Fraser Eason (edgewren97)

1 dBi.Along with early-onset cancers, multiple primary cancers (MPCs) are likely resulting from increased genetic susceptibility; however, the associated predisposition genes or prevalence of the pathogenic variants genes in MPC patients are often unknown. We screened 71 patients with MPC of the stomach, colorectal, and endometrium, sequencing 65 cancer predisposition genes. A subset of 19 patients with early-onset MPC of stomach and colorectum were further evaluated for variants in cancer related genes using both normal and tumor whole exome sequencing. Among 71 patients with MPCs, variants classified to be pathogenic were observed in 15 (21.1%) patients and affected Lynch Syndrome (LS) genes MLH1 (n = 10), MSH6 (n = 2), PMS2 (n = 2), and MSH2 (n = 1). All carriers had tumors with high microsatellite instability and 13 of them (86.7%) were early-onset, consistent with LS. In 19 patients with early-onset MPCs, loss of function (LoF) variants in RECQL5 were more prevalent in non-LS MPC than in matched sporadic cancer patients (OR = 31.6, 2.73-1700.6, p = 0.001). Additionally, there were high-confidence LoF variants at FANCG and CASP8 in two patients accompanied by somatic loss of heterozygosity in tumor, respectively. The results suggest that genetic screening should be considered for synchronous cancers and metachronous MPCs of the LS tumor spectrum, particularly in early-onset. Susceptibility variants in non-LS genes for MPC patients may exist, but evidence for their role is more elusive than for LS patients.Traditionally, the cerebellum has been linked to motor coordination, but growing evidence points to its involvement in a wide range of non-motor functions. Though the number of studies using transcranial magnetic stimulation (TMS) to investigate cerebellar involvement in cognitive processes is growing exponentially, these findings have not yet been synthesized in a meta-analysis. Here, we used meta-analysis to estimate the effects of cerebellar TMS on performance in cognitive tasks for healthy participants. Outcomes included participants' accuracy and response times (RTs) of several non-motor tasks performed either during or after the administration of TMS. We included overall 41 studies, of which 44 single experiments reported effects on accuracy and 41 on response times (RTs). The meta-analyses showed medium effect sizes (for accuracy d = 0.61 [95% CI = 0.48, .073]; for RTs d = 0.40 [95% CI = 0.30, 0.49]), with leave-one-out analyses indicating that cumulative effects were robust, and with moderate heterogeneity. For both accuracy and RTs, the effect of TMS was moderated by the stimulation paradigm adopted but not by the cognitive function investigated, while the timing of the stimulation moderated only the effects on RTs. Further analyses on lateralization revealed no moderation effects of the TMS site. Taken together, these findings indicate that TMS administered over the cerebellum is able to modulate cognitive performance, affecting accuracy or RTs, and suggest that the various stimulation paradigms play a key role in determining the efficacy of cerebellar TMS.Renal sympathetic nerves contribute to renal excretory function during volume expansion. We hypothesized that intact renal innervation is required for excretion of a fluid/electrolyte load in hypertensive chronic kidney disease (CKD) and normotensive healthy settings. Blood pressure, kidney hemodynamic and excretory response to 180 min of isotonic saline loading (0.13 ml/kg/min) were examined in female normotensive (control) and hypertensive CKD sheep at 2 and 11 months after sham (control-intact, CKD-intact) or radiofrequency catheter-based RDN (control-RDN, CKD-RDN) procedure. Basal blood pressure was ~ 7 to 9 mmHg lower at 2, and 11 months in CKD-RDN compared with CKD-intact sheep. Saline loading did not alter glomerular filtration rate in any group. At 2 months, in response to saline loading, total urine and sodium excretion were ~ 40 to 50% less, in con