Brain perfusion changes in beta-thalassemia.

BACKGROUND: Brain injury in hereditary hemoglobinopathies is commonly attributed to anemia-related relative hypoperfusion in terms of impaired oxygen blood supply. Supratentorial and infratentorial vascular watershed regions seem to be especially vulnerable, but data are very scarce. AIMS: We investigated a large beta-thalassemia sample with arterial spin labeling in order to characterize regional perfusion changes and their correlation with phenotype and anemia severity. METHODS: We performed a multicenter single-scanner cross-sectional 3T-MRI study analyzing non-invasively the brain perfusion in 54 transfusion-dependent thalassemia (TDT), 23 non-transfusion-dependent thalassemia (NTDT) patients and 56 Healthy Controls (HC). Age, hemoglobin levels, and cognitive functioning were recorded. RESULTS: Both TDT and NTDT patients showed globally increased brain perfusion values compared to healthy controls, while no difference was found between patient subgroups. Using age and sex as covariates and scaling the perfusion maps for the global cerebral blood flow, beta-thalassemia patients showed relative hyperperfusion in supratentorial/infratentorial watershed regions. Perfusion changes correlated with hemoglobin levels (p = 0.013) and were not observed in the less severely anemic patients (hemoglobin level > 9.5 g/dL). In the hyperperfused regions, white matter density was significantly decreased (p = 0.0003) in both patient subgroups vs. HC. In NTDT, white matter density changes correlated inversely with full-scale Intelligence Quotient (p = 0.007) while in TDT no correlation was found. CONCLUSION: Relative hyperperfusion of watershed territories represents a hemodynamic hallmark of beta-thalassemia anemia challenging previous hypotheses of brain injury in hereditary anemias. A careful management of anemia severity might be crucial for preventing structural white matter changes and subsequent long-term cognitive impairment.

Time effect of dupilumab to treat severe uncontrolled asthma in adolescents: A pilot study.

BACKGROUND: Dupilumab is a new biological drug approved for the treatment of type 2 inflammatory diseases, such as asthma. Dupilumab is a fully humanized monoclonal antibody that acts against both interleukin-4 and interleukin-13 receptors. This study evaluated the time--dependent effect of dupilumab on asthma exacerbations and quality of life in adolescents with uncontrolled severe asthma. MATERIALS AND METHODS: Five adolescents suffering from uncontrolled severe asthma and treated with dupilumab were recruited. All subjects were evaluated for 4, 12, and 24 weeks after the first dose of dupilumab. Outcome measures included lung function, fractional exhaled nitric oxide, asthma control and quality of life assessed by validated questionnaires (Asthma Control Test and Asthma Control Questionnaire). RESULTS: The quality of life improved quickly after 4 weeks of treatment and 80% of adolescents halved the dose of inhaled corticosteroids necessary to control asthma symptoms. These results were still maintained for 24 weeks after start of the therapy. None of the patients had any asthma exacerbation during the study period. CONCLUSION: Results of this study demonstrated that dupilumab was quickly effective to reduce asthma exacerbation and ameliorate quality of life in severe asthmatic adolescents.

Sensitization to nsLTP: A Retrospective Study in An Italian Pediatric Population over the Last Decade.

Background: Food allergy is common in the Mediterranean, especially concerning lipid transfer proteins (LTPs) allergy. LTPs are widespread plant food allergens in fruits, vegetables, nuts, pollen, and latex. Also, LTPs are prevalent food allergens in the Mediterranean area. They can sensitize via the gastrointestinal tract and cause a wide range of conditions: from mild reactions, such as oral allergy syndrome, to severe reactions, such as anaphylaxis. LTP allergy in the adult population is well described in the literature, concerning both the prevalence and clinical characteristics. However, there is poor knowledge about its prevalence and clinical manifestation in children living in the Mediterranean. Materials and Methods: This study, including 800 children aged from 1 to 18 years, investigated the prevalence of 8 different molecules of nonspecific LTP over time in an Italian pediatric population visited over the last 11 years. Results: About 52% of the test population was sensitized to at least one LTP molecule. For all the LTPs analyzed, sensitization increased over time. In particular, using the years 2010 through 2020 as a comparison, the major increases were observed for the LTPs of the English walnut Jug r 3, the peanut Ara h 9, and the plane tree Pla a 3 (about 50%); the increase of the LTP of the Hazelnut Cor a 8 was about 36%, and that of the LTP of the artemisia Art v 3 was approximately 30%. Conclusions: The latest evidence in the literature indicates an increase in food allergy prevalence in the general population, including children. Therefore, the present survey represents an interesting perspective about the pediatric population of the Mediterranean area, exploring the trend of LTP allergy.

Adipocyte differentiation of 3T3-L1 cells under tenofovir alafenamide, tenofovir disoproxil fumarate, and integrase strand transfer inhibitors selective challenge: an in-vitro model.

OBJECTIVE: Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral therapy (ART) medications with a good tolerability profile and a high genetic barrier to HIV drug resistance. However, several studies report significant weight gain among persons receiving INSTI-based ART regimens compared with other regimens. DESIGN: In-vitro model of adipogenesis. METHODS: We used 3T3-L1 cells to investigate the effects of the nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), alone or in combination with INSTIs: raltegravir (RAL), elvitegravir (ELV), dolutegravir (DTG), and bictegravir (BIC) on adipose differentiation. To monitor adipocyte differentiation, expression levels of PPARÉ£ and C/EBPα and the intracellular lipid accumulation by Red Oil staining were used. Furthermore, we evaluated the immunohistochemical expression of ER-TR7, a fibroblastic marker, after INSTIs treatment. RESULTS: Compared with control, INSTIs were able to increase adipogenesis, especially RAL and ELV. TAF and TDF inhibited adipogenesis alone and in combination with INSTIs. This ability was more evident when TAF was used in combination with DTG and BIC. Finally, INSTIs increased the expression of ER-TR7 compared with control and cells treated with TAF or TDF. CONCLUSION: Our data support the evidence that in-vitro challenge of 3T3-L1 cells with INSTIs is able to increase adipocytic differentiation and to drive a number of these cells toward the expression of fibroblastic features, with a different degree according to the various drugs used whereas TAF and TDF have an antagonistic role on this phenomenon.

An Overview on the Primary Factors That Contribute to Non-Allergic Asthma in Children.

The prevalence of non-allergic asthma in childhood is low, peaking in late adulthood. It is triggered by factors other than allergens, like cold and dry air, respiratory infections, hormonal changes, smoke and air pollution. In the literature, there are few studies that describe non-allergic asthma in pediatric age. Even though it is a less common disorder in kids, it is crucial to identify the causes in order to keep asthma under control, particularly in patients not responding to conventional treatments. In this review, we discuss non-IgE-mediated forms of asthma, collecting the latest research on etiopathogenesis and treatment.

Mometasone furoate nasal spray in Italian children with seasonal allergic rhinitis: a comprehensive assessment.

OBJECTIVE: Seasonal allergic rhinitis (SAR) is a common disease of childhood and is characterized by type 2 inflammation, bothersome symptoms, and impaired quality of life (QoL). Intranasal corticosteroids are effective medications in managing SAR. In addition, mometasone furoate nasal spray (MFNS) is a well-known therapeutic option. However, the literature provided no data about the effects of MFNS in European children with SAR. Thus, this study addressed this unmet requirement. METHODS: MFNS was compared to isotonic saline. Both treatments were prescribed: one drop of spray per nostril, twice a day, for 3 weeks. Nasal cytology, total symptom score (TSS), visual analogic scale concerning the parental perception of severity of symptoms, and the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) were assessed at baseline, after 7 and 21 days, and 1 month after discontinuation. RESULTS: MFNS significantly reduced eosinophil and mast cell counts, improved QoL, and relieved symptoms, as assessed by doctors and perceived by parents. These effects persisted over time, even after discontinuation. Both treatments were safe and well-tolerated. CONCLUSIONS: The present study documented that a 3-week MFNS treatment was able to significantly dampen type 2 inflammation, improve QoL, and reduce severity of symptoms in Italian children with SAR, and was safe.

Exercise-Induced Bronchoconstriction in Children.

Exercise-induced bronchoconstriction (EIB) is a transient airflow obstruction, typically 5-15 min after physical activity. The pathophysiology of EIB is related to the thermal and osmotic changes of the bronchial mucosa, which cause the release of mediators and the development of bronchoconstriction in the airways. EIB in children often causes an important limitation to physical activities and sports. However, by taking appropriate precautions and through adequate pharmacological control of the condition, routine exercise is extremely safe in children. This review aims to raise awareness of EIB by proposing an update, based on the latest studies, on pathological mechanisms, diagnosis, and therapeutic approaches in children.

SARS-CoV-2 and inflammatory responses: From mechanisms to the potential therapeutic use of intravenous immunoglobulin.

A novel coronavirus (SARS-CoV-2) is responsible for a severe acute respiratory syndrome called coronavirus disease 2019 (COVID-19). It is originated in Wuhan, China, in December 2019. Due to its extreme transmissibility with droplets and human contacts, in a few months, it has become a pandemic. Nowadays, no effective therapy is available, and the scientific community is moving to find a therapeutic choice to fight this silent enemy. Studies are ongoing on several therapeutic options, including antiviral agents, immunomodulant drugs, and immunotherapy. Due to viral features, including the ability to start an inflammatory response that seems to be the fulcrum of COVID-19 pathogenic action, immunotherapy could represent a promising alternative waiting for the vaccine. High-dose intravenous immunoglobulin (IVIg), already used in other infectious diseases, could represent an effective help. The aim of this narrative review is to reassemble the clinical experiences on the use of IVIg in COVID-19 and the rationale of its use.

Differential expression of several factors involved in placental development in normal and abnormal condition.

The placenta, a temporary organ that forms during pregnancy, is the largest fetal organ and the first to develop. It is recognized as an organ that plays a vital role as a metabolic and physical barrier in the fetoplacental unit; throughout fetal development it acts as the lungs, gut, kidneys, and liver of the fetus. When its two components, the fetal and the maternal one, successfully interact, pregnancy proceeds healthily. However, in some cases there may be pregnancy disorders, such as preeclampsia (PE) and gestational diabetes mellitus (GDM), which can lead to a different outcome for the mother and the newborn. In recent years, several studies have been conducted to try to understand how the expression of factors involved in the development of the placenta varies under pathological conditions compared with normal conditions. The purpose of this review is to summarize recent discoveries in this field.

Adherent-invasive Escherichia coli (AIEC): Cause or consequence of inflammation, dysbiosis, and rupture of cellular joints in patients with IBD?

There are many factors contributing to the development of gastrointestinal diseases, grouped into genetic, environmental, and lifestyle factors. In recent years attention has fallen on pathogens; in particular, Bacteroides fragilis, Fusobacterium nucleatum, Escherichia coli (E. coli) and Helicobacter pylori have been studied. Several points remain to be clarified, and above all, as regards the adherent-invasive E. coli strains of E. coli, one wonders if they are a cause or a consequence of the disease. In this review, we have tried to clarify some points by examining a series of recent publications regarding the involvement of the bacterium in the pathology, even if other studies are necessary.

Therapeutic effects of turmeric in several diseases: An overview.

A nutraceutical product can be defined as a substance that has a physiological benefit or provides protection against chronic diseases. The term nutraceutical is a hybrid term derived from the union of "nutrition" and "pharmaceutical". The list of studied nutraceuticals is constantly changing and reflects ongoing market developments, research and consumer interest. Spices, in addition to giving color and taste to foods, are also important nutraceutical. Spices have been an integral part of human diets and commerce for millennia but recently, the recognition of the link between health and nutrition has strengthened their importance in the food sector and sparked the interest of researchers who increasingly engage in trying to determine the mechanisms of action of spices and the countless beneficial properties attributed to them. Among the many existing spices, turmeric is one of the most studied for its antioxidant, anti-inflammatory, antibacterial and anticancer properties. The purpose of this review is to briefly summarize the fundamental characteristics of turmeric and give an overview of the use of this spice in several diseases.

Effects of curcumin and its adjuvant on TPC1 thyroid cell line.

Previous studies have demonstrated that different curcumin extracts are able to influence cell metabolic activity vitality in human papillary thyroid carcinoma TPC-1 cells. We continued the study using the most effective extract and adding other nutraceuticals such as piperine and vitamin E, in order to define the possible role of these in modulating the genetic expression of cell markers and to understand the effectiveness in modulating the regression of cancer phenotype. Cells were treated with one extract of curcumin (Naturex® Ultimate Botanical Benefits), with Piperine (Piper Longum, A.C.E.F.) and Vitamin E (Dry Vitamin E-Acetate 50% DC, BASF) alone and in combination, dissolved in the culture medium, for 48 h. Treatment with the different nutraceuticals is able to influence cell cycle regulators (cyclin D1, ß-catenin, p21, p53) and activators or inhibitors of apoptosis (BAX, pro-caspase3, Bcl-2). They are able to influence cell cycle distribution and metabolic activity vitality. The inhibitory effect of curcumin, piperine and vitamin E on cell proliferation involves different markers, and in particular inhibits ß-catenin, cyclinD1 and p53, making them candidates for a possible use in alternative therapies although further studies are needed.