Granulomatous fasciitis followed by morphea profunda: Is granulomatous fasciitis part of a spectrum of deep morphea? A case report and review of the literature.

Although eosinophilic fasciitis is known to be part of the deep morphea spectrum, this first report of the coexistence of granulomatous fasciitis and morphea profunda suggests that granulomatous fasciitis may also be a part of the spectrum of deep morphea

AN ADAPTIVE METHOD TO FOCUSING IN AN UNKNOWN SCENARIO

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Clinical, laboratory and immunohistochemical characterization of in situ pulmonary arterial thrombosis in fatal COVID-19

Background: COVID-19 patients carry an increased rate of thrombosis. It is controversial to which extent thrombi in the pulmonary arterial tree really contribute to disease severity with hypoxemia secondary to microvascular/lung parenchymal damage with viral alveolitis considered to play the main role in critical disease. Objectives: The primary objective was to compare post-mortem lung disease from fatal COVID-19 pneumonia in patients with macroscopically evident pulmonary arterial tree thrombosis and patients without, by characterizing the immunohistochemical nature of thrombi, and by comparing clinical and laboratory features of these patients with other COVID-19 patients who died but without evidence of pulmonary arterial thrombosis (controls). Patients and methods: 13 COVID-19 pneumonia cases (mean age ± standard deviation: 74 ± 6.5 years) with macroscopically visible pulmonary arterial thrombosis were compared to 14 controls. Hematoxylin and Eosin stained slides were reviewed choosing those with visible pulmonary thrombi which were further characterized by immunohistochemistry, in particular for the inflammatory infiltrates. Ante mortem serum markers relevant to pulmonary embolism were evaluated in both groups. Results: Twenty arterial thrombi (5 cases with multiple thrombi) were selected for study and were composed by white blood cells (WBC) [median, IQR range: 10 % (5–12.25)], mainly neutrophils [58 % (35.2–64.5)]. Cases with thrombosis showed significantly higher levels of platelet count [median, IQR range: 195000/mmc (157750–274,500) vs 143,500 (113000–175,250), p = 0.011], LDH [854 U/L (731–1315) vs 539 (391.5–660), p = 0.003] at admission, and D-dimer at ICU transfer [25,072 FEU (6951–50,531) vs 1024 (620–5501), p = 0.003]. Conclusions: Immunothrombotically driven arterial thrombi in COVID-19 patients are associated with D-Dimer and LDH elevations, thus linking inflammation, coagulopathy and organ damage in fatal COVID-19

RELATIONSHIP AMONG SYMPTOMS SCORE,PROSTATE VOLUME AND URINARY FLOW RATES IN 543 PATIENTS WITH AND WIHTOUT BPH

BACKGROUND. Studies on the relationship among symptom score, urinary flow rate, and prostate volume in men with lower urinary tract symptoms (LUTS) continue to be of great interest. METHODS. A total of 2,418 men, aged 30-86 years, agreed to participate in an interview and to complete a questionnaire regarding voiding patterns. All subjects answering positively to one or more of the questions were submitted to a diagnostic assessment, based on the algorithm outlined by the guidelines of the International Consultation on Benign Prostatic Hyperplasia (BPH). Five hundred forty-three out of the 2,418 participants (22.45%) were evaluated. At the end of the diagnostic evaluation, 400 men with LUTS but without concomitant conditions (except BPH) known to interfere with normal voiding were selected. Descriptive statistics were used to characterize age, symptom score (International Prostate Symptom Score), prostate volume, and urinary flow rate distribution in these patients. Correlations among the aforementioned parameters were evaluated by means of a multivariate, multiple linear regression and logistic regression model. RESULTS. As reported in other studies, only weak or modest correlations were found. Moreover, the 400 cases were classified according to four age decades. The decrease in peak and mean flow rate per decade of age was similar (0.5 and 0.4 ml/sec); the increase in prostate volume and in total symptom score per decade was 3.3 cc and 0.6, respectively. In patients less than 50 years old, most of the correlations were stronger than those observed in the entire population of 400 men (age and prostate volume, c.c. 0.2864; age and peak flow rate, c.c. -0.2689; age and mean flow rate, c.c. -0.3034). However, symptom score continued to be weakly correlated with age and prostate volume (c.c. 0.0498 and 0.1966, respectively). In the last part of the study, men were assigned to different treatment strategies. Patients who were assigned to surgical treatment had higher prostate volume and IPSS and lower urinary flow rate than those assigned to nonsurgical treatment. CONCLUSIONS. We believe that the reason for the weak statistical association frequently reported in the literature is mainly the urology clinic-based population from which the patient samples were drawn. Data emerging from this analysis support the hypothesis that age is one of the principal factors influencing the relationship among symptom score, urinary flow rate, and prostate volume. (C) 1998 Wiley-Liss, Inc

Axon degeneration assays in Superior Cervical Ganglion explant cultures

The ability of peripheral nervous system neurons to extend long, axon-like neurites in vitro makes them ideally suited for studies on mechanisms of axon survival and degeneration. In this chapter we describe how to prepare explant cultures of sympathetic neurons of the superior cervical ganglion (SCG). We also describe how to induce and assess axon degeneration with an injury or a chemical insult

Mitochondrial apurinic/apyrimidinic endonuclease 1 enhances mtDNA repair contributing to cell proliferation and mitochondrial integrity in early stages of hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is the leading cause of primary liver cancers. Surveillance of individuals at specific risk of developing HCC, early diagnostic markers, and new therapeutic approaches are essential to obtain a reduction in disease-related mortality. Apurinic/apyrimidinic endonuclease 1 (APE1) expression levels and its cytoplasmic localization have been reported to correlate with a lower degree of differentiation and shorter survival rate. The aim of this study is to fully investigate, for the first time, the role of the mitochondrial form of APE1 in HCC. Methods: As a study model, we analyzed samples from a cohort of patients diagnosed with HCC who underwent surgical resection. Mitochondrial APE1 content, expression levels of the mitochondrial import protein Mia40, and mtDNA damage of tumor tissue and distal non-tumor liver of each patient were analyzed. In parallel, we generated a stable HeLa clone for inducible silencing of endogenous APE1 and re-expression of the recombinant shRNA resistant mitochondrially targeted APE1 form (MTS-APE1). We evaluated mtDNA damage, cell growth, and mitochondrial respiration. Results: APE1's cytoplasmic positivity in Grades 1 and 2 HCC patients showed a significantly higher expression of mitochondrial APE1, which accounted for lower levels of mtDNA damage observed in the tumor tissue with respect to the distal area. In the contrast, the cytoplasmic positivity in Grade 3 was not associated with APE1's mitochondrial accumulation even when accounting for the higher number of mtDNA lesions measured. Loss of APE1 expression negatively affected mitochondrial respiration, cell viability, and proliferation as well as levels of mtDNA damage. Remarkably, the phenotype was efficiently rescued in MTS-APE1 clone, where APE1 is present only within the mitochondrial matrix. Conclusions: Our study confirms the prominent role of the mitochondrial form of APE1 in the early stages of HCC development and the relevance of the non-nuclear fraction of APE1 in the disease progression. We have also confirmed overexpression of Mia40 and the role of the MIA pathway in the APE1 import process. Based on our data, inhibition of the APE1 transport by blocking the MIA pathway could represent a new therapeutic approach for reducing mitochondrial metabolism by preventing the efficient repair of mtDNA

Analysis of viral nucleic acids in duodenal biopsies from adult patients with active celiac disease: in search for an etiological relationship

BACKGROUND AND AIM: Celiac Disease (CD) is a multisystemic chronic inflammatory autoimmune disease which develops in genetically predisposed subjects and it is triggered by the ingestion of gluten. After the interaction between HLA-DQ2/DQ8 and gluten-derived peptides, lymphocytes T CD4+ start a specific immune response which ends in a chronic inflammation and mucosal damage. CD pathogenesis is complex and not entirely understood, probably due to an alteration in the gastrointestinal immune system or to its aberrant regulation. Furthermore, many environmental and immune factors could be involved, particularly viral infections. The aim of the study was to observe possible relationships between CD and infections from HHV-6 A/B, EBV, CMV, adenovirus and rotavirus. MATERIAL AND METHODS: Thirty-nine adult patients (aged 18-65 yrs) have been enrolled: specifically, 24 duodenal biopsies from active CD patients and 15 biopsies from non-CD patients were analyzed. CD diagnosis has been performed by means of serological antibodies, histology of duodenal biopsies and duodenal biopsy organ culture. Viral nucleic acids were extracted from duodenal biopsies and then amplified using Real-Time PCR technique. RESULTS: HHV-6B was found in 62.5% of CD patients and in 73.3% of non-CD patients (p=0.13). EBV was found in 4.5% of CD patients and 6.7% of non-CD patients (p=0.35). Nucleic acids from HHV-6A, CMV, adenovirus and rotavirus were not detected in any group. HHV-6B viral load in CD patients was higher than in non-CD patients, but data were not statistically significant (p=0.54). CD patients with HHV-6B viral load >50000 copies/ml resulted to be younger and had lower anti-tTG antibody titers found at organ culture than patients with lower HHV-6B viral load (p>0.05). CONCLUSIONS: There seems to be no difference in viral load and/or in the detection of viruses between CD and non-CD patients. Thus, our data do not support the possible relationship between CD and viral infections, although a larger population is needed to confirm our study results

Recurrence of gastrointestinal and extra-intestinal symptoms in celiac patients affected by nickel allergic contact mucositis: when proper gluten-free diet is not enough

BACKGROUND AND AIM: Nickel (Ni) is a metal widely present in nature and the prevalence of Ni allergy is increasing. Allergic contact mucositis (MAC) induced by Ni-rich foods is often responsible for IBS-like disorders and it can be diagnosed by means of a Ni oral mucosa patch test (omPT). It has been observed that, after several months of correct gluten-free diet (GFD), many celiac disease (CD) patients show a recrudescence of gastrointestinal and extra-intestinal symptoms, although serological and histological remission has been achieved. This can be due to a Ni load induced by GFD: a greater consumption of Ni-rich foods (e.g. corn) would lead to a consequent intestinal sensitization to Ni in predisposed subjects. Our study aimed to assess the role played by Ni in the recurrence of symptoms in CD subjects after strict GFD. MATERIAL AND METHODS: Twenty celiac patients (all female, age 23-65 yrs) in serological and histological remission after at least 12 months of GFD have been consecutively included: they all were complaining recurrence gastrointestinal and extra-intestinal symptoms. Subjects with organic gastrointestinal pathologies were excluded. A symptom questionnaire (GSRS modified according to the Salerno Experts' Criteria) has been administered to all patients in 4 stages: T0 (during free diet - active CD); T1 (after 12 months of GFD - CD remission); T2 (during GFD - recurrence of symptoms); T3 (during GFD and after 3 months of low-Ni diet). Ni omPT was performed at T2. Statistical analysis was performed using Wilcoxon signed rank test. RESULTS: All 20 patients showed positive Ni omPT, with local and/or systemic alterations confirming Ni ACM diagnosis. The analysis obtained by comparing T2-T3 showed p-value <0.01 for: abdominal pain, bloating, swelling, increased number of evacuations, dermatitis, asthenia; p-value values <0.05 for: heartburn, acid regurgitation, borborygmus, flatulence, loose stools, urgent need for defecation, headache. The other variables were statistically not significant. CONCLUSIONS: Our data suggest that gastrointestinal and extra-intestinal symptoms observed in CD subjects after prolonged and correct GFD may be due to the necessary dietary change and an increased Ni intake. Specifically, these patients developed Ni MAC, diagnosed by specific Ni omPT. We also observed that regression of symptoms may occur after a proper low-Ni diet. We can conclude that GFD may lead to an increased consumption of Ni-rich foods and this could explain the recurrence of apparently gluten-dependent symptoms

Agronomic, nutritional and nutraceutical aspects of durum wheat (Triticum durum Desf.) cultivars under low input agricultural management

Among cereals, durum wheat has a central role in the Italian diet and economy, where there is a historical tradition of pasta making. In the present study, we evaluated the nutrient and nutraceutical properties of 2 old and 6 modern durum wheat varieties grown under low input agricultural management. Considering the lack of available data on the adaptability of existing durum wheat varieties to the low input and organic sectors, the research aimed at providing a complete description of the investigated genotypes, considering the agronomic performance as well as the nutrient and phytochemical composition. The experimental trials were carried out at the same location (Bologna, Northern Italy) for two consecutive growing seasons (2006/2007, 2007/2008). No clear distinction between old and modern varieties was observed in terms of grain yield (mean values ranging from 2.5 to 4.0 t/ha), highlighting that the divergence in productivity, normally found between dwarf and non-dwarf genotypes, is strongly reduced when they are cropped under low input management. All durum wheat varieties presented high protein levels and, in addition, provided remarkable amounts of phytochemicals such as dietary fibre, polyphenols, flavonoids and carotenoids. Some of the investigated genotypes, such as Senatore Cappelli, Solex, Svevo and Orobel, emerged with intriguing nutritional and phytochemical profiles, with the highest levels of dietary fibre and antioxidant compounds. The study provided the basis for further investigations into the adaptability of the durum wheat genotypes to low input management, for the selection of genotypes characterised by higher yield and valuable nutrient and nutraceutical quality