Frequency of Mutations in the TPO Gene in Patients with Congenital Hypothyroidism Due to Dyshormonogenesis in Chile.

Background and Objectives: Congenital thyroid dyshormonogenesis is caused by alterations in the synthesis of thyroid hormones in a newborn. Additionally, 10 to 20% of these cases are hereditary, caused by defects in proteins involved in hormonal synthesis. One of the most common causes is mutations in the thyroid peroxidase (TPO) enzyme gene, an autosomal recessive disease. We aimed to detect mutations of the TPO gene in 12 Chilean patients with congenital hypothyroidism due to dyshormonogenesis (CHD) and to characterize these patients clinically and molecularly. Materials and Methods: Twelve patients under 20 years of age with CHD, controlled at San Juan de Dios Hospital in Santiago, Chile, were selected according to the inclusion criteria: elevated neonatal TSH, persistent hypothyroidism, and thyroid normotopic by imaging study. Those with deafness, Down syndrome, and central or transient congenital hypothyroidism were excluded. Blood samples were taken for DNA extraction, and the 17 exons and exon-intron junctions of the TPO gene were amplified by PCR. The PCR products were sequenced by Sanger. Results: Two possibly pathogenic mutations of the TPO gene were detected: c.2242G>A (p.Val748Met) and c.1103C>T (p.Pro368Leu). These mutations were detected in 2 of 12 patients (16.6%): 1 was compound heterozygous c.1103C>T/c.2242G>A, and the other was heterozygous for c.2242G>A. In the diagnostic confirmation test, both patients presented diffuse hyper-uptake goiter on thyroid scintigraphy and high TSH in venous blood (>190 uIU/mL). Conclusions: The frequency of patients with possibly pathogenic mutations in TPO with CHD was 16.6%. Its study would allow for genetic counseling to be offered to the families of affected patients.

Intermittent Fasting and Reduction of Inflammatory Response in a Patient with Ulcerative Colitis.

Ulcerative colitis is an inflammatory disease that affects the colon, generating a crisis period associated with diarrhea and ulcerations. Stress plays a pivotal role in modulating the inflammatory response and aggravating progression. Different studies have shown that fasting reduces inflammation markers, and intermittent fasting decreases inflammatory markers such as IL-2, IL-6, and RCP. Goal: To evaluate the impact of intermittent fasting on a patient diagnosed with ulcerative colitis. A female patient underwent intermittent fasting (10/14) for eight weeks. Clinical tests were performed for blood count, RCP, biochemical profile, glycemia, and T4/TSH levels. Fecal calprotectin was determined. Clinical exams were assessed before and after intermittent fasting. Inflammation markers, such as CRP and calprotectin, were significantly reduced after eight weeks of intermittent fasting. The patient reported feeling better and was seizure-free during the following months when she continued fasting intermittently. Intermittent fasting allowed for a reduction in inflammation markers.

New candidate SNPs for genetic association with Alzheimer's disease: a linkage disequilibrium analysis for the FCGRIIB and PILRA genes.

Background: Two new SNPs have been recently associated to Alzheimer's disease in African American populations: FCGRIIB rs1050501 C/T, and PILRA rs1859788 A/G. The risk of Alzheimer's disease in FCGRIIB C and PILRA A allele carriers is three times higher than in non-carriers. However, the association between these and other single nucleotide polymorphisms (SNPs) has not been assessed. Methods: Linkage disequilibrium analysis, with r= 0.8 as a threshold value, was used to impute new candidate SNPs, on genomic data from both genes in 26 populations worldwide (n= 2504) from the 1000Genomes database. Results: Four SNPs (rs13376485, rs3767640, rs3767639 and rs3767641) were linked to rs1050501 and one (rs2405442) to rs1859788 in the whole sample. Conclusions: Five novel SNPs could be associated with Alzheimer's disease susceptibility and play a causal role, even if none of them are exon variants since their potential roles in the regulation of gene expression.

Antecedentes: Recientemente se han asociado dos nuevos polimorfismos de un solo nucleótido (SNP) a la enfermedad de Alzheimer en poblaciones afroamericanas: FCGRIIB rs1050501 C/T, y PILRA rs1859788 A/G. El riesgo de enfermedad de Alzheimer en los portadores de los alelos FCGRIIB C y PILRA A es tres veces mayor que en los no portadores. Sin embargo, no se ha evaluado la asociación entre estos y otros SNP. Métodos: Se utilizó el análisis de desequilibrio de ligamiento, con r2= 0,8 como valor umbral, para imputar nuevos SNPs candidatos, sobre datos genómicos de ambos genes en 26 poblaciones de todo el mundo (n= 2504) de la base de datos 1000Genomes. Resultados: Cuatro SNPs (rs13376485, rs3767640, rs3767639 y rs3767641) se vincularon al rs1050501 y uno (rs2405442) al rs1859788 en toda la muestra. Conclusiones: Cinco nuevos SNP podrían estar asociados con la susceptibilidad a la enfermedad de Alzheimer y desempeñar un papel causal, aunque ninguno de ellos sea una variante de exón, dado su papel potencial en la regulación de la expresión génica.

Population analysis of the CLOCK rs3749474T-rs4864548A haplotype and its relationship with obesity. / Análisis poblacional in silico del haplotipo CLOCK rs3749474T-rs4864548A y su relación con obesidad.

It has been suggested that the rs3749474T/rs4864548A haplotype of the CLOCK gene increases the risk of obesity, but the population variability of these alleles and the haplotype is unknown. This research aims to determine the linkage between the rs3749474T and rs4864548A alleles from the database of 1000Genomes to confirm the existence of the TA haplotype polymorphisms of these alleles and their frequency in five macro populations. Linkage disequilibrium and haplotype frequencies for 2504 individuals from 26 populations were analyzed using the r statistic and Fisher's exact test. There is a high frequency of the TA haplotype in Latin America (44.8%), a high linkage disequilibrium (r2= 0.92) worldwide between these alleles, a high differentiation between macro populations, and a high homogeneity. The evidence warrants further studies on the association between this haplotype and the risk of obesity and overweight in Latin American populations.

Se ha sugerido que el haplotipo rs3749474T/rs4864548A del gen CLOCK aumentaría el riesgo de obesidad, pero se desconoce el patrón de variabilidad poblacional de estos alelos y del haplotipo. El objetivo de este estudio es determinar el nivel de ligamiento entre los alelos de riesgo rs3749474T y rs4864548A a partir de la base de datos 1000Genomes para confirmar la existencia del haplotipo TA de los polimorfismos rs3749474-rs4864548 del gen CLOCK y su frecuencia cinco macro poblaciones. Se analizó el desequilibrio de ligamiento y las frecuencias haplotípicas para 2504 individuos, de 26 poblaciones, utilizando el estadístico r y la prueba exacta de Fisher. Existe una alta frecuencia del haplotipo TA en Latinoamérica (44,8%), un alto desequilibrio de ligamiento (r= 0,92) a nivel mundial entre esos alelos, una alta diferenciación entre macro poblaciones y una alta homogeneidad al interior de ellas. La evidencia presentada permite sugerir la realización de posteriores estudios de asociación entre este haplotipo y el nivel de riesgo de obesidad y sobrepeso en poblaciones latinoamericanas.

Variation of the acoustic parameters: f0, jitter, shimmer and alpha ratio in relation with different background noise levels.

BACKGROUND AND OBJECTIVES: Research involving acoustic analysis does not always consider the level of background noise in the room where the recording process is going to be carried out, or if they do, the maximum value of background noise used varies from author to author. The objective of this research is to establish if the parameters: f0, Jitter, Shimmer and Alpha ratio vary in relation to different levels of background noise in the room where the recording process is carried out and to establish a maximum value of this. MATERIALS AND METHODS: The Praat program was used to get the average value of the parameters: f0, Jitter, Shimmer and Alpha ratio from a voice sample of 33 subjects inside an Audiometric booth whose background noise level was 28,1 dB(A). A statistical comparison was made between the average value of each parameter as the background noise increased in relation to the average values ​​obtained with the baseline background noise of the cabin for each parameter. RESULTS: The f0 and Alpha ratio parameters show reliable values ​​up to a background noise level of 47,7 dB(A), while the Jitter and Shimmer parameters do so up to a background noise level of 43,8 dB(A). CONCLUSIONS: Considering that the acoustic parameters are all obtained from the same recording, we can point out that the recommended maximum background noise level in the room where the recordings are made should not exceed 43,8 dB(A).

[Prevalence of the GA risk haplotype of the rs1554483 and rs4864548 polymorphisms of the CLOCK gene associated with obesity and overweight in 26 populations]. / Prevalencia del haplotipo de riesgo GA de los polimorfismos rs1554483 y rs4864548 del gen CLOCK asociados a la obesidad y el sobrepeso en 26 poblaciones.

Introduction: Introduction: the GA haplotype of polymorphisms rs1554483 and rs4864548 has been associated with components of the metabolic syndrome such as high blood pressure and triglyceride levels; its carriers have a risk of obesity, 1.5 times higher than the rest of the population. Methodology: SNP rs1554483 and rs4864548 were obtained from 2504 individuals from the "1000genomes phase 3" database. Data were grouped into five macro populations (Africa, East Asia, South Asia, Europe and Latin America) covering a total of 26 populations. Differences in haplotype frequency between macro populations and populations were analyzed, for which Fisher's F statistic was used. Results: the macro population of Africa presented the lowest frequency (17.9 %) and that of East Asia the highest (57.4 %). Within the populations there is a relative homogeneity in the frequencies, except in the case of those that make up the macro population of Latin America where the Peruvian population of Lima and the Puerto Rican population present much higher frequencies than the rest. Conclusions: the GA haplotype presents heterogeneity between macro populations, which suggests highly differentiated micro evolutionary processes between continents. We propose to study the association of the GA haplotype with other polymorphisms such as rs3749474, rs11932595 and rs6859524 that have also been associated with risk of obesity and factors associated with metabolic syndrome.

Introducción: Introducción: el haplotipo GA de los polimorfismos rs1554483 y rs4864548 se ha asociado con componentes del síndrome metabólico como la hipertensión arterial y los niveles de triglicéridos. Sus portadores presentan un riesgo de obesidad 1,5 veces mayor que el resto de la población. Metodología: se obtuvieron los SNP rs1554483 y rs4864548 de 2504 individuos desde la base de datos "1000genomes phase 3". Los datos se agruparon en cinco macropoblaciones (África, Asia Oriental, Asia Meridional, Europa y Latinoamérica) cubriendo un total de 26 poblaciones. Se analizaron las diferencias en la frecuencia del haplotipo entre las macropoblaciones y las poblaciones, para lo cual se utilizó el estadístico F de Fisher. Resultados: la macropoblación de África presentó la menor frecuencia (17,9 %) y la del Este de Asia la mayor (57,4 %). Dentro de las poblaciones existe una relativa homogeneidad en las frecuencias, excepto en el caso de las que componen la macropoblación de Latinoamérica, donde la población peruana de Lima y la puertorriqueña presentan frecuencias mucho mayores que el resto. Conclusiones: el haplotipo GA presenta heterogeneidad entre las macropoblaciones, lo que sugiere procesos microevolutivos altamente diferenciados entre los continentes. Se propone estudiar la asociación del haplotipo GA con otros polimorfismos, como rs3749474, rs11932595 y rs6859524, que también se han asociado con el riesgo de obesidad y factores asociados al síndrome metabólico.

Investigating the Mechanical, Thermal, and Crystalline Properties of Raw and Potassium Hydroxide Treated Butea Parviflora Fibers for Green Polymer Composites.

The only biotic factor that can satisfy the needs of human species are plants. In order to minimize plastic usage and spread an immediate require of environmental awareness, the globe urges for the development of green composite materials. Natural fibers show good renewability and sustainability and are hence utilized as reinforcements in polymer matrix composites. The present work concerns on the usage of Butea parviflora fiber (BP), a green material, for high end applications. The study throws light upon the characterization of raw and potassium hydroxide (KOH)-treated Butea Parviflora plant, where its physical, structural, morphological, mechanical, and thermal properties are analyzed using the powder XRD, FTIR spectroscopy, FESEM micrographs, tensile testing, Tg-DTA, Thermal conductivity, Chemical composition, and CHNS analysis. The density values of untreated and KOH-treated fibers are 1.238 g/cc and 1.340 g/cc, respectively. The crystallinity index of the treated fiber has significantly increased from 83.63% to 86.03%. The cellulose content of the treated fiber also experienced a substantial increase from 58.50% to 60.72%. Treated fibers exhibited a reduction in both hemicelluloses and wax content. Spectroscopic studies registered varying vibrations of functional groups residing on the fibers. SEM images distinguished specific changes on the raw and treated fiber surfaces. The Availability of elements Carbon, Nitrogen, and Hydrogen were analyzed using the CHNS studies. The tensile strength and modulus of treated fibers has risen to 192.97 MPa and 3.46 Gpa, respectively. Thermal conductivity (K) using Lee's disc showed a decrement in the K values of alkalized BP. The activation energy Ea lies between 55.95 and 73.15 kJ/mol. The fibers can withstand a good temperature of up to 240 °C, presenting that it can be tuned in for making sustainable composites.

Characterisation of Sodium Acetate Treatment on Acacia pennata Natural Fibres.

The present study concerns the physico-chemical, structural, mechanical and thermal characterization of Acacia pennata, a natural and almost inexpensive fibre, as a potential reinforcement in polymer composites. The effect of treating the fibre with sodium acetate to increase its qualities has been seen through the use of thermogravimetric analysis, scanning electron microscope (SEM) analysis, X-ray diffraction (XRD), mechanical property tester, and Fourier transform infrared spectroscopy (FTIR). According to XRD analysis, the elimination of lignin and wax-like impurities resulted in an increase in the AP fibre's crystalline index (79.73%). The fibre's thermal stability was also discovered to be 365 °C. Tensile strength (557.58 MPa) and elongation at break both increased by 2.9% after treatment with sodium acetate. The surface nature and quality of AP fibres improved after sodium acetate treatment. It was confirmed by the reduction of chemical compositions (such as hemicellulose, lignin and pectin). Given its density, the fibre can be suggested as a reinforcement in polymer composites for light-weight applications because its lightweight property will be more useful for composite manufacturing.

Investigation on Properties of Raw and Alkali Treated Novel Cellulosic Root Fibres of Zea Mays for Polymeric Composites.

Today, new materials based on natural fibres have been emerging day by day to completely eradicate plastics to favour our environmental nature. In this view, the present work is based on the extraction and characterisation of the novel root fibres of the Zea mays (Zm) plant, grown by the hydroponic method. Both the dried untreated and alkali treated root fibres are investigated using a variety of structural, morphological, thermal, elemental and mechanical tests by subjecting both the samples to p-XRD, FT-IR, SEM-EDAX, TGA-DTA, CHNS and tensile strength analyses. Thermal conductivity of the untreated and treated fibres is found using Lee's disc experiment. From p-XRD analysis, the Crystallinity Index, Percentage Crystallinity and Crystallite size of the samples are found. FT-IR studies clarify the different vibrational groups associated with the fibre samples. SEM images show that the surface roughness increases for the chemically treated samples, such that it may be effectively utilised as reinforcement for polymeric composites. The diameter of the fibre samples is found using SEM analysis. According to the EDAX spectrum, Zm fibres in both their raw and processed forms have high levels of Carbon (C) and Oxygen (O). The TGA-DTA tests revealed that the samples of natural fibre have good thermal characteristics. CHNS studies show that Carbon content is high for these samples, which is the characteristic of many natural fibres. Chemical analysis is used to ascertain the prepared samples' chemical makeup. It reveals that both samples have significant amounts of cellulose. The density of the fibres is found to be in the range 0.3-0.6 g/cc, which is much less than any other natural fibre. Therefore, it can be used in light weight applications. From the tensile strength analysis, physical properties such as Young's modulus and micro-fibril angle are determined. The fibres in the roots exhibit a lower tensile strength. Thus, these fibres can be used in powdered form as reinforcement for natural rubber or epoxy composites. After examining all of its properties, it could be reasonably speculated that Zea mays root fibres can be considered as an efficient reinforcement for various matrices to produce attractive bio-composites.

Comparison of the Acoustic Parameters Obtained With Different Smartphones and a Professional Microphone.

Smartphones allow good quality recordings; however, it cannot be claimed that the acoustic parameters obtained from them are comparable to those obtained with a professional microphone. The objective of this study is to establish whether there are significant differences when comparing the values ​​of six acoustic parameters obtained from recordings using four smartphones and a professional microphone. The Praat programme was used to obtain the acoustic parameters: f0, Jitter, Shimmer, HNR, Alpha Ratio and L1 - L0 of the recording of a sustained vowel /a/ using iPhone SE, iPhone 6, Samsung S8, Huawei Y7 and the Behringer ECM 8000 microphone. The sample was made up of 26 men and 26 women, from 18 to 26 years old without declared voice pathology. The repeated sample ANOVA test was used to compare the values. All the equipment show reproducibility between consecutive repeated measurements. The parameters f0 and Jitter were the only ones that did not show significant differences between the smartphones and the professional microphone. None of the smartphones studied can replace the professional microphone in voice recording for the evaluation of the six parameters analysed, except for f0 and Jitter.

[Variability of the genetic marker CLOCK rs3749474 and its impact on research and clinical trials on obesity and circadian rhythm]. / Variabilidad del marcador genético CLOCK rs3749474 y su impacto en la investigación y ensayos clínicos sobre obesidad y ritmo circadiano.

Introduction: Introduction: circadian rhythms influence eating behavior, with the CLOCK gene being one of those responsible for its regulation. The rs3749474T/C of the CLOCK gene has been associated with an increased risk of obesity. Those who carry the T allele have greater weight loss on a diet low in carbohydrates and lipids than those who have the CC form. Methodology: using the 1000 Genomes database, the genotype of the single nucleotide polymorphism (SNP) rs3749474 was obtained from 2,504 individuals, covering five macro-populations (Africa, East Asia, South Asia, Europe and Latin America) and 26 populations. CT and TT were treated as non-risk genotypes and CC as risk. Fisher's exact test was used to compare the frequencies of risk and non-risk genotypes among the five macro populations. Results: there is a high differentiation for the frequency of genotypes carrying the T allele among the macro-populations: Africa reached only 31.47 %, Europe 56.86 %; Latin America 66.28 %; South Asia 68.3 % and East Asia 81.15 %, with significant differences (pFisher < 0.05) in all comparisons, except between Latin America and South Asia. Low heterogeneity was observed between populations within each macro population. Conclusions: the high heterogeneity for the genotypic frequencies of CLOCK rs3749474 in the studied macro-populations indicates that the decrease in the consumption of carbohydrates and lipids will have a heterogeneous impact, from the epidemiological point of view. This suggests including the genetic ancestry in later studies of association between circadian cycles, eating behavior and obesity, in order to develop personalized clinical tests.

Introducción: Introducción: los ritmos circadianos influyen en la conducta alimentaria, siendo el gen CLOCK uno de los encargados de su regulación. El rs3749474T/C del gen CLOCK ha sido asociado a un mayor riesgo de obesidad y quienes portan el alelo T presentan una mayor pérdida de peso ante una dieta baja en carbohidratos y lípidos que quienes poseen la forma CC. Material y métodos: usando la base de datos 1000 Genomes se obtuvo el genotipo del polimorfismo de nucleótido único (SNP) rs3749474 de 2.504 individuos, abarcando cinco macropoblaciones (África, Este Asiático, Sur Asiático, Europa y Latinoamérica) y 26 poblaciones. CT y TT fueron tratados como genotipos de no riesgo y CC, como de riesgo. Se utilizó la prueba exacta de Fisher para comparar las frecuencias de los genotipos de riesgo y no riesgo. Resultados: existe una alta diferenciación para la frecuencia de genotipos portadores del alelo T entre las macropoblaciones: África alcanzó solo el 31,47 %; Europa, un 56,86 %; Latinoamérica, un 66,28 %; el Sur Asiático, un 68,3 %; y el Este Asiático, un 81,15 %, con diferencias significativas (pFisher < 0,05) en todas las comparaciones, excepto entre Latinoamérica y Sur Asiático. Se observó una baja heterogeneidad entre poblaciones dentro de cada macropoblación. Conclusiones: la alta heterogeneidad para las frecuencias genotípicas de CLOCK rs3749474 en las macropoblaciones estudiadas indica que la disminución del consumo de carbohidratos y lípidos tendrá un impacto heterogéneo desde el punto de vista epidemiológico. Esto sugiere incluir la ancestría genética en posteriores estudios de asociación entre ciclos circadianos, conducta alimentaria y obesidad, con el objeto de desarrollar pruebas clínicas personalizadas.

Comparison of the acoustic parameters obtained with different smartphones and a professional microphone. / Comparación de parámetros acústicos obtenidos con diferentes teléfonos inteligentes y un micrófono profesional.

Smartphones allow good quality recordings; however, it cannot be claimed that the acoustic parameters obtained from them are comparable to those obtained with a professional microphone. The objective of this study is to establish whether there are significant differences when comparing the values of six acoustic parameters obtained from recordings using four smartphones and a professional microphone. The Praat programme was used to obtain the acoustic parameters: f0, Jitter, Shimmer, HNR, Alpha Ratio and L1 - L0 of the recording of a sustained vowel /a/ using iPhone SE, iPhone 6, Samsung S8, Huawei Y7 and the Behringer ECM8000 microphone. The sample was made up of 26 men and 26 women, from 18 to 26 years old without declared voice pathology. The repeated sample ANOVA test was used to compare the values. All the equipment show reproducibility between consecutive repeated measurements. The parameters f0 and Jitter were the only ones that did not show significant differences between the smartphones and the professional microphone. None of the smartphones studied can replace the professional microphone in voice recording for the evaluation of the six parameters analysed, except for f0 and Jitter.

Variation of the acoustic parameter harmonic-to-noise ratio in relation to different background noise levels. / Variación del parámetro acústico harmonic-to-noise ratio en relación con distintos niveles de ruido de fondo.

INTRODUCTION AND OBJECTIVES: Acoustic analysis is a tool widely used by professionals related to the study of voice that gives us information from a recording. It has been identified that in investigations carried out today that involve acoustic analysis, the recording process takes place in rooms with different levels of background noise. The objective of this study is to establish whether the acoustic parameter harmonic-to-noise ratio (HNR) varies in relation to the different background noise levels of the premises where the recording is made and recommend a maximum level of background noise. METHODS: Through the Praat programme, the average value of the acoustic parameter HNR of 43 subjects was obtained, inside the audiometric booth of the Universidad Autónoma de Chile, whose background noise level is 28.1dB(A) and it was compared with the HNR average values obtained with higher background noise levels. RESULTS: The HNR average values decreased from 19.8 to 14.0dB(A) as the background noise level of the premises increased from 28.1 to 57.8dB(A). The t-test for dependent samples was performed, with which the HNR average values obtained were compared with the baseline background noise level (28.1dB[A]). Significant differences were found with the baseline background noise level when the room noise level was higher than 47.7dB(A). CONCLUSIONS: The background noise of the premises where the voice recording for the acoustic analysis is performed, influences the value of the acoustic parameter HNR, which decreases as the background noise of the premises increases. It is recommended that the background noise level should not exceed 43.8dB(A).