Introduction Obesity is a pathological state that involves the dysregulation of different metabolic pathways and adipose tissue cells, constituting a risk factor for the development of other ...diseases. Bariatric surgery is the most effective treatment. The study of the behavior of pollutants in situations of extreme weight loss can provide biomonitoring information and tools to manage diseases of environmental etiology. Aim To determine the prevalence of serum persistent and non-persistent pollutants in obese patients subjected to bariatric surgery and analyze the impact of sociodemographic variables on these changes. Methods GC-MS/MS and UHPLC-MS/MS were utilized to determine the detection rates and concentrations of 353 compounds, including persistent organic pollutants (POPs), pesticides, pharmaceuticals, and rodenticide, in serum samples of 59 obese patients before and after undergoing bariatric surgery. Results Detection rates of p,p’-DDE, HCB, β-HCH, naphthalene, phenanthrene and PCB congeners 138, 153 and 180 significantly increased due to surgery-induced weight loss. Serum levels of p,p’-DDE, PCB-138, PCB-153 and PCB-180 also increased after surgery. Correlations between naphthalene levels, weight loss, variation of total lipids and time after surgery were found. Additionally, correlations were observed between concentrations of PCB-138 and weight loss, and between phenanthrene levels and reduction of total lipids. No statistically significant differences were observed for other groups of contaminants, pharmaceuticals and other chemicals included in the quantification methods. Conclusions Increment of POPs was observed after bariatric surgery. Serum concentrations of POPs after surgery were influenced by adiposity-related variables. Although biomonitoring studies show a decreasing tendency of exposure, rapid weight loss leads to an increase of circulating POPs. Further research on the interplay between adipose tissue, POPs and peripheral organs is required.
Next-Generation Sequencing (NGS) is widely used to investigate genomic variation. In several studies, the genetic variation of Mycobacterium tuberculosis has been analyzed in sputum samples without ...previous culture, using target enrichment methodologies for NGS. Alignments obtained by different programs generally map the sequences under default parameters, and from these results, it is assumed that only Mycobacterium reads will be obtained. However, variants of interest microorganism in clinical samples can be confused with a vast collection of reads from other bacteria, viruses, and human DNA. Currently, there are no standardized pipelines, and the cleaning success is never verified since there is a lack of rigorous controls to identify and remove reads from other sputum-microorganisms genetically similar to M. tuberculosis. Therefore, we designed a bioinformatic pipeline to process NGS data from sputum samples, including several filters and quality control points to identify and eliminate non-M. tuberculosis reads to obtain a reliable genetic variant report. Our proposal uses the SURPI software as a taxonomic classifier to filter input sequences and perform a mapping that provides the highest percentage of Mycobacterium reads, minimizing the reads from other microorganisms. We then use the filtered sequences to perform variant calling with the GATK software, ensuring the mapping quality, realignment, recalibration, hard-filtering, and post-filter to increase the reliability of the reported variants. Using default mapping parameters, we identified reads of contaminant bacteria, such as Streptococcus, Rhotia, Actinomyces, and Veillonella. Our final mapping strategy allowed a sequence identity of 97.8% between the input reads and the whole M. tuberculosis reference genome H37Rv using a genomic edit distance of three, thus removing 98.8% of the off-target sequences with a Mycobacterium reads loss of 1.7%. Finally, more than 200 unreliable genetic variants were removed during the variant calling, increasing the report's reliability.
Bariatric surgery therapy (BST) is an effective treatment for obesity; however, little is known about its impacts on health-related quality of life (HRQoL) and related factors. This study aimed to ...evaluate changes in HRQoL and its relationship with weight loss, depression status, physical activity (PA), and nutritional habits after BST. Data were obtained before and 18 months postprocedure from 56 obese patients who underwent BST. We administered four questionnaires: Short Form-36 health survey for HRQoL, 14-item MedDiet adherence questionnaire, Rapid Assessment of PA (RAPA) questionnaire, and Beck's Depression Inventory-II. Multivariable linear regression analysis was used to identify factors associated with improvement in HRQoL. After the surgery, MedDiet adherence and HRQoL improved significantly, especially in the physical component. No changes in PA were found. Patients without previous depression have better mental quality of life, and patients who lost more than 25% of %TBWL have better results in physical and mental quality of life. In the multivariable analysis, we found that %TBWL and initial PCS (inversely) were related to the improvement in PCS and initial MCS (inversely) with the MCS change. In conclusion, BST is an effective intervention for obesity, resulting in significant weight loss and improvements in HRQoL and nutritional habits.
Worldwide, prostate cancer (PCa) is the second cause of death from malignant tumors among men. Establishment of aberrant epigenetic modifications, such as histone post-translational modifications ...(PTMs) and DNA methylation (DNAme) produce alterations of gene expression that are common in PCa. Genes of the SFRP family are tumor suppressor genes that are frequently silenced by DNA hypermethylation in many cancer types. The SFRP family is composed of 5 members (SFRP1–5) that modulate the WNT pathway, which is aberrantly activated in PCa. The expression of SFRP genes in PCa and their regulation by DNAme has been controversial. Our objective was to determine the gene expression pattern of the SFRP family in prostatic cell lines and fresh frozen tissues from normal prostates (NP), benign prostatic hyperplasia (BPH) and prostate cancer (PCa), by qRT-PCR, and their DNAme status by MSP and bisulfite sequencing. In prostatic cancer cell lines, the 5 SFRPs showed significantly decreased expression levels compared to a control normal prostatic cell line (p<0.0001). In agreement, SFRP1 and SFRP5 genes showed decreased expression levels in CaP fresh frozen tissues compared to NP (p<0.01), while a similar trend was observed for SFRP2. Conversely, increased levels of SFRP4 expression were found in PCa compared to BPH (p<0.01). Moreover, SFRP2, SFRP3, and SFRP5 showed DNA hypermethylation in PCa cell lines. Interestingly, we observed DNA hypermethylation at the promoter of SFRP1 in the PC3 cell line, but not in LNCaP. However, in the LNCaP cell line we found an aberrant gain of the repressive histone posttranslational modification Histone H3 lysine 27 trimethylation (H3K27me3). In conclusion, decreased expression by DNA hypermethylation of SFRP5 is a common feature of PCa, while decreased expression of SFRP1 can be due to DNA hypermethylation, but sometimes an aberrant gain of the histone mark H3K27me3 is observed instead.
•In PCa decreased SFRP1 expression can be due to occupancy of H3K27me3 or to promoter DNA hypermethylation.•SFRP5 is silenced by DNA hypermethylation at their promoter regions in PCa.•SFRP4 expression is higher in PCa than in BPH.•Hypermethylation of the SFRP family genes is a common feature of PCa.
Seagrasses, as key ecosystem engineers in coastal ecosystems, contribute to enhancing diversity in comparison with nearby bare areas. It has been proved mainly for epifauna, but data on infauna are ...still scarce. The present study addresses how seagrass structural complexity (i.e., canopy properties) affects the diversity of infaunal organisms inhabiting those meadows. Canopy attributes were achieved using seagrass mimics, which were used to construct in situ vegetation patches with two contrasting canopy properties (i.e., shoot density and morphology) resembling the two seagrass species thriving in the inner Cadiz Bay: Zostera noltei and Cymodocea nodosa. After three months, bare nearby areas, two mimicked seagrass patches (‘Zostera’ and ‘Cymodocea’), and the surrounding natural populations of Zostera noltei were sampled in a spatially explicit way. Shifts in organism diets were also determined using 15N and 13C analyses in available food sources and main infaunal organisms, mixing models, and niche metrics (standard ellipse area). Seagrass-mimicked habitats increased the species richness (two-fold), organism abundance (three to four times), and functional diversity compared with bare nearby areas. The clam Scrobicularia plana (deposit/filter feeder) and the worm Hediste diversicolor (omnivore) were dominant in all of the samples (> 85%) and showed an opposite spatial distribution in the reconstructed patches: whilst S. plana accumulated in the outer-edge parts of the meadow, H. diversicolor abounded in the center. Changes in the isotopic signature of both species depending on the treatment suggest that this faunal distribution was associated with a shift in the diet of the organisms. Based on our results, we concluded that facilitation processes (e.g., reduction in predation and in bioturbation pressures) and changes in food availability (quality and quantity) mediated by seagrass canopies were the main driving forces structuring this community in an intertidal muddy area of low diversity.
Background:
Young maternal age is associated with negative outcomes at birth and with offspring's growth. In low- and middle-income countries, adolescents' offspring growth little has been studied.
...Objective:
To determine the association of maternal sociodemographic characteristics with weight, length, and BMI change in adolescents' offspring in their first year of life.
Methods:
This is a one-year follow-up study that included adolescent mothers and their offspring from 2010 to 2017. The infant anthropometric variables were performed at birth, 3, 6, and 12 months. Maternal health, pregnancy, and social variables were evaluated as well as birth outcomes. Crude, percentage, Z score, and percentile changes of weight, length, and BMI were evaluated from birth to 1-year-old. Statistical analyses were adjusted by maternal chronological age, socioeconomic status, breastfeeding duration, the timing of introduction of complementary feeding, among other variables.
Results:
We examined 186 dyads (mother-infant). The median maternal age was 15.5 years, and the mean pre-pregnancy BMI was 20. The mean gestational age was 39.1 weeks for infants, birth weight was 3,039 g, and length at birth was 49.5-cm. Maternal chronological age, the timing of introduction of complementary feeding, socioeconomic status, and maternal occupation were associated with offspring's weight gain at 12 months. Length gain was associated with exclusive breastfeeding. Socioeconomic status and occupation were associated with offspring's BMI change. When performing adjusted multivariable analyses, weight and length at birth were associated weight and BMI at 12 months.
Conclusions:
Weight at birth may negatively predict infant's weight and BMI changes at 12 months, while length at birth may positively predict the changes. Maternal chronological age, socioeconomic level, occupation, and the timing of the introduction of complementary feeding were associated with the weight change. Only exclusive breastfeeding was associated with length Z-score change in adolescents' offspring in their first 12-months of life.
Fluoxetine is one of the most prescribed antidepressants, yet it still faces challenges due to high intersubject variability in patient response. Mainly metabolized by the highly polymorphic gene ...CYP2D6, important differences in plasma concentrations after the same doses are found among individuals. This study investigated the association of fluoxetine pharmacokinetics (PK) with pharmacogenetic variants. A bioequivalence crossover trial (two sequences, two periods) was conducted with fluoxetine 20 mg capsules, in 24 healthy subjects. Blood samples for fluoxetine determination were collected up to 72 h post-dose. Subjects were genotyped and single nucleotide variants (SNV) were selected using a candidate gene approach, and then associated with the PK parameters. Bioequivalence was confirmed for the test formulation. We found 34 SNV on 10 genes with a quantifiable impact on the PK of fluoxetine in the randomized controlled trial. Out of those, 29 SNVs belong to 7 CYPs (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5), and 5 SNVs to 3 genes impacting the pharmacodynamics and efficacy of fluoxetine (SLC6A4, TPH1, ABCB1). Moreover, decreased/no function SNVs of CYP2D6 (rs1065852, rs28371703, rs1135840) and CYP2C19 (rs12769205) were confirmed phenotypically. Our research contributes to deepening the catalog of genotype-phenotype associations in pharmacokinetics, aiming to increase pharmacogenomics knowledge for rational treatment schemes of antidepressants.
Os animais vivem em ambientes altamente incertos, e qualquer informação que reduza a incerteza é considerada valiosa uma vez que os ajuda a prever eventos futuros e a comportarem-se de acordo com os ...mesmos. A presente dissertação explora uma situação em que os pombos podem trocar comida por informação: usando um procedimento de esquemas encadeados concorrentes, os pombos escolhem entre duas alternativas sendo que cada uma delas leva a dois sinais possíveis que, após um atraso, são seguidos por comida com uma determinada probabilidade. As alternativas diferem (1) na probabilidade global de reforço (2) na probabilidade de reforço de cada sinal. Nesta tarefa, os animais preferem a alternativa mais informativa mesmo quando esta é globalmente menos reforçada; a maioria dos modelos teóricos explicam este fenómeno assumindo que os pombos sobre-estimam os sinais que são sempre reforçados e ignoram os sinais não reforçados. O objetivo desta dissertação foi avaliar sistematicamente duas das variáveis que tem sido sugeridas como responsáveis por esta escolha subótima. Propomos um novo modelo, a hipótese Delta-Sigma, que considera que a diferença na probabilidade de reforço entre os sinais, Delta (Δ); e o rácio das probabilidades globais de reforço das alternativas, Sigma (Σ), podem explicar o comportamento dos pombos. Na experiência 1, avaliamos o papel de Δ e na experiência 2, o papel de Σ. Os resultados foram consistentes com a hipótese Delta-Sigma, demonstrando que os pombos preferem o Δ maior e que a preferência é modulada por Σ. Nas experiências 3 e 4, testamos a independência da construção do Δ, demonstrando que Δ iguais construídos com diferentes probabilidades de reforço podem ter valores diferentes. Os resultados são parcialmente explicados pela nossa hipótese e sugerem que existem outros fatores que podem afetar a preferência. Finalmente, as experiências 5 e 6 propõe um mecanismo sobre o que é aprendido acerca do sinal não reforçado. Os resultados demonstraram que este sinal desenvolveu propriedades inibitórias e que estas propriedades estão correlacionadas com o desenvolvimento da preferência subótima. No geral, os resultados aqui apresentados são a primeira avaliação sistemática das variáveis sugeridas como responsáveis pela preferência subótima.
Next-Generation Sequencing (NGS) is widely used to investigate genomic variation. In several studies, the genetic variation of Mycobacterium tuberculosis has been analyzed in sputum samples without ...previous culture, using target enrichment methodologies for NGS. Alignments obtained by different programs generally map the sequences under default parameters, and from these results, it is assumed that only Mycobacterium reads will be obtained. However, variants of interest microorganism in clinical samples can be confused with a vast collection of reads from other bacteria, viruses, and human DNA. Currently, there are no standardized pipelines, and the cleaning success is never verified since there is a lack of rigorous controls to identify and remove reads from other sputum-microorganisms genetically similar to M. tuberculosis. Therefore, we designed a bioinformatic pipeline to process NGS data from sputum samples, including several filters and quality control points to identify and eliminate non-M. tuberculosis reads to obtain a reliable genetic variant report. Our proposal uses the SURPI software as a taxonomic classifier to filter input sequences and perform a mapping that provides the highest percentage of Mycobacterium reads, minimizing the reads from other microorganisms. We then use the filtered sequences to perform variant calling with the GATK software, ensuring the mapping quality, realignment, recalibration, hard-filtering, and post-filter to increase the reliability of the reported variants. Using default mapping parameters, we identified reads of contaminant bacteria, such as Streptococcus, Rhotia, Actinomyces, and Veillonella. Our final mapping strategy allowed a sequence identity of 97.8% between the input reads and the whole M. tuberculosis reference genome H37Rv using a genomic edit distance of three, thus removing 98.8% of the off-target sequences with a Mycobacterium reads loss of 1.7%. Finally, more than 200 unreliable genetic variants were removed during the variant calling, increasing the report’s reliability.
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