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Background: Male contraceptive approaches besides tubal sterilization involve vasectomy and represent the method of choice among midlife men in developing countries thanks to many advantages. However, the subsidiary consequences of this intervention are insufficiently explored since the involved mechanisms may offer insight into a much more complex picture. Methods: Thus, in this manuscript, we aimed to reunite all available data by searching three separate academic database(s) (PubMed, Web of Knowledge, and Scopus) published in the past two decades by covering the interval 2000–2023 and using a predefined set of keywords and strings involving "oxidative stress" (OS), "inflammation", and "semen microbiota" in combination with "humans", "rats", and "mice". Results: By following all evidence that fits in the pre-, post-, and vasectomy reversal (VR) stages, we identified a total of n = 210 studies from which only n = 21 were finally included following two procedures of eligibility evaluation. Conclusions: The topic surrounding this intricate landscape has created debate since the current evidence is contradictory, limited, or does not exist. Starting from this consideration, we argue that further research is mandatory to decipher how a vasectomy might disturb homeostasis. [ABSTRACT FROM AUTHOR]

The risk stratification of patients with atrial fibrillation (AF) for subsequent cardiovascular events could help in guiding prevention strategies. In this study, we aimed at investigating circulating microRNAs as prognostic biomarkers for major adverse cardiovascular events (MACE) in AF patients. We conducted a three-stage nested case–control study within the framework of a prospective registry, including 347 AF patients. First, total small RNA-sequencing was performed in 26 patients (13 cases with MACE) and the differential expression of microRNAs was analyzed. Seven candidate microRNAs with promising results in a subgroup analysis on cardiovascular death were selected and measured via using RT-qPCR in 97 patients (42 cases with cardiovascular death). To further validate our findings and investigate broader clinical applicability, we analyzed the same microRNAs in a subsequent nested case–control study of 102 patients (37 cases with early MACE) by using Cox regression. In the microRNA discovery cohort (n = 26), we detected 184 well-expressed microRNAs in circulation without overt differential expression between the cases and controls. A subgroup analysis on cardiovascular death revealed 26 microRNAs that were differentially expressed at a significance level < 0.05 (three of which with an FDR-adjusted p-value <0.05). We, therefore, proceeded with a nested case–control approach (n = 97) focusing on patients with cardiovascular death and selected, in total, seven microRNAs for further RT-qPCR analysis. One microRNA, miR-411-5p, was significantly associated with cardiovascular death (adjusted HR (95% CI): 1.95 (1.04–3.67)). Further validation (n = 102) in patients who developed early MACE showed similar results (adjusted HR (95% CI) 2.35 (1.17–4.73)). In conclusion, circulating miR-411-5p could be a valuable prognostic biomarker for MACE in AF patients. [ABSTRACT FROM AUTHOR]

Emergency department (ED) overcrowding is a global issue setting challenges to all care providers. Elderly patients are frequent visitors of the ED and their risk stratification is demanding due to insufficient assessment methods. A prospective cohort study was conducted to determine the risk-predicting value of a prognostic biomarker, soluble urokinase plasminogen activator receptor (suPAR), in the ED, concentrating on elderly patients. SuPAR levels were determined as part of standard blood sampling of 1858 ED patients. The outcomes were assessed in the group of <75 years (=younger) and ≥75 years (=elderly). The elderly had higher median suPAR levels than the younger (5.4 ng/mL vs. 3.7 ng/mL, p < 0.001). Increasing suPAR levels were associated with higher probability for 30-day mortality and hospital admission in all age groups. SuPAR also predicted 30-day mortality when adjusted to other clinical factors. SuPAR acts successfully as a nonspecific risk predictor for 30-day mortality, independently and with other risk-assessment tools. Low suPAR levels predict positive outcomes and could be used in the discharging process. A cut-off value of 4 ng/mL could be used for all ED patients, 5 ng/mL being a potential alternative in elderly patients. [ABSTRACT FROM AUTHOR]

This is a focused review of imaging literature to scope the utility of hybrid brain imaging in neuropsychiatric disorders. The review focuses on brain imaging modalities that utilize hybrid (fusion) techniques to characterize abnormal brain molecular signals in combination with structural and functional changes that have been observed in neuropsychiatric disorders. An overview of clinical hybrid brain imaging technologies for human use is followed by a selective review of the literature that conceptualizes the use of these technologies in understanding basic mechanisms of major neuropsychiatric disorders and their therapeutics. Neuronal network abnormalities are highlighted throughout this review to scope the utility of hybrid imaging as a potential biomarker for each disorder. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with pancreatic cancer and other advanced cancers suffer from progressive weight loss that reduces treatment response and quality of life and increases treatment toxicity and mortality. Effective interventions to prevent such weight loss, known as cachexia, require molecular markers to diagnose, stage, and monitor cachexia. No such markers are currently validated or in clinical use. This study used a discovery platform to measure changes in plasma proteins in patients with pancreatic cancer compared with normal controls. We found proteins specific to pancreatic cancer and cancer stage, as well as proteins that correlate with cachexia. These include some previously known proteins along with novel ones and implicates both well-known and new molecular mechanisms. Thus, this study provides novel insights into the molecular processes underpinning cancer and cachexia and affords a basis for future validation studies in larger numbers of patients with pancreatic cancer and cachexia. Patients with pancreatic ductal adenocarcinoma (PDAC) suffer debilitating and deadly weight loss, known as cachexia. Development of therapies requires biomarkers to diagnose, and monitor cachexia; however, no such markers are in use. Via Somascan, we measured ~1300 plasma proteins in 30 patients with PDAC vs. 11 controls. We found 60 proteins specific to local PDAC, 46 to metastatic, and 67 to presence of >5% cancer weight loss (FC ≥ |1.5|, p ≤ 0.05). Six were common for cancer stage (Up: GDF15, TIMP1, IL1RL1; Down: CCL22, APP, CLEC1B). Four were common for local/cachexia (C1R, PRKCG, ELANE, SOST: all oppositely regulated) and four for metastatic/cachexia (SERPINA6, PDGFRA, PRSS2, PRSS1: all consistently changed), suggesting that stage and cachexia status might be molecularly separable. We found 71 proteins that correlated with cachexia severity via weight loss grade, weight loss, skeletal muscle index and radiodensity (r ≥ |0.50|, p ≤ 0.05), including some known cachexia mediators/markers (LEP, MSTN, ALB) as well as novel proteins (e.g., LYVE1, C7, F2). Pathway, correlation, and upstream regulator analyses identified known (e.g., IL6, proteosome, mitochondrial dysfunction) and novel (e.g., Wnt signaling, NK cells) mechanisms. Overall, this study affords a basis for validation and provides insights into the processes underpinning cancer cachexia. [ABSTRACT FROM AUTHOR]

Carotenoids include C30, C40 and C50 terpenoid-based molecules, many of which constitute coloured pigments. However, >1100 of these are known to occur in nature and only about a dozen are known to play a role in our daily diet. Carotenoids have received much attention due to their proposed health benefits, including reducing the incidence of chronic diseases, such as cardiovascular disease and diabetes. Many of these diseases are characterized by chronic inflammation co-occurring with oxidative stress, characterized by, for example, enhanced plasma F2-isoprostane concentrations, malondialdehyde, and 8-hydroxyguanosine. Though carotenoids can act as direct antioxidants, quenching, for example, singlet oxygen and peroxide radicals, an important biological function appears to rest also in the activation of the body's own antioxidant defence system, related to superoxide-dismutase, catalase, and glutathione-peroxidase expression, likely due to the interaction with transcription factors, such as nuclear-factor erythroid 2-related factor 2 (Nrf-2). Though mostly based on small-scale and observational studies which do not allow for drawing conclusions regarding causality, several supplementation trials with isolated carotenoids or food items suggest positive health effects. However, negative effects have also been reported, especially regarding beta-carotene for smokers. This review is aimed at summarizing the results from human observational studies/intervention trials targeting carotenoids in relation to chronic diseases characterized by oxidative stress and markers thereof. [ABSTRACT FROM AUTHOR]