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IntroductionThe aim of this paper was to give a complete overview of all published complications associated with ureteroscopy and their according management and prevention in current urological practice.Materials and methodsThis review was registered in PROSPERO with registration number CRD42018116273. A bibliographic search of the Medline, Scopus, Embase and Web of Science databases was performed by two authors (V.D.C. and E.X.K.). According to the Population, Intervention, Comparator, Outcome (PICO) study design approach and Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) standards, a consensus between these authors was found relating to the thematic structure of this review.ResultsUreteral stent discomfort, ureteral wall injury and stone migration are the most frequently reported complications. The worst complications include urosepsis, multi-organ failure and death. Incidence rates on these and other complications varied extensively between the reviewed reports.ConclusionUreteroscopy seems to be associated with more complications than currently reported. The present overview may help urologists to prevent, recognize and solve complications of ureteroscopy. It may also stimulate colleagues to perform prospective studies using standardized systems for classifying complications. These are warranted to compare results among different studies, to conduct meta-analyses, to inform health care workers and to counsel patients correctly about possible risks of ureteroscopy.

Cancer is one of the highest prevalent diseases in humans. The chances of surviving cancer and its prognosis are very dependent on the affected tissue, body location, and stage at which the disease is diagnosed. Researchers and pharmaceutical companies worldwide are pursuing many attempts to look for compounds to treat this malignancy. Most of the current strategies to fight cancer implicate the use of compounds acting on DNA damage checkpoints, non-receptor tyrosine kinases activities, regulators of the hedgehog signaling pathways, and metabolic adaptations placed in cancer. In the last decade, the finding of a lipid peroxidation increase linked to 15-lipoxygenases isoform 1 (15-LOX-1) activity stimulation has been found in specific successful treatments against cancer. This discovery contrasts with the production of other lipid oxidation signatures generated by stimulation of other lipoxygenases such as 5-LOX and 12-LOX, and cyclooxygenase (COX-2) activities, which have been suggested as cancer biomarkers and which inhibitors present anti-tumoral and antiproliferative activities. These findings support the previously proposed role of lipid hydroperoxides and their metabolites as cancer cell mediators. Depletion or promotion of lipid peroxidation is generally related to a specific production source associated with a cancer stage or tissue in which cancer originates. This review highlights the potential therapeutical use of chemical derivatives to stimulate or block specific cellular routes to generate lipid hydroperoxides to treat this disease.

Vascular smooth muscle cell (VSMC) proliferation is essential for arteriogenesis to restore blood flow after artery occlusion, but the mechanisms underlying this response remain unclear. Based on our previous findings showing increased VSMC proliferation in the neonatal aorta of mice lacking the protease MT4-MMP, we aimed at discovering new players in this process. We demonstrate that MT4-MMP absence boosted VSMC proliferation in vitro in response to PDGF-BB in a cell-autonomous manner through enhanced p38 MAPK activity. Increased phospho-p38 in basal MT4-MMP-null VSMCs augmented the rate of mitochondrial degradation by promoting mitochondrial morphological changes through the co-activator PGC1α as demonstrated in PGC1α −/− VSMCs. We tested the in vivo implications of this pathway in a novel conditional mouse line for selective MT4-MMP deletion in VSMCs and in mice pre-treated with the p38 MAPK activator anisomycin. Priming of p38 MAPK activity in vivo by the absence of the protease MT4-MMP or by anisomycin treatment led to enhanced arteriogenesis and improved flow recovery after femoral artery occlusion. These findings may open new therapeutic opportunities for peripheral vascular diseases.

Chronic kidney disease (CKD) is one of the fastest growing causes of death worldwide, emphasizing the need to develop novel therapeutic approaches. CKD predisposes to acute kidney injury (AKI) and AKI favors CKD progression. Mitochondrial derangements are common features of both AKI and CKD and mitochondria-targeting therapies are under study as nephroprotective agents. PGC-1α is a master regulator of mitochondrial biogenesis and an attractive therapeutic target. Low PGC-1α levels and decreased transcription of its gene targets have been observed in both preclinical AKI (nephrotoxic, endotoxemia, and ischemia-reperfusion) and in experimental and human CKD, most notably diabetic nephropathy. In mice, PGC-1α deficiency was associated with subclinical CKD and predisposition to AKI while PGC-1α overexpression in tubular cells protected from AKI of diverse causes. Several therapeutic strategies may increase kidney PGC-1α activity and have been successfully tested in animal models. These include AMP-activated protein kinase (AMPK) activators, phosphodiesterase (PDE) inhibitors, and anti-TWEAK antibodies. In conclusion, low PGC-1α activity appears to be a common feature of AKI and CKD and recent characterization of nephroprotective approaches that increase PGC-1α activity may pave the way for nephroprotective strategies potentially effective in both AKI and CKD.

Background C3H10T1/2 is a mesenchymal cell line capable of differentiating into osteoblasts, adipocytes and chondrocytes. The differentiation of these cells into osteoblasts is modulated by various transcription factors, such as RUNX2. Additionally, several interconnected signaling pathways, including the NOTCH pathway, play a crucial role in modulating their differentiation into mature bone cells. We have investigated the roles of DLK1 and DLK2, two non-canonical inhibitory ligands of NOTCH receptors, in the osteogenic differentiation of C3H10T1/2 cells. Results Our results corroborate existing evidence that DLK1 acts as an inhibitor of osteogenesis. In contrast, we demonstrate for the first time that DLK2 enhances this differentiation process. Additionally, our data suggest that NOTCH2, 3 and 4 receptors may promote osteogenesis, as indicated by their increased expression during this process, whereas NOTCH1 expression, which decreases during cell differentiation, might inhibit osteogenesis. Moreover, treatment with DAPT, a NOTCH signaling inhibitor, impeded osteogenic differentiation. We have confirmed the increase in ERK1/2 MAPK and p38 MAPK phosphorylation in C3H10T1/2 cells induced to differentiate to osteoblasts. Our new findings reveal increased ERK1/2 MAPK phosphorylation in differentiated C3H10T1/2 cells with a decrease in DLK1 expression or an overexpression of DLK2, which is coincident with the behavior of those transfectants where we have detected an increase in osteogenic differentiation. Additionally, p38 MAPK phosphorylation increases in differentiated C3H10T1/2 cells with reduced DLK1 levels. Conclusions Our results suggest that DLK1 may inhibit osteogenesis, while DLK2 may promote it, by modulating NOTCH signaling and the phosphorylation of ERK1/2 and p38 MAPK pathways. Given the established inhibitory effect of DLK proteins on NOTCH signaling, these new insights could pave the way for developing future therapeutic strategies aimed at treating bone diseases.

The role of NOTCH signaling in adipogenesis is highly controversial, with data indicating null, positive or negative effects on this differentiation process. We hypothesize that these contradictory results could be due to the different global NOTCH signaling levels obtained in different experimental settings, because of a specific modulation of NOTCH receptors’ activity by their ligands. We have previously demonstrated that DLK1 and DLK2, two non-canonical NOTCH1 ligands that inhibit NOTCH1 signaling in a dose-dependent manner, modulate the adipogenesis process of 3T3-L1 preadipocytes. In this work, we show that over-expression of any of the four NOTCH receptors enhanced adipogenesis of 3T3-L1 preadipocytes. We also determine that DLK proteins inhibit not only the activity of NOTCH1, but also the activity of NOTCH2, 3 and 4 receptors to different degrees. Interestingly, we have observed, by different approaches, that NOTCH1 over-expression seems to stimulate the differentiation of 3T3-L1 cells towards a brown-like adipocyte phenotype, whereas cells over-expressing NOTCH2, 3 or 4 receptors or DLK proteins would rather differentiate towards a white-like adipocyte phenotype. Finally, our data also demonstrate a complex feed-back mechanism involving Notch and Dlk genes in the regulation of their expression, which suggest that a precise level of global NOTCH expression and NOTCH-dependent transcriptional activity of specific targets could be necessary to determine the final phenotype of 3T3-L1 adipocytes.

PurposeDuring endourological procedures, the eye of the urologist is exposed to hazards such as contact with body fluids and irrigation solutions as well as laser injury, and X-ray radiation absorption. The resulting potential injuries and damages to the eye have not been summarily reviewed to date. The objective was to review the different risks of exposure to the eyes of urologists during endourological procedures.MethodsThe Medline database was searched for identification of studies on hazards to the eye of the endourologist. All articles published in English until September 2018 were considered.ResultsTwenty-three publications were included in this analysis. The incidence of eye contact with patient body fluids or irrigation solutions during endoscopic procedures ranged between 37.50 and 100%. Laser-induced eye injuries were reported in 37.9% of all kind of adverse events related to laser use in urology. The eye lens dose of radiation ranged from 0.04 to 1600 µSv per endourological procedures.ConclusionsWhile the risks of infection, laser injury, lens opacity and cataract are generally low, the wear of protective glasses is recommended. Lead glasses may protect against all these risks in case of Ho:YAG laser use with concomitant X-ray radiation. If Ho:YAG laser is used without any concomitant X-ray radiation, proper laser safety glasses or at least conventional eyeglasses should be recommended. When other types of laser are used, we recommend wearing laser eye protection glasses covering the adequate range of wavelength. For endourological procedures without laser use and X-ray radiation, specific protection devices such as goggles or face shields are recommended.

Background-Objective Trichinella spiralis drug development and control need an objective high throughput system to assess first stage larvae (L1) viability. YOLOv5 is an image recognition tool easily trained to count muscular first stage larvae (L1) and recognize morphological differences. Here we developed a semi-automated system based on YOLOv5 to capture photographs of 96 well microplates and use them for L1 count and morphological damage evaluation after experimental drug treatments. Material and methods Morphological properties were used to distinguish L1 from debris after pepsin muscle digestion and distinguish healthy (serpentine) or damaged (coiled) L1s after 72 h untreated or treated with albendazole or mebendazole cultures. An AxiDraw robotic arm with a smartphone was used to scan 96 well microplates and store photographs. Images of L1 were manually annotated, and augmented based on exposure, bounding, blur, noise, and mosaicism. Results A total of 1309 photographs were obtained that after L1 labeling and data augmentation gave 27478 images. The final dataset of 12571 healthy and 14907 affected L1s was used for training, testing, and validating in a ratio of 70/20/10 respectively. A correlation of 92% was found in a blinded comparison with bare-eye assessment by experienced technicians. Conclusion YOLOv5 is capable of accurately counting and distinguishing between healthy and affected L1s, thus improving the performance of the assessment of meat inspection and potential new drugs. Graphical Abstract

Prolonged use of atypical antipsychotics (AAPs) is commonly associated with increased cardiovascular disease risk. While weight gain and related health issues are generally considered the primary contributors to this risk, direct interference with mitochondrial bioenergetics, particularly in the liver where these drugs are metabolized, is emerging as an additional contributing factor. Here, we compared the effects of two AAPs with disparate metabolic profiles on the response of Fao hepatoma cells to oxidative stress: olanzapine (OLA), which is obesogenic, and aripiprazole (ARI), which is not. Results showed that cells treated with ARI exhibited resistance to H2O2-induced oxidative stress, while OLA treatment had the opposite effect. Despite enhanced survival, ARI-treated cells exhibited higher apoptotic rates than OLA-treated cells when exposed to H2O2. Gene expression analysis of pro- and anti-apoptotic factors revealed that ARI-treated cells had a generally blunted response to H2O2, contrasting with a heightened response in OLA-treated cells. This was further supported by the reduced activation of MAPKs and STAT3 in ARI-treated cells in response to H2O2, whereas OLA pre-treatment enhanced their activation. The loss of stress response in ARI-treated cells was consistent with the observed increase in the mitochondrial production of O2•-, a known desensitizing factor. The physiological relevance of O2•- in ARI-treated cells was demonstrated by the increase in mitophagy flux, likely related to mitochondrial damage. Notably, OLA treatment protected proteasome activity in Fao cells exposed to H2O2, possibly due to the better preservation of stress signaling and mitochondrial function. In conclusion, this study highlights the underlying changes in cell physiology and mitochondrial function by AAPs. ARI de-sensitizes Fao cells to stress signaling, while OLA has the opposite effect. These findings contribute to our understanding of the metabolic risks associated with prolonged AAP use and may inform future therapeutic strategies.

This study proposes a sustainable Innovation Management Model (MGI) for the plantain agroindustrial chain, applied to the Quindío region of Colombia. A mixed-methods approach was employed, incorporating various techniques, including a systematic literature review using the Scopus database, which analyzed 95 documents through the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. The identification and prioritization of relevant variables, along with the validation of the proposed model, were also conducted through the use of three questionnaires, supplemented by relevance and congruence indices. The analysis identified 53 variables for the entry stage, 36 for the transformation stage, and 31 for the exit stage. The findings revealed significant gaps within the agroindustrial chain, particularly in areas such as leadership, strategic management, and resilience among key stakeholders. The MGI, as prioritized by stakeholders, provides a framework that integrates variables and information flows, facilitating the development of new open innovation challenges. These challenges engage not only seekers—entities that require innovation—but also solvers—organizations that offer solutions. The implementation of this model will require supportive public policies, projects, and web platforms, such as Innocentive/Wazoku, Ninesigma, Ruta N, Yet2.com, Itonics, and Ennomotive, which, with the aid of artificial intelligence, can connect innovation supply and demand through open challenges.