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Cell-free DNA (cfDNA) consists of fragments of double stranded DNA that are found in the circulation. They are released from the apoptosis of both normal haemopoietic cells and malignant cells. The use of cfDNA from easily accessible peripheral blood samples has created a new strategy in studying molecular genomics in haematological malignancies. Its use in diagnosis, prognosis and monitoring potentially precludes the need for repeated tissue samples, i.e., bone marrow biopsy or primary tissue biopsy. It also potentially provides a more comprehensive analysis of the disease as cfDNA are released from tumours from multiple sites of the body. While cfDNA research is still in its infancy, given its potential and the expansion in next generation sequencing (NGS) it has attracted a lot of attention in recent years. This review will focus on acute leukaemia, multiple myeloma and lymphoma and the potential diagnostic and prognostic implications of cfDNA, its role in response assessment and in detection of disease relapse.
To promote the early diagnosis of pediatric cancers in Ivory Coast, we have initiated a program to train local physicians in the warning signs and to raise public awareness. The aim of this work was to compare the times, stages and survival of patients before and three years after the initiation of the program.
This retrospective study involved children 0-17 years of age admitted from January to December 2014 and from May 2018 to April 2019. The Mann-Whitney non-parametric test and the Fisher's exact test were used to compare time limits, stages and survival.
One hundred and fifty-nine doctors were trained and 1020 people were sensitized. The median age of the 216 children included was 7 years, sex ratio 1.4. For both periods, the median consultation times were 75 and 30 days (P=0.003) and the median diagnostic times were 120 and 105 days (P=0.033). High-risk lymphomas accounted for 60.5% and 58.5% (P=0.99) respectively and nephroblastoma 46.1% and 56.2% (P=0.51). The overall survival was 31% and 30.2% (P=0.92).
The early diagnosis program had no impact. The diagnosis times and the proportion of cancer classified as high risk are comparable to the data reported in sub-Saharan Africa, which vary respectively from 7 to 15.8 weeks and from 60 to 71%. This program must be intensified, extended to all health workers and include improving access to care.
The early diagnosis program had no impact. The diagnosis times and the proportion of cancer classified as high risk are comparable to the data reported in sub-Saharan Africa, which vary respectively from 7 to 15.8 weeks and from 60 to 71%. This program must be intensified, extended to all health workers and include improving access to care.
The origin of sex differences in prevalence and presentation of neuropsychiatric and behavioral traits is largely unknown. Given established genetic contributions and correlations, we tested for a sex-differentiated genetic architecture within and between traits.
Using European ancestry genome-wide association summary statistics for 20 neuropsychiatric and behavioral traits, we tested for sex differences in single nucleotide polymorphism (SNP)-based heritability and genetic correlation (r
< 1). For each trait, we computed per-SNP z scores from sex-stratified regression coefficients and identified genes with sex-differentiated effects using a gene-based approach. We calculated correlation coefficients between z scores to test for shared sex-differentiated effects. Finally, we tested for sex differences in across-trait genetic correlations.
We observed no consistent sex differences in SNP-based heritability. check details Between-sex, within-trait genetic correlations were high, although <1 for educational attan the common autosomal genetic architecture of neuropsychiatric and behavioral phenotypes are small and polygenic and unlikely to fully account for observed sex-differentiated attributes. Larger sample sizes are needed to identify sex-differentiated effects for most traits. For well-powered studies, we identified genes with sex-differentiated effects that were enriched for neuron-related and other biological functions. This work motivates further investigation of genetic and environmental influences on sex differences.Major depressive disorder (MDD) is a leading cause of disability, affecting more than 300 million people worldwide. We first review the well-known sex difference in incidence of MDD, with women being twice as likely to be diagnosed as men, and briefly summarize how the impact of MDD varies between men and women, with sex differences in symptoms, severity, and antidepressant drug response. We then attempt to deconstruct the biological bases for MDD and discuss implications for sex differences research. Next, we review findings from human postmortem studies, both from selected candidate gene studies and from well-powered, unbiased transcriptomics studies, which suggest distinct, and possibly opposite, molecular changes in the brains of depressed men and women. We then discuss inherent challenges of research on the human postmortem brain and suggest paths forward that rely on thoughtful cohort design. Although studies indicate that circulating gonadal hormones might underlie the observed sex differences in MDD, we discuss how additional sex-specific factors, such as genetic sex and developmental exposure to gonadal hormones, may also contribute to altered vulnerability, and we highlight various nuances that we believe should be considered when determining mechanisms underlying observed sex differences. Altogether, this review highlights not only how various sex-specific factors might influence susceptibility or resilience to depression, but also how those sex-specific factors might result in divergent pathology in men and women.
We hypothesize that intraoperative parathyroid hormone (ioPTH) measurement after a total thyroidectomy predicts children at risk for hypoparathyroidism and allow for outpatient procedure.
Between 2015 and 2019, we reviewed all patients under the age of 21 undergoing a thyroidectomy (total or lobectomy). Based on the ioPTH concentration, the patients were treated by the following protocol a) PTH ≥20pg/mL no treatment; b) PTH=10-19pg/mL 1000mg calcium orally TID; c) PTH=5-9pg/mL calcitriol 250μg orally BID plus 1000mg calcium orally TID; or d) PTH <5pg/mL calcitriol 500 μg orally BID plus 1000mg calcium orally TID.
Fifty-two patients were included with a median age of 16 (range 6-21 years). Thirty-two patients (62%) had normal PTH (≥10pg/mL) while 20 (38%) had low PTH levels (<10pg/mL). Of those patients with low PTH, 60% had normalization of levels within 2 weeks of surgery.
Thyroid surgery in children can be performed as an outpatient procedure. The ioPTH measurements and a protocol to treat patients with low PTH assists in safe discharge.
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