Using diffusion MRI data acquired with ultra-high gradient strength to improve tractography in routine-quality data.

The development of scanners with ultra-high gradient strength, spearheaded by the Human Connectome Project, has led to dramatic improvements in the spatial, angular, and diffusion resolution that is feasible for in vivo diffusion MRI acquisitions. The improved quality of the data can be exploited to achieve higher accuracy in the inference of both microstructural and macrostructural anatomy. However, such high-quality data can only be acquired on a handful of Connectom MRI scanners worldwide, while remaining prohibitive in clinical settings because of the constraints imposed by hardware and scanning time. In this study, we first update the classical protocols for tractography-based, manual annotation of major white-matter pathways, to adapt them to the much greater volume and variability of the streamlines that can be produced from today's state-of-the-art diffusion MRI data. We then use these protocols to annotate 42 major pathways manually in data from a Connectom scanner. Finally, we show that, when we use these manually annotated pathways as training data for global probabilistic tractography with anatomical neighborhood priors, we can perform highly accurate, automated reconstruction of the same pathways in much lower-quality, more widely available diffusion MRI data. The outcomes of this work include both a new, comprehensive atlas of WM pathways from Connectom data, and an updated version of our tractography toolbox, TRActs Constrained by UnderLying Anatomy (TRACULA), which is trained on data from this atlas. Both the atlas and TRACULA are distributed publicly as part of FreeSurfer. We present the first comprehensive comparison of TRACULA to the more conventional, multi-region-of-interest approach to automated tractography, and the first demonstration of training TRACULA on high-quality, Connectom data to benefit studies that use more modest acquisition protocols.

The colorectal cancer screening program in the local health unit n. 6 of Livorno: evaluation of the screening activity in the period 2000-2011.

INTRODUCTION: The colorectal cancer screening program in the Local Health Unit n. 6 of Livorno is running since July 2000 and is meant to residents, aged between 50 and 70, who are invited to perform the test for faecal occult blood every 2 years. The aim of this work is an evaluation of the screening activity in the period 2000-2011. METHODS: The evaluation is based on the analysis of the main quality indicators formulated by GISCoR (Italian Group for Colorectal screening). RESULTS: The screening activity extension reached 93% in 2006 and 100% in 2009. The compliance level was maintained above the acceptable GISCoR value (> 45%) with a maximum of 54.9%. Values around 80% were recorded for the compliance to colonoscopy. The detection rate (DR) for cancer and advanced adenoma showed, as expected, the highest values in the early years and then move on values consistently lower than the regional average. In 2011, the raw DR for cancer was 0.9 x 1000 and the raw DR for advanced adenoma 5.3 x 1000. The distribution by stage at diagnosis of screen-detected carcinomas shows that 58.1% of these were identified at stage I while the proportion of cases in stage III+ is 19.5%. CONCLUSIONS: The overall analysis shows a good performance of the program. The proportion of colonoscopies performed on the total number of positive subjects remains a critical point of the system. The distribution by stage of screen-detected cancers shows an excellent diagnostic anticipation of the screening program.

Murine model of invasive pulmonary Aspergillosis: Follow-up of tissue injury, fungal burden and mortality with distinct elastase production strains.

To study invasive pulmonary Aspergillosis (IPA), we depleted neutrophils in mice using the monoclonal antibody anti-Gr-1/Ly-6G. Immunocompetent and neutropenic mice were infected via intratracheal with conidia of Aspergillus fumigatus clinical isolates, characterized as either higher or lower elastase producers. Neutropenic animals exhibited 100% mortality in 5 days, for both strains, and were observed survival curves overlapped, lungs with angioinvasion, rupture of bronchial and vascular walls, associated with exuberance of conidia filamentation. The immunocompetent animals infected with the lower elastase producer strain presented with upregulated inflammatory processes, and a lack of conidia filamentation in the tissue. The fungal burden in the lungs was not different in the immunocompetent and neutropenic groups. These findings confirm the protective role of neutrophils against A. fumigatus and suggest that the fungal elastinolytic activity is not a critical virulence factor but may be involved in tissue injury.

Prediction of adherence to antiretroviral therapy: can patients' gender play some role? An Italian pilot study.

Recent literature has shown that adherence to HAART is a multi-faceted phenomenon, which involves both behavioural and psychological features. Therefore, the results obtained so far, though promising, have not yet unambiguously identified the factors that could predict non-adherence. Since any support for strengthening the adherence should take into account the HIV+ patients' perception of both their state of health and their relational style, this study tried to identify some psychological characteristics involved in the adherence phenomenon. A self-administered battery of tests including the Attachment Style Questionnaire (ASQ) and the Multidimensional Health Locus of Control Form-C (MHLC-C) was administered to an Italian sample. Results showed significant gender differences between non-adherent and adherent subjects. Specifically, the psychological profile of non-adherent males seemed focused less on relational aspects and perceived relevance of physicians and of 'significant other people', whilst that of non-adherent females seemed more 'relationship-oriented'. This study means to encourage clinicians to plan specific, gender-focused support for enhancing adherence.

The usefulness of the Multidimensional Health Locus of Control Form C (MHLC-C) for HIV+ subjects: an Italian study.

In the last few years, highly active antiretroviral therapy (HAART) has resulted in a remarkable decrease in HIV-related morbidity and mortality. This "new deal" encouraged clinical research in investigating patients' manifest behaviours and their beliefs regarding their health status, which likely influence not only their treatment-linked behaviours but also their quality of life. Locus of control has been shown to be a construct that can predict and explain health-related behaviours. The Multidimensional Health Locus of Control Form C (MHLC-C) is a condition-specific locus of control scale that can be easily adapted for use with any medical or health-related condition. With the aim to enhance the knowledge about the HIV+ patients' point of view of their complex health condition, this study preliminarily investigated the psychometrics properties of the MHLC-C Italian version and its generalizability across samples defined both by being adherent or not and by gender. Two more samples of chronic patients (Cardiac Surgery and Cancer) were enrolled to better characterize the HIV+ patient's MHLC-C profile. The results showed the validity, reliability and generalizability of the 4-factor structure of MHLC-C. More interestingly, HIV+ subjects revealed a peculiar pattern of beliefs regarding their health condition that clinicians should take into account when managing patients' complex bio-psychosocial condition.

Increasing hepatitis B vaccination coverage among healthcare workers in Italy 10 years apart.

BACKGROUND: In Italy, vaccination against hepatitis B virus infection was strongly recommended for healthcare workers since 1985. Update findings on vaccination coverage are lacking. AIM: To assess current vaccination coverage against hepatitis B in this job category. METHODS: In 2006, 1,632 healthcare workers randomly selected in 15 Italian public hospitals completed a self-administered precoded questionnaire. RESULTS: The overall vaccination coverage was 85.3%, a figure higher than the 64.5% observed in 1996. Vaccine coverage showed a significant downtrend (p<0.01) from the Northern (93.1%) to the Southern (77.7%) areas. Logistic regression analysis showed that residence in the North (Odds ratio 4.2; 95% confidence interval 2.6-6.7) and youngest age (Odds ratio 4.5; 95% confidence interval 2.6-7.8), both were independent predictors of vaccine acceptance. CONCLUSIONS: Ten years apart, vaccine coverage has markedly increased, closely paralleling the downtrend in the incidence of acute B hepatitis among healthcare workers in Italy.

Patient mortality after graft failure reduces kidney transplant patient survival only in the long term: an "intention to treat" analysis.

The benefits of kidney transplantation over dialysis on patient survival have been demonstrated without considering the outcomes of patients with graft loss. To determine whether mortality after graft failure reduced the transplantation advantage in patient survival, we retrospectively reviewed the outcomes of 918 first-deceased renal transplant recipients from May 1979 to August 2005. Patient survivals were 88% and 72% at 10 and 20 years; cancer (26%) and cardiovascular disease (25%) were the major causes of death. Graft survivals were 72% and 50% at 10 and 20 years; chronic rejection was the major cause of graft loss (50%). Patient outcomes after return to dialysis were reviewed in 224 of 240 patients. The survivals were 97%, 83%, and 70% at 1, 5, and 10 years, respectively; cardio-cerebrovascular disease (56%), infections (9%), cachexia (9%), and cancer (8%) were the major causes of death. Mortality correlated with patient age at transplantation (P< .001). Re-listed patients (96 of 224) were younger (32+/-10 vs 43+/-11 years; P< .001), had a shorter dialysis period pretransplant (3.2+/-3.1 vs 4.3+/-3.9 years; P< .03), and a better survival at 10 years (98% vs 56%; P< .001). Ten-year mortality for patients who returned to dialysis was 20% higher than for patients with a functioning graft (P< .001). The reduction in overall patient survival was 2.2% at 10 years (P=NS), 5% at 15 years (P=NS), and 14% at 20 years (P< .05). The same results have been demonstrated for patients >50 years at transplantation. In conclusion, the mortality rate after return to dialysis did not influence the long-term benefits of kidney transplantation.

[Outpatient monitoring after renal transplantation: protocols shared between transplant center and local nephrology units]. / Protocolli condivisi per il follow-up decentrato del paziente trapiantato.

Outpatient monitoring plays a key role in the long-term success of kidney transplantation. Shared management of transplanted patients between transplant centers and local nephrology units is becoming common practice and is a benefit both for the patients, who can be followed in an outpatient office closer to their homes, and for the transplant centers, which are overwhelmed by an increasing number of follow-up patients. The program is also well accepted by the referring nephrology units, which are interested in improving their skills. In this article a model of clinical collaboration is discussed, although it is well known that it is impossible to apply the same rules to all centers. However, to make any collaborative program feasible, two main requirements must be met. First, every local unit should have a referent nephrologist responsible for the clinical follow-up of transplant recipients and for the waiting list; second, every transplant center should organize transplant refresher courses for their referring nephrologists.

Effects of personality on metabolic control in IDDM patients.

OBJECTIVE: The aim of this study was to evaluate the relationship between poor metabolic control and maladaptive personality traits (according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised) in an adult-onset insulin-dependent diabetes mellitus sample group (n = 77). RESEARCH DESIGN AND METHODS: Metabolic control was evaluated through glycosylated hemoglobin (HbA1c). Personality traits were assessed with the Personality Diagnostic Questionnaire-Revised, a self-administered questionnaire. Residual pancreatic secretion (fasting serum C-peptide) was also evaluated. RESULTS: Principal components analysis revealed three personality profiles: "withdrawn-suspicious" (P1), "dramatic-dependent" (P2), and "aggressive-irresponsible" (P3). Multiple linear regression analysis showed that C-peptide levels and P2 personality profiles were significant and independent predictors of HbA1c plasma levels: P2 predicted high HbA1c values and C-peptide predicted low HbA1c levels. CONCLUSIONS: These data suggest that a P2 personality profile is a significant predictor of poor metabolic control.

[Successful treatment with liposomal doxorubicin and foscarnet in a patient with widespread Kaposi's sarcoma and human herpes virus 8-related, serious hemophagocytic syndrome, after renal transplantation]. / Efficacia del trattamento con doxorubicina liposomiale e foscarnet in un caso di sarcoma di Kaposi disseminato e grave sindrome emofagocitica herpes virus 8 correlate, nel post-trapianto di rene.

BACKGROUND: It is well known that the human herpes virus 8 (HHV8) is linked to several malignancies such as Kaposi's sarcoma (KS). Moreover, pancytopenia due to hemophagocytic syndrome could be associated with HHV8 infection. In renal transplant recipients affected by KS, the tapering of immunosuppression often leads to KS remission, but also results in graft loss in >50% of cases. Chemotherapy and antiviral therapy have also been used, mainly in the presence of visceral involvement. CASE REPORT: We describe a transplant recipient with widespread cutaneous and visceral KS HHV8 associated, complicated by hemophagocytic syndrome. At transplantation the patient's serology for HHV8 was negative, but thereafter it became positive. The first step in treatment (cyclosporine dose reduction until suspension) failed to improve the clinical course. Therefore, therapy combining liposomal doxorubicin and foscarnet was started. Clearance of HHV8 in the blood and complete resolution of the KS lesions were achieved. Immunosuppression with cyclosporine was resumed. No KS relapse has occurred, blood tests for HHV8 are negative, and graft function is good after a 5-yr follow-up. CONCLUSIONS: Therapy combining liposomal doxorubicin and foscarnet was effective in this renal transplant recipient with KS and HHV8 infection and enabled us to resume immunosuppressive therapy; therefore, reducing the risk of acute/chronic rejection.

An international perspective on assessment of negative and positive symptoms in schizophrenia.

The authors used the Scale for Assessment of Negative Symptoms and the Scale for Assessment of Positive Symptoms in interviews of 96 psychiatric inpatients in Italy. They evaluated the interrater reliability and the internal consistency of these scales for the assessment of negative and positive symptoms in schizophrenia. Their findings indicate that the results of these scales are similar in Italy and the United States, countries with different languages and cultures.

Leukotrienes are involved in leukocyte recruitment induced by live Histoplasma capsulatum or by the beta-glucan present in their cell wall.

1. The inflammatory cell influx towards the peritoneal cavity in mice inoculated i.p. with live or dead Histoplasma capsulatum or with its subcellular preparations was studied. We also evaluated the effects of dexamethasone (Dexa) or MK886, an inhibitor of leukotriene (LT) biosynthesis, on the recruitment of leukocytes. 2. Live yeast form of fungus (LYH) induced an increase in neutrophils (NE) which was highest 4 to 24 h after inoculation. Mononuclear cell (MN) migration beginning at 24 h with a gradual increase over 48 and 168 h, and an eosinophil (EO) recruitment occurs between 24 and 48 h. 3. NE and EO recruitment induced by dead mycelial form of fungus (DMH) was greater than that observed for dead yeast form of fungus (DYH). A similar leukocyte migration pattern was seen after i.p. injection of the alkali-insoluble fraction (F1) from DYH (F1Y) and F1 from DMH (F1M) this being more active than former. The difference in concentration of beta-glucan in DYH and DMH could explain the different inflammatory capacity exhibited by the two forms of H. capsulatum. 4. LT seems to be the principal mediator of leukocyte migration in response to LYH, DYH or DMH or to beta-glucan. However, other mediators appear to contribute to NE and EO migration since the treatment with Dexa was more effective in inhibiting cell migration than MK886. Complement dependent leukocyte migration may participate in this recruitment. Treatment with MK886 completely abolished MN cell migration, indicating its dependence on the presence of LT.

Low-dose clozapine in acute and continuation treatment of severe borderline personality disorder.

BACKGROUND: Psychotic-like symptoms in patients affected by borderline personality disorder (BPD) are usually treated with low-dose neuroleptics, which show controversial acute effects and lead to a worsening of affective-related symptoms and to severe neurologic side effects after prolonged administration. Clozapine lacks the neurologic side effects of traditional neuroleptics and has been shown to successfully treat psychotic-like symptoms in BPD patients at medium dose. We performed an open-label trial of low-dose clozapine in severe BPD patients. METHOD: Twelve BPD inpatients (DSM-IV criteria) with severe psychotic-like symptoms were studied. Exclusion criteria included comorbid Axis I and medical pathologies. All patients had followed a therapeutic program without improvement for at least 4 months before admission. The clozapine dose was titrated upward on an individual basis until the complete disappearance of psychotic-like symptoms was achieved. Clinician-rated scales were completed at the beginning of the study and after 4 and 16 weeks. RESULTS: All patients completed the 16-week study. Individual clozapine doses ranged from 25 to 100 mg/day. Psychotic-like symptoms decreased within the first 3 weeks of treatment, as confirmed by a statistically significant decrease in Brief Psychiatric Rating Scale scores. This amelioration was coupled with an overall improvement, including a reduction in impulsive behaviors and in affective-related symptoms (Hamilton Rating Scale for Depression) and an increase in global functioning (Global Assessment of Functioning). CONCLUSION: Low-dose clozapine for acute and continuation treatment led to improvement in overall symptomatology in a small sample of severe BPD patients.

Nosocomial outbreak of systemic candidosis associated with parenteral nutrition.

Eight patients in two surgical units developed systemic candidosis during a 40-day period from June 5 to July 13, 1987 (in five cases Candida albicans was identified). Three of them died. All cases belonged to a group of 27 patients receiving parenteral nutrition (PN), while among the 108 patients who did not receive PN, no cases were observed (p = .000001). Candida was cultured from two PN bags administered to the cases. A specialized nutrition nurse was responsible for the PN compounding and for maintaining administration sets in the two wards involved. An epidemiological investigation, in which 19 uninfected patients who had had PN were used as controls, showed no significant difference between cases and controls except that lipids were more frequently added to bags administered to cases (p = .0005). Furthermore, the bags administered to cases contained a higher average number of multidose constituents (p = .0008) when the comparison was focused on the two days before the onset of symptoms. Given the favorable medium provided by lipids, even a low level contamination of PN solutions during compounding and/or administration could have been responsible for the exposure of cases to multidose vials suggests, although not conclusively, that an extrinsic contamination occurred during compounding. Six isolates of C albicans were available from four cases. C albicans was cultured from the pharyngeal swabs of two physicians and three nurses, including the specialized nutrition nurse.

A psychometric-genetic study of schizotypal disorder.

This study aimed to clarify the structure and the etiological constituents of schizotypal disorder (SPD) by directly interviewing pairs of twins. A latent class analysis was applied to each individual's outcome for specified SPD items, such that each subject's phenotype could be redefined in terms of individual probabilities of class membership. Intraclass correlations were then calculated for each twin pair, and a standard univariate twin model applied. The best latent class analysis solution encompassed a model with four latent classes (three latent classes of SPD subjects, one of non-SPD). The intraclass correlations revealed a moderate to high heritability for two out of three SPD classes and for the modal class (a class composed of subjects that possessed a conditional probability of belonging to any of the SPD classes). Model fittings revealed considerable variation in the extent to which the different classes of SPD were influenced by additive genetic constituents or non-genetic factors. Although these data confirm the importance of genetic contributors in determining liability to SPD and the schizophrenia spectrum, they indicate that there is a relationship between psychometric multidimensionality and etiological heterogeneity in SPD.

Latent class analysis of DSM-IV schizotypal personality disorder criteria in psychiatric patients.

The aim of the study was to evaluate the latent structure of DSM-IV schizotypal personality disorder (SPD) diagnostic criteria. The sample consisted of 564 consecutively admitted inpatients and outpatients. Exploratory latent class analysis identified a four-class model as the best fitting model for DSM-IV SPD criteria. The first of the SPD latent classes was mainly characterized by odd thinking, inappropriate affect, and interpersonal features; the second class by cognitive/perceptual difficulties; the third class by paranoid features; and the fourth class by absence of SPD features. The conditional probability pattern of the fourclass solution could be safely replicated across confounder strata. Unlike previous findings, oddness, aloofness, and social withdrawal, rather than positive symptoms, best characterized SPD even in clinical samples.

Personality disorders and psychopathologic symptoms in patients with androgenetic alopecia.

BACKGROUND AND DESIGN: The few articles published on the interactions between psychological factors and alopecia seem to yield contrasting results. To assess the relationships between alopecia, gender, Diagnostic Statistical Manual of Mental Disorders, Revised Third Edition personality disorders, and psychopathologic symptoms reactive to alopecia, we administered the Personality Disorders Questionnaire-Revised and the Symptoms Checklist-90 to a randomly selected sample of 116 outpatients with androgenetic alopecia. RESULTS: The prevalence of personality disorders in subjects with androgenetic alopecia proved to be significantly higher than the prevalence of such diagnoses in the general population. Women did not show a higher prevalence of personality disorders or more psychopathologic symptoms than men. The factor analysis demonstrated the existence of three personality profiles (F1, F2, and F3) significantly and specifically associated with the subject's gender and with the psychopathologic reactive symptoms, measured using the Symptoms Checklist-90. CONCLUSIONS: The most important factor in developing a psychopathologic reaction to alopecia seems to be the presence of a Diagnostic Statistical Manual of Mental Disorders, Revised Third Edition personality disorder and not the subject's gender.

beta-N-acetyl-D-glucosaminidase isoenzymes by chromatofocusing from serum and skin in diabetes.

beta-N-Acetyl-D-glucosaminidase and its kinetic characteristics were determined in serum and skin from both diabetes mellitus and impaired glucose tolerance patients and controls. Mean total activity was reduced (p less than 0.05) in the skin of both patient groups. beta-N-Acetyl-D-glucosaminidase isoenzyme expression was investigated using chromatofocusing on PBE-94 coupled with automated enzyme assay. The isoenzyme profiles from serum showed two major forms (A and B) whose ratio varied from 2:1 in controls to 3:1 in diabetics. Moreover, diabetes mellitus and impaired glucose tolerance subjects displayed an intermediate (I) form. The A/B isoenzyme ratio was completely reversed in skin.

alpha-L-Fucosidase activity and isoenzyme characteristics analyzed by chromatofocusing in normal and leukemic lymphocytes.

alpha-L-Fucosidase (EC 3.2.1.51) activity and isoenzyme characteristics were analyzed in normal lymphocyte subpopulations, chronic lymphocytic leukemia subpopulations, and acute lymphoblastic leukemia blasts. Similar pH activity profiles revealed that pH 5.0 was optimal in normal and leukemic cells. Unfractionated CLL lymphocytes had a lower specific activity than normal unfractionated lymphocytes (2.5 +/- 1.0 u/10(6) cells v. 4.0 +/- 1.1). CLL B cells and T-cells had lower specific activity than their respective normal counterparts (1.8 +/- 0.2 v. 5.9 +/- 2.0) (B-cells); (2.2 +/- 0.5 v. 3.7 +/- 1.0) (T-cells) suggesting T and B cells in CLL are abnormal. ALL blasts had a higher specific activity compared to unfractionated normal lymphocytes (9.7 +/- 3.0 v. 4.0 +/- 1.1; p less than 0.001). The isoenzyme pattern of normal, CLL and ALL lymphocytes were obtained by automated chromatofocusing on PBE 94 microcolumns using 0.025 M histidine and polybuffer 74. Two major isoenzyme components (B and A) were isolated. The activity ratio of B/A was different in normal, ALL, and CLL cells.

Risk management of HBsAg or anti-HCV positive healthcare workers in hospital.

Recommendations are made for controlling the transmission of the hepatitis B and hepatitis C viruses from healthcare workers to patients. These recommendations were based both on the literature and on experts' opinions, obtained during a Consensus Conference. The quality of the published information and of the experts' opinions was classified into 6 levels, based on the source of the information. The recommendations can be summarised as follows: all healthcare workers must undergo hepatitis B virus vaccination and adopt the standard measures for infection control in hospitals; healthcare workers who directly perform invasive procedures must undergo serological testing and the evaluation of markers of viral infection. Those found to be positive for: 1) HBsAg and HBeAg, 2) HBsAg and hepatitis B virus DNA, or 3) anti-hepatitis C virus and hepatitis C virus RNA must abstain from directly performing invasive procedures; no other limitations in their activities are necessary. Infected healthcare workers are urged to inform their patients of their infectious status, although this is left to the discretion of the healthcare worker; whose privacy is guaranteed by law. If exposure to hepatitis B virus occurs, the healthcare worker must undergo prophylaxis with specific immunoglobulins, in addition to vaccination.