Search

Worldwide the incidence of andrological diseases is rising every year and, together with it, also the interest in them is increasing due to their strict association with disorders of the reproductive system, including impairment of male fertility, alterations of male hormones production, and/or sexual function. Prevention and early diagnosis of andrological dysfunctions have long been neglected, with the consequent increase in the incidence and prevalence of diseases otherwise easy to prevent and treat if diagnosed early. In this review, we report the latest evidence of the effect of andrological alterations on fertility potential in both young and adult patients, with a focus on the link between gonadotropins’ mechanism of action and mitochondria. Indeed, mitochondria are highly dynamic cellular organelles that undergo rapid morphological adaptations, conditioning a multitude of aspects, including their size, shape, number, transport, cellular distribution, and, consequently, their function. Since the first step of steroidogenesis takes place in these organelles, we consider that mitochondria dynamics might have a possible role in a plethora of signaling cascades, including testosterone production. In addition, we also hypothesize a central role of mitochondria fission boost on the decreased response to the commonly administrated hormonal therapy used to treat urological disease in pediatric and adolescent patients as well as infertile adults.

Aims The prevalence of arterial hypertension (AH) during pregnancy is ranging from 2% to 10%. Diagnostic criteria are based on rest blood pressure measurements. Exercise testing (ET) is a useful approach to detect latent hypertensive condition and may allow early diagnosis. Despite physical activity is encouraged during pregnancy in order to prevent systemic disorders, ET is not commonly performed during pregnancy due to limited data of safety. The aim of the study is to test the safety of ET during pregnancy and to explore its role in predicting the development of AH. Methods Pregnant women were tested through submaximal ET at Dyspnoea Unit of Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milano. The exercise was performed on a stationary cycle on which the power was increased of 15 W every 2 min starting from 5 W (first step). Subjects were continuously monitored during exercise through EKG, non-invasive blood pressure measurements every 2 min and peripheral oxygen saturation. 3 months clinical follow-up was made in order to assess the presence of AH or other pregnancy disorders. U-test analysis was performed in order to verify statistical difference between hypertensive and non-hypertensive women. Heart rate, systolic and diastolic blood pressure (SBP and DBP) were measured at rest, at the first step and at peak of ET and have been considered in analysis. U-test (Mann–Whitney analysis) was adopted to test difference between hypertensive and non-hypertensive group. Women were followed-up at second trimester (22nd–25th week of pregnancy) in order to monitor the clinical condition, the development of AH or any gestational disorders (e.g. diabetes and pre-eclampsia). Results All 73 women (mean age 32 years, gestational age 12–14 weeks) consecutively enrolled have completed the ET. The mean maximum load achieved was 65 W, no abrupt interruption of ET was needed because of symptoms or intolerance. Mean HR at rest, at the first step and at the peak was 80 b.p.m., 91 b.p.m. and 128 b.p.m., respectively. Mean arterial pressure reached values of 97/62 mmHg at rest, 107/66 mmHg at the first step and 140/73 mmHg at peak exercise. At follow-up 9 of 73 showed clinical disorders (12%) of which 5 patients had hypertension (6.8%), 3 patients had diabetes (4.1%) and 1 had pre-eclampsia (1.4%). Comparing the group with AH (n 5) with the group without AH (n 68), SBP at the first step (median values 127 mmHg vs 104 mmHg, P = 0.009), the DBP at rest (median values 72 mmHg vs 60 mmHg, P = 0.039) and the DBP at the peak (median values 90 mmHg vs 69.5 mmHg, P = 0.038) were significantly higher in the group with AH. Among these parameters a logistic regression selected the SBP as best predictor for developing AH (OR 1.139, 95% IC 029–1.261, P = 0.012). Conclusions Our results showed that submaximal ET is safe in pregnancy. Although limited, our data seem to support the validity of ET, even submaximal, in order to stratify the risk of developing AH in pregnancy. Moreover, even SBP response at first step could be considered in a normal and expected range, we can speculate that a relatively excessive increase of BP in the early phase of exercise could reflect a pre-clinical impairment of vascular compliance predisposing AH during the second gestational trimester. Further data are needed to validate our results.

Simple Summary Neurofibromatosis type 1 is a genetic disease that predisposes to tumors of the nervous system, primarily the neurofibroma. Plexiform neurofibromas (Pnfs) are of the greatest concern because of location, size, and frequent progression to malignancy. Although research is making great progress, the lack of in-depth understanding of the molecular mechanisms driving neoplastic progression results in the absence of prognostic indicators and therapeutic targets. We document that cell–cell cooperativity and the dynamics of the extracellular matrix play important roles in the growth and transformation of Pnf cells, directly through the cooperation of RAS and focal adhesion kinase (FAK) signaling. In turn, we found that treatment of Pnf cells with both MEK and FAK inhibitors is effective in abolishing the transforming ability of these cells. Abstract Plexiform neurofibromas (Pnfs) are benign peripheral nerve sheath tumors that are major features of the human genetic syndrome, neurofibromatosis type 1 (NF1). Pnfs are derived from Schwann cells (SCs) undergoing loss of heterozygosity (LOH) at the NF1 locus in an NF1+/− milieu and thus are variably lacking in the key Ras-controlling protein, neurofibromin (Nfn). As these SCs are embedded in a dense desmoplastic milieu of stromal cells and abnormal extracellular matrix (ECM), cell–cell cooperativity (CCC) and the molecular microenvironment play essential roles in Pnf progression towards a malignant peripheral nerve sheath tumor (MPNST). The complexity of Pnf biology makes treatment challenging. The only approved drug, the MEK inhibitor Selumetinib, displays a variable and partial therapeutic response. Here, we explored ECM contributions to the growth of cells lacking Nfn. In a 3D in vitro culture, NF1 loss sensitizes cells to signals from a Pnf-mimicking ECM through focal adhesion kinase (FAK) hyperactivation. This hyperactivation correlated with phosphorylation of the downstream effectors, Src, ERK, and AKT, and with colony formation. Expression of the GAP-related domain of Nfn only partially decreased activation of this signaling pathway and only slowed down 3D colony growth of cells lacking Nfn. However, combinatorial treatment with both the FAK inhibitor Defactinib (VS-6063) and Selumetinib (AZD6244) fully suppressed colony growth. These observations pave the way for a new combined therapeutic strategy simultaneously interfering with both intracellular signals and the interplay between the various tumor cells and the ECM.

The physiological role of autophagy in the progression of liver diseases is still debated. To understand the clinical relevance of autophagy in primary e secondary hepatic tumors, we analyzed the expression of mTOR (mammalian target of rapamycin), a key regulator of autophagy; Raptor (regulatory-associated protein of mTOR); ULK1 (Unc-51 like kinase 1) determinant in the autophagy initiation; LC3 (microtubule-associated protein 1A/1B-light chain 3), a specific marker of autophagosomes; and p62, a selective autophagy receptor. Samples from subjects with chronic hepatitis (n.58), cirrhosis (n.12), hepatocellular carcinoma (HCC, n.56), metastases (n.48) from colorectal cancer and hyperplasia or gallbladder stones (n.7), the latter considered as controls, were examined. Gene expression analysis was carried out in n.213 tissues by absolute q-PCR, while protein expression by Western Blot in n.191 lysates, including tumoral, surrounding tumoral and normal tissues. Nonparametric statistical tests were used for comparing expression levels in the above-mentioned groups. Subgroup analysis was performed considering viral infection and chemotherapy treatment. The mTOR transcriptional level was significantly lower in metastases compared to HCC (P = 0.0001). p-mTOR(Ser2448) and LC3II/LC3I protein levels were significantly higher in metastases compared to HCC (P = 0.008 and PConclusions:the different expression of proteins considered, owning their interaction and diverse tissue microenvironment, indicate an impairment of the autophagy flux in primary liver tumors that is critical for the promotion of tumorigenesis process and a coexistence of autophagy inhibition and activation mechanisms in secondary liver tumors. Differences in mTOR and LC3 transcripts emerged in tumor-free tissues, therefore particular attention should be considered in selecting the control group.

Objectives: The goal of this study was to assess the diagnostic performance of coronary computed tomography angiography (CTA) alone, adenosine-stress myocardial perfusion assessed by computed tomography (CTP) alone, and coronary CTA + CTP by using a 16-cm Z-axis coverage scanner versus invasive coronary angiography (ICA) and fractional flow reserve (FFR) as the clinical standard. Background: Diagnostic performance of coronary CTA for in-stent restenosis detection is still challenging. Recently, CTP showed additional diagnostic power over coronary CTA in patients with suspected coronary artery disease. However, few data are available on CTP performance in patients with previous stent implantation. Methods: Consecutive stable patients with previous coronary stenting referred for ICA were enrolled. All patients underwent stress myocardial CTP and rest CTP + coronary CTA. Invasive FFR was performed during ICA when clinically indicated. The diagnostic rate and diagnostic accuracy of coronary CTA, CTP, and coronary CTA + CTP were evaluated in stent-, territory-, and patient-based analyses. Results: In the 150 enrolled patients (132 men; mean age 65.1 ± 9.1 years), the CTP diagnostic rate was significantly higher than that of coronary CTA in all analyses (territory based [96.7% vs. 91.1%; p < 0.0001] and patient based [96% vs. 68%; p < 0.0001]). When ICA was used as gold standard, CTP diagnostic accuracy was significantly higher than that of coronary CTA in all analyses (territory based [92.1% vs. 85.5%, p < 0.03] and patient based [86.7% vs. 76.7%, p < 0.03]). The concordant coronary CTA + CTP assessment exhibited the highest diagnostic accuracy values versus ICA (95.8% in the territory-based analysis). The diagnostic accuracy of CTP was significantly higher than that of coronary CTA (75% vs. 30.5%; p < 0.001). The radiation exposure of coronary CTA + CTP was 4.15 ± 1.5 mSv. Conclusions: In patients with coronary stents, CTP significantly improved the diagnostic rate and accuracy of coronary CTA alone compared with both ICA and invasive FFR as gold standard.

Testicular torsion is a pathology that occurs in young males generally before the age of 25. Despite surgery representing the only effective approach, there is still a need to identify a marker that can predict whether a preserved testicle will be functional. In addition, no therapeutic approach is currently considered in the post-operative phase. Through an approach based on the in vitro culture of a tissue strictly linked to the testicle, the gubernaculum, we defined the healthy state of the organ and the possible responsiveness to a therapy used in the andrology field, chorionic gonadotropin (hCG). Firstly, we optimized a protocol to obtain viable cells starting from a small piece of gubernacular tissue harvested during surgery with the aim to amplify cells in vitro. Intriguingly, only for a patient whose testicle had been removed during surgery due to an excessive necrotic area, gubernacular cells were not able to grow in culture. These data support the possibility of exploiting the gubernaculum to evaluate the healthy state of the testicle. Then, as we demonstrate that gubernacular cells express a luteinizing hormone receptor, to which hCG is specific, we analyzed the cellular response to hCG treatment on in vitro cultured cells derived from patients affected by testicular torsion. Our study opens the way for the possibility of evaluating testicle wellbeing after derotation through in vitro culture of a small piece of gubernaculum together with predicting the response to the treatment with hCG, which can have a positive effect on cell proliferation and vascularization.

The main purpose of this paper is to describe a software platform dedicated to sea surveillance, capable of detecting and identifying illegal maritime traffic. This platform results from the cascade pipeline of several image processing algorithms that input Radar or Optical imagery captured by satellite-borne sensors and try to identify vessel targets in the scene and provide quantitative descriptors about their shape and motion. This platform is innovative since it integrates in its architecture heterogeneous data and data processing solutions with the goal of identifying navigating vessels in a unique and completely automatic processing streamline. More in detail, the processing chain consists of: (i) the detection of target vessels in an input map, (ii) the estimation of each vessel&rsquo, s most descriptive geometrical and scatterometric (for radar images) features, (iii) the estimation of the kinematics of each vessel, (iv) the prediction of each vessel&rsquo, s forthcoming route, and (v) the visualization of the results in a dedicated webGIS interface. The resulting platform represents a novel tool to counteract unauthorized fishing and tackle irregular migration and the related smuggling activities.