• Tuttle Kara posted an update 6 months, 2 weeks ago

    Nearly 39% of the EM cohort initiated AS monitoring; age <77, White race, being married/partnered, higher median ZIP code income, and lower PSA levels were associated with initiating AS. By three years after diagnosis, 21.3% of the EM cohort had switched to AT, usually after undergoing AS monitoring procedures.

    We found increasing uptake of EM over time, though over 50% still received AT. About 60% of EM patients did not initiate AS monitoring, even among those with life expectancy >10 years, implying that a substantial proportion was being managed by watchful waiting. AS monitoring was associated with switching to AT, suggesting that treatment decisions likely were based on cancer progression.

    10 years, implying that a substantial proportion was being managed by watchful waiting. AS monitoring was associated with switching to AT, suggesting that treatment decisions likely were based on cancer progression.

    Recent publications have shown patients with defects in the DNA mismatch repair (MMR) pathway driven by either MSH2 or MSH6 loss experience a significant increase in the incidence of prostate cancer. Moreover, this increased incidence of prostate cancer is accompanied by rapid disease progression and poor clinical outcomes.

    We show that androgen-receptor activation, a key driver of prostate carcinogenesis, can disrupt the MSH2 gene in prostate cancer. We screened tumours from two cohorts (recurrent/non-recurrent) of prostate cancer patients to confirm the loss of MSH2 protein expression and identified decreased MSH2 expression in recurrent cases. Stratifying the independent TCGA prostate cancer cohort for MSH2/6 expression revealed that patients with lower levels of MSH2/6 had significant worse outcomes, in contrast, endometrial and colorectal cancer patients with lower MSH2/6 levels. MMRd endometrial and colorectal tumours showed the expected increase in mutational burden, microsatellite instability and enhanced immune cell mobilisation but this was not evident in prostate tumours.

    We have shown that loss or reduced levels of MSH2/MSH6 protein in prostate cancer is associated with poor outcome. However, our data indicate that this is not associated with a statistically significant increase in mutational burden, microsatellite instability or immune cell mobilisation in a cohort of primary prostate cancers.

    We have shown that loss or reduced levels of MSH2/MSH6 protein in prostate cancer is associated with poor outcome. However, our data indicate that this is not associated with a statistically significant increase in mutational burden, microsatellite instability or immune cell mobilisation in a cohort of primary prostate cancers.

    Screen viewing in adults has been associated with greater abdominal adiposity, with the magnitude of associations varying by sex and ethnicity, but the evidence is lacking at younger ages. We aimed to investigate sex- and ethnic-specific associations of screen-viewing time at ages 2 and 3 years with abdominal adiposity measured by magnetic resonance imaging at age 4.5 years.

    The Growing Up in Singapore Towards healthy Outcomes is an ongoing prospective mother-offspring cohort study. Parents/caregivers reported the time their child spent viewing television, handheld devices, and computer screens at ages 2 and 3 years. Superficial and deep subcutaneous and visceral abdominal adipose tissue volumes were quantified from magnetic resonance images acquired at age 4.5 years. Associations between screen-viewing time and abdominal adipose tissue volumes were examined by multivariable linear regression adjusting for confounding factors.

    In the overall sample (n = 307), greater total screen-viewing time and handheons for preventing excessive abdominal adiposity and its adverse cardiometabolic consequences.

    Greater total screen-viewing time (and in particular, handheld device viewing time) was associated with higher abdominal adiposity in boys and Malay children. Additional studies are necessary to confirm these associations and to examine screen-viewing interventions for preventing excessive abdominal adiposity and its adverse cardiometabolic consequences.Human Y chromosomes frequently acquire structural and numerical alterations. Known alterations include germline copy-number variations (CNVs) in the azoospermia factor (AZF) region and somatic mosaic loss of the Y chromosome (mLOY). U0126 in vitro Here, we explored Y chromosomal variations in 160 Japanese men aged 75-90 years. Multiplex ligation-dependent probe amplification (MLPA) identified ten types of AZF-linked CNVs in 77 men and mLOY of various degrees in 37. Seventeen men carried both a CNV and mLOY. MLOY levels estimated by MLPA were closely correlated with those determined by droplet digital PCR. No association was found between AZF-linked CNVs and the frequency or levels of mLOY. These results emphasize the high frequency and large inter-individual variability of AZF-linked CNVs and mLOY, and demonstrate the usefulness of MLPA in the detection of these variations. More importantly, this study provides the first evidence that AZF-linked CNVs do not increase the risk of aging-related mLOY.SPG6 accounts for 1% of autosomal dominant Hereditary Spastic Paraplegia (HSP) and is caused by pathogenic variants in NIPA1, which encodes a magnesium transporter located in plasma membrane and early endosomes, implicated in neuronal development and maintenance. Here we report a 39-year-old woman affected by progressive gait disturbance associated to absence seizures episodes within childhood. Clinical exome sequencing identified a likely pathogenic de novo heterozygous variant in NIPA1 (NM_144599.5 c.249 C > G; p.Asn83Lys). Molecular modelling was performed to evaluate putative functional consequence of the NIPA1 protein. Indeed, the Asn83Lys modification is predicted to induce a significant perturbation of the protein structure, altering signal transduction or small-molecule transport by modulating the length of the second transmembrane domain. This is the first study reporting a SPG6-affected patient harbouring the NIPA1 p.Asn83Lys mutation.Endoscopic therapy is currently the standard of care for the treatment of high-grade dysplasia (HGD) or intramucosal adenocarcinoma (IMC) in patients with Barrett’s esophagus (BE). Visible lesions are treated with endoscopic mucosal resection (EMR), which is often coupled with radiofrequency ablation (RFA). However, endoscopic therapy may require multiple sessions (one session every 2-3 months) and does not always assure complete eradication of neoplasia. Furthermore, despite complete eradication, recurrences are not uncommon. This study assesses which potential risk factors can predict a poor response after endoscopic sessions. Forty-five BE patients who underwent at least one endoscopic session (EMR alone or ablation with or without preceding EMR) for the treatment of HGD/IMC, low-grade dysplasia (LGD), or indefinite for dysplasia (IND) were analyzed. DNA flow cytometry was performed on 82 formalin-fixed paraffin-embedded samples from the 45 patients, including 78 HGD/IMC, 2 LGD, and 2 IND. Eight non-dysplastic BE samples were used as controls.

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