Massive pulmonary embolism as a rare complication of a stab in the inguinal region in a HIV-positive patient: a case report

Venous thromboembolism (VTE) is a severe preventable disease; HIV-infection represents a prothrombotic condition, because of specific factors due to the virus itself, the host response and the antiretroviral therapy. Our aim is to raise awareness of thromboembolic risk when dealing with HIV-positive patients presenting to the Emergency Department for treatment of injuries, even though small

Lenvatinib Targets PDGFR-β Pericytes and Inhibits Synergy with Thyroid Carcinoma Cells: Novel Translational Insights

Context: Pericyte populations abundantly express tyrosine kinases (eg, platelet-derived growth factor receptor-β [PDGFR-β]) and impact therapeutic response. Lenvatinib is a clinically available tyrosine kinase inhibitor that also targets PDGFR-β. Duration of therapeutic response was shorter in patients with greater disease burden and metastasis. Patients may develop drug resistance and tumor progression. Objectives: Develop a gene signature of pericyte abundance to assess with tumor aggressiveness and determine both the response of thyroid-derived pericytes to lenvatinib and their synergies with thyroid carcinoma-derived cells. Design: Using a new gene signature, we estimated the relative abundance of pericytes in papillary thyroid carcinoma (PTC) and normal thyroid (NT) TCGA samples. We also cocultured CD90+;PAX8- thyroid-derived pericytes and BRAFWT/V600E-PTC-derived cells to determine effects of coculture on paracrine communications and lenvatinib response. Results: Pericyte abundance is significantly higher in BRAFV600E-PTC with hTERT mutations and copy number alterations compared with NT or BRAFWT-PTC samples, even when data are corrected for clinical-pathologic confounders. We have identified upregulated pathways important for tumor survival, immunomodulation, RNA transcription, cell-cycle regulation, and cholesterol metabolism. Pericyte growth is significantly increased by platelet-derived growth factor-BB, which activates phospho(p)-PDGFR-β, pERK1/2, and pAKT. Lenvatinib strongly inhibits pericyte viability by down-regulating MAPK, pAKT, and p-p70S6-kinase downstream PDGFR-β. Critically, lenvatinib significantly induces higher BRAFWT/V600E-PTC cell death when cocultured with pericytes, as a result of pericyte targeting via PDGFR-β. Conclusions: This is the first thyroid-specific model of lenvatinib therapeutic efficacy against pericyte viability, which disadvantages BRAFWT/V600E-PTC growth. Assessing pericyte abundance in patients with PTC could be essential to selection rationales for appropriate targeted therapy with lenvatinib

A clinical trial of oral hyposensitization in systemic allergy to nickel.

Nickel allergy is the most common contact allergy. Some nickel-sensitive patients present systemic (cutaneous and/or digestive) symptoms related to the ingestion of high nickel-content foods, which significantly improve after a specific low nickel-content diet. The etiopathogenetic role of nickel in the genesis of systemic disorders is, furthermore, demonstrated by the relapse of previous contact lesions, appearance of widespread eczema and generalized urticaria-like lesions after oral nickel challenge test. The aim of this study is to investigate the safety and efficacy of a specific oral hyposensitization to nickel in patients with both local contact disorders and systemic symptoms after the ingestion of nickel-containing foods. Inclusion criteria for the recruitment of these patients were (other than a positive patch test) a benefit higher than 80% from a low nickel-content diet and a positive oral challenge with nickel. Based on the previous experiences, our group adopted a therapeutic protocol by using increasing oral doses of nickel sulfate associated to an elimination diet. Results have been excellent: this treatment has been effective in inducing clinical tolerance to nickel-containing foods, with a low incidence of side effects (gastric pyrosis, itching erythema)

Clinical and quality of life assessment in patients with latex allergy during COVID-19 pandemic: Possible protective role of continuous latex immunotherapy

Introduction: During COVID-19 pandemic, the massive use of Personal Protective Equipment could provoke severe adverse reactions in latex allergy patients and could negatively affect their quality of life. Methods: Trough a survey the study aimed: (a) to evaluate the incidence of allergic reactions in patients with latex allergy during the SARS-CoV-2 pandemic; (b) to evaluate the protective role of continuous latex sublingual immunotherapy (SLIT) during this period; and (c) to evaluate quality of life of natural rubber latex allergy (NRLA) patients during the pandemic. Results: 67 patients (9 males and 58 females, mean age of 45.9 +/- 11.4 years) suffering from latex allergy were included in the present study. We recorded among our patients 13 cases (34.2%) of urticarial/angioedema (U/A), 9 cases (23.6%) of respiratory symptoms (dyspnoea, shortness of breath and wheezing) and 7 cases (18.4%) of anaphylaxis. In patients who underwent continuous SLIT, we observed less cases of U/A (p < 0.001), respiratory symptoms (p < 0.001), anaphylaxis (p = 0.003), hospitalizations (p = 0.014) and a lower therapy administration. We compared the results of SF-36 questionnaire in patients who underwent continuous and not-continuous SLIT with a significance differences score between these two groups. Conclusions: Our study is the first that investigated the clinical and quality of life effects of COVID-19 pandemic in NRLA patients

Antimicrobial effects of black soldier fly and yellow mealworm fats and their impact on gut microbiota of growing rabbits

This study aimed to evaluate the in vitro antimicrobial activities of two types of insect fats extracted from black soldier fly larvae (HI, Hermetia illucens L.) and yellow mealworm larvae (TM, Tenebrio molitor L.) and their effects as dietary replacement of soybean oil (S) on cecal fermentation pattern, and fecal and cecal microbiota in rabbits. A total of 120 weaned rabbits were randomly allotted to three dietary treatments (40 rabbits/group) —a control diet (C diet) containing 1.5% of S and two experimental diets (HI diet (HID) and TM diet (TMD)), where S was totally substituted by HI or TM fats during the whole trial that lasted 41 days. Regarding the in vitro antimicrobial activities, HI and TM fats did not show any effects on Salmonella growth. Yersinia enterocolitica showed significantly lower growth when challenged with HI fats than the controls. The insect fat supplementation in rabbit diets increased the contents of the cecal volatile fatty acids when compared to the control group. A metataxonomic approach was adopted to investigate the shift in the microbial composition as a function of the dietary insect fat supplementation. The microbiotadid not show a clear separation as a function of the inclusion, even if a specific microbial signature was observed. Indeed, HI and TM fat supplementation enriched the presence of Akkermansia that was found to be correlated with NH3-N concentration. An increase in Ruminococcus, which can improve the immune response of the host, was also observed. This study confirms the potential of HI and TM fats as antibacterial feed ingredients with a positive influence on the rabbit cecal microbiota, thus supporting the possibility of including HI and TM fats in rabbit diets

Inter-familial and intra-familial phenotypic variability in three Sicilian families with Anderson-Fabry disease.

Abstract BACKGROUND: Anderson-Fabry disease (AFD) is an inborn lysosomal enzymopathy resulting from the deficient or absent activity of the lysosomal exogalactohydrolase, α-galactosidase A. This deficiency, results in the altered metabolism of glycosphingolipids which leads to their accumulation in lysosomes, thus to cellular and vascular dysfunction. To date, numerous mutations (according to recent data more than 1000 mutations) have been reported in the GLA intronic and exonic mutations. Traditionally, clinical manifestations are more severe in affected hemizygous males than in females. Nevertheless, recent studies have described severe organ dysfunction in women. THE AIM OF THE STUDY: This study reports clinical, biochemical, and molecular findings of the members of three Sicilian families. The clinical history of these patients highlights a remarkable interfamilial and intrafamilial phenotypic variability which characterizes Fabry disease relative to target organs and severity of clinical manifestations. DISCUSSION: Our findings, in agreement with previous data, report a little genotype-phenotype correlation for the disease, suggesting that the wide phenotypic variability of Anderson-Fabry disease is not completely ascribable to different gene mutations but other factors and mechanisms seem to be involved in the pathogenesis and clinical expression of the disease. Moreover, this study emphasies the importance of pedigree analysis in the family of each proband for identifying other possibly affected relatives

miRNA-126 Orchestrates an Oncogenic Program in B Cell Precursor Acute Lymphoblastic Leukemia

MicroRNA (miRNA)-126 is a known regulator of hematopoietic stem cell quiescence. We engineered murine hematopoiesis to express miRNA-126 across all differentiation stages. Thirty percent of mice developed monoclonal B cell leukemia, which was prevented or regressed when a tetracycline-repressible miRNA-126 cassette was switched off. Regression was accompanied by upregulation of cell-cycle regulators and B cell differentiation genes, and downregulation of oncogenic signaling pathways. Expression of dominant-negative p53 delayed blast clearance upon miRNA-126 switch-off, highlighting the relevance of p53 inhibition in miRNA-126 addiction. Forced miRNA-126 expression in mouse and human progenitors reduced p53 transcriptional activity through regulation of multiple p53-related targets. miRNA-126 is highly expressed in a subset of human B-ALL, and antagonizing miRNA-126 in ALL xenograft models triggered apoptosis and reduced disease burden

New Zinc-Based Active Chitosan Films: Physicochemical Characterization, Antioxidant, and Antimicrobial Properties

The improvement of the antioxidant and antimicrobial activities of chitosan (CS) films can be realized by incorporating transition metal complexes as active components. In this context, bioactive films were prepared by embedding a newly synthesized acylpyrazolonate Zn(II) complex, [Zn(QPhtBu)2(MeOH)2], into the eco-friendly biopolymer CS matrix. Homogeneous, amorphous, flexible, and transparent CS@Znn films were obtained through the solvent casting method in dilute acidic solution, using different weight ratios of the Zn(II) complex to CS and characterized by powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR), Raman, and scanning electron microscopy (SEM) techniques. The X-ray single-crystal analysis of [Zn(QPhtBu)2(MeOH)2] and the evaluation of its intermolecular interactions with a protonated glucosamine fragment through hydrogen bond propensity (HBP) calculations are reported. The effects of the different contents of the [Zn(QPhtBu)2(MeOH)2] complex on the CS biological proprieties have been evaluated, proving that the new CS@Znn films show an improved antioxidant activity, tested according to the DPPH method, with respect to pure CS, related to the concentration of the incorporated Zn(II) complex. Finally, the CS@Znn films were tried out as antimicrobial agents, showing an increase in antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus) with respect to pure CS, when detected by the agar disk-diffusion method

Age, sex, and setting in the etiology of stroke study (ASSESS): Study design and protocol

RATIONALE: Stroke etiology and risk factors vary by age, sex, setting (hospital or community-based) and by region. Identifying these differences would improve our understanding of stroke etiology, diagnosis, and treatment. AIM: The Age, Sex and Setting in the Etiology of Stroke Study (ASSESS) is a multicenter cohort study to assess differences in stroke etiology. METHODS AND DESIGN: Data from all centers will be categorized according to age, sex, setting, stroke subtypes. Centers with extensive hospital- or community-based data regarding stroke from Argentina, Australia, Canada, India, Iran, Italy, Ghana, Nigeria, Thailand, the United Kingdom and the United States have agreed to participate so far. STUDY OUTCOMES: The primary outcome includes differences in stroke etiology in study centers. The secondary outcomes include stroke incidence, risk factors, preventive strategies, and short- and long-term outcomes. CONCLUSION: ASSESS will enable comparisons of data from different regions to determine the age and sex distribution of the most common causes of stroke in each setting. This will help clinicians to tailor the assessment and treatment of stroke patients on the basis of their specific local characteristics. It will also empower stroke epidemiologists to design preventive measures by targeting the specific characteristics of each population

Mometasone Furoate in Non-Allergic Rhinitis: A Real-Life Italian Study

Background: In order to evaluate the efficacy of intranasal mometasone furoate in patients with non-allergic rhinitis (NAR), a real-life, observational, prospective study is performed. Methods: Thirty-one patients (age 18-64 years) receive intranasal (mometasone furoate, 200 mu g b.i.d. for 15 consecutive days per month for 6 consecutive months), plus isotonic nasal saline. The cytologic pattern of local inflammation, nasal airflow, through peak nasal inspiratory flow (PNIF), quality of life (QoL), through the rhinitis quality of life questionnaire (RQLQ), the sinonasal outcome test (SNOT-22), the short-form 36-item health survey (SF-36v2), and the combined symptom medication score (CSMS), and, finally, olfactory function, through Sniffin' sticks-16 identification test (SSIT-16), are evaluated at baseline and after treatment. Results: NARNE is the most frequent cytological pattern (48% of the total sample). The therapeutic response shows improvement in olfactory function and QoL. Conclusions: The results of this study confirm that intranasal mometasone furoate is an effective treatment for patients with NAR