Inflammatory expression profile in peripheral blood mononuclear cells from patients with Nasu-Hakola Disease.

Homozygous mutations in Triggering Receptor Expressed on Myeloid cells 2 gene (TREM2) are one of the major causes of Nasu Hakola Disease (NHD). We analysed Peripheral Blood Mononuclear Cells (PBMC) profile of 164 inflammatory factors in patients with NHD carrying the TREM2 Q33X mutation as compared with heterozygous and wild type individuals. Several molecules related to bone formation and angiogenesis were altered in NHD compared to non-carriers: Bone Morphogenetic Protein (BMP)-1 mRNA levels were significantly increased in PBMC (2.32 fold-increase; P = 0.01), as were Transforming Growth Factor Beta (TGFB)3 levels (1.51 fold-increase; P = 0.02). Conversely, CXCL5 and Pro Platelet Basic Protein (PPBP) were strongly downregulated (-28.26, -9.85 fold-decrease over non-carriers, respectively, P = 0.01), as well as Platelet Factor 4 Variant 1 (PF4V1; -41.44, P = 0.03). Among other inflammatory factors evaluated, Interleukin (IL)-15 and Tumor Necrosis Factor Superfamily Member (TNFSF)4 mRNA levels were decreased in NHD as compared with non-carriers (-2.25 and -3.87 fold-decrease, P = 0.01 and 0.001, respectively). In heterozygous individuals, no significant differences were observed, apart from IL-15 mRNA levels, that were decreased at the same extent as NHD (-2.05 fold-decrease over non-carriers, P = 0.002). We identified a signature in PBMC from patients with NHD consisting of strongly decreased mRNA levels of CXCL5, PPBP, PF4V1, mildly decreased IL-15 and TNFSF4 and mildly increased BMP-1 and TGFB3.

Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis patients.

BACKGROUND: Dimethyl fumarate (DMF) alters the phenotype of circulating immune cells and causes lymphopenia in a subpopulation of treated multiple sclerosis (MS) patients. OBJECTIVE: To phenotypically characterize circulating leukocytes in DMF-treated MS patients. METHODS: Cross-sectional observational comparisons of peripheral blood from DMF-treated MS patients (n = 17 lymphopenic and n = 24 non-lymphopenic), untreated MS patients (n = 17) and healthy controls (n = 23); immunophenotyped using flow cytometry. Longitudinal samples were analyzed for 13 DMF-treated patients. RESULTS: Lymphopenic DMF-treated patients had significantly fewer circulating CD8(+) and CD4(+) T cells, CD56(dim) natural killer (NK) cells, CD19(+) B cells and plasmacytoid dendritic cells when compared to controls. CXCR3(+) and CCR6(+) expression was disproportionately reduced among CD4(+) T cells, while the proportion of T-regulatory (T-reg) cells was unchanged. DMF did not affect circulating CD56(hi) NKcells, monocytes or myeloid dendritic cells. Whether lymphopenic or not, DMF-treated patients had a lower proportion of circulating central and effector memory T cells and concomitant expansion of naïve T cells compared to the controls. CONCLUSIONS: DMF shifts the immunophenotypes of circulating T cells, causing a reduction of memory cells and a relative expansion of naïve cells, regardless of the absolute lymphocyte count. This may represent one mechanism of action of the drug. Lymphopenic patients had a disproportionate loss of CD8(+) T-cells, which may affect their immunocompetence.

Inflammatory molecules in Frontotemporal Dementia: cerebrospinal fluid signature of progranulin mutation carriers.

Mutations in progranulin gene (GRN) are one of the major causes of autosomal dominant Frontotemporal Lobar Degeneration (FTLD). Progranulin displays anti-inflammatory properties and is likely a ligand of Tumor Necrosis Factor (TNF) receptor 2, expressed on microglia. A few cytokines and chemokines are altered in cerebrospinal fluid (CSF) from patients with sporadic FTLD, whereas no information is available in familial cases. We evaluated, through BioPlex, levels of 27 inflammatory molecules, including cytokines, chemokines, and related receptors, in CSF and matched serum, from FTLD patients carrying GRN mutations as compared with sporadic FTLD with no GRN mutations and controls. Mean±SD Monocyte Chemoattractant Protein-1 (MCP-1) levels were significantly increased in CSF from sporadic FTLD patients as compared with controls (334.27±151.5 versus 159.7±49pg/ml; P⩽0.05). In GRN mutation carriers versus controls, CSF levels of MCP-1 were unchanged, whereas Interferon-γ-inducible protein-10 (IP-10) levels were increased (809.17±240.0 versus 436.61±202.5pg/ml; P=0.012). In the same group, TNFα and Interleukin (IL)-15 levels were decreased (3.18±1.41 versus 35.68±30.5pg/ml; P=0.013 and 9.34±5.54 versus 19.15±10.03pg/ml; P=0.023, respectively). Conversely, Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES) levels were decreased in patients, with or without mutations, as compared with controls (4.63±3.30 and 2.58±20 versus 87.57±70pg/ml, respectively; P<0.05). Moreover, IP-10, IL-15 and RANTES CSF levels were not influenced by age, whereas MCP-1 levels increased with age (ρ=0.48; P=0.007). In conclusion, inflammatory de-regulation was observed in both sporadic FTLD and GRN carriers compared to controls, with a specific inflammatory profile for the latter group.

Optical fiber imaging for high speed plasma motion diagnostics: applied to low voltage circuit breakers.

An integrated portable measurement system is described for the study of high speed and high temperature unsteady plasma flows such as those found in the vicinity of high current switching arcs. An array of optical fibers allows the formation of low spatial resolution images, with a maximum capture rate of 1 x 10(6) images per second (1 MHz), with 8 bit intensity resolution. Novel software techniques are reported to allow imaging of the arc; and to measure arc trajectories. Results are presented on high current (2 kA) discharge events in a model test fixture and on the application to a commercial low voltage circuit breaker.

Conformations and biological activities of amyloid beta peptide 25-35.

Amyloid-beta (Abeta) peptide is commonly found in human Alzheimer's disease (AD) brain and is the main component of Alzheimer amyloid plaques. The predominant forms of Abeta in the human brain are Abeta(1-40) and Abeta(1-42), but Abeta(25-35) fragment, physiologically present in elderly people, is the more toxic region and has been recently found to play a relevant role in AD, due to its peculiar aggregation properties. In this work, we review the current understanding on the conformations and biological activity of Abeta(25-35) exploring aggregation, cytotoxic and neurodegenerative properties of this fundamental Abeta fragment, in order to provide an effective starting point to better approach a pathology spread and problematic as AD.

[Diagnosis and insurance compensation of occupational diseases in construction industry]. / Malattie professionali segnalate e riconosciute in edilizia.

The aim of this study is to evaluate the outcome of 302 occupational diseases in building workers detected by UOOML Ospedali Riuniti of Bergamo and notified to INAIL from 2000 to 2005. The 41.3% of cases were accepted as work-related. Among remaining cases (58.7%), INAIL rejected 40.9% for lack or absence of documentation. 59.1% for no adhesion to legal medicine criteria. By analysis of occupational diseases detected in the last 5 years, we found an increase of muscle-skeletal disorders, for which, now, diagnostic procedure and insurance evaluation are difficult. This work shows a wide gap between reported occupational diseases of buildings workers and compensation given by INAIL. These results underlines the need of comparison among involved institutions in order to standardize statistical and diagnostic instruments.

Postoperative blood salvage in hip and knee arthroplasty. A prospective study on cost effectiveness in 161 patients.

We conducted a prospective controlled study on 161 patients who underwent primary or revision total hip or knee arthroplasty to assess the efficacy and limitations of postoperative blood salvage. The actual quantity of blood salvaged after washing, the theoretical increase in hemoglobin concentration caused by its reinfusion and the cost of this procedure were studied. The mean amount of packed red cells after washing was 117 g. The average increase in hemoglobin concentration, which theoretically would have been achieved by retransfusion, was 0.47 g/dL. One third of the devices used were discarded as not effective enough and, in order to obtain an increase of 1 g/dL in the hemoglobin concentration, an average of 3.4 postoperative Solcotrans Plus Orthopaedic devices were used. To obtain the same increase in hemoglobin concentration as that given by an allogeneic blood transfusion, the overall cost of materials alone was more than five times the price of a single blood unit transfusion.

[The hospitalized terminal cancer patient and privacy: patient needs and the perception on the part of the professional nurse]. / Malato oncologico terminale ospedalizzato e privacy: bisogni del paziente e percezione da parte dell'infermiere professionale.

The perception of privacy in a sample of 43 oncology patients admitted to cremona Hospital was evaluated with an ad hoc questionnaire administered by nursing students. The same questionnaire was completed by the nurse responsible for the patient and results were thereafter compared. The questionnaire, of 13 items, explored 4 domains of privacy: environment, physical care, communication with relatives, communication with care providers. Patients and nurses were asked to score each question from 0 (not important) to 3 (very important). Situations which involved modesty-physical care and communication-socialization were perceived as most important for privacy. Areas perceived very important for privacy by the patient received a very high score from the nurses as well.

Plasma selenium levels of the general population of an area in northern Italy.

Plasma selenium (Se) levels of 293 subjects (160 males and 133 females) living in Desio (a small town near Milan) were determined. Analyses were performed by graphite-furnace atomic absorption spectrophotometry with Zeeman background correction. Plasma samples were not subjected to any treatment before analysis and serum samples containing a certified Se content were used as reference materials to control the quality of the analytical determinations. Plasma Se levels were found to be distributed normally with an average value of 118.8 micrograms/l and a S.D. of 27.2 (95% of the subjects lie between 64.4 and 173.2 micrograms/l). No statistically significant difference was found between males and females, and no correlation was found between plasma Se levels and age or smoking habits.

[New strategies for prevention of dental caries: identification of high caries risk subjects]. / Nuove strategie di prevenzione della carie dentale: l'identificazione dei soggetti ad alto rischio di carie.

The Authors present a review of the reports about methods developed in the latest years for screening high caries risk-subjects. They discuss some basic concepts necessary to assess limits and further possibilities of development of such diagnostic methods.

[Relations between sodium fluoride sensitivity and cariogenic potential in Streptococcus mutans]. / Rapporti fra sensibilità al fluoruro di sodio e potenziale cariogeno in Streptococcus mutans.

Supragingival plaque samples of a group of 59 schoolchildren were taken. The samples were cultivated on a selective medium for Streptococcus mutans and the isolated wild strains were tested for resistance to sodium fluoride (NaF). The results show the existence of a positive statistic correlation between the degree of resistance to NaF caries experience, obtained by DMFS of the experimental group.

[Biological basis of fluoride resistance]. / Le basi biologiche della resistenza al fluoro.

The authors synthetically illustrate some fundamental concepts about the mechanisms through which the oral flora develops fluoride resistance and the main consequences of this phenomenon at a biochemical and microbiological level. They briefly discuss the most recent experimental contributes of the literature in this field.

[Dentinal hypersensitivity: the etiopathogenetic mechanisms and treatment. The current state of knowledge]. / L'ipersensibilità dentinale: meccanismi eziopatogenetici e trattamento. Stato attuale delle conoscenze.

The anatomical and physiological characteristics of the pulpal and dentinal sensitive system are described. Some different theories about the transmission of the dentinal sensitivity are also explained. Finally, the different desensitizing agents, their main characteristics and mechanisms of action are analyzed.

[Septic thrombosis of the cavernous sinus. Presentation of a clinical case]. / Trombosi settica del seno cavernoso. Presentazione di un caso clinico.

This paper describes a case of cavernous sinus septic thrombosis with cerebellar complication. The CNS was involved after a primitive piodermitis of the face. The diagnostic tools employed in the management of the case and the therapeutic procedures in the acute phase and in the convalescence are discussed. The patient completely recovered after chemotherapeutic treatment.

[Protocols for the diagnostic verification of lymph node toxoplasmosis]. / Protocolli di accertamento diagnostico della toxoplasmosi linfonodale.

The protocol we have fixed for the diagnosis of lymphonodal toxoplasmosis includes a precise succession of tests: 1) specific repeated serological tests (I.H.A.T., I.F.A.T., IgM--I.F.A.T. on total serum and on pure IgM fraction); 2) lymphonodal biopsy for histological examination and biological test (isolation procedure in mouse). We have evaluated the effectiveness of our protocol in 20 cases that we observed during 1980.

Diagnostic protocols for lymphoglandular toxoplasmosis.

The diagnostic protocol for lymph node toxoplasmosis presented in this study is based on the following sequence: 1. specific serologic tests (IHAT, IFAT, IgM-IFAT) on total serum and on purified IgM serum fraction, performed twice, within a time interval of 21-28 days; 2. Lymph node biopsy for histologic studies and for isolation of the parasite in mice (biologic test). A critical analysis is reported for 20 cases submitted to this protocol in the course of the year 1980.