differences by diverse labeling of persons with epilepsy could be universally accepted with the actual literature evidence. The manner in which questions are constructed could also have an impact in final results. The purpose of this systematic review was to examine the published articles regarding changes in public´s attitude towards epilepsy by labeling a person as epileptic, person with epilepsy or with the acronym PWE. METHODS: We undertook a systematic review of the literature using common databases with specific keywords and combinations searching for original articles, meta-analysis and systematic reviews. Sociodemographic variables, attitude results and questions style were analyzed in included articles. RESULTS: Four original articles were found. Significant attitudinal changes were described in three studies with the label person with epilepsy. One study failed to demonstrate an attitudinal change by distinct labeling of a person with epilepsy. All questions were formulated in a personal way. Few neutral and mostly induced questions were found in the studies. CONCLUSION: By the use of the label "person with epilepsy" there is a trend towards positive changes in public's attitudes, although evidence is scarce to consider this tendency as universally applicable. More studies are needed considering widespread social and cultural backgrounds and patient opinion. Language power by wording type could be a key consideration for future studies.

RIM-BP2 primes synaptic vesicles via recruitment of Munc13-1 at hippocampal mossy fiber synapses.

All synapses require fusion-competent vesicles and coordinated Ca2+-secretion coupling for neurotransmission, yet functional and anatomical properties are diverse across different synapse types. We show that the presynaptic protein RIM-BP2 has diversified functions in neurotransmitter release at different central murine synapses and thus contributes to synaptic diversity. At hippocampal pyramidal CA3-CA1 synapses, RIM-BP2 loss has a mild effect on neurotransmitter release, by only regulating Ca2+-secretion coupling. However, at hippocampal mossy fiber synapses, RIM-BP2 has a substantial impact on neurotransmitter release by promoting vesicle docking/priming and vesicular release probability via stabilization of Munc13-1 at the active zone. We suggest that differences in the active zone organization may dictate the role a protein plays in synaptic transmission and that differences in active zone architecture is a major determinant factor in the functional diversity of synapses.

Spermidine protects from age-related synaptic alterations at hippocampal mossy fiber-CA3 synapses.

Aging is associated with functional alterations of synapses thought to contribute to age-dependent memory impairment (AMI). While therapeutic avenues to protect from AMI are largely elusive, supplementation of spermidine, a polyamine normally declining with age, has been shown to restore defective proteostasis and to protect from AMI in Drosophila. Here we demonstrate that dietary spermidine protects from age-related synaptic alterations at hippocampal mossy fiber (MF)-CA3 synapses and prevents the aging-induced loss of neuronal mitochondria. Dietary spermidine rescued age-dependent decreases in synaptic vesicle density and largely restored defective presynaptic MF-CA3 long-term potentiation (LTP) at MF-CA3 synapses (MF-CA3) in aged animals. In contrast, spermidine failed to protect CA3-CA1 hippocampal synapses characterized by postsynaptic LTP from age-related changes in function and morphology. Our data demonstrate that dietary spermidine attenuates age-associated deterioration of MF-CA3 synaptic transmission and plasticity. These findings provide a physiological and molecular basis for the future therapeutic usage of spermidine.

Minimally Invasive Microelectrode Biosensors Based on Platinized Carbon Fibers for in Vivo Brain Monitoring.

The ability to monitor the chemical composition of brain interstitial fluid remains an important challenge in the field of bioanalytical chemistry. In particular, microelectrode biosensors are a promising resource for the detection of neurochemicals in interstitial fluid in both animals and humans. These biosensors can provide second-by-second temporal resolution and enzymatic recognition of virtually any redox or nonredox molecule. However, despite miniaturization of these sensors to 50-250 µm in diameter to avoid vascular and cellular injury, inflammation and foreign-body reactions still occur following their implantation. Here, we fabricated microelectrodes with platinized carbon fibers to create biosensors that have an external diameter that is less than 15 µm. Platinization was achieved with physical vapor deposition, and increased sensitivity to hydrogen peroxide and improved enzymatic detection were observed for these carbon fiber microelectrodes. When these devices were implanted in the brains of rats, no injuries to the parenchyma or brain blood vessels were detected. In addition, these microelectrodes provided different estimates of basal glucose, lactate, and oxygen concentrations compared to conventional biosensors. Induction of spreading depolarization in the cerebral cortex further demonstrated the greater sensitivity of our microelectrodes to dynamic neurochemical changes. Thus, these minimally invasive devices represent a major advance in our ability to analyze brain interstitial fluid.

[Human leucocyte antigen gene (HLA-A, HLA-B, HLA-DRB1) frequencies in deceased organ donors]. / Frecuencias alélicas, genotípicas y haplotípicas HLA-A, HLA-B, HLA-DRB1 en donantes fallecidos, Medellín, Colombia.

INTRODUCTION: Genetic characterization of the human leucocyte antigen (HLA) system has provided insights into mechanisms of susceptibility to diverse diseases and immunological phenomena during pregnancy, as well as providing evidence for compatibility in the selection of organ transplant donors and recipients. OBJECTIVE: The HLA-A,-B,-DRB1 allele, genotype and haplotype frequencies were determined in deceased organ donors in Medellín, Colombia. MATERIALS AND METHODS: The genotypes of 926 deceased donors were evaluated over a 17-year period (1989- 2006). HLA-A, HLA-B and HLA-DRB1 typing was performed by sequence specific primer-polymerase chain reaction (SSP-PCR). Maximum likelihood frequencies were estimated by the zipper version of expectation maximation algorithm. Hardy-Weinberg equilibrium were determined by an exact test analogous to Fishers test by using Markovs chain, and linkage disequilibrium between pairs of loci. RESULTS: Twenty-two, 43 and 14 alleles were identified for HLA-A, -B and -DRB loci, respectively. The most frequent were A*02, A*24, B*35, and DRB1*04. A deficiency in the proportion of heterozygotes in HLA-A and B loci (p<0.01 and p<0.00001, respectively). The most frequent haplotypes were as follows: HLA-A*24, B*35 (7.7%) for HLA-A,-B; HLA-B*35, DRB1*04 (6.4%) for HLA-B,-DRB1 and HLA-A*24, DRB1*04 (8.9%) for HLA-A,-DRB1. For the 3 loci HLA-A,-B,-DRB1, the most frequent haplotypes were A*24, B*35, DRB1*04 (4.6%) and A*24, B*61, DRB1*04 (2.0%). CONCLUSIONS: These results confirm the three-ethnic ancestry of the Medellin population. The predominance of Caucasian admixture differs from many other Latin-American populations and can serve as a reference for comparative studies of these populations as well as applications within the Medellin population.