Strategies to Reverse Endothelial Progenitor Cell Dysfunction in Diabetes

Bone-marrow-derived cells-mediated postnatal vasculogenesis has been reported as the main responsible for the regulation of vascular homeostasis in adults. Since their discovery, endothelial progenitor cells have been depicted as mediators of postnatal vasculogenesis for their peculiar phenotype (partially staminal and partially endothelial), their ability to differentiate in endothelial cell line and to be incorporated into the vessels wall during ischemia/damage. Diabetes mellitus, a condition characterized by cardiovascular disease, nephropathy, and micro- and macroangiopathy, showed a dysfunction of endothelial progenitor cells. Herein, we review the mechanisms involved in diabetes-related dysfunction of endothelial progenitor cells, highlighting how hyperglycemia affects the different steps of endothelial progenitor cells lifetime (i.e., bone marrow mobilization, trafficking into the bloodstream, differentiation in endothelial cells, and homing in damaged tissues/organs). Finally, we review preclinical and clinical strategies that aim to revert diabetes-induced dysfunction of endothelial progenitor cells as a means of finding new strategies to prevent diabetic complications

Artificial Intelligence in Supply Chain and Operations Management: A Multiple Case Study Research

Artificial intelligence (AI) is increasingly considered a source of competitive advantage in operations and supply chain management (OSCM). However, many organisations still struggle to adopt it successfully and empirical studies providing clear indications are scarce in the literature. This research aims to shed light on how AI applications can support OSCM processes and to identify benefits and barriers to their implementation. To this end, it conducts a multiple case study with semi-structured interviews in six companies, totalling 17 implementation cases. The Supply Chain Operations Reference (SCOR) model guided the entire study and the analysis of the results by targeting specific processes. The results highlighted how AI methods in OSCM can increase the companies' competitiveness by reducing costs and lead times and improving service levels, quality, safety, and sustainability. However, they also identify barriers in the implementation of AI, such as ensuring data quality, lack of specific skills, need for high investments, lack of clarity on economic benefits and lack of experience in cost analysis for AI projects. Although the nature of the study is not suitable for wide generalisation, it offers clear guidance for practitioners facing AI dilemmas in specific SCOR processes and provides the basis for further future research

Privileged Scaffold Decoration for the Identification of the First Trisubstituted Triazine with Anti-SARS-CoV-2 Activity

: Current therapy against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are based on the use of Remdesivir 1, Molnupiravir 2, and the recently identified Nirmatrelvir 3. Unfortunately, these three drugs showed some limitations regarding potency and possible drug-drug interactions. A series of derivatives coming from a decoration approach of the privileged scaffold s-triazines were synthesized and evaluated against SAR-CoV-2. One derivative emerged as the hit of the series for its micromolar antiviral activity and low cytotoxicity. Mode of action and pharmacokinetic in vitro preliminary studies further confirm the role as candidates for a future optimization campaign of the most active derivative identified with this work. © 2022 by the authors

The ISTH DIC-score predicts early mortality in patients with non-promyelocitic acute myeloid leukemia

coagulation disorders frequently complicate the clinical course of acute myeloid leukemia (AML) patients. this study examined the frequency and prognostic significance, with regards of early mortality, of the presence of overt disseminated intravascular coagulation (DIC) at AML diagnosis and its correlation with clinical and biological characteristics. a retrospective analysis of 351 newly diagnosed non-promyelocytic AML patients was conducted, utilizing the 2018 ISTH DIC-Score criteria to evaluate the presence of overt DIC at AML onset. the study cohort had a median age of 65 years with a predominance of male gender (59%). overt DIC was present in 21% of cases and was associated with advanced age, comorbidities, poor performance status, hyperleukocytosis, LDH levels, NPM1 mutations, expression of CD33 and CD4, and lack of expression of CD34. With a median follow-up of 72 months (3–147 months), the 6-year overall survival (OS) was 17.4%, with patients having overt DIC showing significantly poorer outcomes (7.2% compared to 20.3 % of those without DIC, p < 0.001). patients with overt DIC showed markedly high early mortality rates at 30 (42.5% vs 8 %), 60 (49.3% vs 16.9%), and 120 days (64.4% vs 25.6%) from disease onset. In multivariate analysis overt DIC retained its independent prognostic value for early mortality. In conclusion, the prevalence and clinical relevance of DIC in non-promyelocytic AML is not negligible, underlining its potential as an unfavorable prognostic marker. In newly diagnosed patients with AML, early recognition and measure to counteract coagulation disturbances might help mitigate the elevated mortality risk associated with DIC

Epidemiological surveillance for <i>Trichinella britovi</i> infection in free-ranging pigs of Sardinia

The aim of the present work was to investigate on Trichinella sp. infection in free-ranging pigs of the Orgosolo municipality

ACUTE LEUKEMIA AND LATENT TUBERCULOSIS INFECTION IN ITALY: QUANTIFERON-TB TEST SCREENING IN A LOW TUBERCULOSIS INCIDENCE COUNTRY

background: identification of latent tuberculosis infection (LTBI) is a critical step of tuberculosis surveillance, especially in low-incidence countries. however, it is limited to situations with a higher probability of developing active disease, e.g., patients with hematological malignancies. according to guidelines, in TB non-endemic countries, no clear screening program is established at diagnosis for patients with acute leukemia (AL). the primary endpoint of this study was to establish the prevalence of LTBI in patients with a diagnosis of AL using quanti FERON (QFT)-TB. Secondarily, radiological and clinical features driving the increased risk of LTBI were evaluated. methods: QFT-TB screening was performed before induction or consolidation in all patients with AL (myeloid and lymphoid) treated at our Institution between october 2019 and august 2023. results: we accrued 62 patients, of whom 7 (11,3%) tested positive, without any symptoms or signs of active TB, and 2 (3,2%) resulted as indeterminate. all positive patients started prophylaxis with isoniazid 300 mg daily, while patients whose test was indeterminate did not receive any prophylaxis. active TB was excluded by imaging, as well as microscopic, cultural, and molecular examination on bronchoalveolar lavage if signs of any infection were detected. during the 46 months of observation, no patients developed TB reactivation. conclusions: despite the low sample size, 1/10 of our patients had prior TB exposure, hinting that LTBI could be more common than expected in italy. this finding suggests implementing TB screening in the pre-treatment setting, particularly at a time when more active treatments are becoming available also for patients ineligible for intensive chemotherapy

Adherence to antibiotic treatment guidelines and outcomes in the hospitalized elderly with different types of pneumonia

Background: Few studies evaluated the clinical outcomes of Community Acquired Pneumonia (CAP), Hospital-Acquired Pneumonia (HAP) and Health Care-Associated Pneumonia (HCAP) in relation to the adherence of antibiotic treatment to the guidelines of the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) in hospitalized elderly people (65 years or older). Methods: Data were obtained from REPOSI, a prospective registry held in 87 Italian internal medicine and geriatric wards. Patients with a diagnosis of pneumonia (ICD-9 480-487) or prescribed with an antibiotic for pneumonia as indication were selected. The empirical antibiotic regimen was defined to be adherent to guidelines if concordant with the treatment regimens recommended by IDSA/ATS for CAP, HAP, and HCAP. Outcomes were assessed by logistic regression models. Results: A diagnosis of pneumonia was made in 317 patients. Only 38.8% of them received an empirical antibiotic regimen that was adherent to guidelines. However, no significant association was found between adherence to guidelines and outcomes. Having HAP, older age, and higher CIRS severity index were the main factors associated with in-hospital mortality. Conclusions: The adherence to antibiotic treatment guidelines was poor, particularly for HAP and HCAP, suggesting the need for more adherence to the optimal management of antibiotics in the elderly with pneumonia