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Ultrasound elastography was proposed for the evaluation of testicular focal lesions, but no studies verified the agreement between the whole histological architecture of the testis and the stiffness measured by elastography. The present study explored the use of strain elastography in the evaluation of testis with normal or abnormal spermatogenesis, classified based on epididymal sperm attributes, and the consistency between elastographic parameters and the testicular histological feature. Strain elastography was performed during the routine andrological examination in 22 dogs presented for elective orchiectomy. Epididymal sperm attributes and testicular histology were analyzed after orchiectomy. Based on the epididymal sperm characteristics, testes were classified according to normal or abnormal spermatogenesis, and strain elastographic attributes were compared between groups. Possible correlations between strain elastography and histological features were also explored. Consistent with the literature in humans, testes with abnormal spermatogenesis were stiffer (mean strain elastographic index 3.6 ± 0.6) compared with normal testes (mean strain elastographic index 1.9 ± 0.2; P < 0.01). The strain elastographic index was negatively correlated with the area occupied by seminiferous tubules (Pearson's rho = -0.716; P = 0.0003), the mean diameter (Pearson's rho = -0.742; P = 0.0002), and thickness of the seminiferous tubule (Pearson's rho = -0.728; P = 0.0002). Surprisingly, no correlations were found between the area occupied by connective tissue in histological sections and elastographic attributes, suggesting that the increased stiffness was not related to the increased amount of connective tissue. This study demonstrated that strain elastography could be used to support the andrological examination, but measurements should be acquired in specific regions to be reliable., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The Covid-19 pandemic has caused an unprecedented global crisis and led to a huge number of deaths, economic hardship and the disruption of everyday life. Measures to restrict accessibility adopted by many countries were a swift yet effective response to contain the spread of the virus. Within this topic, this paper aims to support policies and decision makers in defining the most appropriate strategies to manage the Covid-19 crisis. Precisely the correlation between positive Covid-19 cases and transport accessibility of an area was investigated through a multiple linear regression model. Estimation results show that transport accessibility was the variable that better explained the number of Covid-19 infections (about 40% in weight), meaning that the greater is the accessibility of a certain geographical area, the easier the virus reaches its population. Furthermore, other context variables were also significant, i.e. socio-economic, territorial and pollutant variables. Estimated findings show that accessibility, which is often used to measure the wealth of an area, becomes its worst enemy during a pandemic, providing to be the main vehicle of contagion among its citizens. These original results allow the definition of possible policies and/or best practices to better manage mobility restrictions. The quantitative estimates performed show that a possible and probably more sustainable policy for containing social interactions could be to apply lockdowns in proportion to the transport accessibility of the areas concerned, in the sense that the higher the accessibility, the tighter should be the mobility restriction policies adopted., (© 2020 Elsevier Ltd. All rights reserved.)

Pulse-wave Doppler (PWD) ultrasonography of the testicular artery was recently used to compare parameters in fertile and infertile males, or males with normal and abnormal semen quality, while no studies verified the concomitant histological feature of the testis. The experimental hypothesis of the present study was that the blood flow parameters measured by PWD at different levels of the testicular artery reflect sperm attributes evaluated on spermatozoa collected from the tail of the epididymis and testicular histological characteristics. Pulse-wave Doppler parameters were recorded on both testes from 16 dogs of unknown fertility. After routine castration, epididymal spermatozoa were collected and evaluated for sperm total and progressive motility, membrane integrity, and sperm morphology. Testes were submitted to histological and immunohistochemical evaluations to quantify microscopic attributes and connective tissue and vascular area extent, respectively. The findings showed that the increased PWD indexes were suggestive of testicular histological alteration since negative correlations were found between pulsatility index and resistive index, measured in the marginal testicular artery, and histological attributes such as the seminiferous epithelial thickness (R = -0.528, P = 0.016 and R = -0.554, P = 0.005, respectively) and the tubular area/total area ratio (R = -0.494, P = 0.024 and R = -0.563, P = 0.004, respectively). Some histological characteristics, such as tubular diameter, seminiferous epithelium thickness, and the tubular area/total area ratio of the testis are correlated with the percentage of primary abnormalities (R = -0.874, P = 0.001, and R = -0.847, P = 0.001, and R = - 0.865, P = 0.001, respectively). In testes with increased sperm primary abnormalities, higher pulsatility index was found compared with testes with normal spermatogenesis in supratesticular artery (1.07 ± 0.06 vs 0.82 ± 0.23, P < 0.05), marginal artery (0.73 ± 0.04 vs 0.61 ± 0.07, P < 0.05), and intratesticular artery (0.67 ± 0.03 vs 0.43 ± 0.1, P < 0.05). Similarly, the resistive index was found significantly higher in the same vessel tracts in testes with abnormal and normal spermatogenesis (0.62 ± 0.02, 0.53 ± 0.02, and 0.46 ± 0.02 vs 0.51 ± 0.06, 0.44 ± 0.04, and 0.32 ± 0.06, respectively; P < 0.05). Our data demonstrated for the first time the relationship between PWD indexes and the contextual testicular architecture, suggesting that the pulsatility and resistive indexes could be an effective tool in andrology. In light of different histological alterations in the testis, caution is warranted in the definition of thresholds for normal and abnormal testicular blood flow indexes., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier Inc.)

Starting from December 2019 the world has faced an unprecedented health crisis caused by the new Coronavirus (COVID-19) due to the SARS-CoV-2 pathogen. Within this topic, the aim of the paper was to quantify the effect of mobility habits in the spread of the Coronavirus in Italy through a multiple linear regression model. Estimation results showed that mobility habits represent one of the variables that explains the number of COVID-19 infections jointly with the number of tests/day and some environmental variables (i.e. PM pollution and temperature). Nevertheless, a proximity variable to the first outbreak was also significant, meaning that the areas close to the outbreak had a higher risk of contagion, especially in the initial stage of infection (time-decay phenomena). Furthermore, the number of daily new cases was related to the trips performed three weeks before. This threshold of 21 days could be considered as a sort of positivity detection time, meaning that the mobility restrictions quarantine commonly set at 14 days, defined only according to incubation-based epidemiological considerations, is underestimated (possible delays between contagion and detection) as a containment policy and may not always contribute to effectively slowing down the spread of virus worldwide. This result is original and, if confirmed in other studies, will lay the groundwork for more effective containment of COVID-19 in countries that are still in the health emergency, as well as for possible future returns of the virus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Creutzfeldt-Jakob disease (CJD) is a neurodegenerative disorder characterized by the deposition of the pathological conformer (PrP(CJD)) of the host encoded cellular prion protein (PrP(C)). In genetic CJD associated with V210I or R208H PrP substitutions, the pathogenic role of mutant residues is still poorly understood. To understand how V210I or R208H PrP mutations facilitate the development of the disease, we determined by mass spectrometry the quantitative ratio of mutant/wild-type PrP(CJD) allotypes in brains from affected subjects. We found that the mutant PrP(CJD) allotypes moderately exceeds of 2- or 3-fold the amount of the wild-type counterpart suggesting that these mutations mainly exert their pathogenic effect on the onset of the pathogenic cascade. Different mechanisms can be hypothesized to explain the pathogenic role of mutant residues: V210I and R208H substitutions can increase the concentration of PrP(C) and the probability to form insoluble aggregates, or they may facilitate the formation of pathological intermediates, or, alternatively, they may increase the affinity for ligands that are involved in the initial phases of PrP(CJD) formation and aggregation. Whatever the mechanism, the enrichment found for the mutated PrP(CJD) species indicates that these altered structures are more prone, with respect to the non-mutated ones, to be captured in the polymerization process either at the onset or during the development of the disease., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Even though the acetylation of platelet cyclooxygenase (COX)-1 at serine-529 is the direct mechanism of action of low-dose aspirin, its antiplatelet effect has been characterized using indirect indexes of COX-1 activity., Objectives: We performed a clinical study with enteric-coated low-dose aspirin (EC-aspirin), in healthy subjects, to evaluate the effects on the extent and duration of platelet COX-1 acetylation, using a novel proteomic strategy for absolute protein quantification (termed AQUA), as compared with traditional pharmacokinetic and pharmacodynamic parameters., Subjects and Methods: In a phase I, single-arm, open-label study of EC aspirin (100 mg day(-1) ) administered to 24 healthy subjects, we compared, over a 24 h-period on day 1 and 7, % platelet acetylated COX-1 (AceCOX-1) with traditional pharmacokinetic and pharmacodynamics [i.e. serum thromboxane (TX) B2 , platelet function by monitoring CEPI(collagen/epinephrine) closure time (CT) using whole-blood PFA-100 and urinary excretion of 11-dehydro-TXB2 ] parameters., Results: Acetylation of platelet COX-1 was measurable before detection of aspirin levels in the systemic circulation and increased in a cumulative fashion upon repeated dosing. After the last dose of EC-aspirin, %AceCOX-1, serum TXB2 and CEPI-CT values were maximally and persistently modified throughout 24 h; they averaged 76 ± 2%, 99.0 ± 0.4% and 271 ± 5 s, respectively. EC-aspirin caused 75% reduction in urinary 11-dehydro-TXB2 excretion. After chronic dosing with aspirin, the pharmacokinetics of acetylsalicylic acid was completely dissociated from pharmacodynamics., Conclusions: The demonstrated feasibility of quantifying the extent and duration of platelet COX-1 acetylation will allow characterizing the genetic, pharmacokinetic and pharmacodynamic determinants of the inter-individual variability in the antiplatelet response to low-dose aspirin as well as identifying extra-platelet sites of drug action., (© 2014 International Society on Thrombosis and Haemostasis.)