Association of tyrosine hydroxylase 01 (TH01) microsatellite and insulin gene (INS) variable number of tandem repeat (VNTR) with type 2 diabetes and fasting insulin secretion in Mexican population.

PURPOSE: A variable number of tandem repeats (VNTR) in the insulin gene (INS) control region may be involved in type 2 diabetes (T2D). The TH01 microsatellite is near INS and may regulate it. We investigated whether the TH01 microsatellite and INS VNTR, assessed via the surrogate marker single nucleotide polymorphism rs689, are associated with T2D and serum insulin levels in a Mexican population. METHODS: We analyzed a main case-control study (n = 1986) that used univariate and multivariate logistic regression models to calculate the risk conferred by TH01 and rs689 loci for T2D development; rs689 results were replicated in other case-control (n = 1188) and cross-sectional (n = 1914) studies. RESULTS: TH01 alleles 6, 8, 9, and 9.3 and allele A of rs689 were independently associated with T2D, with differences between sex and age at diagnosis. TH01 alleles with ≥ 8 repeats conferred an increased risk for T2D in males compared with ≤ 7 repeats (odds ratio, ≥ 1.46; 95% confidence interval, 1.1-1.95). In females, larger alleles conferred a 1.5-fold higher risk for T2D when diagnosed ≥ 46 years but conferred protection when diagnosed ≤ 45 years. Similarly, rs689 allele A was associated with T2D in these groups. In males, larger TH01 alleles and the rs689 A allele were associated with a significant decrease in median fasting plasma insulin concentration with age in T2D cases; the reverse occurred in controls. CONCLUSION: Larger TH01 alleles and rs689 A allele may potentiate insulin synthesis in males without T2D, a process disabled in those with T2D.

The role of single nucleotide variant rs3819817 of the Histidine Ammonia-Lyase gene and 25-Hydroxyvitamin D on bone mineral density, adiposity markers, and skin pigmentation, in Mexican population.

PURPOSE: Vitamin D (VD) deficiency and osteoporosis have become a global public health problem. A variant in the Histidine Ammonia-Lyase (HAL) gene has been associated with VD levels and bone mineral density (BMD). However, whether this variant has an influence on VD levels and BMD in Mexican adults remain unclear. METHODS: This cross-sectional analysis included 1,905 adults participating in the Health Worker Cohort Study and 164 indigenous postmenopausal women from the Metabolic Analysis in an Indigenous Sample (MAIS) cohort. The rs3819817 variant was genotyped by TaqMan probe assay. Total 25 hydroxyvitamin D levels were measured by DiaSorin Liaison. BMD at the different sites was assessed through dual-energy X-ray absorptiometry. Linear and logistic regression models were performed to evaluate the associations of interest. RESULTS: The prevalence of VD deficiency was 41%, showing differences between sexes. Obesity and skin pigmentation were associated with lower levels of VD in males and females. rs3819817-T allele was associated with low levels of 25-hydroxyvitamin D, VD deficiency, and hip and femoral neck BMD values (g/cm2). We found two interactions with VD levels, one between adiposity and rs3819817-T allele (P = 0.017) and another between skin pigmentation and rs3819817-T allele (P = 0.019). In indigenous postmenopausal women, we observed higher VD levels in the southern region compared to the northern region (P < 0.001); however, we did not observe differences by genotype. CONCLUSION: Our findings confirm that the genetic variant rs3819817 has an essential function in VD levels and BMD and suggests a role in skin pigmentation in the Mexican population.

Association between vitamin D deficiency and common variants of Vitamin D binding protein gene among Mexican Mestizo and indigenous postmenopausal women.

PURPOSE: Vitamin D deficiency (VDD) and polymorphisms in the group-specific component (GC) gene are known to be associated in different populations. However, the effects of such genetic variants may vary across different populations. Thus, the objective of this study was to estimate the association between Vitamin D-Binding Protein (VDBP) haplotypes and VDD in mestizo postmenopausal women and Mexican Amerindian ethnic groups. METHODS: This was a cross-sectional study of 726 postmenopausal Mexican women from the Health Workers Cohort Study (HWCS) and 166 postmenopausal women from the Metabolic Analysis in an Indigenous Sample (MAIS) cohort in Mexico. GC polymorphisms (rs7045 and rs4588) were analyzed by TaqMan probes. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured by Chemiluminescent Microparticle Immuno Assay. RESULTS: The prevalence of VDD serum 25(OH)D < 20 ng/mL was 43.7% in mestizo women and 44.6% in indigenous women. In HWCS, the single nucleotide polymorphisms (SNPs) rs7041 and rs4588 were associated with VDD. In addition, women from the HWCS, carrying the haplotypes GC2/2 and GC1f/2 had higher odds of VDD (OR = 2.83, 95% CI 1.14, 7.02; and OR = 2.30, 95% CI 1.40, 3.78, respectively) compared to women with haplotype 1f/1 s. These associations were not statistically significant in the MAIS cohort. CONCLUSIONS: Our results show genetic association of the analyzed SNPs and related haplotypes, on the GC gene, with VDD in mestizo Mexican postmenopausal women. Moreover, a high prevalence of VDD with high genetic variability within the country was observed. Our results support the need for national policies for preventing VDD.

Effect of natural genetic variation on enhancer selection and function.

The mechanisms by which genetic variation affects transcription regulation and phenotypes at the nucleotide level are incompletely understood. Here we use natural genetic variation as an in vivo mutagenesis screen to assess the genome-wide effects of sequence variation on lineage-determining and signal-specific transcription factor binding, epigenomics and transcriptional outcomes in primary macrophages from different mouse strains. We find substantial genetic evidence to support the concept that lineage-determining transcription factors define epigenetic and transcriptomic states by selecting enhancer-like regions in the genome in a collaborative fashion and facilitating binding of signal-dependent factors. This hierarchical model of transcription factor function suggests that limited sets of genomic data for lineage-determining transcription factors and informative histone modifications can be used for the prioritization of disease-associated regulatory variants.

A primer in artificial intelligence in cardiovascular medicine.

Driven by recent developments in computational power, algorithms and web-based storage resources, machine learning (ML)-based artificial intelligence (AI) has quickly gained ground as the solution for many technological and societal challenges. AI education has become very popular and is oversubscribed at Dutch universities. Major investments were made in 2018 to develop and build the first AI-driven hospitals to improve patient care and reduce healthcare costs. AI has the potential to greatly enhance traditional statistical analyses in many domains and has been demonstrated to allow the discovery of 'hidden' information in highly complex datasets. As such, AI can also be of significant value in the diagnosis and treatment of cardiovascular disease, and the first applications of AI in the cardiovascular field are promising. However, many professionals in the cardiovascular field involved in patient care, education or science are unaware of the basics behind AI and the existing and expected applications in their field. In this review, we aim to introduce the broad cardiovascular community to the basics of modern ML-based AI and explain several of the commonly used algorithms. We also summarise their initial and future applications relevant to the cardiovascular field.

Enhancing cardiovascular artificial intelligence (AI) research in the Netherlands: CVON-AI consortium.

BACKGROUND: Machine learning (ML) allows the exploration and progressive improvement of very complex high-dimensional data patterns that can be utilised to optimise specific classification and prediction tasks, outperforming traditional statistical approaches. An enormous acceleration of ready-to-use tools and artificial intelligence (AI) applications, shaped by the emergence, refinement, and application of powerful ML algorithms in several areas of knowledge, is ongoing. Although such progress has begun to permeate the medical sciences and clinical medicine, implementation in cardiovascular medicine and research is still in its infancy. OBJECTIVES: To lay out the theoretical framework, purpose, and structure of a novel AI consortium. METHODS: We have established a new Dutch research consortium, the CVON-AI, supported by the Netherlands Heart Foundation, to catalyse and facilitate the development and utilisation of AI solutions for existing and emerging cardiovascular research initiatives and to raise AI awareness in the cardiovascular research community. CVON-AI will connect to previously established CVON consortia and apply a cloud-based AI platform to supplement their planned traditional data-analysis approach. RESULTS: A pilot experiment on the CVON-AI cloud was conducted using cardiac magnetic resonance data. It demonstrated the feasibility of the platform and documented excellent correlation between AI-generated ventricular function estimates as compared to expert manual annotations. The resulting AI solution was then integrated in a web application. CONCLUSION: CVON-AI is a new consortium meant to facilitate the implementation and raise awareness of AI in cardiovascular research in the Netherlands. CVON-AI will create an accessible cloud-based platform for cardiovascular researchers, demonstrate the clinical applicability of AI, optimise the analytical methodology of other ongoing CVON consortia, and promote AI awareness through education and training.

Buccal micronucleus cytome assay of populations under chronic heavy metal and other metal exposure along the Santiago River, Mexico.

The Santiago River is one of the most contaminated rivers in Mexico, with heavy metal levels above the allowed limits. Scientific evidence indicates that chronic heavy metal exposure leads to cytogenotoxic effects. The aims of this study were to evaluate the genotoxic and cytotoxic effects of such exposure in buccal mucosa cells by micronucleus (MN) assay and to identify other nuclear abnormalities (NAs), such as nuclear buds (NBUDs), binucleated cells (BNs), pyknotic nuclei (PNs), karyorrhexis (KX), karyolysis (KL), and abnormally condensed chromatin (CC). Assays were performed on samples from four populations located alongside the Santiago River that are under chronic exposure to heavy metals and other metals (HMMs), and the results were compared with those of a population without exposure to HMMs. The exposed group showed increased frequencies of NAs (KX, CC, and KL), which are associated with cytotoxic damage, and NBUDs, which are associated with genotoxic damage. Increased frequencies of NBUDs and CC were observed in subjects from El Salto/Juanacatlán, Ocotlán, and Paso de Guadalupe, and an increase in KX frequency was observed in subjects from El Salto/Juanacatlán. Significant differences in KL frequency were observed in subjects from La Barca, El Salto/Juanacatlán, Paso de Guadalupe, and Ocotlán. Predictors for increased development of MNs and NBUDs were high concentrations of Al, Zn, and Cu. In conclusion, chronic exposure to HMMs, especially Al, Cu, and Zn, in the studied population could be related to increased frequencies of NAs, such as NBUDs, KX, CC, and KL, in the buccal mucosa cells.

New amino acid changes in drug resistance sites and HBsAg in hepatitis B virus genotype H.

Long-term treatment with retrotranscriptase (RT) inhibitors eventually leads to the development of drug resistance. Drug-related mutations occur naturally and these can be found in hepatitis B virus (HBV) carriers who have never received antiviral therapy. HBsAg are overlapped with RT domain, thus nucleot(s)ide analogues (NAs) resistance mutations and naturally-occurring mutations can cause amino acid changes in the HBsAg. Twenty-two patients with chronic hepatitis B were enrolled; three of them were previously treated with NAs and 19 were NAs-naïve treated. HBV reverse transcriptase region was sequenced; genotyping and analysis of missense mutations were performed in both RT domain and HBsAg. There was predominance of genotype H. Drug mutations were present in 18.2% of patients. Classical lamivudine resistance mutations (rtM204V/rtL180M) were present in one naïve-treatment patient infected with genotype G. New amino acid changes were identified in drug resistance sites in HBV strains from patients infected with genotype H; rtQ215E was present in two naïve-NAs treatment patients and rtI169M was identified in a patient previously treated with lamivudine. Mutations at sites rt169, rt204, and rt215 resulted in the Y161C, I195M, and C206W mutations at HBsAg. Also, new amino acid changes were identified in B-cell and T-cell epitopes and were more frequent in HBsAg compared to RT domain. In conclusion, new amino acid changes at antiviral resistance sites, B-cell and T-cell epitopes in HBV genotype H were identified in Mexican patients.

Environment-Assisted Speed-up of the Field Evolution in Cavity Quantum Electrodynamics.

We measure the quantum speed of the state evolution of the field in a weakly driven optical cavity QED system. To this end, the mode of the electromagnetic field is considered as a quantum system of interest with a preferential coupling to a tunable environment: the atoms. By controlling the environment, i.e., changing the number of atoms coupled to the optical cavity mode, an environment-assisted speed-up is realized: the quantum speed of the state repopulation in the optical cavity increases with the coupling strength between the optical cavity mode and this non-Markovian environment (the number of atoms).

Hyperfine Anomalies in Fr: Boundaries of the Spherical Single Particle Model.

We have measured the hyperfine splitting of the 7P_{1/2} state at the 100 ppm level in Fr isotopes (^{206g,206m,207,209,213,221}Fr) near the closed neutron shell (N=126 in ^{213}Fr). The measurements in five isotopes and a nuclear isomeric state of francium, combined with previous determinations of the 7S_{1/2} splittings, reveal the spatial distribution of the nuclear magnetization, i.e., the Bohr-Weisskopf effect. We compare our results with a simple shell model consisting of unpaired single valence nucleons orbiting a spherical nucleus, and find good agreement over a range of neutron-deficient isotopes (^{207-213}Fr). Also, we find near-constant proton anomalies for several even-N isotopes. This identifies a set of Fr isotopes whose nuclear structure can be understood well enough for the extraction of weak interaction parameters from parity nonconservation studies.

SPINK5 and ADRB2 haplotypes are risk factors for asthma in Mexican pediatric patients.

BACKGROUND: Asthma is one of the most common respiratory diseases worldwide, and the complexity of its etiology has been widely documented. Chromosome 5q31-33 is one of the main loci implicated in asthma and asthma-related traits. IL13, CD14 and ADRB2, which are located in this risk locus, are among the genes most strongly associated with asthma susceptibility. OBJECTIVES: This study evaluated whether single-nucleotide polymorphisms or haplotypes at 5q31-33 conferred risk for asthma in Mexican-Mestizo pediatric patients. METHODS: We performed a case-controlled study including 851 individuals, 421 of them affected with childhood-onset asthma and 430 ethnically matched unaffected subjects. We used the TaqMan Allelic Discrimination Assay to genotype 20 single-nucleotide polymorphisms within IL5, RAD50, IL13, IL4, CD14, SPINK5, HTR4, ADRB2 and IL12B. RESULTS: Although no association was detected for any risk allele, three SPINK5 haplotypes (GGCT: p = 6 × 10(-6); AATC: p = 0.0001; AGTT: p = 0.0001) and five ADRB2 haplotypes (AGGACC: p = 0.0014; AGGAAG: p = 0.0002; TGAGAG: p = 0.0001; AGGAAC: p = 0.0002; AAGGAG: p = 0.003) were associated with asthma. Notably, the AGTT SPINK5 haplotype exhibited a male gender-dependent association (p = 7.6 × 10(-5)). CONCLUSION: Our results suggest that SPINK5 and ADRB2 haplotypes might play a role in the susceptibility to childhood-onset asthma.

A low-loss photonic silica nanofiber for higher-order modes.

Optical nanofibers confine light to subwavelength scales, and are of interest for the design, integration, and interconnection of nanophotonic devices. Here we demonstrate high transmission (> 97%) of the first family of excited modes through a 350 nm radius fiber, by appropriate choice of the fiber and precise control of the taper geometry. We can design the nanofibers so that these modes propagate with most of their energy outside the waist region. We also present an optical setup for selectively launching these modes with less than 1% fundamental mode contamination. Our experimental results are in good agreement with simulations of the propagation. Multimode optical nanofibers expand the photonic toolbox, and may aid in the realization of a fully integrated nanoscale device for communication science, laser science or other sensing applications.

Intermodal energy transfer in a tapered optical fiber: optimizing transmission.

We present an experimental and theoretical study of the energy transfer between modes during the tapering process of an optical nanofiber through spectrogram analysis. The results allow optimization of the tapering process, and we measure transmission in excess of 99.95% for the fundamental mode. We quantify the adiabaticity condition through calculations and place an upper bound on the amount of energy transferred to other modes at each step of the tapering, giving practical limits to the tapering angle.

Relationship of aquatic environmental factors with the abundance of Vibrio cholerae, Vibrio parahaemolyticus, Vibrio mimicus and Vibrio vulnificus in the coastal area of Guaymas, Sonora, Mexico.

Members of the genus Vibrio are common in aquatic environments. Among them are V. cholerae, V. vulnificus, V. parahaemolyticus and V. mimicus. Several studies have shown that environmental factors, such as temperature, salinity, and dissolved oxygen, are involved in their epidemiology. Therefore, the main objective of this study is to determine if there is a correlation between the presence/amount of V. cholerae, V, vulnificus, V. parahaemolyticus and V. mimicus and the environmental conditions of the seawater off the coast of Guaymas, México. Quantification of all four pathogenic bacteria was performed using the most probable number method, and suspected colonies were identified by polymerase chain reaction (PCR). Correlations were found using principal component analysis. V. parahaemolyticus was the most abundant and widely distributed bacteria, followed by V. vulnificus, V. mimicus and V. cholerae. Positive correlations between V. parahaemolyticus, V. vulnificus and V. mimicus with temperature, salinity, electric conductivity, and total dissolved solids were found. The abundance of V. cholerae was mainly affected by the sampling site and not by physicochemical parameters.

MiR-146a polymorphism is associated with asthma but not with systemic lupus erythematosus and juvenile rheumatoid arthritis in Mexican patients.

Extensive research has shown that aberrant expression of microRNAs (miRNAs) plays an important role in innate and adaptive immune responses. The rs2910164 polymorphism has been identified as a functional variant, which affects the transcription and expression level of miR-146a and, thereby, contributes to the pathogenesis of several inflammatory and autoimmune diseases. To investigate whether the rs2910164 G/C polymorphism was associated with asthma, systemic lupus erythematosus (SLE) or juvenile rheumatoid arthritis (JRA), we performed an association study in a pediatric Mexican cohort. We included 979 pediatric patients (asthma: 402, SLE: 367 and JRA: 210) and 531 control subjects without inflammatory or immune diseases. Genotyping was performed using the 5' exonuclease technique. The genotype distribution of the rs2910164 polymorphism was in Hardy-Weinberg equilibrium in each group. No significant differences were detected in the distribution of this polymorphism between cases and controls (P = 0.108, 0.609 and 0.553 for subjects with asthma, JRA and SLE, respectively). However, stratification by gender showed a statistically significant difference between asthmatic and control females, where the C allele was significantly associated with protection to asthma (odds ratio = 0.694, 95% confidence interval 0.519-0.929, P = 0.0138). Our results provide evidence that rs2910164 may play a role in the susceptibility to childhood-onset asthma, but not SLE or JRA in Mexicans. Further association studies may contribute to determining the role of miR-146a single-nucleotide polymorphisms in immune-mediated diseases.

Pigmentary mosaicism as a recurrent clinical manifestation in three new patients with mosaic trisomy 12 diagnosed postnatally: cases report and literature review.

BACKGROUND: To date, only twenty-one cases diagnosed postnatally with mosaic trisomy 12 have been reported. The most frequent phenotypic manifestations are developmental delay, dysmorphic facial features, congenital heart defects, digital alterations, and pigmentary disorders. In the present report, detailed clinical and genetic profiles of three unrelated new patients with mosaic trisomy 12 are described and compared with previously reported cases. CASE PRESENTATION: In the present report, we include the clinical, cytogenetic, and molecular description of three Mexican patients diagnosed postnatally with mosaic trisomy 12. At phenotypic level, the three patients present with developmental delay, dysmorphic facial features, congenital heart defects and skin pigmentary anomalies. Particularly, patient 1 showed unique eye alterations as bilateral distichiasis, triple rows of upper lashes, and digital abnormalities. In patient 2 redundant skin, severe hearing loss, and hypotonia were observed, and patient 3 presented with hypertelorism and telecanthus. Hyperpigmentation with disseminated pigmentary anomalies is a common trait in all of them. The cytogenetic study was carried out under the strict criteria of analysis, screening 50-100 metaphases from three different tissues, showing trisomy 12 mosaicism in at least one of the three different tissues analyzed. With SNParray, the presence of low-level mosaic copy number variants not previously detected by cytogenetics, and uniparental disomy of chromosome 12, was excluded. STR markers allowed to confirm the absence of uniparental disomy as well as to know the parental origin of supernumerary chromosome 12. CONCLUSIONS: The detailed clinical, cytogenetic, and molecular description of these three new patients, contributes with relevant information to delineate more accurately a group of patients that show a heterogeneous phenotype, although sharing the same chromosomal alteration. The possibility of detecting mosaic trisomy 12 is directly associated with the sensitivity of the methodology applied to reveal the low-level chromosomal mosaicism, as well as with the possibility to perform the analysis in a suitable tissue.

Photon statistics and polarization correlations at telecommunications wavelengths from a warm atomic ensemble.

We present measurements of the polarization correlation and photon statistics of photon pairs that emerge from a laser-pumped warm rubidium vapor cell. The photon pairs occur at 780 nm and 1367 nm and are polarization entangled. We measure the autocorrelation of each of the generated fields as well as the cross-correlation function, and observe a strong violation of the two-beam Cauchy-Schwartz inequality. We evaluate the performance of the system as source of heralded single photons at a telecommunication wavelength. We measure the heralded autocorrelation and see that coincidences are suppressed by a factor of ≈ 20 from a Poissonian source at a generation rate of 1500 s(-1), a heralding efficiency of 10%, and a narrow spectral width.

Observation of ground-state quantum beats in atomic spontaneous emission.

We report ground-state quantum beats in spontaneous emission from a continuously driven atomic ensemble. Beats are visible only in an intensity autocorrelation and evidence spontaneously generated coherence in radiative decay. Our measurement realizes a quantum eraser where a first photon detection prepares a superposition and a second erases the "which path" information in the intermediate state.