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Antimicrobial resistance is a threat to probiotic microorganisms due to their potential role in harboring and transmitting resistance genes. This study focuses on two Bifidobacterium species (B. animalis subsp. lactis and B. longum) by analyzing 657 Minimal Inhibitory Concentration (MIC) values extracted from research articles indexed in Scopus, PubMed, and Web of Science, published since 2014, and considering 17 different antibiotics. MIC values were used for descriptive statistical analysis (boxplots and violin plots) to evaluate both inter- and intraspecies distributions. The results showed an overall increase in MIC values compared to historical data, with B. longum exhibiting high resistance to tetracyclines and streptomycin—approximately 25% to 50% of the strains had MIC values > EFSA cut-offs. The violin plots revealed the presence of resistant subpopulations, particularly within B. longum. These findings support the relevance of longitudinal MIC analysis as a tool for detecting early shifts in antimicrobial susceptibility and highlight the importance of data-driven approaches for microbiological risk assessment in probiotic applications.

Radiotherapy can trigger immune-related out-of-field “abscopal” response. We report a patient with advanced NSCLC (non-small cell lung cancer) receiving long-term anti-PD1 (programmed cell death protein 1) who have developed out-of-field immune-related arthritis following pelvic irradiation.

Nearly one-third of the patients who undergo prostatectomy for prostate cancer have a biochemical recurrence (BCR) during follow-up. While several randomized trials have shown that adjuvant radiation therapy (aRT) improves biochemical control, this strategy has not been widely used because of the risk of toxicity and the fear of overtreating patients who would not have relapsed. In addition, the possibility of close PSA monitoring in the era of ultrasensitive assays enables to anticipate early salvage strategies (sRT). Three recent randomized trials and their meta-analysis have confirmed that aRT does not improve event-free survival compared to sRT, imposing the latter as the new standard of treatment. The addition of androgen deprivation therapy (ADT) to RT has been shown to improve biochemical control and metastasis-free survival, but the precise definition of to whom it should be proposed is still a matter of debate. The development of genomic tests or the use of artificial intelligence will allow more individualized treatment in the future. Therapeutic intensification with the combination of new-generation hormone therapy and RT is under study. Finally, the growing importance of metabolic imaging (PET/CT) due to its performance especially for low PSA levels will help in further personalizing management strategies.

Up to 25% of patients with metastatic prostate cancer present with germline or somatic DNA damage repair alterations, some of which are associated with aggressive disease and poor outcomes. New data have brought poly(ADP-ribose) polymerase (PARP) inhibitors into sharp focus in the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Olaparib improved survival after at least one new hormonal therapy (NHT) in a cohort of patients harboring BRCA1 , BRCA2 or ATM mutations in the PROfound trial, while rucaparib, talazoparib and niraparib demonstrated compelling activity in phase II trials. While patients with prostate cancer and BRCA1 or BRCA2 mutations may derive greatest benefit of PARP inhibition, the magnitude of benefit seems much lower in the context of most other homologous recombination gene mutations. Several PARP inhibitors are currently developed in combination with conventional therapy, including chemotherapy, NHT, and alpha-particle emitters, at different disease stages. Herein, we review the rationale for PARP inhibition in patients with prostate cancer, discuss the impact of PARP inhibitors on outcomes, and explore underlying challenges for future developments.

Background: Brachytherapy (BT) has a major role in pediatric cancers of the lower genital tract, as part of a multimodal organ conservative strategy. Scarce data are available on the location of image-guided BT. Methods: Medical records of all consecutive girls treated in our center between 2005 and 2020 for a vaginal tumor with exclusive image-guided PDR-BT were retrospectively examined, with a focus on treatment parameters, patient compliance, and clinical outcome, including analysis of local control, survival and late toxicity rates. Results: Twenty-six patients were identified, with a median age of 25 months. Histological types were rhabdomyosarcoma, malignant germ cell tumor (MGCT) and clear cell adenocarcinoma in 18 (69%), 7 (27%) and 1 (4%) patients, respectively. Ten (33%) patients had prior surgery and 25 (96%) received chemotherapy prior to BT. The median prescribed dose was 60 Gy through pulses of 0.42 Gy. Global compliance was satisfactory, but three (12%) patients required replanning because of applicator displacement. After a median follow-up of 47.5 months, one patient with MGCT referred for salvage treatment of a local recurrence had a local and metastatic relapse. The local control rate probability was 96% at the last follow-up. Late toxicity rates ≥ grade 2 and ≥ grade 3 were reported in 23% and 11%, respectively, with gynecological toxicities being the most frequent side effect. Two patients required dilatation for vaginal stenosis. Conclusions: PDR-BT allowed similar local control compared to the historical low-dose rate technique. An indirect comparison suggests fewer treatment-related toxicities by integrating image guidance and optimization capabilities, but longer follow-up is necessary. Due to the rarity of the disease and the technical aspects of BT in these very young patients, referral to specialized high-volume centers is recommended.

A novel prize-winner algorithm designed for a path following problem within the Unmanned Aerial Vehicle (UAV) field is presented in this paper. The proposed approach exploits the advantages offered by the pure pursuing algorithm to set up an intuitive and simple control framework. A path fora quad-rotor UAV is obtained by using downward facing camera images implementing an Image-Based Visual Servoing (IBVS) approach. Numerical simulations in MATLAB together with the MathWorks Virtual Reality (VR) toolbox demonstrate the validity and the effectiveness of the proposed solution. The code is released as open-source making it possible to go through any part of the system and to replicate the obtained results.

In the present paper a new multi-objective optimisation procedure for the design of a shell-and-tube Latent Heat Thermal Energy Storage (LHTES) is proposed. A simple arrangement of a cylindrical shell with multiple vertical tubes has been examined. The optimisation considers, as design variables, the number of tubes, the tube internal radius and the device height-to-diameter ratio, H/D, while the storage volume is kept constant. This analysis aims to detect the set of solutions which optimises the LHTES performances evaluated in terms of charging and discharging times and overall thermal energy capacity. To accomplish the multi-objectives optimal thermal storage design, a simplified mathematical model of the LHTES has been employed. This model can evaluate the prescribed performances for a given set of design variables. The proposed optimisation procedure evaluates new solutions along the most promising directions in the design variables domain, leading to a significant improvement in storage performances. The Design of the Experiment, together with the Pareto dominance relationship, gives a starting optimal solutions subset. The proposed optimisation procedure permits to enhance the starting optimal solutions subset letting approach the Pareto barrier. The paper shows that, at the end of the optimisation procedure, the designer can select the solutions on the Pareto barrier with the best performance and the corresponding design variables for each chosen solution. The proposed optimisation procedure will also allow for maintaining low computational costs due to the low number of the new design variables evaluated only in the promising directions.

Type 2 diabetes mellitus (T2DM) as a comorbidity in amyotrophic lateral sclerosis (ALS) has sparked interest for its potential impact on disease expression and prognosis. In this retrospective cohort study, we investigated the prevalence and clinical correlates of T2DM in a large cohort of patients from the ALS registry of a Northern Italy region, Emilia Romagna, established in 2009. Out of 1756 ALS patients enrolled up to 2021, 145 were affected by T2DM (diALS). Patients with diALS were older than those without T2DM (ndALS) (71.56 vs. 65.76 years, p < 0.001), had a higher body mass index (25.63 vs. 24.23, p < 0.001), but experienced greater weight loss at diagnosis (6.87% vs. 5.44%, p < 0.007). Respiratory onset (6.2% vs. 2.6%, p = 0.013) and respiratory phenotype (4.2% vs. 1.4%, p = 0.04) were more frequent among diALS. Coherently, diALS presented a lower forced vital capacity (74.9% vs. 87.9%, p ≤ 0.001) and more frequently adopted Non-Invasive Ventilation (NIV) (50.35% vs. 37.61%, p = 0.003), with significant influence on time to NIV (HR 1.71, 95% CI 1.07–2.74, p = 0.024). Exploring genetic background, among all the genes examined C9ORF72 emerged as underrepresented among diALS (7.64% in ndALS vs. 0% in diALS, p = 0.039). In conclusion, we confirmed a more severe respiratory dysfunction in diALS, suggesting a specific frailty in respiratory muscles, together with some peculiar clinical features consistent with the previous literature data, such as a later onset. The lower prevalence of C9ORF72 expansion in this population may hint towards a specific role of the gene in metabolism and inflammation, granting more space to non-genetic causes, warranting further studies for confirmation.

Chronic obstructive pulmonary disease (COPD) is considered the fourth-leading causes of death worldwide; COPD is caused by inhalation of noxious indoor and outdoor particles, especially cigarette smoke that represents the first risk factor for this respiratory disorder. To mimic the effects of particulate matter on COPD, we isolated peripheral blood mononuclear cells (PBMCs) and treated them with combustion-generated ultrafine particles (UFPs) obtained from two different fuel mixtures, namely, pure ethylene and a mixture of ethylene and dimethylfuran (the latter mimicking the combustion of biofuels). UFPs were separated in two fractions: (1) sub-10 nm particles, named nano organic carbon (NOC) particles and (2) primarily soot particles of 20-40 nm and their agglomerates (200 nm). We found that both NOC and soot UFPs induced the release of IL-18 and IL-33 from unstable/exacerbated COPD-derived PBMCs. This effect was associated with higher levels of mitochondrial dysfunction and derived reactive oxygen species, which were higher in PBMCs from unstable COPD patients after combustion-generated UFP exposure. Moreover, lower mRNA expression of the repairing enzyme OGG1 was associated with the higher levels of 8-OH-dG compared with non-smoker and smokers. It was interesting that IL-18 and IL-33 release from PBMCs of unstable COPD patients was not NOD-like receptor 3/caspase-1 or caspase-8-dependent, but rather correlated to caspase-4 release. This effect was not evident in stable COPD-derived PBMCs. Our data suggest that combustion-generated UFPs induce the release of caspase-4-dependent inflammasome from PBMCs of COPD patients compared with healthy subjects, shedding new light into the biology of this key complex in COPD.

Sepsis is a challenging condition increasingly managed in medical wards, however literature and clinical evidence in this hospital setting are lacking. Using the computational i2b2 framework, we retrospectively analyzed data from patients admitted to internal medicine units of four hospitals in Lombardy (Italy) between January 2012 and December 2023, with a discharge diagnosis of sepsis, septic shock, or septicemia. A total of 4,375 patients were recruited. Median length of stay (LOS) was 14 days, and mean ward-to-intensive care unit (ICU) transfer and in-hospital mortality rates were 11 and 26%, respectively; significant differences were observed over the years, with LOS peaks preceding mortality peaks by 1 year. Blood culture-negative sepses showed shorter stays and higher mortality (acute kidney injury and fast deterioration) compared to culture-positive ones; polymicrobial sepses showed higher ICU transfer rates (acute respiratory distress); while multidrug-resistant (MDR ) and/or polymicrobial sepses showed longer stays and higher mortality (complicated course) compared to drug-sensitive or monomicrobial ones. C-reactive protein elevation predicted rapidly evolving culture-negative sepsis, whereas lower leukocyte counts predicted prolonged hospitalization; higher fractions of inspired oxygen predicted polymicrobial sepsis, while lactate elevation predicted ICU transfer; ferritin elevation and increased leukocyte counts predicted MDR sepsis, while further ferritin elevation and decreased platelet counts predicted death. From 2016 to 2023, MDR sepsis frequency declined, due to decreased resistance to several antibiotic classes, such as cephalosporins, fluoroquinolones, and aminoglycosides; however, carbapenemase- and extended-spectrum beta-lactamase-producing Gram-negative bacteria, as well as vancomycin-resistant enterococci, increased, as did the frequency of polymicrobial sepsis following the COVID-19 outbreak. This work provides novel insights into sepsis management in internal medicine units, highlighting the need for validated biomarkers and implemented therapies in this scenario.