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The close connections between the intestine and distal systems, known as axes, are a growing focus of scientific research; however, the gut–vascular axis, particularly as a target of microbial metabolites, remains underexplored. In this study, three supernatants derived from probiotic formulations composed of Lactobacillus and Bifidobacterium strains (MIX-1, MIX-2, and MIX-3) were evaluated in counteracting vascular alterations associated with dysbiosis. Human aortic smooth muscle (HASMCs) and endothelial (HAECs) cells were exposed to pro-oxidative (H2O2) and pro-inflammatory (TMAO) stimuli. Concentrations up to 5–10% (v/v) were tolerated in both cell lines, with MIX-1 and MIX-3 showing the greatest protective efficacy. These formulations exerted antioxidant effects by reducing H2O2-induced ROS production and cell viability loss, and anti-inflammatory effects by limiting TMAO-induced IL-1β release. MIX-1 also attenuated TMAO-induced IL-6 release. Further analyses indicated a partial involvement of the SIRT1-pathway in its vascular antioxidant effects. Chromatographic profiling revealed comparable qualitative metabolites among the probiotic supernatants, while quantitative differences were observed, with higher lactate levels in MIX-1 and MIX-3 compared to MIX-2. Finally, we have determined that Limosilactobacillus reuteri-PBS072 is mainly responsible for the antioxidant effect of MIX-1 and MIX-3. Overall, these findings highlight the potential of probiotic-derived metabolites in modulating the gut–vascular axis and promoting vascular protection.

Background: Colds are widespread infectious diseases that affect daily life, increasing healthcare costs and limiting productivity. Objectives: The aim of this study was to investigate the effects of a dietary supplement containing specific probiotic strains (L. plantarum PBS067, L. acidophilus PBS066, B. lactis BL050) on cold symptom relief, immune response enhancement, and quality of life. Methods This randomized, double-blind, placebo-controlled trial included 65 healthy volunteers (age range: 18–44 years), divided into two groups: 40 received the probiotic treatment (with vitamins and bulking agents), and 25 received placebo (vitamins and bulking agents only) for 12 weeks. Cold symptoms and systemic inflammation were assessed at three time points (baseline T0, post-treatment T1, and 6 weeks after treatment T2). Results: Probiotics were associated with a shorter average duration of cold symptoms (4.5 vs. 6.7% for Placebo, p < 0.05). At T1, fever and muscle pain occurred in 20% of participants in the Probiotic group vs. 28% and 44% in the Placebo group, respectively (p < 0.05 for muscle pain vs. Placebo). For muscle pain, a trend was maintained also at T2 (17.5% vs. 20%). The pro-inflammatory cytokine IFN-γ levels significantly decreased in the Probiotic group vs. T0 (p < 0.0001 at T1 and p < 0.01 at T2), while they increased in the Placebo group (22.279 ± 3.538 vs. 19.432 ± 3.143 pg/mL, p = NS). Although not statistically significant, at T1 the Probiotic group had higher levels of IL-10 vs. T0 (266.98 ± 78.432 vs. 240.967 ± 70.238, pg/mL p = NS). Conclusions: The probiotic mix effectively alleviated cold symptoms and reduced pro-inflammatory cytokine levels, suggesting anti-inflammatory effects.

A substantial proportion of cancer patients do not benefit from platinum-based chemotherapy (CT) due to the emergence of drug resistance. Here, we apply elemental imaging to the mapping of CT biodistribution after therapy in residual colorectal cancer and achieve a comprehensive analysis of the genetic program induced by oxaliplatin-based CT in the tumor microenvironment. We show that oxaliplatin is largely retained by cancer-associated fibroblasts (CAFs) long time after the treatment ceased. We determine that CT accumulation in CAFs intensifies TGF-beta activity, leading to the production of multiple factors enhancing cancer aggressiveness. We establish periostin as a stromal marker of chemotherapeutic activity intrinsically upregulated in consensus molecular subtype 4 (CMS4) tumors and highly expressed before and/or after treatment in patients unresponsive to therapy. Collectively, our study underscores the ability of CT-retaining CAFs to support cancer progression and resistance to treatment. Standard platinum-based chemotherapy is the basis of treatment of many cancers, however a proportion of patients do not derive benefit. Here the authors show that the platinum-based drug oxaliplatin accumulates in cancer-associated fibroblasts, activating pathways associated with cancer progression and resistance to therapy.

Background The proportion of health-related searches on the internet is continuously growing. ChatGPT, a natural language processing (NLP) tool created by OpenAI, has been gaining increasing user attention and can potentially be used as a source for obtaining information related to health concerns. This study aims to analyze the quality and appropriateness of ChatGPT’s responses to Urology case studies compared to those of a urologist. Methods Data from 100 patient case studies, comprising patient demographics, medical history, and urologic complaints, were sequentially inputted into ChatGPT, one by one. A question was posed to determine the most likely diagnosis, suggested examinations, and treatment options. The responses generated by ChatGPT were then compared to those provided by a board-certified urologist who was blinded to ChatGPT’s responses and graded on a 5-point Likert scale based on accuracy, comprehensiveness, and clarity as criterias for appropriateness. The quality of information was graded based on the section 2 of the DISCERN tool and readability assessments were performed using the Flesch Reading Ease (FRE) and Flesch-Kincaid Reading Grade Level (FKGL) formulas. Results 52% of all responses were deemed appropriate. ChatGPT provided more appropriate responses for non-oncology conditions (58.5%) compared to oncology (52.6%) and emergency urology cases (11.1%) ( p  = 0.03). The median score of the DISCERN tool was 15 (IQR = 5.3) corresponding to a quality score of poor. The ChatGPT responses demonstrated a college graduate reading level, as indicated by the median FRE score of 18 (IQR = 21) and the median FKGL score of 15.8 (IQR = 3). Conclusions ChatGPT serves as an interactive tool for providing medical information online, offering the possibility of enhancing health outcomes and patient satisfaction. Nevertheless, the insufficient appropriateness and poor quality of the responses on Urology cases emphasizes the importance of thorough evaluation and use of NLP-generated outputs when addressing health-related concerns.

Background Long-term antiretroviral therapy (ART) perpetually suppresses HIV load and has dramatically altered the prognosis of HIV infection, such that HIV is now regarded as a chronic disease. Side effects of ART in Patients With HIV (PWH), has introduced new challenges including “metabolic” (systemic) and oral complications. Furthermore, inflammation persists despite great viral load suppression and normal levels of CD4 + cell count. The impact of ART on the spectrum of oral diseases among PWH is often overlooked relative to other systemic complications. There is paucity of data on oral complications associated with ART use in PWH. This is in part due to limited prospective longitudinal studies designed to better understand the range of oral abnormalities observed in PWH on ART. Methods We describe here the study design, including processes associated with subject recruitment and retention, study visit planning, oral health assessments, bio-specimen collection and preprocessing procedures, and data management and statistical plan. Discussion We present a procedural roadmap that could be modelled to assess the extent and progression of oral diseases associated with ART in PWH. We also highlight the rigors and challenges associated with our ongoing participant recruitment and retention. A rigorous prospective longitudinal study requires proper planning and execution. A great benefit is that large data sets are collected and biospecimen repository can be used to answer more questions in future studies including genetic, microbiome and metabolome-based studies. Trial registration National Institute of Health Clinical Trials Registration (NCT) #: NCT04645693.

Purpose Transperineal laser ablation (TPLA) is a new minimally-invasive surgical treatment for patients with benign prostatic obstruction (BPO). We report the perioperative and mid-term functional results of the first 100 consecutively patients undergoing TPLA at our institution. Methods Clinical data from consecutive patients undergoing TPLA at our institution from April 2021 to July 2023 were prospectively collected. Primary endpoints were the postoperative changes in IPSS, QoL and MSHQ 3-item questionnaires and in Qmax and post-void residual volume (PVR). Results Overall, 100 consecutive patients underwent the procedure. Median age and prostate volume were 66 (IQR 60–75) years and 50 (IQR 40–70) ml, respectively. In the cohort, 14 (14%) patients had an indwelling catheter and 81 (81%) were under oral BPO therapy at the time of TPLA. Baseline median Qmax (ml/s) and PVR (ml) were 9.1 (IQR 6.9–12) and 90 (IQR 50–150), respectively, while median IPSS and QoL were 18 (IQR 15–23) and 4 (IQR 3–4). At all the follow-up timepoints, the evaluated outcomes on both symptoms and functional parameters showed a statistically significant improvement ( p  < 0.001). Antegrade ejaculation was preserved in all sexually active patients. No postoperative Clavien-Dindo > 2 complications were recorded. Conclusions TPLA represents a safe option for selected well-informed patients swith LUTS due to BPO. Our prospective study confirms the feasibility and favorable perioperative and functional outcomes in a real-world cohort with heterogenous prostate volumes and patient characteristics.

In this study, calcite crystals within 42 lapis lazuli reference rocks coming from four distinct mining regions (in present-day Afghanistan, Tajikistan, Siberia and Myanmar) were characterised in terms of their compositional and luminescence properties in order to identify potential provenance markers. A non-destructive approach based on Ion Beam Analysis was employed, in particular using μ-Particle Induced X-rays Emission (μ-PIXE) and μ-Ion Beam Induced Luminescence (μ-IBIL). The results indicate that calcite crystals in Afghan rocks are characterised by the highest quantity of Mg and Mn; whereas, Siberian calcite exhibit the highest Sr content. The application of Principal Component Analysis also enhanced the possibility of discriminating between the Myanmar and Tajik rocks, as well as between the four provenances in general, by exploiting the compositional variability of Mg, Mn, Sr and Y elements. Regarding the luminescence properties, notable differences in the intensity ratio between the 360 nm and the 620 nm luminescence bands were detected among the provenances. In the second part of this study, the new results were employed to infer the origin of the raw material of certain archaeological findings discovered in two different historical sites: four lapis lazuli fragments from Shahr-i Sokhta (Iran, 3rd millennium BCE) and a lapis lazuli tessera from the city of Tanis (Egypt, 1050–700 BCE). The results of the analysis indicate that, among the four provenances considered in the reference rocks database, the best compatibility of the data from both case studies is found with the Afghan dataset. This suggests that the area of Afghanistan is the most probable source for the raw materials of the investigated findings.

This work presents an upgrade to the methodology adopted to investigate the provenance of the raw lapis lazuli material used in antiquity for carving precious artefacts. Samples from archaeological excavation contexts frequently display superficial degradation processes affecting the crystals of the mineral phases useful for provenance attribution (especially pyrite). To address this issue, an innovative workflow has been developed, centred on the application of X-ray micro-computed tomography (μ-CT) and micro-ablation treatments with a pulsed laser source prior to investigation with ion beam analysis (IBA). High-resolution μ-CT is employed to evaluate the alteration state of pyrite crystals within the entire volume of the lapis lazuli rock, and, if required, to identify the most suitable crystals on the surface for subsequent laser treatment. The micro-ablation procedure aims to create a small breach in the superficial altered layer (the irradiated areas are approximately 65 × 65 μm 2 ), thereby exposing the preserved crystal beneath and allowing for the analysis of its trace element contents with IBA. The methodology of the workflow is presented, together with its first application to archaeological lapis lazuli material: three precious beads from the ancient Royal Cemetery of Ur (Mesopotamia, 3rd millennium BCE). The results are complemented by the application of a provenance protocol already validated that proved, for the first time using a micro-invasive analytical approach, a match between the Afghan quarry district and the raw material used to carve these beads.

ObjectiveTo identify baseline factors associated with disease activity in patients with relapsing–remitting multiple sclerosis (RRMS) under teriflunomide treatment.MethodsThis was an independent, multi-centre, retrospective post-marketing study. We analysed data of 1,507 patients who started teriflunomide since October 2014 and were regularly followed in 28 Centres in Italy. We reported the proportions of patients who discontinued treatment (after excluding 32 lost to follow-up) and who experienced clinical disease activity, i.e., relapse(s) and/or confirmed disability worsening, as assessed by the Expanded Disability Status Scale (EDSS). Decision tree-based analysis was performed to identify baseline factors associated with clinical disease activity during teriflunomide treatment.ResultsAt database lock (September 2020), approximately 29% of patients (430 out of 1,475) discontinued teriflunomide because of disease activity (~ 46%), adverse events (~ 37%), poor tolerability (~ 15%), pregnancy planning (~ 2%). Approximately 28% of patients experienced disease activity over a median follow-up of 2.75 years: ~ 9% had relapses but not disability worsening; ~ 13% had isolated disability worsening; ~ 6% had both relapses and disability worsening. The most important baseline factor associated with disease activity (especially disability worsening) was an EDSS > 4.0 (p < 0.001). In patients with moderate disability level (EDSS 2.0–4.0), disease activity occurred more frequently in case of ≥ 1 pre-treatment relapses (p = 0.025). In patients with milder disability level (EDSS < 2.0), disease activity occurred more frequently after previous exposure to ≥ 2 disease-modifying treatments (p = 0.007).ConclusionsOur study suggests a place-in-therapy for teriflunomide in naïve patients with mild disability level or in those who switched their initial treatment for poor tolerability. Adverse events related with teriflunomide were consistent with literature data, without any new safety concern.