Singlet-Contrast Magnetic Resonance Imaging: Unlocking Hyperpolarization with Metabolism*.

Hyperpolarization-enhanced magnetic resonance imaging can be used to study biomolecular processes in the body, but typically requires nuclei such as 13 C, 15 N, or 129 Xe due to their long spin-polarization lifetimes and the absence of a proton-background signal from water and fat in the images. Here we present a novel type of 1 H imaging, in which hyperpolarized spin order is locked in a nonmagnetic long-lived correlated (singlet) state, and is only liberated for imaging by a specific biochemical reaction. In this work we produce hyperpolarized fumarate via chemical reaction of a precursor molecule with para-enriched hydrogen gas, and the proton singlet order in fumarate is released as antiphase NMR signals by enzymatic conversion to malate in D2 O. Using this model system we show two pulse sequences to rephase the NMR signals for imaging and suppress the background signals from water. The hyperpolarization-enhanced 1 H-imaging modality presented here can allow for hyperpolarized imaging without the need for low-abundance, low-sensitivity heteronuclei.

Women in surgery. Myth, history, actuality.

This work synthetically documents the history of women's efforts to be professionally acknowledged as surgeon. The examined timeline goes back from ancient civilizations to our days. It highlights the difficulties that women have had in time, particularly in the last two centuries, trying to make their aspirations come true and their will in becoming surgeons. The attention goes to the difficulties that are faced in our time regarding the medical field and the academic career. Moreover, corrective organizational and behavioural advice is given to solve specific problems still actual, in order to promote sex equality and working collaboration.

The impact of TACI mutations: from hypogammaglobulinemia in infancy to autoimmunity in adulthood.

Common variable immunodeficiency (CVID) is considered the most common symptomatic antibody deficiency and, although mainly reported in adults, it may present from childhood. Few data on the impact of TACI defects on the clinical and immunological status of children are available. We screened 42 hypogammaglobulinemic children to investigate the frequency and mutational features of TACI defects. The genetic, clinical and immunological characterization was extended to 31 relatives of 11 children with TACI mutations. Of interest, our analysis showed a considerably higher mutation frequency in hypogammaglobulinemic children (13/42; 31%) than in other cohorts of adult patients. In seven out of nine families with the C104R variant, the prevalence of autoimmunity was significantly higher in C104R heterozygous relatives (8/15; 53%) than in those with no C104R mutation (1/11; 9%). Our data suggest a different impact of TACI mutations, from hypogammaglobulinemia in children to autoimmune disease in adulthood.

Visceral leishmaniasis revealing chronic granulomatous disease in a child.

We report the first description of visceral leishmaniasis (VL) infection as a harbinger of chronic granulomatous disease (CGD) in a 3-year old child. Although VL is not frequently suspected in CGD patients, our case emphasises the importance of a complete evaluation of the immune system in children presenting with VL in order to exclude underlying immunodeficiency states. As the prognosis of CGD is poor, with high morbidity and mortality, establishing an early diagnosis has important practical implications in the successful treatment of these patients. Following the diagnosis, the patient received Human Leukocyte Antigen (HLA) identical sibling bone marrow transplantation (BMT). The child is now 2 years post-transplant and is in good general conditions with normal blood counts, and evidence of full-donor chimerism in repeated fluorescence in situ hybridization (FISH) studies.

Nuclear factor kappaB activity is increased in peripheral blood mononuclear cells of children affected by atopic and non-atopic eczema.

Atopic and non-atopic eczema is an inflammatory cutaneous disease which is common in childhood and is associated with a dysregulation of the immune system. Many genes encoding immune receptors, cytokines, chemokines, chemokine receptors, and adhesion molecules involved in the development of the disease are under the control of transcription factors belonging to the nuclear factor (NF)-kappaB family. To investigate the role of NF-kappaB in the development of eczema, 20 children, affected by relapsing chronic eczema, were enrolled in this study. Eleven of the 20 children showed IgE immunoreactivity and had a positive prick test. The DNA binding activity of NF-kappaB in nuclear extracts of the patients' peripheral blood mononuclear cells (PBMC) was examined by electrophoretic mobility shift assay. We found that basal NF-kappaB-DNA binding activity in PBMC was significantly higher in the eczema patient group in comparison with the same parameter in the healthy age-matched control group. Moreover, we observed a significant correlation between NF-kappaB-DNA binding activity and patients clinical score (SCORAD). Based on these observations we speculate that NF-kappaB can play an important role in the immunopathogenesis of eczema and therefore could be considered as a potential therapeutic target.