p53, first described four decades ago, is now established as a master regulator of cellular stress response, the "guardian of the genome". p53 contributes to biological robustness by behaving in a cellular-context dependent manner, influenced by several factors (e.g., cell type, active signalling pathways, the type, extent and intensity of cellular damage, cell cycle stage, nutrient availability, immune function). The p53 isoforms regulate gene transcription and protein expression in response to the stimuli so that the cell response is precisely tuned to the cell signals and cell context. Twelve isoforms of p53 have been described in humans. In this review, we explore the interactions between p53 isoforms and other proteins contributing to their established cellular functions, which can be both tumour-suppressive and oncogenic in nature. Evidence of p53 isoform in human cancers is largely based on RT-qPCR expression studies, usually investigating a particular type of isoform. Beyond p53 isoform functions in cancer, it is implicated in neurodegeneration, embryological development, progeroid phenotype, inflammatory pathology, infections and tissue regeneration, which are described in this review.
Background: ultrasound-based shear wave elastography (SWE) can non-invasively assess prostate tissue stiffness. This systematic review aims to evaluate SWE for the detection of prostate cancer (PCa) and compare diagnostic estimates between studies reporting the detection of all PCa and clinically significant PCa (csPCa). Methods: a literature search was performed using the MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, and CINAHL databases. Studies evaluating SWE for the detection of PCa using histopathology as reference standard were included. Results: 16 studies including 2277 patients were included for review. Nine studies evaluated SWE for the detection of PCa using systematic biopsy as a reference standard at the per-sample level, with a pooled sensitivity and specificity of 0.85 (95% CI = 0.74–0.92) and 0.85 (95% CI = 0.75–0.91), respectively. Five studies evaluated SWE for the detection of PCa using histopathology of radical prostatectomy (RP) specimens as the reference standard, with a pooled sensitivity and specificity of 0.71 (95% CI = 0.55–0.83) and 0.74 (95% CI = 0.42–0.92), respectively. Sub-group analysis revealed a higher pooled sensitivity (0.77 vs. 0.62) and specificity (0.84 vs. 0.53) for detection of csPCa compared to all PCa among studies using RP specimens as the reference standard. Conclusion: SWE is an attractive imaging modality for the detection of PCa.
Home blood pressure monitor (HBPM) ownership prevalence and the factors that influence it are unclear. This study aimed to investigate factors associated with HBPM ownership among participants in the Treatment in Morning versus Evening (TIME) hypertension study. This study is a sub-analysis of the TIME study, a randomised trial investigating the effect of day-time versus night-time dosing of antihypertensive medication on cardiovascular outcomes in adults with hypertension. As part of the TIME study online registration process, participants were asked to indicate whether they owned an HBPM. A multivariable logistic regression model was constructed to determine factors associated with HBPM ownership. Of 21,104 randomised participants, 11,434 (54.2%) reported owning an HBPM. The mean age of all participants at enrolment was 67.7 ± 9.3 years, 12,134 (57.5%) were male, and 8892 (42.1%) reported a current or previous history of smoking. Factors associated with an increased likelihood of reporting HBPM owned include being male (OR:1.47; 95% CI 1.39–1.56) or residing in a less deprived socioeconomic region (IMD Decile 6–10) (OR:1.31; 95% CI 1.23–1.40). Participants with a history of diabetes mellitus (OR:0.74; 95% CI:0.64–0.86) or current smokers, compared to non-smokers, (OR:0.71; 95% CI:0.62–0.82) were less likely to report owning an HBPM. This study has identified important patient factors influencing HBPM ownership. Further qualitative research would be valuable to identify and explore potential patient-level barriers to engagement with self-monitoring of blood pressure.
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