Oxidative Stress Induced by Cortisol in Human Platelets

Hypercortisolism is known to affect platelet function. However, few studies have approached the effect of exogenous cortisol on human platelets, and the results obtained are conflicting and unconvincing. In this study, the effect of exogenous cortisol on several parameters indicative of oxidative status in human platelets has been analysed. We have found that cortisol stimulates ROS production, superoxide anion formation, and lipid peroxidation, with these parameters being in strict correlation. In addition, cortisol decreases GSH and membrane SH-group content, evidencing that the hormone potentiates oxidative stress, depleting platelet antioxidant defence. The involvement of src, syk, PI3K, and AKT enzymes in oxidative mechanisms induced by cortisol is shown. The main sources of ROS in cells can include uncontrolled increase of NADPH oxidase activity and uncoupled aerobic respiration during oxidative phosphorylation. Both mechanisms seem to be involved in ROS formation induced by cortisol, as the NADPH oxidase 1 inhibitor 2(trifluoromethyl)phenothiazine, and rotenone and antimycin A, complex I and III inhibitor, respectively, significantly reduce oxidative stress. On the contrary, the NADPH oxidase inhibitor gp91ds-tat, malate and NaCN, complex II and IV inhibitor, respectively, have a minor effect. It is likely that, in human platelets, oxidative stress induced by cortisol can be associated with venous and arterial thrombosis, greatly contributing to cardiovascular diseases

Long-term outcome of 9G MRI-guided vacuum-assisted breast biopsy: results of 293 single-center procedures and underestimation rate of high-risk lesions over 12 years

Purpose: Breast magnetic resonance imaging (MRI) can detect some malignant lesions that are not visible on mammography (MX) or ultrasound (US). If a targeted, second-look fails, MRI-guided breast biopsy is the only available tool to obtain a tissue sample and pathological proof of these “MRI-only lesions”. The aim of this study is to report the performance and underestimation rate of 9G MRI-guided vacuum-assisted breast biopsy (VABB) over 12 years at a single center. Material and methods: All 9G MRI-VABB procedures performed from January 2010 to December 2021 were retrospectively reviewed. Two MRI scanners (1.5 T and 3 T) were used with the same image resolution and contrast media. All suspicious lesions detected only by breast MRI underwent biopsy. Reference standard was histological diagnosis or at least 1-year negative follow-up. All malignant and atypical lesions underwent surgery, which was used as the reference standard. Results: A total of 293 biopsies were retrospectively reviewed. Histopathological VABB results revealed 142/293 (48.4%) benign lesions, 77/293 (26.2%) high-risk lesions, and 74/293 (25.2%) malignant lesions. No significant complications were observed. Surgical pathology results allowed for the reclassification of n = 7/48 B3b lesions: n = 4 were ductal carcinoma in situ, while n = 3 presented invasive features at surgical histology (2 IDC; 1 ILC). B3b underestimation occurred overall in 14.6% of B3 cases. Breast follow-up was achieved for all benign VABB results, and only one false-negative case was observed. Conclusion: Our results confirm that 1.5 T and 3 T MRI-guided VABB is an accurate and safe procedure for histopathologic final diagnosis of MRI-only lesions. Critical issues remain the potential high-risk underestimation rate of B3b VABB results and management of follow-up of benign lesions

Exceptional magnetic and magnetoelastic behavior of rare-earth non-centrosymmetric Sm7Pd3

Magnetic compounds possessing an intrinsic combination of near-zero magnetization with high magnetic anisotropy are highly desirable for spinronic applications and memory recording. A comprehensive study of Sm7Pd3 binary compound uncovered a unique combination of strong magnetoelastic behavior, very low net magnetization, and exceptionally high magnetic coercivity. The temperature-dependent X-ray synchrotron powder diffraction study indicates the abrupt changes in the compound's lattice parameters at the magnetic ordering temperature of TC=169 K, although the crystal structure remains non-centrosymmetric hexagonal Th7Fe3-type down to 6 K. Density functional theory calculations confirm high intrinsic magnetocrystalline anisotropy of Sm7Pd3, which explains the extremely large coercivity of the polycrystalline sample, up to Hcr = 130 kOe at 2 K. This discovery brings to life a novel class of highly anisotropic materials that are distinctly different from known spintronic materials, making them interesting future systems for magnetic memory research

Legacy Results of the ANTARES Neutrino Telescope

The ANTARES neutrino telescope was operational in the Mediterranean Sea from 2006 to 2022. The detector array, consisting of 12 vertical string-like structures hosting a total of 885 optical modules, was designed to detect high-energy neutrinos covering energies from a few tens of GeV up to the PeV range. Despite the relatively small size of the detector, the results obtained are relevant in the field of neutrino astronomy, due to the view of the Southern sky and the good angular resolution of the telescope. This document will give an overview of the legacy results of ANTARES, including searches for point sources, neutrinos from the Galactic Ridge, from dark matter annihilation, and from transients, as well as limits on new physics

The Institutional Channeling of Transnational Economic Mobilization in Three Moroccan Regions

This chapter analyses the interaction between transnational economic mobilization between Europe and Morocco, on the one hand, and diaspora policies deployed in Morocco on the other hand. The objective is to better understand how transnational economic exchanges contribute to redefining the links between home societies and emigrant communities while at the same time redefining the latter as diasporas. These processes lie at the crossroads of new migration dynamics, new modes of economic action among emigrant communities and new State responses to these demands. Dwelling on the authors’ previous research on Moroccans in Europe and on a new project conducted in three Moroccan administrative regions (Oriental, Beni-Mellal-Khenifra and Souss Massa), the paper looks more particularly at how diaspora policies are being formulated at sub-state level and thus providing insights into how the transnational economic mobilization of Moroccan diasporic entrepreneurs is institutionally channeled

International multidisciplinary consensus on the integration of radiotherapy with new systemic treatments for breast cancer: European Society for Radiotherapy and Oncology (ESTRO)-endorsed recommendations

: Novel systemic therapies for breast cancer are being rapidly implemented into clinical practice. These drugs often have different mechanisms of action and side-effect profiles compared with traditional chemotherapy. Underpinning practice-changing clinical trials focused on the systemic therapies under investigation, thus there are sparse data available on radiotherapy. Integration of these new systemic therapies with radiotherapy is therefore challenging. Given this rapid, transformative change in breast cancer multimodal management, the multidisciplinary community must unite to ensure optimal, safe, and equitable treatment for all patients. The aim of this collaborative group of radiation, clinical, and medical oncologists, basic and translational scientists, and patient advocates was to: scope, synthesise, and summarise the literature on integrating novel drugs with radiotherapy for breast cancer; produce consensus statements on drug-radiotherapy integration, where specific evidence is lacking; and make best-practice recommendations for recording of radiotherapy data and quality assurance for subsequent studies testing novel drugs

The impact of margins in laryngeal cancer patients treated with transoral laser microsurgery: a systematic review and meta-analysis

PurposeIn laryngeal squamous cell carcinoma (LSCC) treated with transoral laser microsurgery (TOLMS), the status of margins significantly affected local control. When a positive or close margin is present, there is no ubiquitous consensus regarding further treatments. The rationale of the present systematic review and meta-analysis is to investigate the survival impact of the status of the margins in patients affected by LSCC treated with TOLMS.Data sourcesPubMed, EMBASE, and Cochrane Library.MethodsWe performed a systematic search, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria were: patients affected by LSCC, staged according to the American Joint Committee on Cancer Staging System and treated by TOLMS without any previous treatment; margins status (close, positive, negative) and the adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) of overall survival, disease-specific survival, and disease-free survival has to be reported.ResultsNine studies were deemed eligible for the qualitative analysis, and 3 for the quantitative analysis to investigate the association between margin status and OS. The cumulative number of patients was 3130. The sample size ranged from 96 to 747 patients. The follow-up period ranged from 0 to 201 months. The meta-analysis results show that positive margins have an aHR of 1.30 yet with CI range (0.56 to 2.97).ConclusionsOur current meta-analysis results are unable to definitively assess the real impact of resection margins on OS. Few authors provide accurate data regarding position and types of margins. Further prospective or high-quality studies are required

Balto and Togo during the cold winter of Alaska (1925): the two canine heroes in the fight against diphtheria

In recent years, diphtheria has re-emerged in areas with inadequate vaccination coverage, and Europe has not been spared with several cases among migrants. Diphtheria is a potentially fatal infection caused mainly by toxigenic strains of Corynebacterium diphtheriae. Due to the high mortality rate, especially among young children, the fight against diphtheria is considered one of the first conquests of immunization. In the history of medicine, there is a unique case of an unconventional response to a diphtheria outbreak in which sled dogs were used to overcome the supply difficulties of diphtheria antitoxin. The mass media followed the medical response to the outbreak and raised audience awareness of public health issues. The facts of Nome, Alaska, in 1925 can serve as a catalyst to rethink conventional responses to diphtheria outbreaks in low-income countries today and promote mass media awareness of public health importance

Nano-superhydrophilic and bioactive surface in poor bone environment. Part 1: transition from primary to secondary stability. A controlled clinical trial : Bioactive implant surfaces in poor density bone

Objectives: Bioactive surfaces were designed to increase the interaction between the surface and the cells. This may speed up the biological stability and loading protocols. Materials and methods: 36 patients with D3-D4 bone density were recruited and allocated into two groups. 30 bioactive (test group) and 30 traditional (control group) surfaced implants were placed. Insertion torque value (Ncm), insertion torque curve integral (cumulative torque, Ncm), torque density (Ncm/sec), implant stability quotient (ISQ) measured at three timepoints (baseline (T0), 30 (T30) and 45 (T45) days after surgery), and marginal bone loss (MBL) at 6 months of loading were assessed. Results: The mean ISQ and standard deviation at T0, T30, T45 were respectively 74.57 ± 7.85, 74.78 ± 7.31, 74.97 ± 6.34 in test group, and 77.12 ± 5.83, 73.33 ± 6.13, 73.44 ± 7.89 in control group, respectively. Data analysis showed significant differences between groups in ΔISQ at T0-T30 (p = 0.005) and T30-T45 (p = 0.012). Control group showed a significant decrease in ISQ at T30 (p = 0.01) and T45 (p = 0.03) compared to baseline, while no significant change was observed in test group. Due to the stability of the ISQ value ≥ 70, 26 test group and 23 control group implants were functionally loaded after 45 days. Conversely, due to the ISQ < 70 at T45, four test group implants and one control group implant were loaded after 90 days, and 6 control group implants were loaded after 180 days. Neither insertion torque nor ISQ at baseline were correlated with bone density (in Hounsfield units). There was no significant correlation between cumulative torque and ISQ at baseline. There was a significant positive slope in the correlation between torque density and ISQ at baseline, more accentuated in D3 than D4. This correlation remained significant for the test group in D3 bone at day 30 and 45 (p < 0.01 in both time frames), but not in D4 bone, and it was not significant in CG. Conclusions: The bioactive surface showed better behavior in terms of implant stability in D3-D4 bone quality in the early stages of bone healing. Clinical relevance This study demonstrated that the transition from primary to secondary stability is improved using bioactive surface, especially in cases of poor bone environment (D3/D4 bone)

Laboratory and clinical management capacity for invasive fungal infections: the Italian landscape

Background: We assessed the laboratory diagnosis and treatment of invasive fungal disease (IFD) in Italy to detect limitations and potential for improvement. Methods: The survey was available online at www.clinicalsurveys.net/uc/IFI management capacity/, and collected variables such as (a) institution profile, (b) perceptions of IFD in the respective institution, (c) microscopy, (d) culture and fungal identification, (e) serology, (f) antigen detection, (g) molecular tests, (h) susceptibility testing and (i) therapeutic drug monitoring (TDM). Results: The laboratory capacity study received responses from 49 Italian centres, with an equitable geographical distribution of locations. The majority of respondents (n = 36, 73%) assessed the occurrence of IFD as moderate-high, with Aspergillus spp. being the pathogen of highest concern, followed by Candida spp. and Mucorales. Although 46 (94%) of the institutions had access to microscopy, less than half of them performed direct microscopy on clinical specimens always when IFD was suspected. Cultures were available in all assessed laboratories, while molecular testing and serology were available in 41 (83%), each. Antigen detection tests and antifungal drugs were also generally accessible (> 90%) among the participating institutions. Nevertheless, access to TDM was limited (n = 31, 63%), with a significant association established between therapeutic drug monitoring availability and higher gross domestic product per capita. Conclusions: Apart from TDM, Italy is adequately prepared for the diagnosis and treatment of IFD, with no significant disparities depending on gross domestic product. Future efforts may need to focus on enhancing the availability and application of direct microscopic methods, as well as TDM, to promote optimal treatment and better patient outcomes