Mediterranean diet effects on vascular health and serum levels of adipokines and ceramides.

BACKGROUND: A randomized clinical trial to evaluate the effect of a Mediterranean-style diet on vascular health indices such as endothelial function indices, serum lipid and ceramide plasma and some adipokine serum levels. We recruited all consecutive patients at high risk of cardiovascular diseases admitted to the Internal Medicine and Stroke Care ward at the University Hospital of Palermo between September 2017 and December 2020. MATERIALS AND METHODS: The enrolled subjects, after the evaluation of the degree of adherence to a dietary regimen of the Mediterranean-style diet, were randomised to a Mediterranean Diet (group A) assessing the adherence to a Mediterranean-style diet at each follow up visit (every three months) for the entire duration of the study (twelve months) and to a Low-fat diet (group B) with a dietary "counselling" starting every three months for the entire duration of the study (twelve months).The aims of the study were to evaluate: the effects of adherence to Mediterranean Diet on some surrogate markers of vascular damage, such as endothelial function measured by means of the reactive hyperaemia index (RHI) and augmentation index (AIX), at the 6-(T1) and 12-month (T2) follow-ups; the effects of adherence to Mediterranean Diet on the lipidaemic profile and on serum levels of ceramides at T1 and T2 follow-ups; the effects of adherence to Mediterranean Diet on serum levels of visfatin, adiponectin and resistin at the 6- and 12-month follow-ups. RESULTS: A total of 101 patients were randomised to a Mediterranean Diet style and 52 control subjects were randomised to a low-fat diet with a dietary "counselling". At the six-month follow-up (T1), subjects in the Mediterranean Diet group showed significantly lower mean serum total cholesterol levels, and significantly higher increase in reactive hyperaemia index (RHI) values compared to the low-fat diet group. Patients in the Mediterranean Diet group also showed lower serum levels of resistin and visfatin at the six-month follow-up compared to the control group, as well as higher values ​​of adiponectin, lower values of C24:0, higher values of C22:0 and higher values of the C24:0/C16:0 ratio. At the twelve-month follow-up (T2), subjects in the Mediterranean Diet group showed lower serum total cholesterol levels and lower serum LDL cholesterol levels than those in the control group. At the twelve-month follow-up, we also observed a further significant increase in the mean RHI in the Mediterranean Diet group, lower serum levels of resistin and visfatin, lower values of C24:0 and of C:18:0,and higher values of the C24:0/C16:0 ratio. DISCUSSION: The findings of our current study offer a further possible explanation with regard to the beneficial effects of a higher degree of adherence to a Mediterranean-style diet on multiple cardiovascular risk factors and the underlying mechanisms of atherosclerosis. Moreover, these findings provide an additional plausible interpretation of the results from observational and cohort studies linking high adherence to a Mediterranean-style diet with lower total mortality and a decrease in cardiovascular events and cardiovascular mortality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04873167. https://classic.clinicaltrials.gov/ct2/show/NCT04873167.

Stereotactic Radiotherapy for penile metastasis: case report and systematic literature review.

Introduction Penile metastases (PM) are a rare clinical presentation mainly related to advanced stages of disease. Considering the low incidence, an optimal treatment approach has not yet been defined; surgery, chemotherapy, and radiotherapy are different options used in the vast majority with palliative intent. The advances in modern RT can represent an innovative tool in PM management and a curative option. This paper aims to report the case of a PM patient treated with Stereotactic Body Radiotherapy (SBRT) and perform a systematic literature review of current evidence on the RT approach to PM. Case report We reported the case of an 80-year-old patient with PM from primary bladder cancer. Following the surgical approach for the primary tumor, evidence of PM was shown, and the patient was admitted to SBRT treatment on PM after an adjuvant RT course on the pelvis. A 25 Gy in 5 fractions SBRT treatment was performed, and a complete clinical response was shown at the first follow-up. Methods A Pubmed/MEDLINE and Embase systematic review was carried out. The search strategy terms were [('penile metastasis'/exp OR 'penile metastasis' OR (penile AND ('metastasis'/exp OR metastasis))) AND ('radiotherapy'/exp OR radiotherapy)] and only original articles up to the 24.10.2023 were considered. Results A total of 174 studies were obtained using the previously mentioned search strategy, and the analysis was performed on 15 papers obtained following the complete selection process. All reported evidence was focused on the palliative approach of PM showing good results in terms of symptom control. Discussion The potential role of modern RT in the management of PM has yet to be defined. The reported case showed the feasibility and the clinical impact of SBRT in PM treatment.

Biodistribution Assessment of a Novel 68Ga-Labeled Radiopharmaceutical in a Cancer Overexpressing CCK2R Mouse Model: Conventional and Radiomics Methods for Analysis.

The aim of the present study consists of the evaluation of the biodistribution of a novel 68Ga-labeled radiopharmaceutical, [68Ga]Ga-NODAGA-Z360, injected into Balb/c nude mice through histopathological analysis on bioptic samples and radiomics analysis of positron emission tomography/computed tomography (PET/CT) images. The 68Ga-labeled radiopharmaceutical was designed to specifically bind to the cholecystokinin receptor (CCK2R). This receptor, naturally present in healthy tissues such as the stomach, is a biomarker for numerous tumors when overexpressed. In this experiment, Balb/c nude mice were xenografted with a human epidermoid carcinoma A431 cell line (A431 WT) and overexpressing CCK2R (A431 CCK2R+), while controls received a wild-type cell line. PET images were processed, segmented after atlas-based co-registration and, consequently, 112 radiomics features were extracted for each investigated organ / tissue. To confirm the histopathology at the tissue level and correlate it with the degree of PET uptake, the studies were supported by digital pathology. As a result of the analyses, the differences in radiomics features in different body districts confirmed the correct targeting of the radiopharmaceutical. In preclinical imaging, the methodology confirms the importance of a decision-support system based on artificial intelligence algorithms for the assessment of radiopharmaceutical biodistribution.

Paraneoplastic Cerebellar Degeneration Associated with Breast Cancer: A Case Report and a Narrative Review.

Paraneoplastic neurological syndromes (PNSs) are an uncommon complication of cancer, affecting nearby 1/10,000 subjects with a tumour. PNSs can involve all the central and peripheral nervous systems, the muscular system, and the neuromuscular junction, causing extremely variable symptomatology. The diagnosis of the paraneoplastic disease usually precedes the clinical manifestations of cancer, making an immediate recognition of the pathology crucial to obtain a better prognosis. PNSs are autoimmune diseases caused by the expression of common antigens by the tumour and the nervous system. Specific antibodies can help clinicians diagnose them, but unfortunately, they are not always detectable. Immunosuppressive therapy and the treatment of cancer are the cornerstones of therapy for PNSs. This paper reports a case of PNSs associated with breast tumours and focuses on the most common paraneoplastic neurological syndromes. We report a case of a young female with a clinical syndrome of the occurrence of rigidity in the right lower limb with postural instability with walking supported and diplopia, with a final diagnosis of paraneoplastic cerebellar degeneration and seronegative rigid human syndrome associated with infiltrating ductal carcinoma of the breast.

Recent Developments in Nanoparticle Formulations for Resveratrol Encapsulation as an Anticancer Agent.

Resveratrol is a polyphenolic compound that has gained considerable attention in the past decade due to its multifaceted therapeutic potential, including anti-inflammatory and anticancer properties. However, its anticancer efficacy is impeded by low water solubility, dose-limiting toxicity, low bioavailability, and rapid hepatic metabolism. To overcome these hurdles, various nanoparticles such as organic and inorganic nanoparticles, liposomes, polymeric nanoparticles, dendrimers, solid lipid nanoparticles, gold nanoparticles, zinc oxide nanoparticles, zeolitic imidazolate frameworks, carbon nanotubes, bioactive glass nanoparticles, and mesoporous nanoparticles were employed to deliver resveratrol, enhancing its water solubility, bioavailability, and efficacy against various types of cancer. Resveratrol-loaded nanoparticle or resveratrol-conjugated nanoparticle administration exhibits excellent anticancer potency compared to free resveratrol. This review highlights the latest developments in nanoparticle-based delivery systems for resveratrol, focusing on the potential to overcome limitations associated with the compound's bioavailability and therapeutic effectiveness.

Relationship Between Mediterranean Diet, Cardiovascular Risk Factors, and Meningiomas: A Retrospective Study.

BACKGROUND/AIM: The Mediterranean diet may be deemed as the best combination of nutrients to play a protective role against cancer. Previous studies have demonstrated how a healthy lifestyle, and the adherence to the Mediterranean diet might affect the onset of most common cancers, focusing less on their relationship with central nervous system (CNS) tumoral pathologies, especially benign ones, such as meningiomas. PATIENTS AND METHODS: This was a retrospective multicenter study, involving 52 patients who underwent meningioma resection and a group of 100 subjects not affected by brain tumors. This preliminary study aimed to investigate whether the non-adherence to a dietary pattern, such as the Mediterranean diet, and pre-existing cardiovascular risk factors can affect the onset of cranial meningiomas. RESULTS: Patients affected by meningioma had a significantly lower mean Mediterranean Diet Score (MDS), and a similar distribution of the main cardiovascular risk factors. CONCLUSION: A larger patient cohort is required to corroborate our findings. However, these promising results open up a new avenue for further exploration of the role of the Mediterranean diet in the development of meningiomas.

Epidemiology and geographic clustering of Erdheim-Chester disease in Italy and France.

This geoepidemiological study, performed in Italy and France, shows that Erdheim-Chester disease is increasingly diagnosed and cases cluster in specific geographic areas, namely southern Italy and central France. Disease frequency inversely correlates with the Human Development Index.

Role of Mediterranean diet in the development and recurrence of meningiomas: a narrative review.

Several studies through the years have proven how an unhealthy nutrition, physical inactivity, sedentary lifestyle, obesity, and smoking represent relevant risk factors in cancer genesis. This study aims to provide an overview about the relationship between meningiomas and food assumption in the Mediterranean diet and whether it can be useful in meningioma prevention or it, somehow, can prevent their recurrence. The authors performed a wide literature search in PubMed and Scopus databases investigating the presence of a correlation between Mediterranean diet and meningiomas. The following MeSH and free text terms were used: "Meningiomas" AND "Diet" and "Brain tumors" AND "diet." Databases' search yielded a total of 749 articles. After duplicate removal, an abstract screening according to the eligibility criteria has been performed and 40 articles were selected. Thirty-one articles were excluded because they do not meet the inclusion criteria. Finally, a total of 9 articles were included in this review. It is widely established the key and protective role that a healthy lifestyle and a balanced diet can have against tumorigenesis. Nevertheless, studies focusing exclusively on the Mediterranean diet are still lacking. Thus, multicentric and/or prospective, randomized studies are mandatory to better assess and determine the impact of food assumptions in meningioma involvement.

The Natriuretic Peptide System: A Single Entity, Pleiotropic Effects.

In the modern scientific landscape, natriuretic peptides are a complex and interesting network of molecules playing pleiotropic effects on many organs and tissues, ensuring the maintenance of homeostasis mainly in the cardiovascular system and regulating the water-salt balance. The characterization of their receptors, the understanding of the molecular mechanisms through which they exert their action, and the discovery of new peptides in the last period have made it possible to increasingly feature the physiological and pathophysiological role of the members of this family, also allowing to hypothesize the possible settings for using these molecules for therapeutic purposes. This literature review traces the history of the discovery and characterization of the key players among the natriuretic peptides, the scientific trials performed to ascertain their physiological role, and the applications of this knowledge in the clinical field, leaving a glimpse of new and exciting possibilities for their use in the treatment of diseases.

Metabolic memory in diabetic foot syndrome (DFS): MICRO-RNAS, single nucleotide polymorphisms (SNPs) frequency and their relationship with indices of endothelial function and adipo-inflammatory dysfunction.

BACKGROUND: Diabetic foot is a significant cause of morbidity in diabetic patients, with a rate that is approximately twice that of patients without foot ulcers. "Metabolic memory" represents the epigenetic changes induced by chronic hyperglycaemia, despite the correction of the glucose levels themselves. These epigenetic modifications appear to perpetuate the damage caused by persistently elevated glucose levels even in their absence, acting at various levels, mostly affecting the molecular processes of diabetic ulcer healing. METHODS: The aim of our cross-sectional study was to analyse a cohort of patients with diabetes with and without lower limb ulcers. We examined the effects of epigenetic changes on miRNA 126, 305, and 217 expression and the frequency of the SNPs of genes encoding inflammatory molecules (e.g., IL-6 and TNF-alpha) and their correlations with serum levels of proangiogenic molecules (e.g., ENOS, VEGF and HIF-1alpha) and several adipokines as well as with endothelial dysfunction, assessed noninvasively by reactive hyperaemia peripheral artery tonometry. Between March 2021 and June 2022, 110 patients were enrolled into the study: 50 diabetic patients with diabetic foot injuries, 40 diabetic patients without ulcerative complications and 20 nondiabetic patients as the control group. RESULTS: Diabetic subjects with lower limb ulcerative lesions exhibited higher levels of inflammatory cytokines, such as VEGF (191.40 ± 200 pg/mL vs. 98.27 ± 56.92 pg/mL vs. 71.01 ± 52.96 pg/mL; p = 0.22), HIF-1alpha (40.18 ± 10.80 ng/mL vs. 33.50 ± 6.16 ng/mL vs. 33.85 ± 6.84 ng/mL; p = 0.10), and Gremlin-1 (1.72 ± 0.512 ng/mL vs. 1.31 ± 0.21 ng/mL vs. 1.11 ± 0.19 ng/mL; p < 0.0005), than those without lower limb ulcers and healthy controls. Furthermore, we observed that miR-217-5p and miR-503-5p were 2.19-fold (p < 0.05) and 6.21-fold (p = 0.001) more highly expressed in diabetic foot patients than in healthy controls, respectively. Additionally, diabetic patients without lower limb ulcerative complications showed 2.41-fold (p = 0) and 2.24-fold (p = 0.029) higher expression of miR-217-5p and miR-503-5p, respectively, than healthy controls. Finally, diabetic patients with and without ulcerative complications of the lower limbs showed higher expression of the VEGFC2578A CC polymorphism (p = 0.001) and lower expression of the VEGFC2578A AC polymorphism (p < 0.005) than the healthy control population. We observed a significant increase in Gremlin-1 levels in patients with diabetic foot, suggesting that this inflammatory adipokine may serve as a predictive marker for the diagnosis of diabetic foot. CONCLUSIONS: Our results highlighted that patients with diabetic foot showed predominant expression of the VEGF C2578A CC polymorphism and reduced expression of the AC allele. Additionally, we found an overexpression of miR-217-5p and miR-503-5p in diabetic patients with and without diabetic foot syndrome compared with healthy controls. These results align with those reported in the literature, in which the overexpression of miR-217-5p and miR-503-5p in the context of diabetic foot is reported. The identification of these epigenetic modifications could therefore be helpful in the early diagnosis of diabetic foot and the treatment of risk factors. However, further studies are necessary to confirm this hypothesis.

An Overview of In Vitro Assays of 64Cu-, 68Ga-, 125I-, and 99mTc-Labelled Radiopharmaceuticals Using Radiometric Counters in the Era of Radiotheranostics.

Radionuclides are unstable isotopes that mainly emit alpha (α), beta (ß) or gamma (γ) radiation through radiation decay. Therefore, they are used in the biomedical field to label biomolecules or drugs for diagnostic imaging applications, such as positron emission tomography (PET) and/or single-photon emission computed tomography (SPECT). A growing field of research is the development of new radiopharmaceuticals for use in cancer treatments. Preclinical studies are the gold standard for translational research. Specifically, in vitro radiopharmaceutical studies are based on the use of radiopharmaceuticals directly on cells. To date, radiometric ß- and γ-counters are the only tools able to assess a preclinical in vitro assay with the aim of estimating uptake, retention, and release parameters, including time- and dose-dependent cytotoxicity and kinetic parameters. This review has been designed for researchers, such as biologists and biotechnologists, who would like to approach the radiobiology field and conduct in vitro assays for cellular radioactivity evaluations using radiometric counters. To demonstrate the importance of in vitro radiopharmaceutical assays using radiometric counters with a view to radiogenomics, many studies based on 64Cu-, 68Ga-, 125I-, and 99mTc-labeled radiopharmaceuticals have been revised and summarized in this manuscript.

Anti-Arthritic and Anti-Cancer Activities of Polyphenols: A Review of the Most Recent In Vitro Assays.

Polyphenols have gained widespread attention as they are effective in the prevention and management of various diseases, including cancer diseases (CD) and rheumatoid arthritis (RA). They are natural organic substances present in fruits, vegetables, and spices. Polyphenols interact with various kinds of receptors and membranes. They modulate different signal cascades and interact with the enzymes responsible for CD and RA. These interactions involve cellular machinery, from cell membranes to major nuclear components, and provide information on their beneficial effects on health. These actions provide evidence for their pharmaceutical exploitation in the treatment of CD and RA. In this review, we discuss different pathways, modulated by polyphenols, which are involved in CD and RA. A search of the most recent relevant publications was carried out with the following criteria: publication date, 2012-2022; language, English; study design, in vitro; and the investigation of polyphenols present in extra virgin olive, grapes, and spices in the context of RA and CD, including, when available, the underlying molecular mechanisms. This review is valuable for clarifying the mechanisms of polyphenols targeting the pathways of senescence and leading to the development of CD and RA treatments. Herein, we focus on research reports that emphasize antioxidant properties.

Molecular Pathogenesis of Central and Peripheral Nervous System Complications in Anderson-Fabry Disease.

Fabry disease (FD) is a recessive monogenic disease linked to chromosome X due to more than two hundred mutations in the alfa-galactosidase A (GLA) gene. Modifications of the GLA gene may cause the progressive accumulation of globotriaosylceramide (Gb3) and its deacylated form, globotriasylsphingosine (lyso-Gb3), in lysosomes of several types of cells of the heart, kidneys, skin, eyes, peripheral and central nervous system (not clearly and fully demonstrated), and gut with different and pleiotropic clinical symptoms. Among the main symptoms are acroparesthesias and pain crisis (involving the peripheral nervous system), hypohidrosis, abdominal pain, gut motility abnormalities (involving the autonomic system), and finally, cerebrovascular ischemic events due to macrovascular involvement (TIA and stroke) and lacunar strokes and white matter abnormalities due to a small vessel disease (SVS). Gb3 lysosomal accumulation causes cytoplasmatic disruption and subsequent cell death. Additional consequences of Gb3 deposits are inflammatory processes, abnormalities of leukocyte function, and impaired trafficking of some types of immune cells, including lymphocytes, monocytes, CD8+ cells, B cells, and dendritic cells. The involvement of inflammation in AFD pathogenesis conflicts with the reported poor correlation between CRP levels as an inflammation marker and clinical scores such as the Mainz Severity Score Index (MSSI). Also, some authors have suggested an autoimmune reaction is involved in the disease's pathogenetic mechanism after the α-galactosidase A deficiency. Some studies have reported a high degree of neuronal apoptosis inhibiting protein as a critical anti-apoptotic mediator in children with Fabry disease compared to healthy controls. Notably, this apoptotic upregulation did not change after treatment with enzymatic replacement therapy (ERT), with a further upregulation of the apoptosis-inducing factor after ERT started. Gb3-accumulation has been reported to increase the degree of oxidative stress indexes and the production of reactive oxygen species (ROS). Lipids and proteins have been reported as oxidized and not functioning. Thus, neurological complications are linked to different pathogenetic molecular mechanisms. Progressive accumulation of Gb3 represents a possible pathogenetic event of peripheral nerve involvement. In contrast, central nervous system participation in the clinical setting of cerebrovascular ischemic events seems to be due to the epitheliopathy of Anderson-Fabry disease with lacunar lesions and white matter hyperintensities (WMHs). In this review manuscript, we revised molecular mechanisms of peripheral and central neurological complications of Anderson-Fabry Disease. The management of Fabry disease may be improved by the identification of biomarkers that reflect the clinical course, severity, and progression of the disease. Intensive research on biomarkers has been conducted over the years to detect novel markers that may potentially be used in clinical practice as a screening tool, in the context of the diagnostic process and as an indicator of response to treatment. Recent proteomic or metabolomic studies are in progress, investigating plasma proteome profiles in Fabry patients: these assessments may be useful to characterize the molecular pathology of the disease, improve the diagnostic process, and monitor the response to treatment.

Olive Oil in the Mediterranean Diet and Its Biochemical and Molecular Effects on Cardiovascular Health through an Analysis of Genetics and Epigenetics.

Human nutrition is a relatively new science based on biochemistry and the effects of food constituents. Ancient medicine considered many foods as remedies for physical performance or the treatment of diseases and, since ancient times, especially Greek, Asian and pre-Christian cultures similarly thought that they had beneficial effects on health, while others believed some foods were capable of causing illness. Hippocrates described the food as a form of medicine and stated that a balanced diet could help individuals stay healthy. Understanding molecular nutrition, the interaction between nutrients and DNA, and obtaining specific biomarkers could help formulate a diet in which food is not only a food but also a drug. Therefore, this study aims to analyze the role of the Mediterranean diet and olive oil on cardiovascular risk and to identify their influence from the genetic and epigenetic point of view to understand their possible protective effects.

Pathogenesis and Molecular Mechanisms of Anderson-Fabry Disease and Possible New Molecular Addressed Therapeutic Strategies.

Anderson-Fabry disease (AFD) is a rare disease with an incidenceof approximately 1:117,000 male births. Lysosomal accumulation of globotriaosylceramide (Gb3) is the element characterizing Fabry disease due to a hereditary deficiency α-galactosidase A (GLA) enzyme. The accumulation of Gb3 causes lysosomal dysfunction that compromises cell signaling pathways. Deposition of sphingolipids occurs in the autonomic nervous system, dorsal root ganglia, kidney epithelial cells, vascular system cells, and myocardial cells, resulting in organ failure. This manuscript will review the molecular pathogenetic pathways involved in Anderson-Fabry disease and in its organ damage. Some studies reported that inhibition of mitochondrial function and energy metabolism plays a significant role in AFD cardiomyopathy and in kidney disease of AFD patients. Furthermore, mitochondrial dysfunction has been reported as linked to the dysregulation of the autophagy-lysosomal pathway which inhibits the mechanistic target of rapamycin kinase (mTOR) mediated control of mitochondrial metabolism in AFD cells. Cerebrovascular complications due to AFD are caused by cerebral micro vessel stenosis. These are caused by wall thickening resulting from the intramural accumulation of glycolipids, luminal occlusion or thrombosis. Other pathogenetic mechanisms involved in organ damage linked to Gb3 accumulation are endocytosis and lysosomal degradation of endothelial calcium-activated intermediate-conductance potassium ion channel 3.1 (KCa3.1) via a clathrin-dependent process. This process represents a crucial event in endothelial dysfunction. Several studies have identified the deacylated form of Gb3, globotriaosylsphingosine (Lyso-Gb3), as the main catabolite that increases in plasma and urine in patients with AFD. The mean concentrations of Gb3 in all organs and plasma of Galactosidase A knockout mice were significantly higher than those of wild-type mice. The distributions of Gb3 isoforms vary from organ to organ. Various Gb3 isoforms were observed mainly in the kidneys, and kidney-specific Gb3 isoforms were hydroxylated. Furthermore, the action of Gb3 on the KCa3.1 channel suggests a possible contribution of this interaction to the Fabry disease process, as this channel is expressed in various cells, including endothelial cells, fibroblasts, smooth muscle cells in proliferation, microglia, and lymphocytes. These molecular pathways could be considered a potential therapeutic target to correct the enzyme in addition to the traditional enzyme replacement therapies (ERT) or drug chaperone therapy.

Ketogenic Diet, Physical Activity, and Hypertension-A Narrative Review.

Several studies link cardiovascular diseases (CVD) with unhealthy lifestyles (unhealthy dietary habits, alcohol consumption, smoking, and low levels of physical activity). Therefore, the strong need for CVD prevention may be pursued through an improved control of CVD risk factors (impaired lipid and glycemic profiles, high blood pressure, and obesity), which is achievable through an overall intervention aimed to favor a healthy lifestyle. Focusing on diet, different recommendations emphasize the need to increase or avoid consumption of entire classes of food, with only partly known and only partly foreseeable consequences on the overall level of health. In recent years, the ketogenic diet (KD) has been proposed to be an effective lifestyle intervention for metabolic syndrome, and although the beneficial effects on weight loss and glucose metabolism seems to be well established, the effects of a prolonged KD on the ability to perform different types of exercise and the influence of KD on blood pressure (BP) levels, both in normotensives and in hypertensives, are not so well understood. The objective of this review is to analyze, on the basis of current evidence, the relationship between KD, regular physical activity, and BP.

Effects of intravenous furosemide plus small-volume hypertonic saline solutions on markers of heart failure.

AIMS: We sought to compare the effects of furosemide + hypertonic saline solution (HSS) treatment in patients with acute decompensated heart failure in comparison with furosemide alone and the response in a compensated state after an acute saline load with regard to serum levels of heart failure biomarkers. METHODS AND RESULTS: We enrolled 141 patients with acute decompensated heart failure with reduced ejection fraction admitted to our Internal Medicine ward from March 2017 to November 2019. A total of 73 patients were randomized to treatment with i.v. high-dose furosemide plus HSS, whereas 68 patients were randomized to i.v. high-dose furosemide alone. Patients treated with furosemide plus HSS compared with controls treated with furosemide alone showed a comparable degree of reduction in the serum levels of interleukin (IL)-6, soluble suppression of tumorigenicity 2 (sST2), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the 'between-group' analysis. Nevertheless, patients treated with high-dose furosemide + HSS showed significantly higher absolute delta values of IL-6 (2.3 ± 1.2 vs. 1.7 ± 0.9, P < 0.0005, and 2.0 ± 0.8 vs. 1.85 ± 1.1, P = 0.034), sST2 (41.2 ± 8.6 vs. 27.9 ± 7.6, P < 0.0005, and 37.1 ± 6.6 vs. 28.4 ± 6.7, P < 0.0005), high-sensitivity troponin T (0.03 ± 0.02 vs. 0.02 ± 0.01, P = 0.001, and 0.03 ± 0.02 vs. 0.02 ± 0.01, P = 0.009), NT-proBNP (7237 ± 7931 vs. 3244 ± 4159, P < 0.005, and 5381 ± 4829 vs. 4466 ± 4332, P = 0.004), and galectin-3 (15.7 ± 3.2 ng/mL vs. 11.68 ± 1.9 ng/mL, P < 0.0005, and 16.7 ± 3.9 ng/mL vs. 11.8 ± 2.4 ng/mL, P < 0.0005) than patients treated with furosemide alone. After acute saline load, patients treated with i.v. furosemide + HSS in comparison with subjects treated with furosemide alone showed a significantly lower increase in the serum concentrations of IL-6 (-0.26 ± 0.42 pg/mL vs. -1.43 ± 0.86 pg/mL, P < 0.0005), high-sensitivity troponin T (0 vs. -0.02 ± 0.02 ng/mL, P < 0.0005), sST2 (-8.5 ± 5.9 ng/mL vs. -14.6 ± 6.2 ng/mL, P < 0.0005), galectin-3 (-2.1 ± 1.5 ng/mL vs. -7.1 ± 3.6 ng/mL, P < 0.0005), and NT-proBNP (77 ± 1373 vs. -1706 ± 2259 pg/mL, P < 0.0005). CONCLUSIONS: Our findings concerning a comparable degree of reduction in the serum levels of three cardinal biomarkers indicate that a reduction in serum heart failure markers is not linked to the higher degree of congestion relief with a more rapid achievement of a clinical compensation state. This issue may have possible benefits on clinical practice concerning its therapeutic effects over and beyond the simple amelioration of clinical congestion signs and symptoms. Nevertheless, our findings of higher delta values after treatment with i.v. furosemide plus HSS indicate a possible higher efficacy by means of modulation of the stretching and fibrosis mechanisms.

A case of infective colitis due to Yersinia enterocolitica complicated by microliver abscesses mimicking multiple liver occult metastases: a case report.

BACKGROUND: We report an unusual case of infective colitis by Yersinia enterocolitica complicated by microliver abscesses mimicking multiple liver metastases in a 79 yr old female without any risk factors for bacteriaemia by this pathogen. CASE PRESENTATION: The patient was admitted to the Internal Medicine with Stroke Care ward of University Policlinico "P. Giaccone" in Palermo because of the appearance of diarrhoea. After the antimicrobial treatment for infective colitis, the clinicians observed a persistently increased white blood cells (WBC) count and multiple hepatic lesions; after having excluded any neoplastic disease and inflammatory bowel disease (IBD), blood cultures positive for Y. enterocolitica allowed to establish the final diagnosis was infective micro liver abscesses consequent to infective colitis due to Y. enterocolitica, which were successfully treated with cefixime and doxycycline. CONCLUSIONS: This case report should make clinicians reflect on how complex the differential diagnosis between microliver abscesses and metastasis could be and the possibility of bacteriaemia by Y. enterocolitica even without iron overload conditions.

Non-coding RNAs and other determinants of neuroinflammation and endothelial dysfunction: regulation of gene expression in the acute phase of ischemic stroke and possible therapeutic applications.

Ischemic stroke occurs under a variety of clinical conditions and has different pathogeneses, resulting in necrosis of brain parenchyma. Stroke pathogenesis is characterized by neuroinflammation and endothelial dysfunction. Some of the main processes triggered in the early stages of ischemic damage are the rapid activation of resident inflammatory cells (microglia, astrocytes and endothelial cells), inflammatory cytokines, and translocation of intercellular nuclear factors. Inflammation in stroke includes all the processes mentioned above, and it consists of either protective or detrimental effects concerning the "polarization" of these processes. This polarization comes out from the interaction of all the molecular pathways that regulate genome expression: the epigenetic factors. In recent years, new regulation mechanisms have been cleared, and these include non-coding RNAs, adenosine receptors, and the activity of mesenchymal stem/stromal cells and microglia. We reviewed how long non-coding RNA and microRNA have emerged as an essential mediator of some neurological diseases. We also clarified that their roles in cerebral ischemic injury may provide novel targets for the treatment of ischemic stroke. To date, we do not have adequate tools to control pathophysiological processes associated with stroke. Our goal is to review the role of non-coding RNAs and innate immune cells (such as microglia and mesenchymal stem/stromal cells) and the possible therapeutic effects of their modulation in patients with acute ischemic stroke. A better understanding of the mechanisms that influence the "polarization" of the inflammatory response after the acute event seems to be the way to change the natural history of the disease.