Glutathione Depletion Is Linked with Th2 Polarization in Mice with a Retrovirus-Induced Immunodeficiency Syndrome, Murine AIDS: Role of Proglutathione Molecules as Immunotherapeutics

Injection of the LP-BM5 murine leukemia virus into mice causes murine AIDS, a disease characterized by many dysfunctions of immunocompetent cells. To establish whether the disease is characterized by glutathione imbalance, reduced glutathione (GSH) and cysteine were quantified in different organs. A marked redox imbalance, consisting of GSH and/or cysteine depletion, was found in the lymphoid organs, such as the spleen and lymph nodes. Moreover, a significant decrease in cysteine and GSH levels in the pancreas and brain, respectively, was measured at 5 weeks postinfection. The Th2 immune response was predominant at all times investigated, as revealed by the expression of Th1/Th2 cytokines. Furthermore, investigation of the activation status of peritoneal macrophages showed that the expression of genetic markers of alternative activation, namely, Fizz1, Ym1, and Arginase1, was induced. Conversely, expression of inducible nitric oxide synthase, a marker of classical activation of macrophages, was detected only when Th1 cytokines were expressed at high levels. In vitro studies revealed that during the very early phases of infection, GSH depletion and the downregulation of interleukin-12 (IL-12) p40 mRNA were correlated with the dose of LP-BM5 used to infect the macrophages. Treatment of LP-BM5-infected mice with N-(N-acetyl-L-cysteinyl)-S-acetylcysteamine (I-152), an N-acetyl-cysteine supplier, restored GSH/cysteine levels in the organs, reduced the expression of alternatively activated macrophage markers, and increased the level of gamma interferon production, while it decreased the levels of Th2 cytokines, such as IL-4 and IL-5. Our findings thus establish a link between GSH deficiency and Th1/Th2 disequilibrium in LP-BM5 infection and indicate that I-152 can be used to restore the GSH level and a balanced Th1/Th2 response in infected mice

Computed Tomography Predictors of Mortality or Disease Progression in Systemic Sclerosis–Interstitial Lung Disease: A Systematic Review

OBJECTIVE: Although interstitial lung disease (ILD) is a major cause of morbidity and mortality in systemic sclerosis (SSc), its prognostication remains challenging. Given that CT represents the gold standard imaging technique in ILD assessment, a systematic review on chest CT findings as predictors of mortality or ILD progression in SSc-ILD was performed. MATERIALS AND METHODS: Three databases (Medline, Embase, and Web of Science) were searched to identify all studies analyzing CT mortality or ILD progression predictors in SSc-ILD, from inception to December 2020. ILD progression was defined by worsening of forced vital capacity and/or CT ILD findings. Manuscripts not written in English, with not available full-text, not focusing on SSc-ILD or with SSc-ILD not extrapolated, otherwise with overlap syndromes, pediatric patients, <10 cases or predictors other than CT features were excluded. RESULTS: Out of 3,513 citations, 15 full-texts (2,332 patients with SSc-ILD) met the inclusion criteria. ILD extent and extensive ILD, ILD densitometric analysis parameters, fibrotic extent and reticulation extent resulted as independent mortality predictors. Extensive ILD is also an independent predictor of death, need for supplemental oxygen or lung transplantation. Honeycombing extent is an independent risk factor for respiratory mortality. Independent predictors of ILD progression were not identified. CONCLUSIONS: ILD extent and extensive ILD independently predict mortality in SSc-ILD on CT, as well as ILD densitometric analysis, fibrotic extent and reticulation extent. Extensive ILD is also a predictor of death, need for supplemental oxygen, or lung transplantation. Honeycombing extent predicts respiratory mortality. CT predictors of ILD progression need to be further investigated. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, PROSPERO, identifier: CRD420202005001

Artificial Intelligence and Radiomics at the University of Florence

This paper provides an overview of current research at the Department of Radiology of the University of Florence. It concerns radiomics along with Artificial Intelligence (AI) applied to various medical fields. The need for personalised medicine and the transition from qualitative to quantitative imaging are at the heart of the projects described in this text. The purpose of this paper is to extend the collaborations of the group and find innovative ideas

Empathy and behavior in children affected by Autism Spectrum Disorders

Many studies have already shown that individuals suffering from Autism Spectrum Disorders (ASD) present low levels of empathy: in fact, reduced emotional reciprocity is considered a clinically significant indicator of autistic functioning. We decided to investigate the role of empathy in determining pathological behaviors in children affected by ASD considering parents' point of view and to evaluate the presence of differences between mothers and fathers' perception of their child's empathy and behaviors

Techniques, Tricks, and Stratagems of Oral Cavity Computed Tomography and Magnetic Resonance Imaging

The oral cavity constitutes a complex anatomical area that can be affected by many developmental, inflammatory, and tumoural diseases. MultiSlice Computed Tomography (MSCT) and Magnetic Resonance Imaging (MRI) currently represent the essential and complementary imaging techniques for detecting oral cavity abnormalities. Advanced MRI with diffusion-weighted imaging (DWI) and dynamic contrast-enhanced perfusion-weighted imaging (DCE-PWI) has recently increased the ability to characterise oral lesions and distinguish disease recurrences from post therapy changes. The analysis of the oral cavity area via imaging techniques is also complicated both by mutual close appositions of different mucosal surfaces and metal artifacts from dental materials. Nevertheless, an exact identification of oral lesions is made possible thanks to dynamic manoeuvres and specific stratagems applicable on MSCT and MRI acquisitions. This study summarises the currently available imaging techniques for oral diseases, with particular attention to the role of DWI, DCE-PWI, and dynamic manoeuvres. We also propose MSCT and MRI acquisition protocols for an accurate study of the oral cavity area

Advanced and traditional chest MRI sequence for the clinical assessment of systemic sclerosis related interstitial lung disease, compared to CT:disease extent analysis and correlations with pulmonary function tests

Background: MRI is a radiation-free emerging alternative to CT in systemic sclerosis related interstitial lung disease (SSc-ILD) assessment. We aimed to compare a T2 radial TSE and a PD UTE MRI sequence with CT in SSc-ILD extent evaluation and correlations with pulmonary function tests (PFT). Material and methods: 29 SSc-ILD patients underwent CT, MRI and PFT. ILD extent was visually assessed. Lin's concordance correlation coefficients (CCC) and Kruskal Wallis test (p-value &lt; 0.05) were computed for inter-method comparison. Patients were divided in limited and extended disease, defining extended ILD with two methods: (A) ILD&gt;30% or 10%&lt;ILD≤30% with FVC%&lt;70%; (B) ILD&gt;20% or 20% with FVC%&lt;70%. MRI Sensitivity, Specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV) and Accuracy were assessed. Pearson correlation coefficients r (p-value&lt;0.025) were computed between ILD extents and PFT (FVC% and DLCO%). Results: Median ILD extents were 11%, 11%, 10% on CT, radial TSE and UTE, respectively. CCC between CT and MRI was 0.95 for both sequences (Kruskal-Wallis p-value=0.64). Sensitivity, Specificity, PPV, NPV and Accuracy in identifying extended disease were: (A) 87.5 %, 100 %, 100 %, 95.5 and 96.6 % with radial TSE and 87.5 %, 95.2 %, 87.5 %, 95.2 and 93.1 % with UTE; (B) 86.7 %, 86.4 %, 66.7 %, 95.0 % and 86.2 % for both sequences. Pearson r of CT, radial TSE and UTE ILD extents with FVC were −0.66, –0.60 and −0.68 with FVC, −0.59, −0.56 and −0.57 with DLCO, respectively (p&lt;0.002). Conclusions: MRI sequences may have similar accuracy to CT to determine SSc-ILD extent and severity, with analogous correlations with PFT.</p

Advanced and traditional chest MRI sequence for the clinical assessment of systemic sclerosis related interstitial lung disease, compared to CT:disease extent analysis and correlations with pulmonary function tests

Background: MRI is a radiation-free emerging alternative to CT in systemic sclerosis related interstitial lung disease (SSc-ILD) assessment. We aimed to compare a T2 radial TSE and a PD UTE MRI sequence with CT in SSc-ILD extent evaluation and correlations with pulmonary function tests (PFT). Material and methods: 29 SSc-ILD patients underwent CT, MRI and PFT. ILD extent was visually assessed. Lin's concordance correlation coefficients (CCC) and Kruskal Wallis test (p-value &lt; 0.05) were computed for inter-method comparison. Patients were divided in limited and extended disease, defining extended ILD with two methods: (A) ILD&gt;30% or 10%&lt;ILD≤30% with FVC%&lt;70%; (B) ILD&gt;20% or 20% with FVC%&lt;70%. MRI Sensitivity, Specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV) and Accuracy were assessed. Pearson correlation coefficients r (p-value&lt;0.025) were computed between ILD extents and PFT (FVC% and DLCO%). Results: Median ILD extents were 11%, 11%, 10% on CT, radial TSE and UTE, respectively. CCC between CT and MRI was 0.95 for both sequences (Kruskal-Wallis p-value=0.64). Sensitivity, Specificity, PPV, NPV and Accuracy in identifying extended disease were: (A) 87.5 %, 100 %, 100 %, 95.5 and 96.6 % with radial TSE and 87.5 %, 95.2 %, 87.5 %, 95.2 and 93.1 % with UTE; (B) 86.7 %, 86.4 %, 66.7 %, 95.0 % and 86.2 % for both sequences. Pearson r of CT, radial TSE and UTE ILD extents with FVC were −0.66, –0.60 and −0.68 with FVC, −0.59, −0.56 and −0.57 with DLCO, respectively (p&lt;0.002). Conclusions: MRI sequences may have similar accuracy to CT to determine SSc-ILD extent and severity, with analogous correlations with PFT.</p

Morphological, Functional and Texture Analysis Magnetic Resonance Imaging Features in the Assessment of Radiotherapy-Induced Xerostomia in Oropharyngeal Cancer

The aim of this single-center, observational, retrospective study was to investigate magnetic resonance imaging (MRI) biomarkers for the assessment of radiotherapy (RT)-induced xerostomia. Twenty-seven patients who underwent radiation therapy for oropharyngeal cancer were divided into three groups according to the severity of their xerostomia—mild, moderate, and severe—clinically confirmed with the Common Terminology Criteria for Adverse Events (CTCAE). No severe xerostomia was found. Conventional and functional MRI (perfusion- and diffusion- weighted imaging) performed both pre- and post-RT were studied for signal intensity, mean apparent diffusion coefficient (ADC) values, k-trans, and area under the perfusion curves. Contrast-enhanced T1 images and ADC maps were imported into 3D slicer software, and salivary gland volumes were segmented. A total of 107 texture features were derived. T-Student and Wilcoxon signed-rank tests were performed on functional MRI parameters and texture analysis features to identify the differences between pre- and post-RT populations. A p-value 0.7). Values lower than the cut-off of −1.473 × 10−11 were associated with moderate xerostomia, enabling the differentiation of mild xerostomia from moderate xerostomia with a 73% sensitivity, 75% specificity, and 75% diagnostic accuracy. Therefore, the texture feature IMC 1 on the ADC maps allowed the distinction between different degrees of severity of RT-induced xerostomia in the pre-RT population. Accordingly, texture analysis on ADC maps should be considered a useful tool to evaluate salivary gland radiosensitivity and help identify patients at risk of developing more serious xerostomia before radiation therapy is administered

Moncorvo Filho e o problema da infância: modelos institucionais e ideológicos da assistência à infância no Brasil

O artigo investiga os modelos ideológicos e institucionais de assistência à infância idealizados e promovidos por Arthur Moncorvo Filho no começo do século XX. Este médico brasileiro expressamente associava criança e assistência infantil à nação, defendendo o controle, por parte do governo federal, de todas as instituições destinadas a proteger a infância. Ele acreditava que o poder público deveria assumir o papel reservado aos pais das crianças pobres, a fim de protegê-las da miséria e da delinqüência prevalecentes nas cidades brasileiras. Para Moncorvo Filho, as crianças possuíam um valor intrínseco, pois representavam a matéria-prima a partir da qual a futura força de trabalho poderia ser moldada. Por meio das instituições que organizou, esperava instaurar um modelo institucional de assistência à infância, a partir do qual o governo poderia criar um sistema nacional centralizado de proteção aos menores carentes.<br>This essay explores the ideological and institutional models for child welfare created and promoted by Dr. Arthur Moncorvo Filho in early twentieth-century Brazil. Moncorvo Filho explicitly connected children and child welfare with the nation and promoted the idea that the national government should centralize control over existing child welfare institutions. In so doing, he asserted that the government should assume the role of parent to the nations poor children to protect them from the poverty and delinquency then prevalent in Brazil's cities. In his model, children had intrinsic value because they were the raw material from which the future labor force could be molded. Through the institutions he had created he hoped to set up a institutional model of comprehensive child welfare upon which the government could draw to create a centralized system of national child welfare