Hormonal responses to water deficit in cambial tissues of Populus alba L.

Changes of the concentration of bioactive gibberellins and abscisic acid in the cambial region of white poplar (Populus alba L.) were investigated in one-year-old plants, to highlight how these phytohormone signals are modulated in response to water deficit. Plants were cultivated in pots outdoor and, at the time of maximum cambial growth (T0), irrigation was withdrawn for 8 d, inducing a mild water deficit, thus mimicking a condition that is recurrent in mediterranean climates when white poplar attains its maximum growth rate. The water deficit was suspended by resuming irrigation (Tmax), throughout a recovery period of two weeks (Trec). Cambial tissues were sampled at T0, Tmax and Trec. Significant changes of leaf and stem relative water content, leaf water potential, stomatal conductance, transpiration, carbon assimilation, stem shrinkage and leaf number were induced by soil water shortage, which also negatively affected cambium development. Nevertheless, these responses were almost fully reversed following the resumption of irrigation. Water deficit induced the accumulation of large amounts of abscisic acid in cambial tissues, but the hormone was brought back to pre-stress levels after the recovery period. With regard to bioactive gibberellins, GA1 was several fold more abundant than GA4 and reached the greatest level in the plants recovering from the water status imbalance. The possible functions of gibberellins and abscisic acid in the response of cambial tissues to water deficit are discussed in view of the known physiological roles and molecular mechanisms of action of these hormonal signals

Rational Use of Monoclonal Antibodies as Therapeutic Treatment in an Oncologic Patient with Long COVID

We present the case of a 76-year-old male patient persistently infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the setting of a stage IIIC cutaneous melanoma and non-Hodgkin’s lymphoma (NHL). Due to the persistent coronavirus disease 19 (COVID-19), all cancer treatments were discontinued. Because of the worsening of his clinical state and the persistence of SARS-CoV-2 positivity for more than six months, the patient was treated with sotrovimab, which was ineffective due to resistance mutations acquired during that time. In order to resume cancer treatment and make the patient free from SARS-CoV-2, an in vitro screening of Evusheld monoclonal antibodies (tixagevumab–cilgavimab) against the viral strains isolated from the subject was performed. The promising results obtained during in vitro testing led to the authorization of the off-label use of Evusheld, which made the patient negative for SARS-CoV-2, thus, allowing him to resume his cancer treatment. This study highlights the Evusheld monoclonal antibodies’ efficacy, not only in prevention but also in successful therapy against prolonged COVID-19. Therefore, testing neutralizing monoclonal antibodies in vitro against SARS-CoV-2 mutants directly isolated from patients could provide useful information for the treatment of people affected by long COVID

Gender effect on the Relation between Diabetes and Hospitalization for Heart Failure

Aims: Cardiovascular risk among diabetic patients is at least twice as much the one for nondiabetic individuals and even greater when diabetic women are considered. Heart failure (HF) is a common unfavorable outcome of cardiovascular disease in diabetes. However, since the comparison among sexes of heart failure prevalence in diabetic patients remains limited, this study is aimed at expanding the information about this point. Methods: We have evaluated the association between diabetes and HF by reviewing the medical records of all subjects discharged from the Internal Medicine and Cardiology Units of all hospitals in the Tuscany region, Italy, during the period January 2002 through December 2008. In particular we sought concomitance of ICD-9-CM codes for diabetes and HF. Results: Patients discharged by Internal Medicine were on average older, more represented by women, and had a lesser number of individuals coded as diabetic (p < 0.05 for all). Relative risk for HF (95 % CI) was signifi cantly higher in patients with diabetes, irrespective of gender 1.39 (1.36– 1.41) in males; 1.40 (1.37–1.42) in females. When the diabetes-HF association was analyzed according to decades of age, a “horse-shoe” pattern was apparent with an increased risk in 40–59 years old in female patients discharged by Internal Medicine. Conclusions: Although there is not a diff erence in the overall HF risk between hospitalized male and female diabetic patients, women have an excess risk at perimenopausal ag

SARS-CoV-2 infection in cancer patients on active therapy after the booster dose of mRNA vaccines

The protective role against SARS-CoV-2 infection by the third booster dose of mRNA vaccines in cancer patients with solid malignancies is presently un- known. We prospectively investigated the occurrence of COVID-19 in cancer patients on active therapy after the booster vaccine dose. Methods: Cancer patients on treatment at the Center for Immuno-Oncology (CIO) of the University Hospital of Siena, Italy, and health care workers at CIO who had received a booster third dose of mRNA vaccine entered a systematic follow-up monitoring period to prospectively assess their potential risk of SARS-CoV-2 infection. Serological and microneu- tralization assay were utilized to assess levels of anti-spike IgG, and of neutralizing antibodies to the SARS-CoV-2 Wild Type, Delta and Omicron variants, respectively, after the booster dose and after negativization of the nasopharyngeal swab for those who had developed COV- ID-19. Results: Ninety cancer patients with solid tumors on active treatment (Cohort 1) and 30 health care workers (Cohort 2) underwent a booster third dose of mRNA vaccine. After the booster dose, the median value of anti-spike IgG was higher (p Z 0.009) in patients than in healthy subjects. Remarkably, 11/90 (12%) patients and 11/30 (37%) healthy subjects tested positive to SARS-CoV-2 infection during the monitoring period. Similar levels of anti-spike IgG and of neutralizing antibodies against all the investigated variants, with geometric mean titers of neutralizing antibodies against the Omicron being the lowest were detected after the booster dose and after COVID-19 in both Cohorts. Conclusions: The occurrence of SARS-CoV-2 infection we observed in a sizable proportion of booster-dosed cancer patients and in healthy subjects during the Omicron outbreak indicates that highly specific vaccines against SARS-CoV-2 variants are urgently required

Artificial Antigen Presenting Cells With Preclustered anti-CD28/-CD3/-LFA-1 Monoclonal Antibodies Are Highly Effective To Induce The Ex-Vivo Expansion Of Functional Human Antitumor T Cells

Effective adoptive T cell therapy requires the _ex vivo_ generation of functional T lymphocytes with a long lifespan _in vivo_. We evaluated _in vitro_ T cell expansion by artificial antigen presenting cells (aAPC) generated with activating (human anti-CD3), co-stimulating (human anti-CD28) and adhesion (human anti-LFA-1) monoclonal antibodies pre-clustered in microdomains (MDs) held by a liposome scaffold. The co-localization of T cell ligands in MDs and the targeting of an adhesion protein, increasing the efficiency of immunological synapse formations, represent the novelties of our system. These aAPCs allowed increased expansion of polyclonal CD4^+^ and CD8^+^ T cells and of tumor antigen-specific CD8^+^ T cells compared to anti-CD28- and anti-CD3-coated microbeads and to immobilized anti-CD3. These aAPCs allowed the generation of T cells displaying an immunophenotype consistent with long-term _in vivo_ persistence, without increasing the frequency of regulatory T cells. Finally, our aAPCs proved to be suitable for large scale T cell expansion required in immunotherapy trials

An Expanded Peripheral T Cell Population to a Cytotoxic T Lymphocyte (Ctl)-Defined, Melanocyte-Specific Antigen in Metastatic Melanoma Patients Impacts on Generation of Peptide-Specific Ctls but Does Not Overcome Tumor Escape from Immune Surveillance in Metastatic Lesions

It is not known if immune response to T cell–defined human histocompatibility leukocyte antigen (HLA) class I–restricted melanoma antigens leads to an expanded peripheral pool of T cells in all patients, affects cytotoxic T lymphocyte (CTL) generation, and correlates with anti-tumor response in metastatic lesions. To this end, a limiting dilution analysis technique was developed that allowed us to evaluate the same frequency of peptide-specific T cells as by staining T cells with HLA–peptide tetrameric complexes. In four out of nine patients, Melan-A/Mart-127–35–specific CTL precursors (CTLp) were ≥1/2,000 peripheral blood lymphocytes and found mostly or only in the CD45RO+ memory T cell subset. In the remaining five patients, a low (<1/40,000) peptide-specific CTLp frequency was measured, and the precursors were only in the CD45RA+ naive T cell subset. Evaluation of CTL effector frequency after bulk culture indicated that peptide-specific CTLs could be activated in all patients by using professional antigen-presenting cells as dendritic cells, but CTLp frequency determined the kinetics of generation of specificity and the final number of effectors as evaluated by both limiting dilution analysis and staining with HLA-A*0201–Melan-A/Mart-1 tetrameric complexes. Immunohistochemical analysis of 26 neoplastic lesions from the nine patients indicated absence of tumor regression in most instances, even in patients with an expanded peripheral T cell pool to Melan-A/Mart-1 and whose neoplastic lesions contained a high frequency of tetramer-positive Melan-A/Mart-1–specific T cells. Furthermore, frequent lack of a “brisk” or “nonbrisk” CD3+CD8+ T cell infiltrate or reduced/absent Melan-A/Mart-1 expression in several lesions and lack of HLA class I antigens were found in some instances. Thus, expansion of peripheral immune repertoire to Melan-A/Mart-1 takes place in some metastatic patients and leads to enhanced CTL induction after antigen-presenting cell–mediated selection, but, in most metastatic lesions, it does not overcome tumor escape from immune surveillance

MACROGLOSSIA AS A CAUSE OF ATYPICAL SWALLOWING: COMPARISON OF EVALUATION AND LOGOPEDIC TREATMENT BETWEEN BECKWITH-WIEDEMANN AND DOWN PATIENTS

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