A founder DBR1 variant causes a lethal form of congenital ichthyosis.

DBR1 encodes the only known human lariat debranching enzyme and its deficiency has been found to cause an autosomal recessive inborn error of immunity characterized by pediatric brainstem viral-induced encephalitis (MIM 619441). We describe a distinct allelic disorder caused by a founder recessive DBR1 variant in four families (DBR1(NM_016216.4):c.200A > G (p.Tyr67Cys)). Consistent features include prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation (collodion membrane, severe skin peeling and xerosis), and death before the first year of life. Patient-derived fibroblasts displayed the characteristic accumulation of intron lariats in their RNA as revealed by targeted and untargeted analysis, in addition to a marked reduction of DBR1 on immunoblot analysis. We propose a novel DBR1-related developmental disorder that is distinct from DBR1-related encephalitis susceptibility and highlight the apparent lack of correlation with the degree of DBR1 deficiency.

Biallelic variants in HECT E3 paralogs, HECTD4 and UBE3C, encoding ubiquitin ligases cause neurodevelopmental disorders that overlap with Angelman syndrome.

PURPOSE: Pathogenic variants in genes encoding ubiquitin E3 ligases are known to cause neurodevelopmental syndromes. Additional neurodevelopmental disorders associated with the other genes encoding E3 ligases are yet to be identified. METHODS: Chromosomal analysis and exome sequencing were used to identify the genetic causes in 10 patients from 7 unrelated families with syndromic neurodevelopmental, seizure, and movement disorders and neurobehavioral phenotypes. RESULTS: In total, 4 patients were found to have 3 different homozygous loss-of-function (LoF) variants, and 3 patients had 4 compound heterozygous missense variants in the candidate E3 ligase gene, HECTD4, that were rare, absent from controls as homozygous, and predicted to be deleterious in silico. In 3 patients from 2 families with Angelman-like syndrome, paralog-directed candidate gene approach detected 2 LoF variants in the other candidate E3 ligase gene, UBE3C, a paralog of the Angelman syndrome E3 ligase gene, UBE3A. The RNA studies in 4 patients with LoF variants in HECTD4 and UBE3C provided evidence for the LoF effect. CONCLUSION: HECTD4 and UBE3C are novel biallelic rare disease genes, expand the association of the other HECT E3 ligase group with neurodevelopmental syndromes, and could explain some of the missing heritability in patients with a suggestive clinical diagnosis of Angelman syndrome.

HIDEA syndrome is caused by biallelic, pathogenic, rare or founder P4HTM variants impacting the active site or the overall stability of the P4H-TM protein.

HIDEA syndrome is caused by biallelic pathogenic variants in P4HTM. The phenotype is characterized by muscular and central hypotonia, hypoventilation including obstructive and central sleep apneas, intellectual disability, dysautonomia, epilepsy, eye abnormalities, and an increased tendency to develop respiratory distress during pneumonia. Here, we report six new patients with HIDEA syndrome caused by five different biallelic P4HTM variants, including three novel variants. We describe two Finnish enriched pathogenic P4HTM variants and demonstrate that these variants are embedded within founder haplotypes. We review the clinical data from all previously published patients with HIDEA and characterize all reported P4HTM pathogenic variants associated with HIDEA in silico. All known pathogenic variants in P4HTM result in either premature stop codons, an intragenic deletion, or amino acid changes that impact the active site or the overall stability of P4H-TM protein. In all cases, normal P4H-TM enzyme function is expected to be lost or severely decreased. This report expands knowledge of the genotypic and phenotypic spectrum of the disease.

Using BAMLET complex in a functional spreadable cheese elaborated with bovine colostrum.

BAMLET is a bioactive complex formed by the interaction between α-Lactoalbumin (α-LA) and oleic acid which exhibits cytotoxic activity against cancer cells. BAMLET is selectively cytotoxic to malignant cells while sparing the healthy ones. There are, however, no reports about its application in a food matrix. The objective of this work was to synthetize the BAMLET complex from oleic acid and bovine colostrum from the second and third milkings which naturally contain α-LA to prepare two functional spreadable cheeses. The complex was successfully formed and retained in the cheeses as verified through SDS-PAGE applied to the whey obtained. The spreadable cheese from the second milking had a higher protein content (13.56 ± 0.02%) and a higher yield (40%) than the product obtained from the third milking. Even though the cheeses did not show any significant differences (p > 0.05) in the inhibition of the angiotensin-converting enzyme 1, their inhibitory activities were good, as a 0.5 g portion of the cheese from the second milking was sufficient to inhibit 57.52 ± 9.17%, while the cheese from the third milking inhibited 51.48 ± 1.07% of the enzyme. The sensory analysis showed a good acceptance for both spreadable cheeses.

Physicochemical Characterization of Yogurt Fortified with Microencapsulated Cinnamon (Cinnamomum zeylanicum) and Its Effects on Metabolic Syndrome Induced in Rabbits (Oryctolagus cuniculus).

Chronic noncommunicable diseases are a global health problem causing increased rates of mortality and sick leaves, which can be reduced by controlling dyslipidemia and hyperglycemia. Experimental and clinical studies have demonstrated the antidiabetic, lipid-lowering, antiobesogenic, anti-inflammatory, and antihypertensive properties of cinnamon; therefore, its use in yogurt can help reverse the effects of these diseases. Our study aims to evaluate the effect of a microencapsulated aqueous extract of cinnamon (Cinnamomum zeylanicum) (MCE Cz) incorporated in a yogurt drink on metabolic syndrome (MS) in a rabbit (Oryctolagus cuniculus). Physicochemical, microbiological, and proximal chemical characterization; total phenol, flavonoid, and 2,2-diphenyl-1-picrylhydrazil activity quantification; intestinal bioaccessibility; sensory analysis; MS induction through diet; and treatment with 5, 10, and 20 mg/kg of flavonoids contained in the MCE Cz were performed to help evaluate morphological, biochemical, and lipid peroxidation measurements in the liver and heart. The results show that the addition of MCE Cz in the yogurt modified the yogurt texture, increased its adhesiveness and firmness, and imparted a characteristic cinnamon color and biological value by providing intestinally bioaccessible antioxidants with antioxidant potential by reducing lipoperoxidation in the liver and heart after treatment. MCE Cz reduced the weight of the animals by up to 38.5% and the abdominal circumference by 29%. Biochemically, it decreased glucose levels by 24.38%, total cholesterol levels by 69.2%, triglyceride levels by 72.69%, and low-density lipoprotein levels by 89.25%; it increased high-density lipoprotein levels by 67.08%. Therefore, adding MCE Cz in doses of 5 and 10 mg of flavonoids in drinkable yogurt can be an alternative to preparing functional foods with physicochemical attributes and biological properties that can be consumed at all stages of life without undesirable effects. Moreover, it can act as a potential adjuvant in the treatment of comorbidities related to MS.

The effects of fermentation time on sourdough bread: An analysis of texture profile, starch digestion rate, and protein hydrolysis rate.

To ensure the best quality bread, it is important to consider the speed of digestion of starch and proteins, as well as how time fermentation and storage time influence the rate of starch digestion and the texture of the bread. This study compared the effect of fermentation time and days of storage on the texture, physicochemical, protein and starch digestibility of sourdough bread. Texture profile analysis showed that the fermentation time in recently baked sourdough bread affects hardness, chewiness, and springiness. The electrophoretic profile showed a decrease in band thickness with increase in fermentation time, consistent with a higher percentage of protein digestion. While fermentation time did not significantly affect rapidly digestible starch (RDS) and slowly digestible starch (SDS), storage time resulted in a decrease in RDS and an increase in SDS. Sourdough breads had higher levels of resistant starch (RS). The digestibility characteristics of protein and starch, as well as texture properties, are significantly influenced by fermentation and storage time. The evidence suggests that sourdough bread has the potential to improve the digestion of protein and to effectively regulate the glycemic response, which is due to its higher levels of SDS and RS.

Application of a Simplex-Centroid Mixture Design to Evaluate the Phenolic Compound Content and Antioxidant Potential of Plants Grown in Mexico.

Nowadays, the food and health industries are generating new products with antioxidant potential; among them are those rich in phenolic compounds that have a beneficial impact on human health. Therefore, the aim of this research was to obtain different types of mixtures from Portulaca oleraceae (P), Chenopodium album (C), Opuntia oligacantha Förster var. Ulapa (O), and Amaranthus tricolor (A) and evaluate the content of total phenols, total flavonoids, and antioxidant potential in order to select the mixture with the highest content of phenolic compounds. An experimental simplex-centroid mixture design with 15 experimental treatments was used; the data were analyzed and adjusted to a quadratic model that allowed for the prediction of the content of phenols, flavonoids, and antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-Azino-bis (3-ethylbenz-thiazoline-6-sulfonic acid) (ABTS) of different experimental mixtures. The results show that the individual components of C and P had the highest content of phenols and antioxidant potential. It was observed that the binary mixtures P-C and P-A presented values of total phenols greater than 11 mg of gallic acid equivalents g-1 DW and values of flavonoids greater than 13 mg of quercetin equivalents g-1 DW. These values were higher than those found in the individual components. The P-C mixture with an antioxidant potential of 66.0 ± 0.07 Trolox equivalents g-1 DW could be used as an additive in food or to obtain a functional food that improves the intake of antioxidant compounds in the population.

Comparison of the Antibacterial Activity and Effect on Membrane Permeability of Hibiscus Acid and a Commercial Chlorhexidine Mouthrinse Against Pathogenic Oral Bacteria and Determination of Hibiscus Acid Toxicity.

The main aim of this study was to determine and compare the antimicrobial effect of hibiscus acid and a commercial 0.12% (w/v) chlorhexidine mouthrinse against Streptococcus mutans, Streptococcus sanguinis, Capnocytophaga gingivalis, and Staphylococcus aureus, and to determine the effect on bacterial cell membrane permeability and the toxicity of hibiscus acid in a mouse model. Hibiscus acid was obtained from acetone extract of Hibiscus sabdariffa calyces. Chlorhexidine (0.12% w/v) mouthrinse was purchased from a local pharmacy. The antimicrobial activity of hibiscus acid and mouthrinse were determined using the gel diffusion technique. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the solutions were determined using the broth dilution method. The effect on bacterial cell membrane permeability of hibiscus acid and mouthrinse was determined by crystal violet assay. The toxicity of hibiscus acid was investigated in a mouse model (registration number: UAEH2019-A1-S-8288). Hibiscus acid and mouthrinse showed antibacterial activity against all oral pathogenic bacteria. However, hibiscus acid showed a lower antibacterial effect compared with chlorhexidine mouthrinse. The MIC and MBC for hibiscus acid were 3 and 5 mg/mL, respectively, and was between 30 and 50 µg/mL for mouthrinse. The crystal violet test results indicate that hibiscus acid and mouthrinse alter the permeability of the bacterial membrane. Finally, hibiscus acid did not show toxicity in mouse studies.

Comparison of the Antimicrobial Activity of Hibiscus sabdariffa Calyx Extracts, Six Commercial Types of Mouthwashes, and Chlorhexidine on Oral Pathogenic Bacteria, and the Effect of Hibiscus sabdariffa Extracts and Chlorhexidine on Permeability of the Bacterial Membrane.

To determine and compare the antimicrobial effect of Hibiscus sabdariffa calyx extracts, six types of commercial mouthwashes, and chlorhexidine on Streptococcus mutans, Streptococcus sanguinis, Capnocytophaga gingivalis, and Staphylococcus aureus. Two varieties of H. sabdariffa cultivated in Mexico were used. Aqueous, methanolic, ethanolic, acetonic, and ethyl acetate extracts were obtained from H. sabdariffa calyces. Six different types of mouthwash (Astringosol®, Colgate plax-ice-infinity®, Crest pro-health®, Dental max®, Equate®, and Listerine zero®) and chlorhexidine (0.12%) were purchased at a pharmacy. The antimicrobial activity of the H. sabdariffa calyx extracts, mouthwashes, and chlorhexidine was determined by the agar disc diffusion technique. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of all solutions were determined by the broth dilution method and the pour plate technique, respectively. Also, the effect of H. sabdariffa extracts and chlorhexidine on permeability of the bacterial membrane was determined by the violet crystal assay. All H. sabdariffa calyx extracts and chlorhexidine showed antibacterial activity against all oral pathogenic bacteria. The mouthwashes showed lower antibacterial effect than H. sabdariffa extracts and chlorhexidine. Dental max showed no antibacterial effect. The MICs and MBCs, respectively, for H. sabdariffa extracts were between 5-20 and 10-20 mg/mL; and for chlorhexidine, between 3-4 and 3-5 mg/mL. For the Listerine®, the MIC and MBC values were between 20-25 and 25-33 mg/mL, respectively. The results of the crystal violet test indicate that H. sabdariffa calyx extracts and chlorhexidine alter the permeability of the bacterial membrane. All H. sabdariffa extracts and chlorhexidine showed significantly greater antimicrobial effect than mouthwashes. This is the first report in which the antimicrobial effect of the H. sabdariffa calyx extracts, mouthwashes, and chlorhexidine is compared.

Birth prevalence of Down syndrome in Argentina. / Prevalencia del síndrome de Down al nacimiento en Argentina.

The aim of this study was to describe the prevalence at birth of Down syndrome in Argentina. The prevalence by jurisdiction and maternal age was calculated for the 2009-2015 period and the prevalence and proportion of prenatal diagnosis was compared according to sub-sector (public and private) and complexity level of the maternity wards. The association of Down syndrome with birth weight and gestational age was analyzed. The data source was the National Network of Congenital Anomalies of Argentina [Red Nacional de Anomalías Congénitas] (RENAC). The prevalence was 17.26 per 10,000 births; by jurisdictions it varied between 10.99 and 23.71; and by maternal age, between 10.32 in women <20 years of age and 158.06 in those ≥45 years of age. In hospitals of the private subsector there was a higher prevalence, attributable to differences in the structure of maternal age, and a greater proportion of prenatal diagnosis. There was a negative correlation between birth weight and Down syndrome (ß=-294.7; p<0.001). No difference in the median gestational age at birth between Down syndrome newborns and newborns without major anomalies was found, but the distribution of gestational age differed. Knowledge of certain epidemiological characteristics of this health issue could contribute to the implementation of health policies.

El objetivo de este trabajo fue describir la prevalencia al nacimiento del síndrome de Down en Argentina. Se calculó la prevalencia por jurisdicción y edad materna para el período 2009-2015 y se comparó la prevalencia y proporción del diagnóstico prenatal según subsector (público y privado) y nivel de complejidad de las maternidades. Se analizó la asociación con el peso y la edad gestacional al nacer. La fuente de datos fue la Red Nacional de Anomalías Congénitas (RENAC). La prevalencia fue de 17,26 por cada 10.000 nacimientos; por jurisdicciones varió entre 10,99 y 23,71, y por edad materna entre 10,32 en <20 años y 158,06 en ≥45 años. En hospitales del subsector privado hubo una mayor proporción de diagnóstico prenatal y una mayor prevalencia, esta última atribuible a diferencias en la estructura de edad materna. Se observó una correlación negativa entre el peso al nacer y este síndrome (ß=-294,7; p<0,001). No se evidenció diferencia en la mediana de la edad gestacional al nacer entre recién nacidos con síndrome de Down y neonatos sin anomalías mayores, pero sí en la distribución de la edad gestacional. El conocimiento de ciertas características epidemiológicas podrá contribuir a la implementación de políticas de salud.

Enzymatic inactivation and antioxidant properties of blackberry juice after thermoultrasound: Optimization using response surface methodology.

The purpose of this research was to optimize the thermoultrasound conditions for blackberry juice using the response surface methodology and considering juice quality parameters and antioxidant capacity. With the exception of microbial growth, the response variables showed high correlation coefficients with the mathematical model (R2adj>0.91). Thermoultrasound treatment inactivated all the evaluated microorganisms, and at the optimum conditions (50±1°C at 17±1min) it increased enzyme inactivation and antioxidant activity in comparison to pasteurized juice. The results demonstrated that thermoultrasound can be an alternative to pasteurization for the production of safe and high-quality juices with the added value of higher concentration of bioactive compounds and antioxidant capacity.

Prevalencia del síndrome de Down al nacimiento en Argentina / Birth prevalence of Down syndrome in Argentina

RESUMEN El objetivo de este trabajo fue describir la prevalencia al nacimiento del síndrome de Down en Argentina. Se calculó la prevalencia por jurisdicción y edad materna para el período 2009-2015 y se comparó la prevalencia y proporción del diagnóstico prenatal según subsector (público y privado) y nivel de complejidad de las maternidades. Se analizó la asociación con el peso y la edad gestacional al nacer. La fuente de datos fue la Red Nacional de Anomalías Congénitas (RENAC). La prevalencia fue de 17,26 por cada 10.000 nacimientos; por jurisdicciones varió entre 10,99 y 23,71, y por edad materna entre 10,32 en <20 años y 158,06 en ≥45 años. En hospitales del subsector privado hubo una mayor proporción de diagnóstico prenatal y una mayor prevalencia, esta última atribuible a diferencias en la estructura de edad materna. Se observó una correlación negativa entre el peso al nacer y este síndrome ( ß=-294,7; p<0,001). No se evidenció diferencia en la mediana de la edad gestacional al nacer entre recién nacidos con síndrome de Down y neonatos sin anomalías mayores, pero sí en la distribución de la edad gestacional. El conocimiento de ciertas características epidemiológicas podrá contribuir a la implementación de políticas de salud.

ABSTRACT The aim of this study was to describe the prevalence at birth of Down syndrome in Argentina. The prevalence by jurisdiction and maternal age was calculated for the 2009-2015 period and the prevalence and proportion of prenatal diagnosis was compared according to sub-sector (public and private) and complexity level of the maternity wards. The association of Down syndrome with birth weight and gestational age was analyzed. The data source was the National Network of Congenital Anomalies of Argentina [Red Nacional de Anomalías Congénitas] (RENAC). The prevalence was 17.26 per 10,000 births; by jurisdictions it varied between 10.99 and 23.71; and by maternal age, between 10.32 in women <20 years of age and 158.06 in those ≥45 years of age. In hospitals of the private subsector there was a higher prevalence, attributable to differences in the structure of maternal age, and a greater proportion of prenatal diagnosis. There was a negative correlation between birth weight and Down syndrome ( ß=-294.7; p<0.001). No difference in the median gestational age at birth between Down syndrome newborns and newborns without major anomalies was found, but the distribution of gestational age differed. Knowledge of certain epidemiological characteristics of this health issue could contribute to the implementation of health policies.