Accidental Father-to-Son HIV-1 Transmission During the Seroconversion Period

A 4-year-old child born to an HIV-1 seronegative mother was diagnosed with HIV-1, the main risk factor being transmission from the child's father who was seroconverting at the time of the child's birth. In the context of a forensic investigation, we aimed to identify the source of infection of the child and date of the transmission event. Samples were collected from the father and child at two time points about 4 years after the child's birth. Partial segments of three HIV-1 genes (gag, pol, and env) were sequenced and maximum likelihood (ML) and Bayesian methods were used to determine direction and estimate date of transmission. Neutralizing antibodies were determined using a single cycle assay. Bayesian trees displayed a paraphyletic-monophyletic topology in all three genomic regions, with the father's host label at the root, which is consistent with father-to-son transmission. ML trees found similar topologies in gag and pol and a monophyletic-monophyletic topology in env. Analysis of the time of the most recent common ancestor of each HIV-1 gene population indicated that the child was infected shortly after the father. Consistent with the infection history, both father and son developed broad and potent HIV-specific neutralizing antibody responses. In conclusion, the direction of transmission implicated the father as the source of transmission. Transmission occurred during the seroconversion period when the father was unaware of the infection and was likely accidental. This case shows how genetic, phylogenetic, and serological data can contribute for the forensic investigation of HIV transmission.info:eu-repo/semantics/publishedVersio

A novel haemoglobin variant mimicking cyanotic congenital heart disease

Screening for critical congenital heart defects in newborn babies can aid in early recognition, with the prospect of improved outcome. However, as this universal newborn screening is implemented, there will be an increasing number of false-positive results. In order to avoid multiple investigations and uncertainty, an haemoglobin (Hb) variant must be included in the differential diagnosis in otherwise well newborns with low oxygen saturation by pulse oximetry. We describe a novel fetal Hb variant (heterozygous γ-globin gene (HBG1) mutation in exon 2 c.202G>A (p.Val68Met)) identified in a newborn with positive pulse oximetry screening for congenital heart disease.info:eu-repo/semantics/publishedVersio

Impact of hydrodynamics on iPSC-derived cardiomyocyte differentiation processes

Cardiomyocytes (CMs), derived from pluripotent stem cells (PSCs), have the potential to be used in cardiac repair. Addition of physical cues, such as electrical and mechanical stimulations, have proven to significantly effect morphology, density, cardiogenesis, maturity and functionality of differentiated CMs. This work combines rigorous fluid dynamics investigation and flow frequency analysis with iPSC differentiation experiments to identify and quantify the flow characteristics leading to a significant increase of differentiation yield. This is towards a better understanding of the physical relationship between frequency modulation and embryoid bodies suspension, and the development of dimensionless correlations applicable at larger scales. Laser Doppler Anemometry and Fast Fourier Transform analysis were used to identify characteristic flow frequencies under different agitation modes. Intermittent agitation resulted in a pattern of low intensity frequencies at reactor scale that could be controlled by varying three identified time components: rotational speed, interval and dwell times. A proof of concept biological study was undertaken, tuning the hydrodynamic environment through variation of dwell time based on the engineering study findings and a significant improvement in CM yield was obtained. This work introduces the concept of fine-tuning the physical hydrodynamic cues within a three-dimensional flow system to improve cardiomyocyte differentiation of iPSC

An Incidental Finding of a Cardiac Sarcoma

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Decreasing population selection rates of resistance mutation K65R over time in HIV-1 patients receiving combination therapy including tenofovir

Objectives The use of tenofovir is highly associated with the emergence of mutation K65R, which confers broad resistance to nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs), especially when tenofovir is combined with other NRTIs also selecting for K65R. Although recent HIV-1 treatment guidelines discouraging these combinations resulted in reduced K65R selection with tenofovir, updated information on the impact of currently recommended regimens on the population selection rate of K65R is presently lacking. Methods In this study, we evaluated changes over time in the selection rate of resistance mutation K65R in a large population of 2736 HIV-1-infected patients failing combination antiretroviral treatment between 2002 and 2010. Results The K65R resistance mutation was detected in 144 patients, a prevalence of 5.3%. A large majority of observed K65R cases were explained by the use of tenofovir, reflecting its wide use in clinical practice. However, changing patterns over time in NRTIs accompanying tenofovir resulted in a persistent decreasing probability of K65R selection by tenofovir-based therapy. The currently recommended NRTI combination tenofovir/emtricitabine was associated with a low probability of K65R emergence. For any given dual NRTI combination including tenofovir, higher selection rates of K65R were consistently observed with a non-nucleoside reverse transcriptase inhibitor than with a protease inhibitor as the third agent. Discussion Our finding of a stable time trend of K65R despite elevated use of tenofovir illustrates increased potency of current HIV-1 therapy including tenofovi

The Ribatejano pig: Rebirth of a local population? First results on growth, and carcass parameters

In order to assess the productive performance of the Ribatejano (RI) pig, resulting from a cross between Alentejano (AL) and Bísaro (BI) breeds, castrated male pigs AL, BI, ALxBI and BIxAL were studied within the framework of the TREASURE project. Ten pigs from each genotype, raised in traditional free-range system and fed commercial diets ad libitum, were slaughtered at ~65 kg live weight (LW). Data obtained show that BI, ALxBI and BIxAL attained slaughter weight faster (P<0.001) than AL pigs. Overall, carcass length (P<0.001), carcass yield (P=0.06), and lean cuts weight (P<0.01) were higher in BI than AL pigs, with intermediate values for both crosses. Conversely, fat cuts weight, ZP fat depth (P<0.01) and average backfat thickness (P<0.001) were higher in AL than in BI, and ALxBI and BIxAL pigs. At 65kg LW, RI crosses presented intermediate characteristics between fatter (AL) and leaner (BI) genotypes. This cross could therefore be an alternative to the use of other (modern) breeds for crossing, helping to increase the revenue of autochthonous pig producers, and also maintain or increase the pure breed populations, contributing to animal biodiversity

A Genomic Signature and the Identification of New Sporulation Genes

Bacterial endospores are the most resistant cell type known to humans, as they are able to withstand extremes of temperature, pressure, chemical injury, and time. They are also of interest because the endospore is the infective particle in a variety of human and livestock diseases. Endosporulation is characterized by the morphogenesis of an endospore within a mother cell. Based on the genes known to be involved in endosporulation in the model organism Bacillus subtilis, a conserved core of about 100 genes was derived, representing the minimal machinery for endosporulation. The core was used to define a genomic signature of about 50 genes that are able to distinguish endospore-forming organisms, based on complete genome sequences, and we show this 50-gene signature is robust against phylogenetic proximity and other artifacts. This signature includes previously uncharacterized genes that we can now show are important for sporulation in B. subtilis and/or are under developmental control, thus further validating this genomic signature. We also predict that a series of polyextremophylic organisms, as well as several gut bacteria, are able to form endospores, and we identified 3 new loci essential for sporulation in B. subtilis: ytaF, ylmC, and ylzA. In all, the results support the view that endosporulation likely evolved once, at the base of the Firmicutes phylum, and is unrelated to other bacterial cell differentiation programs and that this involved the evolution of new genes and functions, as well as the cooption of ancestral, housekeeping functions.FCT grant: (PEst-OE/EQB/LA0004/2011), FCT Ph.D. fellowship: (SFRH/BPD/36328/2007), FCT postdoc fellowship: (SFRH/BPD/65605/2009), Instituto Gulbenkian de Ciência research fellowship

Are Molecular Haplotypes Worth the Time and Expense? A Cost-Effective Method for Applying Molecular Haplotypes

Because current molecular haplotyping methods are expensive and not amenable to automation, many researchers rely on statistical methods to infer haplotype pairs from multilocus genotypes, and subsequently treat these inferred haplotype pairs as observations. These procedures are prone to haplotype misclassification. We examine the effect of these misclassification errors on the false-positive rate and power for two association tests. These tests include the standard likelihood ratio test (LRT(std)) and a likelihood ratio test that employs a double-sampling approach to allow for the misclassification inherent in the haplotype inference procedure (LRT(ae)). We aim to determine the cost–benefit relationship of increasing the proportion of individuals with molecular haplotype measurements in addition to genotypes to raise the power gain of the LRT(ae) over the LRT(std). This analysis should provide a guideline for determining the minimum number of molecular haplotypes required for desired power. Our simulations under the null hypothesis of equal haplotype frequencies in cases and controls indicate that (1) for each statistic, permutation methods maintain the correct type I error; (2) specific multilocus genotypes that are misclassified as the incorrect haplotype pair are consistently misclassified throughout each entire dataset; and (3) our simulations under the alternative hypothesis showed a significant power gain for the LRT(ae) over the LRT(std) for a subset of the parameter settings. Permutation methods should be used exclusively to determine significance for each statistic. For fixed cost, the power gain of the LRT(ae) over the LRT(std) varied depending on the relative costs of genotyping, molecular haplotyping, and phenotyping. The LRT(ae) showed the greatest benefit over the LRT(std) when the cost of phenotyping was very high relative to the cost of genotyping. This situation is likely to occur in a replication study as opposed to a whole-genome association study

Extracorporeal Membrane Oxygenation in an Adolescent with Multisystem Inflammatory Syndrome in Children

Multisystem inflammatory syndrome in children is a rare and potentially life-threatening disease that is associated with SARS-CoV-2 infection, character-ized by hyperinflammation and multiorgan involvement. Cardiovascular involvement is common, including myocardial dysfunction often leading to cardio-genic shock. We present the case of a 17-year-old boy with fever, odynophagia, maculopapular rash and abdominal pain who developed a cardiogenic shock. Due to progressive deterioration of cardiac function despite optimized vasoactive support, veno-arterial extracorporeal membrane oxygenation support was initiated 12 hours after admission, with successful decannulation after seven days and discharge after 23 days, with normal cardiac function. The patient received corticosteroids and intravenous immunoglobulin. Early recognition and intensive care support are crucial for ensuring a successful outcome in severe cases of multisystem inflammatory syndrome. In cases of severe cardiogenic shock, extracorporeal membrane oxygenation support can be critical for survival and rapid recovery.info:eu-repo/semantics/publishedVersio

Biomonitoring PM using transplanted lichens in an urban-industrial area of the Lisbon Metropolitan Area and integration with reference monitoring method

Trabalho apresentado em 11th International Aerosol Conference (IAC2022), 4-9 setembro 2022, Atenas, GréciaN/