Obesità post-neurochirurgia ipotalamica

SommarioLe malattie ipotalamiche e il loro trattamento chirurgico possono determinare un rapido incremento ponderale nei primi sei mesi, seguito da stabilizzazione del peso in un'elevata percentuale (40–80%) di pazienti. Gli interventi sullo stile di vita e i farmaci hanno fornito risultati insoddisfacenti. Maggiori benefici sono stati riportati con gli analoghi del glucagon like peptide-1 o con la chirurgia bariatrica ma gli studi ad oggi disponibili sono di bassa numerosità e di breve durata

The Past, Present, and Future of Non-Viral CAR T Cells

Adoptive transfer of chimeric antigen receptor (CAR) T lymphocytes is a powerful technology that has revolutionized the way we conceive immunotherapy. The impressive clinical results of complete and prolonged response in refractory and relapsed diseases have shifted the landscape of treatment for hematological malignancies, particularly those of lymphoid origin, and opens up new possibilities for the treatment of solid neoplasms. However, the widening use of cell therapy is hampered by the accessibility to viral vectors that are commonly used for T cell transfection. In the era of messenger RNA (mRNA) vaccines and CRISPR/Cas (clustered regularly interspaced short palindromic repeat-CRISPR-associated) precise genome editing, novel and virus-free methods for T cell engineering are emerging as a more versatile, flexible, and sustainable alternative for next-generation CAR T cell manufacturing. Here, we discuss how the use of non-viral vectors can address some of the limitations of the viral methods of gene transfer and allow us to deliver genetic information in a stable, effective and straightforward manner. In particular, we address the main transposon systems such as Sleeping Beauty (SB) and piggyBac (PB), the utilization of mRNA, and innovative approaches of nanotechnology like Lipid-based and Polymer-based DNA nanocarriers and nanovectors. We also describe the most relevant preclinical data that have recently led to the use of non-viral gene therapy in emerging clinical trials, and the related safety and efficacy aspects. We will also provide practical considerations for future trials to enable successful and safe cell therapy with non-viral methods for CAR T cell generation

Mycobiota composition and changes across pregnancy in patients with gestational diabetes mellitus (GDM)

The gut mycobiota has never been studied either during pregnancy or in patients with gestational diabetes (GDM). This study aimed to analyze the fecal mycobiota of GDM patients during the second (T2) and third (T3) trimester of pregnancy and to compare it with the mycobiota of pregnant normoglycemic women (controls). Forty-one GDM patients and 121 normoglycemic women were studied. GDM mycobiota was composed almost exclusively by the Ascomycota phylum; Basidiomicota accounted for 43% of the relative frequency of the controls. Kluyveromyces (p < 0.001), Metschnikowia (p < 0.001), and Pichia (p < 0.001) showed a significantly higher frequency in GDM patients, while Saccharomyces (p = 0.019), were more prevalent in controls. From T2 to T3, a reduction in fungal alpha diversity was found in GDM patients, with an increase of the relative frequency of Candida, and the reduction of some pro-inflammatory taxa. Many associations between fungi and foods and nutrients were detected. Finally, several fungi and bacteria showed competition or co-occurrence. Patients with GDM showed a predominance of fungal taxa with potential inflammatory effects when compared to normoglycemic pregnant women, with a marked shift in their mycobiota during pregnancy, and complex bacteria-fungi interactions

Anti-CD117 CAR T cells incorporating a safety switch eradicate human acute myeloid leukemia and hematopoietic stem cells

Discrimination between hematopoietic stem cells and leukemic stem cells remains a major challenge for acute myeloid leukemia immunotherapy. CAR T cells specific for the CD117 antigen can deplete malignant and healthy hematopoietic stem cells before consolidation with allogeneic hematopoietic stem cell transplantation in absence of cytotoxic conditioning. Here we exploit non-viral technology to achieve early termination of CAR T cell activity to prevent incoming graft rejection. Transient expression of an anti-CD117 CAR by mRNA conferred T cells the ability to eliminate CD117+ targets in vitro and in vivo. As an alternative approach, we used a Sleeping Beauty transposon vector for the generation of CAR T cells incorporating an inducible Caspase 9 safety switch. Stable CAR expression was associated with high proportion of T memory stem cells, low levels of exhaustion markers, and potent cellular cytotoxicity. Anti-CD117 CAR T cells mediated depletion of leukemic cells and healthy hematopoietic stem cells in NSG mice reconstituted with human leukemia or CD34+ cord blood cells, respectively, and could be terminated in vivo. The use of a non-viral technology to control CAR T cell pharmacokinetic properties is attractive for a first-in-human study in patients with acute myeloid leukemia prior to hematopoietic stem cell transplantation

Strategies for Reducing Salt and Sugar Intakes in Individuals at Increased Cardiometabolic Risk

Non-communicable diseases (NCDs) are the first causes of death worldwide. Reduction in the dietary intake of salt and sugars is important lifestyle advice that is useful for NCD prevention. However, the simple recommendations of reducing salt and sugars by healthcare professionals are often ineffective; innovative strategies are therefore necessary. This review aimed at describing the current knowledge about the strategies to reduce dietary salt and sugar intake, including both strategies for the food industry to reduce the salt or sugar of its products and recommendations for health professionals in a clinical context, such as the replacement with substitutes in foods, the gradual reduction to allow a progressive consumer adaptation towards less intense taste, and the different spatial distribution of tastants within the food matrix with taste intensity enhancement. In addition, the cross-modal interaction between two or more different sensory modalities as an innovative strategy for enhancing sweetness and saltiness perception was described. Finally, the dietary tips for salt and sugar reduction were summarized in order to create a comprehensive guide of dietary advices for healthcare professionals for optimizing the management of patients at increased cardiometabolic risk