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Dibothriocephalosis is a fish-borne parasitic zoonosis that is caused by tapeworms of the Dibothriocephalus (syn. Diphyllobothrium) genus. This paper describes a human case of dibothriocephalosis associated with the consumption of a presumably infected fish, prepared at a restaurant near Iseo Lake (northern Italy). A month after, the patient found a segment of a worm in her stool. Molecular analysis identified it as Dibothriocephalus latus (syn. Diphyllobothrium latum). Several studies reported D. latus infections in patients from the subalpine regions of Switzerland, France, and Italy, but no cases have been reported from this area in the last 10 years. This report updates the epidemiology of dibothriocephalosis and emphasises the importance of collaboration among healthcare institutions for a prompt diagnosis and the need for food safety education for Food Business Operators and consumers to reduce transmission risks. [ABSTRACT FROM AUTHOR]

The anatomy of the sciatic nerve allows it to be blocked at different levels using various anesthetic approaches. However, for several reasons, performing these approaches may be challenging or disadvantageous in specific categories of patients, particularly in obese patients. The objective of this brief technical report is to describe a new technical approach to sciatic nerve block, designed to simplify the procedure for certain categories of patients and less experienced practitioners. Since 2010, more than 5000 procedures have been performed by both experienced anesthesiologists and novice trainees in several hospitals. The ultrasound lateral mid-shaft technique appears to be a safe and effective method for performing a sciatic nerve block, even in obese patients with significant subcutaneous fat and unclear ultrasound images. This approach is particularly beneficial given the various anatomical variations that can occur. By targeting the mid-thigh area, the ultrasound beam accesses anatomical structures that are more superficial, improving the technique's efficacy. Various hospital groups have been performing this technique as a routine procedure, achieving a success rate of nearly 100%. This impressive success rate exceeds that of other conventional techniques documented in the literature. Additionally, there have been significant improvements in comfort and ease for anesthetists. This method allows the anesthetic to spread around the paraneural sheath, covering the posterior femoral cutaneous nerve. Finally, it is performed in the supine position without the need to mobilize the lower limbs, ensuring patient comfort, especially in cases of fractures or lower limb injuries. Further studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Diverse spatio-temporal aspects of avian migration rely on relatively rigid endogenous programs. However, flexibility in migratory behavior may allow effective coping with unpredictable variation in ecological conditions that can occur during migration. We aimed at characterizing inter- and intraindividual variation of migratory behavior in a forest-dwelling wader species, the Eurasian woodcock Scolopax rusticola , focusing on spatio-temporal consistency across repeated migration episodes. By satellite-tracking birds from their wintering sites along the Italian peninsula to their breeding areas, we disclosed a remarkable variability in migration distances, with some birds flying more than 6,000 km to Central Asian breeding grounds (up to 101°E). Prebreeding migration was faster and of shorter duration than postbreeding migration. Birds moving over longer distances migrated faster during prebreeding migration, and those breeding at northernmost latitudes left their wintering areas earlier. Moreover, birds making longer migrations departed earlier from their breeding sites. Breeding site fidelity was very high, whereas fidelity to wintering areas increased with age. Migration routes were significantly consistent, both among repeated migration episodes and between pre- and postbreeding migration. Prebreeding migration departure date was not significantly repeatable, whereas arrival date to the breeding areas was highly repeatable. Hence, interindividual variation in migratory behavior of woodcocks was mostly explained by the location of the breeding areas, and spatial consistency was relatively large through the entire annual cycle. Flexibility in prebreeding migration departure date may suggest that environmental effects have a larger influence on temporal than on spatial aspects of migratory behavior. [ABSTRACT FROM AUTHOR]

Objective: Interleukin (IL)-1β is involved in obesity-associated inflammation and in the pathogenesis of type 2 diabetes (T2D) mellitus. Our aim was to correlate serum IL-1β and caspase-1 levels with weight loss, glucose metabolism, and insulin resistance (IR) after bariatric surgery.Methods: A total of 32 patients with morbid obesity and T2D (Ob-T2D) and 29 patients with morbid obesity and normal glucose tolerance (Ob-NGT), treated by Roux-en-Y gastric bypass, were studied before and 1 year after surgery. Sixteen healthy individuals served as a control (HC) group. IR was assessed by the oral glucose insulin sensitivity method. Plasma IL-1β levels and caspase-1 were measured.Results: Presurgery BMI was similar in Ob-NGT and Ob-T2D. IR was progressively impaired in Ob-NGT and Ob-T2D (P < 0.0001). Fasting plasma IL-1β and caspase-1 levels were lower in HCs than in patients with Ob-NGT or Ob-T2D (P < 0.02; P = 0.05), and both were inversely correlated with IR (P = 0.01; P = 0.02). After surgery, BMI decreased and IR improved to a similar extent in Ob-NGT and Ob-T2D (P < 0.0001). Plasma caspase-1 concentrations normalized in both groups (P < 0.0001), whereas plasma IL-1β levels normalized only in Ob-NGT.Conclusions: Plasma IL-1β and caspase-1 levels were inversely correlated with IR. Caspase-1 levels normalized after weight loss, whereas IL-1β normalized only in people without T2D, suggesting the persistence of a systemic inflammatory condition in people with T2D. [ABSTRACT FROM AUTHOR]

Opioid maintenance treatment (OMT) is the most widespread therapy for both females and males opioid addicts. While many studies have evaluated the OMT impact on men's sexuality, the data collected about the change in women's sexual functioning is still limited despite the fact that it is now well-known that opioids - both endogenous and exogenous - affect the endocrine system and play an important role in sexual functioning. The present study aims to determine how OMT with buprenorphine (BUP) or methadone (MTD) affects sexual health in women; examining also any possible emerging correlation between sexual dysfunction (SD), type of opioid and patients' mental health. This multi-center study case recruited 258 female volunteers attending Italian public Addiction Outpatients Centers that were stabilized with OMT for at least 3 months. SD was assessed with the Arizona Sexual Experience Scale. The twelve-item General Health Questionnaire was used to assess participants' mental health conditions. The results show that 56.6% of women receiving OMT for at least 3 months presented SD without significant differences between MTD e BUP groups. The majority of the subjects with SD have a poorer quality of intimate relationships and worse mental health than the average. To the best of our knowledge, the present study is the largest report on the presence of SDs in women as a side effects of MTD and BUP used in OMT. Since SDs cause difficulties in intimate relationships, lower patients' quality of life and interfere with OMT beneficial outcomes, we recommend that women undertaking an opioid therapy have routine screening for SD and we highlight the importance to better examine opioid-endocrine interactions in future studies in order to provide alternative potential treatments such as the choice of opioid, opioid dose reduction and hormone supplementation. [ABSTRACT FROM AUTHOR]

Aims: Stable genetic background makes individuals from the Mediterranean island of Sardinia ideal to define the predictive power of islet-related autoantibodies (IRAs): glutamic acid decarboxylase antibodies (GADA), tyrosine phosphatase-like antibodies (IA-2A), islet cell antibodies (ICA) to identify T1DM progressors. The aims of the present study were: (1) determination of IRAs reference limits in healthy non-diabetic Sardinian schoolchildren (SSc). (2) Predictive power evaluation of IRAs as single or combined determination to identify islet to identify T1DM progressors. Methods: Between 1986 and 1994, 8448 SSc were tested for IRAs. All were followed up for 10 years. The predictive power of single or combination of IRAs was determined as hazard ratio (HR), sensitivity, specificity, area under the ROC curve, negative and positive predictive value (NPV, PPV). Results: All 43 progressors to T1DM, but three showed at least one autoantibody positivity. HR for any single-autoantibody positivity was 55.3 times greater when compared to SSc negative for all IRAs. Any single autoantibody performed at least 64.9 % sensitivity with PPV always lower than 16 %. The best performing combination was ICA, plus IA-2A (showing 52.6 % sensitivity, 99.8 % specificity, 0.76 area under the ROC curve, 51.3 % PPV and 99.8 % NPV. Conclusions: Determination of IRAs reference limits in healthy SSc by standard statistical methods is crucial to establish the power of IRAs as progression markers to T1DM. Our data offer a solid rationale for future testing of ICA and IA-2A as routine laboratory markers to identify individuals at high risk of T1DM in the general population. [ABSTRACT FROM AUTHOR]

Expression of HLA class II molecules on thyrocytes is a characteristic feature of autoimmune thyroid disease and may lead the thyroid cells to present autoantigens to CD4+ T lymphocytes. Since HLA-DM is a critical molecule in class II-restricted antigen processing and presentation, we assessed the expression of HLA-DMB, -invariant chain (Ii), class II transactivator (CIITA) and DRA in an untransformed, pure thyrocyte strain HTV-59A. Here we report that both HLA-DMB mRNA and the protein are expressed in thyrocytes and that CIITA expression is enhanced by interferon-gamma (IFN-γ) treatment and occurs before DMB, Ii and DRA up-regulation, suggesting CIITA expression is a requirement for antigen processing in thyrocytes. These results indicate that thyrocytes are capable of antigen processing and possibly antigen presentation to T cells. [ABSTRACT FROM AUTHOR]

Enzymes and chemicals were used to analyse the biochemical structure of the antigenic epitope recognized by GDA-J/3 monoclonal antibody (MoAb) in the human sperm tail fibrous sheath. Treatment of sperm dried onto slides with trypsin or dispase enzymes abolished their immunofluorescence staining with GDA-J%3 MoAb, thus indicating the proteinaceous nature of the antigen. The proteolytic cleavage of GDA-J%F3 protein by trypsin, which also caused sperm decapitation, indicated the presence of peptide bonds involving the carboxyl groups of the basic amino acids, arginine and%or lysine. The epitope was also glycosylated as demonstrated by its sensitivity to sodium metaperiodate treatment which was dose–dependent. The GDA-J%F3 antigenic epitope lacked sialic acid since pre–treatment of spermatozoa with sialidase enzyme (neur–aminidase) had no effect on their reactivity with the antibody. The lack of collagenous domains in the GDA-J%F3 antigen was demonstrated by the failure of collagenase to abrogate sperm immunostaining with the MoAb. Furthermore, type VII collagen of the skin basement membrane (BM) was previously thought of as a potential target antigen for GDA-J%F3 MoAb. This was ruled out since several monoclonal and polyclonal antibodies failed to detect the antigen in the spermatozoa using immunofluorescence and Western blotting. These data, therefore, show that the target antigen for GDA-J%F3 MoAb is a non-collagenous asialo–glycoprotein, and by inference provide the first evidence for the glycosylation of the sheath proteins as another step of post–translational modification occurring during sperm tail development. [ABSTRACT FROM PUBLISHER]

The isolation and biochemical characterization of the human sperm tail fibrous sheath (FS) is described for the first time. Initially, the solubilization properties of the FS were assessed immunocytochemically using GDA-J/F3 and RT97 monoclonal antibodies (MoAbs) and morphologically by electron microscopy. Following extensive investigations to optimize the conditions for the FS isolation, a simple method was developed which involved sequential extraction of the flageller components with Triton-dithiothreitol (DTT) and urea-DTT. The procedure was monitored by phase contrast microscopy and the purity of the FS preparations was confirmed by electron microscopy. SDS-PAGE of the isolated FS revealed seven major protein bands with mol. wt of 97, 76, 62, 55, 33, 28 and 25 kDa. In Western blotting, the reaction of RT97 MoAb with supernatants from the various extraction steps and the isolated FS indicated that its target antigen (AJ-p97) was an integral FS product and that disulphide bonding was probably involved in its stabilization. The reactivity of normal and aprotruded sperm tails with GDA-J/F3 and RT97 MoAbs was not affected by Triton while the GDA-J/F3 staining of the cytoplasmic matrix of other abnormal spermatids was abolished, thus suggesting variation in the biochemical properties of GDA-J/F3 in normal and abnormal germ cells. These and other data indicate that the FS could be a modified form of intermediate filament. [ABSTRACT FROM AUTHOR]

This study proposes a bioprospection methodology regarding the antimicrobial potential of plant extracts against bacteria with cariogenic relevance. Sixty extracts were obtained from ten plants - (1) Jatropha weddelliana, (2) Attalea phalerata, (3) Buchenavia tomentosa, (4) Croton doctoris, (5) Mouriri elliptica, (6) Mascagnia benthamiana, (7) Senna aculeata, (8) Unonopsis guatterioides, (9) Allagoptera leucocalyx and (10) Bactris glaucescens - using different extraction methods - (A) 70° ethanol 72 h/25°C, (B) water 5 min/100°C, (C) water 1 h/55°C, (D) water 72 h/25°C, (E) hexane 72 h/25°C and (F) 90° ethanol 72 h/25°C. The plants were screened for antibacterial activity at 50 mg/ml using the agar well diffusion test against Actinomyces naeslundii ATCC 19039, Lactobacillus acidophilus ATCC 4356, Streptococcus gordonii ATCC 10558, Streptococcus mutans ATCC 35688, Streptococcus sanguinis ATCC 10556, Streptococcus sobrinus ATCC 33478 and Streptococcus mitis ATCC 9811. The active extracts were tested to determine their minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), cytotoxicity and chemical characterization. Forty-seven extracts (78%) were active against at least one microorganism. Extract 4A demonstrated the lowest MIC and MBC for all microorganisms except S. gordonii and the extract at MIC concentration was non-cytotoxic. The concentrated extracts were slightly cytotoxic. Electrospray ionization with tandem mass spectrometry analyses demonstrated that the extract constituents coincided with the mass of the terpenoids and phenolics. Overall, the best results were obtained for extraction methods A, B and C. The present work proved the antimicrobial activity of several plants. Particularly, extracts from C. doctoris were the most active against bacteria involved in dental caries disease. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Natural rubber/ cis-1,4-polybutadiene (NR/BR) blends with two types of layered nanofillers, montmorillonite (MMT) and layered double hydroxide (LDH), both in pristine and organically modified forms are produced and investigated. Faster curing is found for all the NR/BR blends, except for the one containing the unmodified MMT. This effect can be attributed to the groups placed in the interlayer regions of the clays; more precisely to ammonium groups for the organo-MMTs and to OH groups for LDHs. Mechanical properties and thermal stability of rubber compounds are investigated. It has been demonstrated that the performance of the final nanocomposite is significantly affected by the kind of clay. Particularly, the organo-MMTs provoke an improvement of the mechanical properties and increase the thermal stability of about 4-5° C in respect to the pure NR/BR matrix. On the contrary, the poor compatibility of unmodified MMT and of LDH clays with the rubber blend is evident and no enhancement on the composite performance has been observed. POLYM. ENG. SCI., 2013. © Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

Background: Innate immune system participates actively into inflammatory processes, with immune cells and liver secreting a number of immune peptides. Among them, both soluble CD14 receptor (sCD14) and human neutrophil alpha-defensins (HNDs) may represent serum markers of necro-inflammation in obese patients with non-alcoholic fatty liver disease. Methods: To verify this hypothesis, we investigated changes in circulating levels of sCD14 and HNDs in 11 severely obese young women following surgery-induced weight loss (bilio-pancreatic diversion). Patients were evaluated before surgery and 2 years later, with NAS score evaluated on liver biopsies and whole body glucose uptake ( M value) by euglycemic hyperinsulinemic clamp. Results: NAS score improved in nine patients [median NAS score in the whole sample, 6 (5-6) vs. 3 (3-4), p = 0.016]. Serum concentrations of HNDs decreased significantly in all ( p = 0.016), whilst sCD14 increased only in the nine women who showed the amelioration of the NAS score [2.4 (1.7-2.6) vs. 2.6 (2.3-3.3) μg/ml, p = 0.001]. NAS score and HNDs correlated significantly both before ( r = 0.671, p = 0.02) and after weight loss ( r = 0.683, p = 0.029), NAS score and sCD14 only before surgery ( r = 0.605, p = 0.04). The M value increased in all patients [2.67 (1.99-3.01) vs. 6.89 (6.35-7.32) mg kg min; p = 0.01], but independently of NAS score changes. Conclusions: Changes in levels of HNDs and sCD14 accompany those in hepatic necro-inflammation due to surgical-induced weight loss. Further studies are needed to verify any causative role of these peptides in non-alcoholic steatohepatitis. [ABSTRACT FROM AUTHOR]

Recent data show that regulatory cells with transforming growth factor (TGF)-β1-dependent activity are able to restore self-tolerance in overtly diabetic non-obese diabetic (NOD) mice. Thus, TGF-β1 seems to have a relevant role in protection from autoimmune diabetes. Our aim was to investigate the possible significance of serum TGF-β1 measurement in the natural history of diabetes in NOD mice, as well as in children positive for at least one islet-related antibody. Serum TGF-β1 (both total and active) was measured by enzyme-linked immunosorbent assay at monthly intervals in 26 NOD mice during the spontaneous development of diabetes and, on a yearly basis, in nine siblings of patients with type 1 diabetes (T1D) with a follow-up of 4 years. Diabetes appeared between the 12th week of age and the end of the study period (36 weeks) in 17 mice. TGF-β1 serum level variations occurred in the prediabetic period in both NOD mice and humans and diabetes diagnosis followed a continuing reduction of active TGF-β1 (aTGF-β1) serum levels. In mice, aTGF-β1 serum levels measured at 4 weeks of age correlated positively with severity of insulitis, and negatively with percentage of insulin-positive cells. Our findings suggest that in NOD mice serum TGF-β1 levels during the natural history of the diabetes reflect the course of islet inflammation. The measurement of aTGF-β1 in islet-related antibody-positive subjects may provide insights into the natural history of prediabetic phase of T1D. [ABSTRACT FROM AUTHOR]

Microarray technology is a powerful tool for the global evaluation of gene expression profiles in tissues and for understanding many of the factors controlling the regulation of gene transcription. This technique not only provides a considerable amount of information on markers and predictive factors that may potentially characterize a specific clinical picture, but also promises new applications for therapy. One of the most recent applications of microarrays concerns nutritional genomics. Nutritional genomics, known as nutrigenomics, aims to identify and understand mechanisms of molecular interaction between nutrients and/or other dietary bioactive compounds and the genome. Actually, many nutrigenomic studies utilize new approaches such as microarrays, genomics, and bioinformatics to understand how nutrients influence gene expression. The coupling of these new technologies with nutrigenomics promises to lead to improvements in diet and health. In fact, it may provide new information which can be used to ameliorate dietary regimens and to discover novel natural agents for the treatment of important diseases such as diabetes and cancer. This critical review gives an overview of the clinical relevance of a nutritional approach to several important diseases, and proposes the use of microarray for nutrigenomic studies. [ABSTRACT FROM AUTHOR]

The article presents a study which determines whether a support osteoclast precursor therapy may contribute to improve the osteopetrotic phenotype. The researchers have established a procedure to get the best yield of osteoclast precursors from human peripheral blood or mouse bone marrow mononuclear cells. They found that compared with sham-treated mice, animals presented with longer survival, improved weight and longitudinal growth, increased tibial length, tooth eruption, decreased bone volume, reduced bone marrow fibrosis and improved hematopoiesis.

Background: Type 1 diabetes is an autoimmune disease. Genetics as well as environmental factors seem to play a role in the pathogenesis of type 1 diabetes. Aims: We sought to investigate the possible relationship between migration from Sardinia to a low incidence area of type 1 diabetes (Lombardy) and the prevalence of autoantibody positivity. Methods: We enrolled 554 Sardinian immigrants and 226 of their offspring. All subjects underwent a complete anamnestic evaluation. Fasting blood glucose, HbA1c, GADA and IA-2 were measured in all study participants. Additionally, the presence of risk haplotypes (HLA-DR3 -DR4 and DQB1/0302) was determined. After a seven-year follow-up, high genetic risk and/or autoantibody positivity subjects were re-evaluated. Results: Among Sardinian immigrants, the prevalence of type 1 diabetes was 0.9%, while in the offspring group, the prevalence was 0.4%. After removing type 1 diabetic patients, the GADA prevalence was 2.4% in the immigrant group and 3.8% among their offspring. Among Sardinian immigrants, the IA-2 prevalence was 0.7%, while all offspring were IA-2 negative. After a seven-year follow-up, 85.7% of GADA-positive migrants had persistent GADA positivity. Two GADA-negative offspring subjects turned positive. None of the study participants developed diabetes during the follow-up. Conclusions: The present study showed a higher prevalence of GADA positivity within Sardinian immigrants at high genetic risk; GADA positivity may represent the first detectable phase of type 1 diabetes. After a seven-year follow-up, none of the high genetic/antibody risk group subjects developed type 1 diabetes. However, it seems reasonable to strictly control high-risk individuals in order to diagnose subclinical diabetes. (Tenconi MT, Devoti G, Rizzo M, Federico Roncarolo F, Bernasconi A, Lanati N, Calcaterra V, Songini M, Locatelli M, Gian F. Bottazzo Type 11 diabetes risk and autoantibody positivity in Sardinian migrants in the province of Pavia. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are highly conserved ~22-mer RNA molecules, encoded by plants and animals that regulate the expression of genes binding to the 3 ′-UTR of specific target mRNAs. The amount of miRNAs in a total RNA sample depends on the recovery efficiency that may be significantly affected by the different purification methods employed. Traditional approaches may be inefficient at recovering small RNAs, and common spectrophotometric determination is not adequate to quantify selectively these low molecular weight (LMW) species from total RNA samples. Here, we describe the use of qualitative and quantitative lab-on-a-chip tools for the analysis of these LMW RNA species. Our data emphasize the close correlation of LMW RNAs with the expression levels of some miRNAs. We therefore applied our result to the comparison of some miRNA expression profiles in different tissues. Finally, the methods we used in this paper allowed us to analyze the efficiency of extraction protocols, to study the small (but significant) differences among various preparations and to allow a proper comparison of some miRNA expression profiles in various tissues. [ABSTRACT FROM AUTHOR]

This article looks at pediatric Non Alcoholic Fatty Liver Disease (NAFLD) among co-morbidities. It reviews the concepts about pediatric NAFLD, its pathogenesis, diagnosis and treatment, with particular regard to lifestyle and food habits. It also indicates the possible causes of pediatric NAFLD. It highlights the association of NAFLD with abdominal obesity, insulin resistance and features of metabolic syndrome.

Abstract  Hybrid organic–inorganic materials exhibit so versatile properties that they can be considered one of the most interesting classes of materials for photonic applications, for the development of both passive and active devices. A synthetic route used for the preparation of nanostructured organic/inorganic (O/I) materials is the assembling of nano-building blocks (NBBs). This approach allows controlling the extent of phase interaction, which in its turn governs the structure-properties relationships. The non-hydrolytic sol–gel process is recognized as a useful route for the preparation of nanostructured molecular units. The condensation reaction of methacryloxypropyl trimethoxysilane and diphenylsilanediol in a non-hydrolytic sol–gel process has been exploited in order to synthesize nanostructured molecular units for the preparation of hybrid organic/inorganic coatings. The non-hydrolytic condensation reactions were run adding different compounds such as triethylamine, titanium isopropoxide, titanium chloride, and dibutyldilauryltin as condensation promoters. The NBB synthesis was also run under controlled hydrolitic conditions, by exploiting the in situ water production using an ethanol/acetic acid mixture. These reactions have been compared in terms of the influence of the employed reagents on the condensation degree and the product structure. Multinuclear NMR, ATR-FTIR and FT-Raman techniques have been used to study the reaction steps and characterize the final condensation products. Hybrid O/I materials have been prepared by assembling methacrylate-based NBBs in the presence of suitable thermal and photo-initiators. The study on the progress of the thermal polymerization process using differential scanning calorimetry (DSC) will be presented, as well as the preliminary results on the two photon polymerization (TPP) process for the preparation of patternable films. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The presence of autoantibodies to islet antigens GAD and/or tyrosine phosphatase 2 (IA-2) in type 2 diabetic patients (latent autoimmune diabetes in adults [LADA]) identifies subjects at high risk to develop insulin dependency. The aim of this study was to dissect humoral anti-IA-2 immune response in Caucasian LADA patients, identifying the most sensitive construct to evaluate IA-2 immunoreactivity and comparing LADA IA-2 epitope specificities to those found in type 1 diabetes. RESEARCH DESIGN AND METHODS: We analyzed 177 LADA and 978 type 2 diabetic patients with different disease duration, collected in a nationwide Italian survey, the Non-Insulin Requiring Autoimmune Diabetes (NIRAD) study aimed at assessing prevalence and characteristics of autoimmune diabetes in type 2 diabetic patients and 106 newly diagnosed type 1 diabetic patients (53 children, 53 adults). By radioimmunoassay, we analyzed humoral immunoreactivity to seven IA-2 constructs: IA-2(PTP (687-979)), IA-2((761-964)), IA-2((256-760)), IA-2(JM (601-630)), IA-2(IC (605-979)), IA-2(BDC (256-556:630-979)), and IA-2(FL (1-979)). RESULTS: IA-2((256-760)) fragment was identified as the marker with the highest sensitivity for detection of humoral IA-2 immunoreactivity in LADA patients, identifying IA-2 autoantibodies in approximately 30% of GAD antibody (GADA)-positive LADA patients and in 3.4% of GADA-negative type 2 diabetic patients. LADA IA-2((256-760))A positivity was associated with an increased frequency of autoimmune diabetes HLA-susceptible genotypes and with a higher risk for developing thyroid autoimmunity compared with autoantibody-negative type 2 diabetic patients. At disease diagnosis, adult-onset type 1 diabetic and LADA patients showed a lower IA-2 COOH-terminal immunoreactivity compared with childhood-onset type 1 diabetic patients. CONCLUSIONS: IA-2 immunoreactivity in LADA patients has thus far been underestimated, and IA-2((256-760)) autoantibody detection may represent a novel diagnostic tool for the identification of islet autoimmunity in these patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE--The presence of autoantibodies to islet antigens GAD and/or tyrosine phosphatase 2 (IA-2) in type 2 diabetic patients (latent autoimmune diabetes in adults [LADA]) identifies subjects at high risk to develop insulin dependency. The aim of this study was to dissect humoral anti-IA-2 immune response in Caucasian LADA patients, identifying the most sensitive construct to evaluate IA-2 immunoreactivity and comparing LADA IA-2 epitope specificities to those found in type 1 diabetes. RESEARCH DESIGN AND METHODS--We analyzed 177 LADA and 978 type 2 diabetic patients with different disease duration, collected in a nationwide Italian survey, the Non-Insulin Requiring Autoimmune Diabetes (NIRAD) study aimed at assessing prevalence and characteristics of autoimmune diabetes in type 2 diabetic patients and 106 newly diagnosed type 1 diabetic patients (53 children, 53 adults). By radioimmunoassay, we analyzed humoral immunoreactivity to seven IA-2 constructs: IA-2[sub PTP] (687-979), IA-2[sub (761-964)], IA-2[sub (256-760)], IA-2[sub JM (601-630)], IA-2[sub IC (605-979)], IA-2[sub BDC (256-556:63o-979)], and IA-2[sub FL (1-979)]. RESULTS--IA-2[sub (256-760)] fragment was identified as the marker with the highest sensitivity for detection of humoral IA-2 immunoreactivity in LADA patients, identifying IA-2 autoantibodies in ∼30% of GAD antibody (GADA)-positive LADA patients and in 3.4% of GADA-negative type 2 diabetic patients. LADA IA-2[sub (256-760)]A positivity was associated with an increased frequency of autoimmune diabetes HLA-susceptible genotypes and with a higher risk for developing thyroid autoimmunity compared with autoantibody-negative type 2 diabetic patients. At disease diagnosis, adult-onset type 1 diabetic and LADA patients showed a lower IA-2 COOH-terminal immunoreactivity compared with childhood-onset type 1 diabetic patients. CONCLUSIONS--IA-2 immunoreactivity in LADA patients has thus far been underestimated, and IA-2[sub (256-760)] autoantibody detection may represent a novel diagnostic tool for the identification of islet autoimmunity in these patients. Diabetes 57: 1276-1283, 2008 [ABSTRACT FROM AUTHOR]

Aim The aim of this study, which is part of the ongoing DIABFIN project, was to correlate HLA class II genotypes, classified for their effect on susceptibility to Type 1 diabetes (T1D), with various risk factors during pregnancy and the neonatal period. Methods Cord blood was collected from 4349 neonates; 1.0% were at high HLA risk (HR), 9.0% at moderate HLA risk (MR), and 90.0% at low HLA risk (LR) for T1D. Information about the mother's pregnancy, type of delivery, the neonates’ clinical features at birth, and family history for autoimmune diseases were collected. Results Significant correlations were found between the different HLA risk categories and length of gestation, even when adjusted for sex, weight and length at birth of the neonate, birth order and mother's age (adjusted P = 0.007). The male : female ratio tended to increase from the LR to the HR category, from 1.00 and 1.21, respectively, in the LR and MR groups, to 1.62 in the HR group ( P = 0.05). Conclusions Length of gestation is inversely correlated with HLA risk categories for T1D. The higher the HLA risk for T1D, the shorter the gestational age, especially in male neonates. [ABSTRACT FROM AUTHOR]

In addition to knowledge, the flow of information or efficient organisational communication is an essential condition for the successfulness of every organisation. Although the ideal vertical and horizontal communication is difficult to achieve, training-informational centres and special libraries should also strive to achieve this goal. Advantages of available communication technology, especially the Intranet, should be taken for this purpose as much as possible. The control of the field of management or knowledge transfer is a complex problem, which is practically unmanageable without the tool for knowledge dissemination. This is the reason why portals are used more and more. It is common to them that these are starting pages, where basic information is gathered in a condensed form; portals are starting points for more detailed information. They function on the basis of the technology supported by browsers. The topic of this paper is the development of an organisation in the process of learning, especially the need analysis of an organisation and setting up of a training portal as a tool for Intranet training, submission and flow of information. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: We examined the prevalence of islet autoantibodies and their relationship to glycaemic control over 10 years in patients diagnosed clinically with new-onset type 2 diabetes. Methods: Patient clinical characteristics and auto antibody status were determined at en- try to the UK Prospective Diabetes Study (IJKPDS) before randomisation to different glucose control policies. Patients were followed for 10 years. Results: Data available on 4,545 of the 5,102 UKPDS patients showed that 11.6% had antibodies to at least one of three antigens: islet cell cytoplasm, glutamic acid decarboxylase and islet auto- antibody 2A (IA-2A). Autoantibody-positive patients were younger, more often Caucasian and leaner, with lower beta cell function and higher insulin sensitivity than auto anti- body-negative patients. They also had higher HbA1c, and HDL-cholesterol levels, and lower blood pressure, total cholesterol and plasma triglyceride levels. Despite relative hyperglycaemia, autoantibody-positive patients were less likely to have the metabolic syndrome (as defined by the National Cholesterol Education Program Adult Treatment Program III), reflecting a more beneficial overall risk factor profile. Of 3,867 patients with post-dietary mn-in fasting plasma glucose (FPG) values between 6.0 and 14.9 mmol/l and no hyperglycaemic symptoms, 9.4% were autoanti- body-positive, compared with 25.1% of 678 patients with FPG values of 15.0 mmol/l or higher, or hyperglycaemic symptoms. In both groups, no differences were seen between those with and without autoantibodies in changes to HbA1c over time, but autoantibody-positive patients required insulin treatment earlier, irrespective of the allocated therapy (p'c0.000 1). Conclusions/interpretation: Auto- antibody -positive patients can be treated initially with sulphonylurea, but are likely to require insulin earlier than autoantibody-negative patients. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Established autoimmune mark- ers of type 1 diabetes, including islet cell autoantibodies (ICA) and auto antibodies to glutamic acid decarboxylase (GADA) have been used to screen people presenting with type 2 diabetes for latent autoimmune diabetes in adults. We have examined the prevalence of autoantibodies to protein tyro sine phosphatase iso forms IA-2 (IA-2A) and IA- 2(3/phogrin (IA-2(3A) in a cohort of adult UKPDS patients thought to have type 2 diabetes, and investigated the possible role of these automotive dies in predicting requirement for insulin therapy. Methods: IA-2A and IA-2(3A were measured by a validated radioimmunoassay with human recombinant autoantigens in 4,169 white Caucasian patients aged 25-65 years and newly diagnosed with type 2 diabetes. The clinical requirement for insulin therapy within 6 years was examined in 2,556 patients not insulin. Results: IA-2A and IA-2(3A were present in 2.2 and 1.4%, respectively, of these patients. IA-2A were more prevalent in younger patients (p for trend <0.00001), more often associated with the HLA-DR4 allele (26.3 vs 8.0%, p

Permanent neonatal diabetes mellitus (PNDM) is a rare condition characterized by severe hyperglycemia constantly requiring insulin treatment from its onset. Complete deficiency of glucokinase ( GCK) can cause PNDM; however, the genetic etiology is unknown in most PNDM patients. Recently, heterozygous activating mutations of KCNJ11, encoding Kir6.2, the pore forming subunit of the ATP-dependent potassium (KATP) channel of the pancreatic β-cell, were found in patients with PNDM. Closure of the KATP channel exerts a pivotal role in insulin secretion by modifying the resting membrane potential that leads to insulin exocytosis. We screened the KCNJ11 gene in 12 Italian patients with PNDM (onset within 3 months from birth) and in six patients with non-autoimmune, insulin-requiring diabetes diagnosed during the first year of life. Five different heterozygous mutations were identified: c.149G>C (p.R50P), c.175G>A (p.V59M), c.509A>G (p.K170R), c.510G>C (p.K170N), and c.601C>T (p.R201C) in eight patients with diabetes diagnosed between day 3 and 182. Mutations at Arg50 and Lys170 residues are novel. Four patients also presented with motor and/or developmental delay as previously reported. We conclude that KCNJ11 mutations are a common cause of PNDM either in isolation or associated with developmental delay. Permanent diabetes of non autoimmune origin can present up to 6 months from birth in individuals with KCNJ11 and EIF2AK3 mutations. Therefore, we suggest that the acronym PNDM be replaced with the more comprehensive permanent diabetes mellitus of infancy (PDMI), linking it to the gene product (e.g., GCK-PDMI, KCNJ11-PDMI) to avoid confusion between patients with early-onset, autoimmune type 1 diabetes. Hum Mutat 25:22-27, 2005. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Objective: To describe the treatment and long term outcome after immunosuppressive treatment of children with myocarditis. Methods and results: 114 patients with newly diagnosed dilated cardiomyopathy were divided into three groups, according to the histological pattern: group A, acute myocarditis; group B, borderline myocarditis; and group C, non-inflammatory cardiomyopathy. Groups A and B were treated with cyclosporine and prednisone in addition to conventional treatment. Survivors of the whole cohort were analysed for 13 year transplant-free survival and assessed for left ventricular function. Event-free survival at 13 years was 97 (3)% for group A, 70 (8)% for group B, and 32 (7)% for group C (p < 0.0001). It was 96 (4)% at one year and 83 (5)% at 13 years for the cumulated myocarditis group (A and B). Cardiac function recovered completely in 79% of survivors in group A, 64% in group B, and 36% in group C. The rate of complete recovery in the cumulated group (A and B) was 70%. Conclusions: The high long term survival rate of this cohort of children with myocarditis is probably due to the effect of short term immunosuppression. This result differs from previously published series of conventionally treated children, whose survival probability at one year was about 60%. [ABSTRACT FROM AUTHOR]

HLA class I and class II molecules play a major role in the presentation of short, pathogen-derived peptides to T cells, a process that initiates the adaptive cellular and humoral immune responses. However, the factors governing a cell's ability to respond or not to particular peptides are still not completely understood. Taking the example of a viral infection, in tissues infected with a virus, viral particles are taken up by antigen-presenting cells and uncoated. The viral DNA or RNA enters the nucleus, where it replicates. mRNA enters the cytosol and is transcribed into proteins. These proteins are degraded in proteasomes and the resulting peptides (8-10 residues) are loaded onto class I molecules for export to the surface of the cells. In the meantime, the groove of the class II molecules is also preparing to accommodate peptides (12-24 residues) generated by the endocytic protein-processing pathway. The surface of the infected cell then becomes adorned with peptide-loaded human leukocyte antigen (HLA) molecules. CD4+ T helper lymphocytes engage class II molecules and elicit responses from B cells, which will ultimately lead to antibody production, whereas CD8+ T lymphocytes become cytotoxic T cells. As a consequence, the virus is eliminated from the body. However, certain mysteries and challenges remain. How can, as an exception to this rule, an autoimmune response be the escape from the perfect machinery? This review offers some hypotheses on how to see the problem through to its solution. [ABSTRACT FROM AUTHOR]

Background To develop a sensitive, specific screening strategy for predicting genetic risk for type 1 diabetes mellitus (T1DM) in the low-incidence continental Italian population, and to define with this tool, a cohort of high-to-moderate risk infants for an immunological follow-up study aimed at identifying environmental risk factors for T1DM. Methods 4855 newborns in three regions of continental Italy were screened for T1DM HLA-DRB1-DQB1 risk genotypes using a reverse line blot typing method. Risk classification was based on odds ratios (OR) found in a preliminary case-control study (356 T1DM patients, 412 controls). Screening efficiency was optimized by allele subtyping. Results Screening for well-known T1DM susceptibility genotypes [DRB1*03/*04-DQB1*0302; DRB1*03/*03; DRB1*04/*04-DQB1*0302; DRB1*04-DQB1*0302/X where X ≠ DRB1*03, DRB1*04-DQB1*0302, DQB1*0602 or DQB1*0603] was associated with <60% sensitivity due to their low frequencies in the general Italian population. Inclusion of an additional genotype from which protective DRB1 and DQB1 alleles had been excluded [DRB1*03/X° where DQB1 ≠ *0301, *0503, *0602, or *0603 and X° ≠ DRB1*03, DRB1*04-DQB1*0302 or DRB1*07] increased screening sensitivity to 75% (specificity: 85%). Among 4855 newborns, we have found the high-risk genotype [DRB1*03/*04-DQB1*0302; estimated absolute risk (AR) 1/23] to be present in only 0.9%. The moderate-risk genotypes were found in 13.8% of newborns (estimated AR 1/177). Conclusions Risk classification must be tailored to the characteristics of the individual population, in particular, the allelic frequencies in the background population and T1DM prevalence. We have developed a screening strategy with good levels of sensitivity that should prove effective for use throughout the Italian peninsula. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Autoimmune diseases, with the exception of rheumatoid arthritis and autoimmune thyroiditis, are individually rare, but taken together they occur in up to 3-5% of the population in Western countries. These disorders are generally classified according to what organs and tissues are targeted by the damaging immune response In general, autoimmune diseases appear to have a multi-factorial pathogenesis, in which both genetic and environmental factors play important roles Several organ- and non-organ-specific autoantibodies are produced in organspecific autoimmunity. These antibodies are detectable at the time of diagnosis, but are also present in the latency period which precedes the clinical onset of disease, as best exemplified by the study of the natural history of T1DM. Autoantibodies should serve as indicators of the antigen-specific T cell responses, including those of the CD4+ and CD8+ T cell subpopulations considered separately.

Summary Autoantibodies to 65 kDa glutamic acid decarboxylase (GAD65) are produced in many patients with autoimmune polyendocrine syndrome type II (APS-II) or stiff-man syndrome (SMS) and are heterogeneous in their epitope specificities, recognizing both conformational and linear determinants. Major linear epitopes of GAD, which are recognized by autoantibodies in a minority of these patients, occur in the N-terminal and C-terminal regions. We have investigated antibody recognition of the N- and C-termini of GAD65 in relation to their structural features as an approach to understanding what modifications to the native GAD structure may occur that facilitate the generation of antibodies specific to linear epitopes in these regions during the autoimmune pathogenesis. A monoclonal antibody specific to the N-terminus of GAD65 bound both native and denatured GAD in ELISA, whereas monoclonal and polyclonal antibodies specific to the C-terminus of GAD bound only denatured GAD. These antibodies were epitope mapped using random peptide phage-display libraries and the epitopes related to a previously proposed structural model of GAD65. This has led us to propose that the α -helical secondary structure of the C-terminus of GAD65 must be denatured to generate linear epitopes. In contrast, the N-terminus is both surface exposed and linear in the native structure, but may be masked by membrane interactions, which must be broken to facilitate recognition by B cells. [ABSTRACT FROM AUTHOR]