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OBJECTIVE: To assess the utility of the Curaçao criteria by age over time in children with hereditary hemorrhagic telangiectasia (HHT). STUDY DESIGN: This was a single-center, retrospective analysis of patients attending the HHT clinic at the Hospital for Sick Children (Toronto, Canada) between 2000 and 2019. The evaluation of the Curaçao criteria was completed during initial and follow-up visits. Screening for pulmonary and brain arteriovenous malformations was completed at 5 yearly intervals. RESULTS: A total of 116 patients with genetic confirmation of HHT were included in the analysis. At initial screening at a median (IQR) age of 8.4 (2.8, 12.9) years, 41% met criteria for a definite clinical diagnosis (≥3 criteria). In children <6 years at presentation, only 23% fulfilled at least 3 criteria initially. In longitudinal follow-up, 63% reached a definite clinical diagnosis, with a median (IQR) follow-up duration of 5.2 (3.2, 7.9) years (P = .005). Specifically, more patients met the epistaxis and telangiectasia criteria at last visit compared with initial (79% vs 60%; P = .006; 47% vs 30%; P = .02) but not for the arteriovenous malformation criterion (59% vs 57%; P = .65). CONCLUSIONS: In the pediatric population, most patients do not meet definite clinical criteria of HHT at initial presentation. Although the number of diagnostic criteria met increased over time, mainly due to new onset of epistaxis and telangiectasia, accuracy remained low during follow-up visits. Relying solely on clinical criteria may lead to underdiagnosis of HHT in children.

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OBJECTIVE: To evaluate etonogestrel (ENG)-implant acceptance during the immediate postnatal period among adolescents and young women during the COVID-19 pandemic, and to compare variables according to choice and discuss possible implications of this measure during the pandemic period. METHODS: A cross-sectional study was designed. All women aged up to 24 years, who delivered between April 25, 2020, and June 24, 2020, at Women's Hospital, University of Campinas, São Paulo, Brazil were considered. The ENG-implant or other contraceptive methods were offered prior to hospital discharge. The participants were split into two groups: (1) those who chose the ENG-implant and (2) those that refused the implant. Descriptive, bivariate, and multivariate analyses were performed. RESULTS: 151 women were included, with 76.2% selecting the ENG-implant. The average age was 19.5 years; 73.2% of pregnancies were unplanned, 32.5% already had a previous pregnancy, 74% were single, and 75.5% were not in full time education. Further, 70.5% had previously used contraceptives, with 89.1% unsatisfied with their previous method that opted for the ENG-implant (P = 0.07). CONCLUSION: Offering the ENG-implant to youths during the immediate postnatal period is evidence-based care, and contraceptive provision is an essential health promotion tool, even during a pandemic. Thinking quickly about public policies in times of crisis is important to guarantee sexual and reproductive rights.

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PURPOSE: Determine the variant detection rate for ENG, ACVRL1, and SMAD4 in individuals who meet consensus (Curaçao) criteria for the clinical diagnosis of hereditary hemorrhagic telangiectasia. METHODS: Review of HHT center database for individuals with three or more HHT diagnostic criteria, in whom molecular genetic analysis for ENG, ACVRL1, and SMAD4 had been performed. RESULTS: A variant known or suspected to be causal was detected in ENG in 67/152 (44.1%; 95% confidence interval [CI], 36.0-52.4%), ACVRL1 in 79/152 (52.0%; 95% CI, 43.7-60.1%), and SMAD4 in 2/152 (1.3%; 95% CI, 0.2-4.7%) family probands with definite HHT. Only 4/152 (2.6%; 95% CI, 0.7-6.6%) family probands did not have a variant in one of these genes. CONCLUSION: Previous reports of the variant detection rate for ENG and ACVRL1 in HHT patients have come from laboratories, which receive samples from clinicians with a wide range of expertise in recognizing clinical manifestations of HHT. These studies suggest a significantly lower detection rate (~75-85%) than we have found in patients who meet strictly applied consensus criteria (96.1%). Analysis of SMAD4 adds an additional detection rate of 1.3%. HHT as defined by the Curaçao criteria is highly predictive of a causative variant in either ENG or ACVRL1.

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A more accurate understanding of the molecular mechanisms and signaling pathways underpinning human mesenchymal stem cell (MSC) plasticity and differentiation properties is pivotal for accomplishing solid and diligent translation of MSC-based experimental therapeutics and clinical trials to broad clinical practice. In addition, this knowledge enables selection of MSC subpopulations with increased differentiation potential and/or use of exogenous factors to boost this potential. Here, we report that CD105 (ENG) is a predictive biomarker of osteogenic potential in two types of MSCs: stem cells from human exfoliated deciduous teeth (SHED) and human adipose-derived stem cells (hASC). We also validate that CD105 can be used to select and enrich for subpopulations of SHED and hASC with higher in vitro osteogenic potential. In addition, we show that hsa-mir-1287 regulates CD105 expression, and propose that fine-tuning hsa-mir-1287 levels could be used to control osteopotential in SHED. These findings provide better discernment of the molecular bases behind MSC osteogenic plasticity and open up new perspectives to leverage osteogenic potential in MSCs by modulation of a specific miRNA.

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ABSTRACT: The aim of the present study was to assess heart rate variability (HRV) in Boxer dogs affected by arrhythmogenic right ventricular cardiomyopathy (ARVC). Fourteen Boxer dogs classified as affected and 28 classified as unaffected were included in a prospective case-control study. Dogs underwent 24-hour ambulatory ECG and were classified as affected (>1,000 VPCs/24 hours) or unaffected ( 20 VPCs/24 hours) by ARVC based on the number of ventricular arrhythmias. HRV was assessed using 24-h Holter ECG monitoring; the studied parameters were SDNN, SDANN, SDNNIDX, rMSSD and pNN50. Data were submitted to logarithmic transformation and HRV parameters were compared between groups and correlated according to the disease status, number and severity of ventricular arrhythmias using Students t test, linear regression and Spearmans test. There was no interaction between the HRV parameters and the number and severity of ventricular arrhythmias. SDNNlog (2.35±0.14 vs. 2.46±0.12, P=0.01), SDNNIDXlog (2.18±0.14 vs. 2.24±0.10, P=0.002) and pNN50log (1.47±0.19 vs. 1.64±0.13, P=0.002) were significantly lower in the affected group compared with the unaffected. According to this study, HRV are different in a population of Boxers dogs affected by ARVC compared to a population of unaffected dogs, and these differences are not consequences of low cardiac output caused by ventricular arrhythmias since animals that had higher number and complexity of arrhythmias were not those who had lower values of HRV.

RESUMO: O objetivo do presente estudo foi avaliar a variabilidade da frequência cardíaca (VFC) em cães da raça Boxer acometidos pela cardiomiopatia arritmogênica do ventrículo direito (CAVD). Para isso, foram incluídos, em estudo prospectivo caso-controle, 14 cães classificados como acometidos pela CAVD e 28 classificados como não acometidos. Os cães foram submetidos à eletrocardiografia ambulatorial de 24 horas e então classificados como acometidos (quando apresentaram mais de 1.000 complexos ventriculares prematuros em 24 horas) ou não acometidos (quando apresentaram menos de 20 complexos ventriculares prematuros em 24 horas) pela CAVD, com base no número de arritmias ventriculares. A VFC foi avaliada mediante monitoramento Holter de 24 horas. Os parâmetros estudados foram SDNN, SDANN, SDNNIDX, rMSSD e pNN50. Os dados foram submetidos à transformação logarítmica e os parâmetros da VFC foram comparados e correlacionados de acordo com a presença ou não da doença, número e severidade das arritmias pelo teste t de Student, regressão linear e teste de Spearman. Não houve interação entre as variáveis da VFC e o número e a severidade das arritmias ventriculares. Porém, as variáveis SDNNlog (2,35±0,14 vs. 2,46±0,12, P=0,01), SDNNIDXlog (2,18±0,14 vs. 2,24±0,10, P=0.002) e pNN50log (1,47±0,19 vs. 1,64±0,13, P=0,002) foram significativamente menores no grupo de animais acometidos pela doença. De acordo com os resultados do presente estudo, a VFC é menor nos Boxers acometidos pela CAVD em relação aos cães não acometidos, e essa diferença não pode ser atribuída ao baixo débito cardíaco, supostamente causado pelas arritmias ventriculares, uma vez que os animais que apresentaram maior número e complexidade das arritmias não foram os que apresentaram os menores valores da VFC.

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The typical characteristics of mesenchymal stem cells (MSCs) can be affected by inflammatory microenvironment; however, the exact contribution of HTLV-1 to MSC dysfunction remains to be elucidated. In this study, we demonstrated that MSC cell surface molecules VCAM-1 and ICAM-1 are upregulated by contact with HTLV-1, and HLA-DR was most highly expressed in MSCs co-cultured with MT2 cells. The expression levels of VCAM-1 and HLA-DR were increased in MSCs cultured in the presence of PBMCs isolated from HTLV-1-infected symptomatic individuals compared with those cultured with cells from asymptomatic infected individuals or healthy subjects. HTLV-1 does not impair the MSC differentiation process into osteocytes and adipocytes. In addition, MSCs were efficiently infected with HTLV-1 in vitro through direct contact with HTLV-1-infected cells; however, cell-free virus particles were not capable of causing infection. In summary, HTLV-1 can alter MSC function, and this mechanism may contribute to the pathogenesis of this viral infection.

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The success of a commercial embryo transfer program depends on the production of high numbers of viable embryos from donor cows that result in high numbers of calves born when the embryos are transferred to suitable recipien ts. In recent years, a great deal of effort has been devoted to the development of treatment protocols that permit the efficient use of recipients and result in high pregnancy per recipient synchronized, especially in recipients managed on pasture. One of the most successful alternatives to increase the number of recipients utilized in embryo transfer programs is the use of protocols that allow for embryo transfer without the need for estrus detection, usually called fixed-time embryo transfer (FTET). Pregnancies to FTET have been reported to be similar to those after detection of estrus, but the overall proportion of recipients pregnant over those synchronized are higher because these treatments have increased the proportion of recipients that receive embryos. Treatments that increase pr ogesterone concentrations and pregnancies per embryo transfer have also been investigated in recent years. Most of these treatments have resulted in increased pregnancy per embryo transfer in recipients with Bos indicus influence, while benefit were not so obvious in Bos taurus recipients managed under more optimal conditions. While factors such as the reproductive histor y of the recipients and the stage and quality of embryos may affect pregnancy per embryo transfer, other factors such as estrus detection and the time interval from thawing to transfer do not seem to affect the proportion of recipients pregnant with embryos frozen in ethylene glycol and transferred at a fixed-time.

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The success of a commercial embryo transfer program depends on the production of high numbers of viable embryos from donor cows that result in high numbers of calves born when the embryos are transferred to suitable recipien ts. In recent years, a great deal of effort has been devoted to the development of treatment protocols that permit the efficient use of recipients and result in high pregnancy per recipient synchronized, especially in recipients managed on pasture. One of the most successful alternatives to increase the number of recipients utilized in embryo transfer programs is the use of protocols that allow for embryo transfer without the need for estrus detection, usually called fixed-time embryo transfer (FTET). Pregnancies to FTET have been reported to be similar to those after detection of estrus, but the overall proportion of recipients pregnant over those synchronized are higher because these treatments have increased the proportion of recipients that receive embryos. Treatments that increase pr ogesterone concentrations and pregnancies per embryo transfer have also been investigated in recent years. Most of these treatments have resulted in increased pregnancy per embryo transfer in recipients with Bos indicus influence, while benefit were not so obvious in Bos taurus recipients managed under more optimal conditions. While factors such as the reproductive histor y of the recipients and the stage and quality of embryos may affect pregnancy per embryo transfer, other factors such as estrus detection and the time interval from thawing to transfer do not seem to affect the proportion of recipients pregnant with embryos frozen in ethylene glycol and transferred at a fixed-time.(AU)

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