The research landscape concerning environmental factors in neurodevelopmental disorders: Endocrine disrupters and pesticides-A review.

In recent years, environmental epidemiology and toxicology have seen a growing interest in the environmental factors that contribute to the increased prevalence of neurodevelopmental disorders, with the purpose of establishing appropriate prevention strategies. A literature review was performed, and 192 articles covering the topic of endocrine disruptors and neurodevelopmental disorders were found, focusing on polychlorinated biphenyls, polybrominated diphenyl ethers, bisphenol A, and pesticides. This study contributes to analyzing their effect on the molecular mechanism in maternal and infant thyroid function, essential for infant neurodevelopment, and whose alteration has been associated with various neurodevelopmental disorders. The results provide scientific evidence of the association that exists between the environmental neurotoxins and various neurodevelopmental disorders. In addition, other possible molecular mechanisms by which pesticides and endocrine disruptors may be associated with neurodevelopmental disorders are being discussed.

Predicting Optimal Antimalarial Drug Combinations from a Standardized Plasmodium falciparum Humanized Mouse Model.

The development of new combinations of antimalarial drugs is urgently needed to prevent the spread of parasites resistant to drugs in clinical use and contribute to the control and eradication of malaria. In this work, we evaluated a standardized humanized mouse model of erythrocyte asexual stages of Plasmodium falciparum (PfalcHuMouse) for the selection of optimal drug combinations. First, we showed that the replication of P. falciparum was robust and highly reproducible in the PfalcHuMouse model by retrospective analysis of historical data. Second, we compared the relative value of parasite clearance from blood, parasite regrowth after suboptimal treatment (recrudescence), and cure as variables of therapeutic response to measure the contributions of partner drugs to combinations in vivo. To address the comparison, we first formalized and validated the day of recrudescence (DoR) as a new variable and found that there was a log-linear relationship with the number of viable parasites per mouse. Then, using historical data on monotherapy and two small cohorts of PfalcHuMice evaluated with ferroquine plus artefenomel or piperaquine plus artefenomel, we found that only measurements of parasite killing (i.e., cure of mice) as a function of drug exposure in blood allowed direct estimation of the individual drug contribution to efficacy by using multivariate statistical modeling and intuitive graphic displays. Overall, the analysis of parasite killing in the PfalcHuMouse model is a unique and robust experimental in vivo tool to inform the selection of optimal combinations by pharmacometric pharmacokinetic and pharmacodynamic (PK/PD) modeling.

Natural estrogens enhance the engraftment of human hematopoietic stem and progenitor cells in immunodeficient mice.

Hematopoietic Stem and Progenitor Cells are crucial in the maintenance of lifelong production of all blood cells. These Stem Cells are highly regulated to maintain homeostasis through a delicate balance between quiescence, self-renewal and differentiation. However, this balance is altered during the hematopoietic recovery after Hematopoietic Stem and Progenitor Cell Transplantation. Transplantation efficacy can be limited by inadequate Hematopoietic Stem Cells number, poor homing, low level of engraftment, or limited self-renewal. As recent evidences indicate that estrogens are involved in regulating the hematopoiesis, we sought to examine whether natural estrogens (estrone or E1, estradiol or E2, estriol or E3 and estetrol or E4) modulate human Hematopoietic Stem and Progenitor Cells. Our results show that human Hematopoietic Stem and Progenitor Cell subsets express estrogen receptors, and whose signaling is activated by E2 and E4 on these cells. Additionally, these natural estrogens cause different effects on human Progenitors in vitro. We found that both E2 and E4 expand human Hematopoietic Stem and Progenitor Cells. However, E4 was the best tolerated estrogen and promoted cell cycle of human Hematopoietic Progenitors. Furthermore, we identified that E2 and, more significantly, E4 doubled human hematopoietic engraftment in immunodeficient mice without altering other Hematopoietic Stem and Progenitor Cells properties. Finally, the impact of E4 on promoting human hematopoietic engraftment in immunodeficient mice might be mediated through the regulation of mesenchymal stromal cells in the bone marrow niche. Together, our data demonstrate that E4 is well tolerated and enhances human reconstitution in immunodeficient mice, directly by modulating human Hematopoietic Progenitor properties and indirectly by interacting with the bone marrow niche. This application might have particular relevance to ameliorate the hematopoietic recovery after myeloablative conditioning, especially when limiting numbers of Hematopoietic Stem and Progenitor Cells are available.

A time- and cost-effective strategy to sequence mammalian Y Chromosomes: an application to the de novo assembly of gorilla Y.

The mammalian Y Chromosome sequence, critical for studying male fertility and dispersal, is enriched in repeats and palindromes, and thus, is the most difficult component of the genome to assemble. Previously, expensive and labor-intensive BAC-based techniques were used to sequence the Y for a handful of mammalian species. Here, we present a much faster and more affordable strategy for sequencing and assembling mammalian Y Chromosomes of sufficient quality for most comparative genomics analyses and for conservation genetics applications. The strategy combines flow sorting, short- and long-read genome and transcriptome sequencing, and droplet digital PCR with novel and existing computational methods. It can be used to reconstruct sex chromosomes in a heterogametic sex of any species. We applied our strategy to produce a draft of the gorilla Y sequence. The resulting assembly allowed us to refine gene content, evaluate copy number of ampliconic gene families, locate species-specific palindromes, examine the repetitive element content, and produce sequence alignments with human and chimpanzee Y Chromosomes. Our results inform the evolution of the hominine (human, chimpanzee, and gorilla) Y Chromosomes. Surprisingly, we found the gorilla Y Chromosome to be similar to the human Y Chromosome, but not to the chimpanzee Y Chromosome. Moreover, we have utilized the assembled gorilla Y Chromosome sequence to design genetic markers for studying the male-specific dispersal of this endangered species.

Maternal imprinting at the H19-Igf2 locus maintains adult haematopoietic stem cell quiescence.

The epigenetic regulation of imprinted genes by monoallelic DNA methylation of either maternal or paternal alleles is critical for embryonic growth and development. Imprinted genes were recently shown to be expressed in mammalian adult stem cells to support self-renewal of neural and lung stem cells; however, a role for imprinting per se in adult stem cells remains elusive. Here we show upregulation of growth-restricting imprinted genes, including in the H19-Igf2 locus, in long-term haematopoietic stem cells and their downregulation upon haematopoietic stem cell activation and proliferation. A differentially methylated region upstream of H19 (H19-DMR), serving as the imprinting control region, determines the reciprocal expression of H19 from the maternal allele and Igf2 from the paternal allele. In addition, H19 serves as a source of miR-675, which restricts Igf1r expression. We demonstrate that conditional deletion of the maternal but not the paternal H19-DMR reduces adult haematopoietic stem cell quiescence, a state required for long-term maintenance of haematopoietic stem cells, and compromises haematopoietic stem cell function. Maternal-specific H19-DMR deletion results in activation of the Igf2-Igfr1 pathway, as shown by the translocation of phosphorylated FoxO3 (an inactive form) from nucleus to cytoplasm and the release of FoxO3-mediated cell cycle arrest, thus leading to increased activation, proliferation and eventual exhaustion of haematopoietic stem cells. Mechanistically, maternal-specific H19-DMR deletion leads to Igf2 upregulation and increased translation of Igf1r, which is normally suppressed by H19-derived miR-675. Similarly, genetic inactivation of Igf1r partly rescues the H19-DMR deletion phenotype. Our work establishes a new role for this unique form of epigenetic control at the H19-Igf2 locus in maintaining adult stem cells.

Reverse Transcription Errors and RNA-DNA Differences at Short Tandem Repeats.

Transcript variation has important implications for organismal function in health and disease. Most transcriptome studies focus on assessing variation in gene expression levels and isoform representation. Variation at the level of transcript sequence is caused by RNA editing and transcription errors, and leads to nongenetically encoded transcript variants, or RNA-DNA differences (RDDs). Such variation has been understudied, in part because its detection is obscured by reverse transcription (RT) and sequencing errors. It has only been evaluated for intertranscript base substitution differences. Here, we investigated transcript sequence variation for short tandem repeats (STRs). We developed the first maximum-likelihood estimator (MLE) to infer RT error and RDD rates, taking next generation sequencing error rates into account. Using the MLE, we empirically evaluated RT error and RDD rates for STRs in a large-scale DNA and RNA replicated sequencing experiment conducted in a primate species. The RT error rates increased exponentially with STR length and were biased toward expansions. The RDD rates were approximately 1 order of magnitude lower than the RT error rates. The RT error rates estimated with the MLE from a primate data set were concordant with those estimated with an independent method, barcoded RNA sequencing, from a Caenorhabditis elegans data set. Our results have important implications for medical genomics, as STR allelic variation is associated with >40 diseases. STR nonallelic transcript variation can also contribute to disease phenotype. The MLE and empirical rates presented here can be used to evaluate the probability of disease-associated transcripts arising due to RDD.

Integration and Fixation Preferences of Human and Mouse Endogenous Retroviruses Uncovered with Functional Data Analysis.

Endogenous retroviruses (ERVs), the remnants of retroviral infections in the germ line, occupy ~8% and ~10% of the human and mouse genomes, respectively, and affect their structure, evolution, and function. Yet we still have a limited understanding of how the genomic landscape influences integration and fixation of ERVs. Here we conducted a genome-wide study of the most recently active ERVs in the human and mouse genome. We investigated 826 fixed and 1,065 in vitro HERV-Ks in human, and 1,624 fixed and 242 polymorphic ETns, as well as 3,964 fixed and 1,986 polymorphic IAPs, in mouse. We quantitated >40 human and mouse genomic features (e.g., non-B DNA structure, recombination rates, and histone modifications) in ±32 kb of these ERVs' integration sites and in control regions, and analyzed them using Functional Data Analysis (FDA) methodology. In one of the first applications of FDA in genomics, we identified genomic scales and locations at which these features display their influence, and how they work in concert, to provide signals essential for integration and fixation of ERVs. The investigation of ERVs of different evolutionary ages (young in vitro and polymorphic ERVs, older fixed ERVs) allowed us to disentangle integration vs. fixation preferences. As a result of these analyses, we built a comprehensive model explaining the uneven distribution of ERVs along the genome. We found that ERVs integrate in late-replicating AT-rich regions with abundant microsatellites, mirror repeats, and repressive histone marks. Regions favoring fixation are depleted of genes and evolutionarily conserved elements, and have low recombination rates, reflecting the effects of purifying selection and ectopic recombination removing ERVs from the genome. In addition to providing these biological insights, our study demonstrates the power of exploiting multiple scales and localization with FDA. These powerful techniques are expected to be applicable to many other genomic investigations.

The NFKB Inducing Kinase Modulates Hematopoiesis During Stress.

The genetic programs that maintain hematopoiesis during steady state in physiologic conditions are different from those activated during stress. Here, we show that hematopoietic stem cells (HSCs) with deficiencies in components of the alternative NFκB pathway (the NFκB inducing kinase, NIK, and the downstream molecule NFκB2) had a defect in response to stressors such as supraphysiological doses of cytokines, chemotherapy, and hematopoietic transplantation. NIK-deficient mice had peripheral blood and bone marrow leukocyte numbers within normal ranges (except for the already reported defects in B-cell maturation); however, HSCs showed significantly slower expansion capacity in in vitro cultures compared to wild-type HSCs. This was due to a delayed cell cycle and increased apoptosis. In vivo experiments showed that NIK-deficient HSCs did not recover at the same pace as controls when challenged with myeloablative chemotherapy. Finally, NIK-deficient HSCs showed a significantly decreased competitive repopulation capacity in vivo. Using HSCs from mice deficient in one of two downstream targets of NIK, that is, either NFκB2 or c-Rel, only NFκB2 deficiency recapitulated the defects detected with NIK-deficient HSCs. Our results underscore the role of NIK and the alternative NFκB pathway for the recovery of normal levels of hematopoiesis after stress.

Genomic landscape of human, bat, and ex vivo DNA transposon integrations.

The integration and fixation preferences of DNA transposons, one of the major classes of eukaryotic transposable elements, have never been evaluated comprehensively on a genome-wide scale. Here, we present a detailed study of the distribution of DNA transposons in the human and bat genomes. We studied three groups of DNA transposons that integrated at different evolutionary times: 1) ancient (>40 My) and currently inactive human elements, 2) younger (<40 My) bat elements, and 3) ex vivo integrations of piggyBat and Sleeping Beauty elements in HeLa cells. Although the distribution of ex vivo elements reflected integration preferences, the distribution of human and (to a lesser extent) bat elements was also affected by selection. We used regression techniques (linear, negative binomial, and logistic regression models with multiple predictors) applied to 20-kb and 1-Mb windows to investigate how the genomic landscape in the vicinity of DNA transposons contributes to their integration and fixation. Our models indicate that genomic landscape explains 16-79% of variability in DNA transposon genome-wide distribution. Importantly, we not only confirmed previously identified predictors (e.g., DNA conformation and recombination hotspots) but also identified several novel predictors (e.g., signatures of double-strand breaks and telomere hexamer). Ex vivo integrations showed a bias toward actively transcribed regions. Older DNA transposons were located in genomic regions scarce in most conserved elements-likely reflecting purifying selection. Our study highlights how DNA transposons are integral to the evolution of bat and human genomes, and has implications for the development of DNA transposon assays for gene therapy and mutagenesis applications.

Brief report: reduced expression of CD18 leads to the in vivo expansion of hematopoietic stem cells in mouse bone marrow.

Leukocyte adhesion deficiency type-I is a primary immunodeficiency caused by mutations in the ITGB2 gene (CD18 leukocyte integrin) which lead to defects in leukocyte extravasation. To investigate the role of CD18 in hematopoietic stem cell (HSC) biology, we have thoroughly characterized the HSCs of CD18 Itgb2(tm1bay) hypomorphic mice (CD18(HYP) ) both by flow cytometry and using in vitro and in vivo transplantation assays. Flow cytometry analyses and cultures in methyl cellulose revealed that bone marrow (BM) from CD18(HYP) mice was enriched in hematopoietic precursors, mainly early quiescent short-term and long-term Hematopoietic progenitors cells. Strikingly, BM competition assays showed a progressive expansion of CD18(HYP) -derived hematopoiesis in recipient mice. Additionally, we provide evidence that this HSC expansion was not caused by an increased homing capacity of CD18(HYP) HSCs or by alterations in the hematopoietic environment of CD18(HYP) mice due to defects in neutrophils clearance. On the contrary, our data demonstrated that the reduced expression of CD18 causes a cell-autonomous expansion in the HSC compartment, thus revealing unexpected regulatory functions for CD18 in mouse HSCs.

Rescuing Alu: recovery of new inserts shows LINE-1 preserves Alu activity through A-tail expansion.

Alu elements are trans-mobilized by the autonomous non-LTR retroelement, LINE-1 (L1). Alu-induced insertion mutagenesis contributes to about 0.1% human genetic disease and is responsible for the majority of the documented instances of human retroelement insertion-induced disease. Here we introduce a SINE recovery method that provides a complementary approach for comprehensive analysis of the impact and biological mechanisms of Alu retrotransposition. Using this approach, we recovered 226 de novo tagged Alu inserts in HeLa cells. Our analysis reveals that in human cells marked Alu inserts driven by either exogenously supplied full length L1 or ORF2 protein are indistinguishable. Four percent of de novo Alu inserts were associated with genomic deletions and rearrangements and lacked the hallmarks of retrotransposition. In contrast to L1 inserts, 5' truncations of Alu inserts are rare, as most of the recovered inserts (96.5%) are full length. De novo Alus show a random pattern of insertion across chromosomes, but further characterization revealed an Alu insertion bias exists favoring insertion near other SINEs, highly conserved elements, with almost 60% landing within genes. De novo Alu inserts show no evidence of RNA editing. Priming for reverse transcription rarely occurred within the first 20 bp (most 5') of the A-tail. The A-tails of recovered inserts show significant expansion, with many at least doubling in length. Sequence manipulation of the construct led to the demonstration that the A-tail expansion likely occurs during insertion due to slippage by the L1 ORF2 protein. We postulate that the A-tail expansion directly impacts Alu evolution by reintroducing new active source elements to counteract the natural loss of active Alus and minimizing Alu extinction.

Characterization of spinal hemangioblastomas in patients with and without von Hippel-Lindau, and YAP expression.

INTRODUCTION: Hemangioblastoma (HB) is a benign tumor of the central nervous system, associated with von Hippel-Lindau disease (VHL), or sporadic. The aim of this study was to compare and examine the clinical-pathological profile of patients with spinal hemangioblastoma and YAP expression. METHODS: A retrospective, descriptive, comparative study. All patients who underwent surgery for spinal HB between 2016 and 2023 were included. Clinical and radiological data were collected and analyzed. An immunohistochemistry panel including NeuN, neurofilaments (NF), and YAP-1, was performed. RESULTS: Nine patients were studied, six women and three men. Four patients had previously diagnosed VHL. The tumor location included: four cervical (44.44%), two thoracic (22.22%), two pontine with cervical extension (22.22%) and one patient with two lesions, one cervical and one thoracic (11.11%). Non-significant clinical differences were identified between VHL and sporadic patients. Imaging evidenced seven extramedullary and three intramedullary tumors. Histologically, intra-tumoral and perivascular axonal tracts were observed in all cases. One third of the tumors (two with VHL and one sporadic) presented extramedullary hematopoiesis. Seven cases (77.8%) expressed nuclear YAP (three with VHL and four sporadic HBs). The surgical outcome was good and only one patient with VHL undergoing subtotal resection had recurrence. CONCLUSIONS: Spinal HBs can be associated with VHL or be sporadic. To the best of our knowledge, this is the first study to describe YAP expression in HB. It is important to investigate the involvement of the Hippo pathway in HBs as a possible therapeutic target.

Ancestry informative markers clarify the regional admixture variation in the Costa Rican population.

The genetic structure of Costa Rica's population is complex, both by region and by individual, due to the admixture process that started during the 15th century and historical events thereafter. Previous studies have been done mostly on Amerindian populations and the Central Valley inhabitants using various microsatellites and mitochondrial DNA markers. Here, we study for the first time a random sample from all regions of the country with ancestry informative markers (AIMs) to address the individual and regional admixture proportions. A sample of 160 male individuals was screened for 78 AIMs customized in a GoldenGate platform from Illumina. We observed that this small set of AIMs has the same power of hundreds of microsatellites and thousands of single-nucleotide polymorphisms to evaluate admixture, with the benefit of reducing genotyping costs. This type of investigation is necessary to explore new genetic markers useful for forensic and genetic investigation. Our data showed a mean admixture proportion of 49.2% European (EUR), 37.8% Native American (NAM), and 12.9% African (AFR), with a disproportionate admixture composition by region. In addition, when Chinese (CHB) was included as a fourth component, the proportions changed to 45.6% EUR, 33.5% NAM, 11.7% AFR, and 9.2% CHB. The admixture trend is consistent among all regions (EUR > NAM > AFR), and individual admixture estimates vary broadly in each region. Though we did not find stratification in Costa Rica's population, gene admixture should be evaluated in future genetic studies of Costa Rica, especially for the Caribbean region, as it contains the largest proportion of African ancestry (30.9%).

Frequencies of variants in genes associated with dyslipidemias identified in Costa Rican genomes.

Dyslipidemias are risk factors in diseases of significant importance to public health, such as atherosclerosis, a condition that contributes to the development of cardiovascular disease. Unhealthy lifestyles, the pre-existence of diseases, and the accumulation of genetic variants in some loci contribute to the development of dyslipidemia. The genetic causality behind these diseases has been studied primarily on populations with extensive European ancestry. Only some studies have explored this topic in Costa Rica, and none have focused on identifying variants that can alter blood lipid levels and quantifying their frequency. To fill this gap, this study focused on identifying variants in 69 genes involved in lipid metabolism using genomes from two studies in Costa Rica. We contrasted the allelic frequencies with those of groups reported in the 1000 Genomes Project and gnomAD and identified potential variants that could influence the development of dyslipidemias. In total, we detected 2,600 variants in the evaluated regions. However, after various filtering steps, we obtained 18 variants that have the potential to alter the function of 16 genes, nine variants have pharmacogenomic or protective implications, eight have high risk in Variant Effect Predictor, and eight were found in other Latin American genetic studies of lipid alterations and the development of dyslipidemia. Some of these variants have been linked to changes in blood lipid levels in other global studies and databases. In future studies, we propose to confirm at least 40 variants of interest from 23 genes in a larger cohort from Costa Rica and Latin American populations to determine their relevance regarding the genetic burden for dyslipidemia. Additionally, more complex studies should arise that include diverse clinical, environmental, and genetic data from patients and controls and functional validation of the variants.

Influence of Seminal Metals on Assisted Reproduction Outcome.

Increased levels of metal ions in human seminal fluid have a significant correlation with male fertility. Few publications explain the effect of metals in semen and their influence on assisted reproductive treatments. Semen parameters and the levels of twenty-two metals were measured in the seminal fluid of 102 men attended in a Reproductive Unit. Metals were determined by optical emission spectrophotometry. A statistical relationship was found between spermiogram and iron, which was lower than expected in pathological spermiograms (p = 0.032); zinc (p = 0.066), calcium (p = 0.047), and magnesium (p = 0.048) mean levels were higher in normozoospermics. More days of sexual abstinence correlates with higher seminal zinc (p = 0.001) and magnesium levels (p = 0.002). Lower vanadium values were found to be associated with higher fertilization rates (p = 0.039). Higher values of lead (p = 0.052) and vanadium (p = 0.032) were obtained in patients who did not reach 100% embryo cleavage rate. Aluminium (p = 0.042) and sodium (p = 0.002) were found in lower amounts associated with better blastocyst rates. The implantation rate shows an inverse association with women's age and iron and calcium content, compared to magnesium and sodium which presented a significant direct association with this percentage. A significant direct relationship was found between the positive evolution of pregnancy and the values of zinc (p = 0.004), calcium (p = 0.013), potassium (p = 0.002), and magnesium (p = 0.009). The study confirms that zinc, iron, calcium, sodium, aluminium, magnesium, vanadium, and lead have positive-negative effects on reproduction and support the analysis of metals in semen as a new line of study on male fertility with implications for reproductive outcomes.

Overview of the SARS-CoV-2 genotypes circulating in Latin America during 2021.

Latin America is one of the regions in which the COVID-19 pandemic has a stronger impact, with more than 72 million reported infections and 1.6 million deaths until June 2022. Since this region is ecologically diverse and is affected by enormous social inequalities, efforts to identify genomic patterns of the circulating SARS-CoV-2 genotypes are necessary for the suitable management of the pandemic. To contribute to the genomic surveillance of the SARS-CoV-2 in Latin America, we extended the number of SARS-CoV-2 genomes available from the region by sequencing and analyzing the viral genome from COVID-19 patients from seven countries (Argentina, Brazil, Costa Rica, Colombia, Mexico, Bolivia, and Peru). Subsequently, we analyzed the genomes circulating mainly during 2021 including records from GISAID database from Latin America. A total of 1,534 genome sequences were generated from seven countries, demonstrating the laboratory and bioinformatics capabilities for genomic surveillance of pathogens that have been developed locally. For Latin America, patterns regarding several variants associated with multiple re-introductions, a relatively low percentage of sequenced samples, as well as an increment in the mutation frequency since the beginning of the pandemic, are in line with worldwide data. Besides, some variants of concern (VOC) and variants of interest (VOI) such as Gamma, Mu and Lambda, and at least 83 other lineages have predominated locally with a country-specific enrichments. This work has contributed to the understanding of the dynamics of the pandemic in Latin America as part of the local and international efforts to achieve timely genomic surveillance of SARS-CoV-2.

Supervised blood-based self-sample collection and rapid test performance: a valuable alternative to the use of saliva by HIV testing programmes with no medical or nursing staff.

OBJECTIVES: Some saliva-based HIV testing programmes have resulted in an unacceptable percentage of false positives. Many countries require blood-based testing programmes to have doctors/nurses. The authors evaluate whether, after brief training and under the supervision of a skilled counsellor, blood-based self-sample collection and rapid test performance could be a valuable alternative. METHODS: 208 Spanish-speaking attendees at a street-based HIV testing programme in Madrid participated in the study. Participants were tested twice, first in the study and then in the programme, using the same finger-stick whole-blood rapid test (Determine HIV-1/2 Ag/Ab Combo®). Based on previously adapted instructions, the study counsellor explained the procedure to follow throughout the test. Participants then performed the test under the guidance of the counsellor. Demographic and risk behaviour data were collected by a self-administered questionnaire. The test results in the programme and the study were read by the study counsellor. RESULTS: 99.0% (95% CI 96.6% to 99.9%) of participants had a valid result in the study test, the same percentage as in the programme test conducted by the doctor/nurse. Two persons had invalid test results in both the study and the programme, but they were not the same persons. CONCLUSION: The study provides clear evidence that this methodology is a valuable alternative to saliva for HIV testing programmes when medical or nursing staff required to take blood samples is not available.

Relationship between nutritional treatment compliance and nutritional status improvements in patients with gastrointestinal impairment taking an oral peptide-based supplement.

OBJECTIVES: Compliance in outpatients with gastrointestinal (GI) malabsorption is key in nutritional treatment. The objective of this study was to assess compliance in patients with GI impairment and malnutrition taking a high-calorie, high-protein, peptide-based oral nutritional supplement (ONS-PBD). METHODS: A prospective, multicenter, observational study was conducted in 19 medical sites in Spain where ONS-PBD were prescribed as standard of care. Patients consumed ONS-PBD daily for 12 wk. Compliance was calculated as the percentage consumed of the prescribed amount of ONS per day. RESULTS: A total of 90 adult patients were included in the study, of whom 64 completed the 12-wk regimine. Mean compliance was 78.8% ± 24.5%. Risk of malnutrition decreased in 56.3% of patients at 12 wk, as measured with the malnutrition universal screening tool. A reduction in abdominal pain was observed and stool consistency improved, with a mean of 54.7% and 27.5%, respectively. Improvements in quality of life and a decrease in percentage of patients with severe functional impairment were observed. CONCLUSIONS: These data show that ONS-PBD compliance in malnourished patients with GI symptoms is high, reducing GI symptoms and improving patients' nutritional status.

[The NADYA-SENPE Home Enteral Nutrition Registry in Spain: years 2018 and 2019]. / Registro del Grupo NADYA-SENPE de Nutrición Enteral Domiciliaria en España: años 2018 y 2019.

INTRODUCTION: Aim: to present the results of the Spanish home enteral nutrition (HEN) registry of the NADYA-SENPE group for the years 2018 and 2019. Material and methods: from January 1, 2018 to December 31, 2019 the home enteral nutrition registry was recorded, and afterwards a further descriptive and analytical analysis was done. Results: in 2018, 4756 active patients were registered and the prevalence was 101.79 patients per one million inhabitants; in 2019 there were 4633 patients with a prevalence of 98.51 patients per one million inhabitants. They originated in 46 hospitals: 51.3 % were male, and median age was 71.0 years in both periods. The most frequent diagnosis was a neurological disorder that presents with aphagia or severe dysphagia - 58.7 % and 58.2 %, respectively. The main cause of episode termination was death. A total of 116 pediatric patients were registered in 2018 and 115 in 2019. Females represented 57.8 % and 59.1 %, respectively, in each of the periods. Median age at the beginning of HEN was 5 and 7 months. The most commonly recordered diagnostic group (42.2 % and 42.6 %) was included within the other pathologies group, followed by neurological disorders that present with aphagia or severe dysphagia in 41.4 % and 41.7 % of children. The route of administration was gastrostomy in 46.6 % and 46.1 %, respectively, in each of the periods. Conclusions: the NED registry of the NADYA-SENPE group continues to operate uninterruptedly since its inception. The number of registered patients and the number of participating hospitals remained stable in the last biennium analyzed.

INTRODUCCIÓN: Objetivo: exponer los resultados del registro de nutrición enteral domiciliaria (NED) de los años 2018 y 2019 del Grupo NADYA-SENPE. Material y métodos: se recopilaron los pacientes introducidos en el registro desde el 1 de enero al 31 de diciembre de 2018 y en las mismas fechas para 2019, procediendo al análisis descriptivo y analítico de los datos. Resultados: en el año 2018 se registraron 4756 pacientes activos con una tasa de prevalencia de 101,79 pacientes/millón de habitantes; en 2019 fueron 4633 con una tasa de prevalencia de 98,51 pacientes/millón de habitantes. Procedían de 46 hospitales. Fueron el 51,3 % los varones registrados y la edad mediana fue de 71,0 años en ambos periodos. El diagnóstico más frecuente fue el de enfermedad neurológica que cursa con afagia o disfagia severa (58,7 % y 58,2 %), respectivamente. La causa principal de finalización de los episodios fue el fallecimiento. Los pacientes pediátricos registrados fueron 116 en 2018 y 115 en 2019. Las niñas representaron el 57,8 % y 59,1 %, respectivamente, en cada uno de los periodos. La edad mediana de inicio de la NED fue de 5 y 7 meses. El grupo diagnóstico más registrado (42,2 % y 42,6 %) se englobó dentro del grupo de otras patologías, seguido de la enfermedad neurológica que cursa con afagia o disfagia severa de los niños (41,4 % y 41,7 %). Se alimentaban a través de gastrostomía el 46,6 % y 46,1 %, respectivamente, en cada uno de los periodos. Conclusiones: el registro de NED del grupo NADYA-SENPE sigue operativo de forma ininterrumpida desde sus inicios. El número de pacientes registrados y el de hospitales participantes permanece estable en el último bienio analizado.

Human zygote morphological indicators of higher rate of arrest at the first cleavage stage.

A little studied aspect of developmental arrest (DA) in ART is zygote arrest (ZA). Etiologically, blockage at the first cleavage stage includes molecular and chromosomal anomalies, some of which manifest morphologically. Given considerations on embryo culture, transfer and cryopreservation, optimal zygote selection is very important. The aim of this study was to ascertain whether zygote morphological features were indicators of increased ZA. In this study we performed a prospective, observational study of 2105 zygotes obtained from consecutive patients who were undergoing IVF/ICSI treatment, of which 43 (2%) suffered ZA. Morphological features observed under the inverted microscope were qualitatively categorized: pronuclear size, nucleolar precursor bodies (NPB) alignment, light and dark halos, polar body placement and fragmentation observed at 16-18 h post-insemination. We compared these features in blocked versus cleaved zygotes at 48 h and found significant correlations (p < 0.05) between ZA and three features: the absence of a light halo (p = 0.001), the absence of a dark halo (p < 0.005), and non-aligned NPB (p < 0.05). We can say that certain morphological features are indicators of significantly increased zygote arrest. These findings may be of utility for optimal zygote selection and culture strategies, especially in countries under restrictive conditions.