Physiological mechanisms underlying performance- and health-enhancing effects of high intensity exercise training in human skeletal muscle \u2012 Insights into mitochondrial adaptive responses

In recent years, high-intensity interval training (HIIT) has received considerable attention from the scientific community owing to its effectiveness in enhancing exercise performance and improving cardiovascular and metabolic health. HIIT promotes a number of adaptations resembling those associated with traditional endurance exercise, including quantitative and qualitative changes at the skeletal muscle mitochondrial level. However, the mechanisms underlying these similar adaptive responses in spite of divergent exercise stimuli are not completely clear. Hence, the examination of the skeletal muscle adaptive responses to HIIT with particular emphasis on the cellular pathways regulating mitochondrial quantity, quality and function would provide new insights into the mechanisms involved in the performance- and health-enhancing effects of HIIT. Thus, the overall purpose of this thesis was to investigate the acute and chronic effects of HIIT in humans with specific emphasis on the adaptations occurring in skeletal muscle mitochondria

Synthesis of built-in highly strained monolayer MoS2 using liquid precursor chemical vapor deposition

Strain engineering is an efficient tool to tune and tailor the electrical and optical properties of 2D materials. The built-in strain can be tuned during the synthesis process of a two dimensional semiconductor, as molybdenum disulfide, by employing different growth substrate with peculiar thermal properties. In this work we demonstrate that the built-in strain of MoS2 monolayers, grown on SiO2/Si substrate using liquid precursors chemical vapor deposition, is mainly dominated by the size of the monolayer. In fact, we identify a critical size equal to 20 um, from which the built-in strain increases drastically. The built-in strain is maximized for 60 um sized monolayer, leading to 1.2% tensile strain with a partial release of strain close to the monolayer triangular vertexes due to formation of nanocracks. These findings also imply that the standard method for evaluation of the number of layers based on the Raman modes separation becomes unreliable for monolayer with a lateral size above 20 um

Synthesis and Conformational Analysis of Hydantoin-Based Universal Peptidomimetics

The synthesis of a collection of enantiomerically pure, systematically substituted hydantoins as structural privileged universal mimetic scaffolds is presented. It relies on a chemoselective condensation/cyclization domino process between isocyanates of quaternary or unsubstituted α-amino esters and N-alkyl aspartic acid diesters followed by standard hydrolysis/coupling reactions with amines, using liquid-liquid acid/base extraction protocols for the purification of the intermediates. Besides the nature of the α carbon on the isocyanate moiety, either a quaternary carbon or a more flexible methylene group, conformational studies in silico (molecular modeling), in solution (NMR, circular dichroism (CD), Fourier transform infrared (FTIR)), and in solid state (X-ray) showed that the presented hydantoin-based peptidomimetics are able to project their substituents in positions superimposable to the side chains of common protein secondary structures such as α-helix and β-turn, being the open α-helix conformation slightly favorable according to molecular modeling, while the closed β-turn conformation preferred in solution and in solid state

New strategy for the identification of prostate cancer: The combination of Proclarix and the prostate health index

Prostate health index (PHI) and, more recently, Proclarix have been proposed as serum biomarkers for prostate cancer (PCa). In this study, we aimed to evaluate Proclarix and PHI for predicting clinically significant prostate cancer (csPCa)

Multimodality therapy approaches, local and systemic treatment, compared with chemotherapy alone in recurrent glioblastoma

BACKGROUND: Long-term local control in Glioblastoma is rarely achieved and nearly all patients relapse. In this study we evaluated the clinical effect of different treatment approaches in recurrent patients. METHODS: Forty-three patients, with median age of 51 years were evaluated for salvage treatment: re-resection and/or re-irradiation plus chemotherapy or chemotherapy alone. Response was recorded using the Response Assessment in Neuro-Oncology criteria. Hematologic and non-hematologic toxicities were graded according to Common Terminology Criteria for Adverse Events 4.0. Twenty-one patients underwent chemotherapy combined with local treatment, surgery and/or radiation therapy, and 22 underwent chemotherapy only. RESULTS: The median follow up was 7 months (range 3–28 months). The 1 and 2-years Progression Free Survival was 65 and 10 % for combined treatment and 22 and 0 % for chemotherapy alone (p < 0.01). The 1 and 2-years overall survival was 69 and 29 % for combined and 26 and 0 % for chemotherapy alone (p < 0.01). No toxicity greater than grade 2 was recorded. CONCLUSION: These data showed that in glioblastoma recurrence the combination of several approaches in a limited group of patients is more effective than a single treatment alone. This stress the importance of multimodality treatment whenever clinically feasible

Validation of a Simple, Rapid, and Cost-Effective Method for Acute Rejection Monitoring in Lung Transplant Recipients

Despite advances in immunosuppression therapy, acute rejection remains the leading cause of graft dysfunction in lung transplant recipients. Donor-derived cell-free DNA is increasingly being considered as a valuable biomarker of acute rejection in several solid organ transplants. We present a technically improved molecular method based on digital PCR that targets the mismatch between the recipient and donor at the HLA-DRB1 locus. Blood samples collected sequentially post-transplantation from a cohort of lung recipients were used to obtain proof-of-principle for the validity of the assay, correlating results with transbronchial biopsies and lung capacity tests. The results revealed an increase in dd-cfDNA during the first 2 weeks after transplantation related to ischemia-reperfusion injury (6.36 ± 5.36%, p < 0.0001). In the absence of complications, donor DNA levels stabilized, while increasing again during acute rejection episodes (7.81 ± 12.7%, p < 0.0001). Respiratory tract infections were also involved in the release of dd-cfDNA (9.14 ± 15.59%, p = 0.0004), with a positive correlation with C-reactive protein levels. Overall, the dd-cfDNA percentages were inversely correlated with the lung function values measured by spirometry. These results confirm the value of dd-cfDNA determination during post-transplant follow-up to monitor acute rejection in lung recipients, achieved using a rapid and inexpensive approach based on the HLA mismatch between donor and recipient

Oncoplastic and reconstructive surgery in SENONETWORK Italian breast centers: lights and shadows

Breast cancer (BC) poses a significant worldwide health challenge. In the year 2020, more than 2.3 million cases were detected, and there were approximately 685,000 deaths attributed to BC [1]. Although systemic treatments are gaining importance in BC management, surgery continues to be the fundamental treatment approach for the majority of early-stage patients. A prolonged discussion continues, examining the overall survival rates between mastectomy and breast-conserving therapy (BCT), yielding inconclusive results. Nevertheless, breast-conservative therapy appears to present fewer complications [2, 3]. Patients undergoing BCT experience enhanced cosmetic results and a better quality of life compared to those opting for non-reconstructed mastectom

Investigation of the molecular mechanisms which contribute to the survival of the polychaete Platynereis spp. under ocean acidification conditions in the CO2 vent system of Ischia Island (Italy)

The continuous increase of CO2 emissions in the atmosphere due to anthropogenic activities is one of the most important factors that contribute to Climate Change and generates the phenomenon known as Ocean Acidification (OA). Research conducted at the CO2 vents of Castello Aragonese (Ischia, Italy), which represents a natural laboratory for the study of OA, demonstrated that some organisms, such as polychaetes, thrive under acidified conditions through different adaptation mechanisms. Some functional and ecological traits promoting tolerance to acidification in these organisms have been identified, while the molecular and physiological mechanisms underlying acclimatisation or genetic adaptation are still largely unknown. Therefore, in this study we investigated epigenetic traits, as histone acetylation and methylation, in Platynereis spp. individuals coming from the Castello vent, and from a nearby control site, in two different periods of the year (November-June). Untargeted metabolomics analysis was also carried out in specimens from the two sites. We found a different profile of acetylation of H2B histone in the control site compared to the vent as a function of the sampling period. Metabolomic analysis showed clear separation in the pattern of metabolites in polychaetes from the control site with respect to those from the Castello vent. Specifically, a significant reduction of lipid/sterols and nucleosides was measured in polychaetes from the vent. Overall results contribute to better understand the potential metabolic pathways involved in the tolerance to OA

Cardiovascular toxicity in patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors in the real-life practice: Identification of risk factors and the role of prophylaxis

No abstract availabl