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Management as well as Career Demands-Resources Principle: A planned out Evaluate.
These findings support the outcomes of a previous shorter-term Lab4P intervention study in overweight and obese participants (PROMAGEN, ISRCTN12562026). We conclude that Lab4P has consistent weight modulation capability in free-living overweight adults.The complexities of the informed consent process for participating in research in genomic medicine are well-documented. Inspired by the potential for Dynamic Consent to increase participant choice and autonomy in decision-making, as well as the opportunities for ongoing participant engagement it affords, we wanted to trial Dynamic Consent and to do so developed our own web-based application (web app) called CTRL (control). This paper documents the design and development of CTRL, for use in the Australian Genomics study a health services research project building evidence to inform the integration of genomic medicine into mainstream healthcare. Australian Genomics brought together a multi-disciplinary team to develop CTRL. The design and development process considered user experience; security and privacy; the application of international standards in data sharing; IT, operational and ethical issues. The CTRL tool is now being offered to participants in the study, who can use CTRL to keep personal and contact details up to date; make consent choices (including indicate preferences for return of results and future research use of biological samples, genomic and health data); follow their progress through the study; complete surveys, contact the researchers and access study news and information. While there are remaining challenges to implementing Dynamic Consent in genomic research, this study demonstrates the feasibility of building such a tool, and its ongoing use will provide evidence about the value of Dynamic Consent in large-scale genomic research programs.The advent of personalized medicine has driven the development of novel approaches for obtaining detailed cellular and molecular information from clinical tissue samples. Tissue cytometry is a promising new technique that can be used to enumerate and characterize each cell in a tissue and, unlike flow cytometry and other single-cell techniques, does so in the context of the intact tissue, preserving spatial information that is frequently crucial to understanding a cell's physiology, function, and behavior. However, the wide-scale adoption of tissue cytometry as a research tool has been limited by the fact that published examples utilize specialized techniques that are beyond the capabilities of most laboratories. Here we describe a complete and accessible pipeline, including methods of sample preparation, microscopy, image analysis, and data analysis for large-scale three-dimensional tissue cytometry of human kidney tissues. In this workflow, multiphoton microscopy of unlabeled tissue is first conducted to collect autofluorescence and second-harmonic images. The tissue is then labeled with eight fluorescent probes, and imaged using spectral confocal microscopy. The raw 16-channel images are spectrally deconvolved into 8-channel images, and analyzed using the Volumetric Tissue Exploration and Analysis (VTEA) software developed by our group. We applied this workflow to analyze millimeter-scale tissue samples obtained from human nephrectomies and from renal biopsies from individuals diagnosed with diabetic nephropathy, generating a quantitative census of tens of thousands of cells in each. Such analyses can provide useful insights that can be linked to the biology or pathology of kidney disease. The approach utilizes common laboratory techniques, is compatible with most commercially-available confocal microscope systems and all image and data analysis is conducted using the VTEA image analysis software, which is available as a plug-in for ImageJ.
To investigate the role of urine spermine and Spermine Risk Score in prediction of high-grade prostate cancer (HGPCa, ISUP grade group ≥2).

Nine hundred and five consecutive men with elevated PSA were prospectively recruited from two hospitals. Core analyses focused on consecutive men with PSA 4-20 ng/mL (n = 600). Pre-biopsy urine without prior prostatic massage was analyzed for spermine level with ultra-high performance liquid chromatography with triple quadrupole mass spectrometer (UPLC-MS/MS). The proportions of PCa and HGPCa were compared across different spermine ranges. Logistic regressions were used to form different models, and their performances were compared using area under curve (AUC) and decision curve analysis (DCA).

PCa and HGPCa were diagnosed in 30.8% (185/600) and 17.2% (103/600) men, respectively, and were significantly associated with lower urine spermine levels. Between the lowest and highest quartiles of spermine results, a threefold increase in PCa risk (49.3% vs. 16.7%) and 3.5-fold increase in ISUP grade group ≥2 PCa risk (31.3% vs. 8.7%) were observed. Multivariate analysis showed PSA, prostate volume (PV), digital rectal examination (DRE), and spermine, which were independent predictors for PCa and HGPCa, and a Spermine Risk Score with these factors achieved the highest AUC of 0.78 for PCa and 0.82 for HGPCa. At 90% sensitivity for HGPCa, 36.7% biopsies and 24.4% ISUP grade group 1 diagnoses could have been avoided, with a negative predictive value of 95.4%. DCA revealed net clinical benefit of the Spermine Risk Score. Internal validation with bootstrapping showed good discrimination and calibration.

Urine spermine and Spermine Risk Score identified men at higher risk of HGPCa and reduced unnecessary biopsies.
Urine spermine and Spermine Risk Score identified men at higher risk of HGPCa and reduced unnecessary biopsies.The treatment of prostate cancer is partly guided by patient preferences. Radical prostatectomy and radiation therapy are the standard radical therapies for localized disease and render comparable oncologic outcomes. Considering that survival is high regardless of the chosen treatment, factors such as treatment-related toxicities affecting the patients' quality of life play an important role in their decision. Notably, post-treatment sexual dysfunction, which includes decreased libido, erectile dysfunction, and ejaculatory dysfunction has been shown to be an important and prevalent concern of prostate cancer survivors. In this literature review, we sought to characterize the sexual complications associated with radiation therapy and map the available sexual rehabilitation options for prostate cancer survivors experiencing sexual dysfunction as a result of radiation therapy. We identified medical, non-biomedical, counseling, and lifestyle modification options for prostate cancer survivors seeking sexual rehabilitation. Future research in this area should address the standardization of sexual side-effect reporting and investigate sexual outcomes and rehabilitation in more diverse groups and of transgender and nonheterosexual prostate cancer survivors.Prostate cancer and its treatment frequently lead to sexual side effects that negatively impact personal identity, sexual function, and intimate relationships. The sexual consequences of prostate cancer treatment on men who have sex with men (MSM) differ in some ways from what is observed in heterosexual men. This review summarizes literature from the past two decades exploring how MSM are affected by, and adapt to, prostate cancer treatment. The evidence on whether prostate cancer has a lower prevalence in MSM is unclear but lower screening rates are well-documented within this population. Prostate cancer treatment affects urinary, bowel, and sexual function in both MSM and heterosexual men. These changes may have different sexual and psychological ramifications in MSM when compared to heterosexual men. A common concern among MSM treated for prostate cancer is absence of support, both from the medical profession and in some cases from their own communities. Many MSM with prostate cancer have developed coping strategies and altered sexual practices to accommodate side effects. Lessons learned from this population may have relevance to sexual wellness in non-MSM prostate cancer survivors. Concise recommendations for caring for MSM with prostate cancer are provided.Signaling via interleukin-2 receptor (IL-2R) is a requisite for regulatory T (Treg) cell identity and function. However, it is not completely understood to what degree IL-2R signaling is required for Treg cell homeostasis, lineage stability and function in both resting and inflammatory conditions. Here, we characterized a spontaneous mutant mouse strain endowed with a hypomorphic Tyr129His variant of CD25, the α-chain of IL-2R, which resulted in diminished receptor expression and reduced IL-2R signaling. Under noninflammatory conditions, Cd25Y129H mice harbored substantially lower numbers of peripheral Treg cells with stable Foxp3 expression that prevented the development of spontaneous autoimmune disease. In contrast, Cd25Y129H Treg cells failed to efficiently induce immune suppression and lost lineage commitment in a T-cell transfer colitis model, indicating that unimpaired IL-2R signaling is critical for Treg cell function in inflammatory environments. Moreover, single-cell RNA sequencing of Treg cells revealed that impaired IL-2R signaling profoundly affected the balance of central and effector Treg cell subsets. Thus, partial loss of IL-2R signaling differentially interferes with the maintenance, heterogeneity, and suppressive function of the Treg cell pool.Haploidentical stem cell transplantation (haplo-SCT) achieves superior or at least comparable clinical outcomes to HLA-matched sibling donor transplantation (MSDT) in treating hematological malignancies. To define the underlying regulatory dynamics, we analyzed time courses of leukemia burden and immune abundance of haplo-SCT or MSDT from multiple dimension. First, we employed two nonirradiated leukemia mouse models which carried human AML-ETO or MLL-AF9 fusion gene to establish haplo-identical and major histocompatibility (MHC)-matched transplantation models and investigated the immune cell dynamic response during leukemia development in vivo. We found that haplo-matching the MHCs of leukemia cells with recipient mouse T cells prolonged leukemic mice survival and reduced leukemia burden. The stronger graft-versus-leukemia activity in haplo-SCT group mainly induced by decreased apoptosis and increased cytotoxic cytokine secretion including tumor necrosis factor-α, interferon-γ, pore-forming proteins and CD107a secreted by T cells or natural killer cells. Furthermore, we conducted a prospective clinical trial which enrolled 135 patients with t(8;21) acute myeloid leukemia that displayed minimal residual disease before transplantation and underwent either haplo-SCT or MSDT. PFK15 price The results showed that the haplo-SCT slowed the kinetics of the leukemia burden in vivo and reduced the cumulative incidence of relapse compared with MSDT. Ex vivo experiments showed that, 1 year after transplantation, cytotoxic T lymphocytes from the haplo-SCT group had higher cytotoxicity than those from the MSDT group during the same period. Our results unraveled the role of immune cells in superior antileukemia effects of haplo-SCT compared with MSDT.
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