Brain regions related to fear extinction in obsessive-compulsive disorder and its relation to exposure therapy outcome: a morphometric study.

BACKGROUND: The size of particular sub-regions within the ventromedial prefrontal cortex (vmPFC) has been associated with fear extinction in humans. Exposure therapy is a form of extinction learning widely used in the treatment of obsessive-compulsive disorder (OCD). Here we investigated the relationship between morphometric measurements of different sub-regions of the vmPFC and exposure therapy outcome in OCD. METHOD: A total of 74 OCD patients and 86 healthy controls underwent magnetic resonance imaging (MRI). Cortical thickness and volumetric measurements were obtained for the rostral anterior cingulate cortex (rACC), the medial orbital frontal cortex and the subcallosal cortex. After MRI acquisition, patients were enrolled in an exposure therapy protocol, and we assessed the relationship between MRI-derived measurements and treatment outcome. Baseline between-group differences for such measurements were also assessed. RESULTS: Compared with healthy controls, OCD patients showed a thinner left rACC (p = 0.008). Also, left rACC thickness was inversely associated with exposure therapy outcome (r - 0.32, p = 0.008), and this region was significantly thinner in OCD patients who responded to exposure therapy than in those who did not (p = 0.006). Analyses based on regional volumetry did not yield any significant results. CONCLUSIONS: OCD patients showed cortical thickness reductions in the left rACC, and these alterations were related to exposure therapy outcome. The precise characterization of neuroimaging predictors of treatment response derived from the study of the brain areas involved in fear extinction may optimize exposure therapy planning in OCD and other anxiety disorders.

Improved diagnosis of central venous catheter-related bloodstream infections using the HB&L UROQUATTRO™ system.

The diagnosis of catheter-related bloodstream infections (CRBSIs) in febrile patients with indwelling central venous catheters (CVCs) needs improvement. To diagnose CRBSIs more efficiently, we have developed a novel culture approach using the catheter tips removed from febrile patients. CVCs and blood cultures from 1,070 patients with only CVC-related infections were obtained over a period of 3 years (January 2009 to December 2011). The CVCs were evaluated by a semi-quantitative catheter culture method according to Maki's method and by our novel method, which is based on the use of the HB&L UROQUATTRO™ system (Alifax, Padova, Italy). Using our new method, 571 (571/1,070) of the infections were confirmed as CRBSIs. The remaining 487 patients had infections that were associated with hematologic malignancies, neutropenia, prior exposure to antibiotics, and a decreased CVC removal rate. Twelve samples were identified as false-positives. The percentage of patients with CRBSIs confirmed using the HB&L UROQUATTRO™ system was 53.36 % versus 34.95 % (p-value 0.004) using Maki's method (374/1,070 CVC Maki-positive samples). Our results indicate that our new culture method allows for an improved CRBSI diagnosis rate. A significant number of tip cultures (18.41 %) tested positive for CRBSIs using our system but were negative when tested using Maki's method. Moreover, the use of the HB&L UROQUATTRO™ system allowed us to significantly reduce diagnosis time; a negative CRBSI diagnosis could be made within 6 h and a positive diagnosis could be made within 22-28 h.

The combined use of VIGI@ct (bioMérieux) and fluorescent amplified length fragment polymorphisms in the investigation of potential outbreaks.

Even with good surveillance programmes, hospital-acquired infections (HAIs) are not always recognized and this may lead to an outbreak. In order to reduce this risk, we propose a model for prompt detection of HAIs, based on the use of a real-time epidemiological information system called VIGI@ct (bioMèrieux, Las Balmas, France) and on the rapid confirmation or exclusion of the genetic relationship among pathogens using fluorescent amplified length fragment polymorphism (f-AFLP) microbial fingerprinting. We present the results of one year's experience with the system, which identified a total of 306 suspicious HAIs. Of these, 281 (92%) were 'confirmed' by clinical evidence, 16 (5%) were considered to be simple colonization and the latter nine (3%) were archived as 'not answered' because of the absence of the physician's cooperation. There were seven suspected outbreaks; of these, f-AFLP analysis confirmed the clonal relationship among the isolates in four cases: outbreak 1 (four isolates of Pseudomonas aeruginosa), outbreak 2 (three Escherichia coli isolates), outbreak 6 (two Candida parapsilosis isolates) and outbreak 7 (30 ESbetaL-producing Klebsiella pneumoniae subsp. pneumoniae). Based on our results, we conclude that the combination of VIGI@ct and f-AFLP is useful in the rapid assessment of an outbreak due to Gram-positive or Gram-negative bacteria and yeasts.

Influence of antimalarials chloroquine, quinine, primaquine and mepacrine on the evolution of Ehrlich ascites tumour.

Substances like imidazoles, benzimidazoles and also quinolines, whose chemical structure includes a heterocyclic nitrogen, are known to interfere with the microsomal oxidation and, in some cases, with the metabolism of drugs. Since chloroquine and primaquine exert this effect in vivo and in vitro, we studied the influence of other antimalarials (quinine and mepacrine) in mice with induced Ehrlich ascites tumour (EAT) to find out whether variations in oxygen consumption affected the course of the disease. In vitro data, obtained by a polarographic technique, indicate that primaquine and, in particular, mepacrine increase EAT-cell oxygen consumption, while in vivo data, obtained in mice injected with an inoculum of about 1 x 10(6) tumour cells per mouse, show that both drugs, but notably mepacrine, accelerate tumour growth, as monitored by Cox's statistical method for body weight, and lead to earlier death. In cases of existing neoplasia, therefore, the potentially toxic effects of certain antimalarials must be borne in mind.

Requests of medical examinations after pneumococcal & influenza vaccination in the elderly.

BACKGROUND & OBJECTIVES: There are no specific recommendations about pneumococcal vaccination (PV) in Italy. There are limited data on the requests of medical examination or hospitalization due to side effects of pneumococcal vaccination. In the present study we present our analyses on the requests of medical examination due to side effects of pneumococcal vaccination (PV) in 29,086 elderly aged >/=65 yr. METHODS: Vaccination with influenza vaccine (IV) alone or in association with PV was offered during the IV campaign in the winter 1999-2000 in 8 counties of Sicily. General practitioners (GPs) provided the vaccination and, 72 h later, recorded local and systemic side effects by a telephonic interview with the waccinees. GPs recorded also the requests of medical treatments. RESULTS: A total of 16,601 subjects (57.1%) were vaccinated with IV alone and 12,485 (42.9%) with the association IV+PV. Adverse effects were reported by 14.7 per cent of vaccinees. Out of 4,289 subjects with side effects, 305 (7.1%) looked for a medical examination. The factors associated with a significantly increased risk for medical examination after vaccination were symptoms duration >72 h (OR 2.04; 95% CI 1.38-3.01; P=0.0002); local induration (OR 3.26; 95% CI 2.07-5.13; P<0.0001); general malaise (OR 2.05; 95% CI 1.34-3.13; P=0.0009); fever >/=38 degrees C (OR 3.34; 95% CI 1.90-5.86; P<0.0001); myalgia (OR 2.80; 95% CI 1.46-5.37; P=0.0018) and dyspnea (OR 37.86; 95% CI 9.65-148.60; P=0.0001). INTERPRETATION & CONCLUSION: The few requests for medical examination and the low rate of adverse effects confirmed the tolerability and safety of PV+IV; GPs consultation were related to the severity and duration of symptoms, but independent of the type of vaccine administered.

Variables affecting salivary Streptococcus mutans counts in a cohort of 12-year-old subjects.

BACKGROUND: Several factors such as toothbrushing, diet, acidogenic potential of the mutans streptococci strain and site of the carious lesion can modify the salivary Streptococcus mutans (Sm) counts. In the present investigation the effect of some behavioural, clinical and microbiological variables on Sm salivary counts was evaluated in a cohort of 12-year-olds. METHODS: Forty subjects were examined by two calibrated examiners (GC, AL). The number of surfaces either decayed occlusal, decayed smooth or filled and the number of bleeding sextants, (clinical index for oral hygiene) were reported. Saliva was collected using a tongue depressor and was plated onto mitis salivarius agar with bacitracin and 20% sucrose. The presumptive Sm colonies were counted and the concentrations were logarithmically transformed. One Sm strain per subject was identified and the cariogenic potential evaluated as the minimum pH value recorded, during 5 hrs of incubation in 5% sucrose solution. The children's parents or guardians completed a questionnaire concerning the frequency of toothbrushing, the consumption of sweet foods and soft drinks and at what age the children started brushing their teeth. The effect of the explanatory variables on Sm count logarithms was evaluated by stepwise multiple regression. RESULTS: The regressors with significant additional explanatory power were cariogenic potential (b = -1.335, p = 0.00001, R2 increment = 0.312), decayed smooth surfaces (b = -0.456, p = 0.009, R2 increment = 0.114) and bleeding sextants (b = -0.113, p = 0.004, R2 increment = 0.062), whereas the power of filled surfaces was marginally significant (p = 0.08). CONCLUSIONS: On the basis of these results, it is suggested that acidogenicity is not only a cariogenic factor, but also a factor promoting colonization of oral sites by Sm, especially in subjects with a high frequency of sugar consumption.

Models and molecular orbital semiempirical calculations in the study of the spectroscopic properties of bovine serum amine oxidase quinone cofactor.

The electronic properties of 2,4,5-trihydroxyphenylalanine quinone (TPQ), the cofactor of bovine serum amine oxidase [Janes, S. M., Mu, D., Wemmer, D., Smith, A. J., Kaur, S., Maltby, D., Burlingame, A. L., & Klinman, J. P. (1990) Science 248, 981-987], and some adducts with hydrazines were investigated by means of low-molecular-weight models and semiempirical molecular orbital calculation methods. The enzyme visible band was assigned to the first pi-->pi* transition of the cofactor in p-quinonic form, with the C-4 hydroxyl ionized and hydrogen bonded either to a water molecule or to a basic protein residue. The spectra of the protein adducts with some substituted hydrazines were well accounted for by assuming the inhibitor bound to the C-5 carbonyl, usually in azo form. The adduct with the unsubstituted hydrazine was instead assigned an o-quinone hydrazone form, stabilized by an internal hydrogen bond between the amino group and the ortho carbonyl oxygen, a larger electron delocalization, and formation of a hydrogen bond at the C-6 ionized hydroxyl. On the basis of these assignments, the reaction of the protein with benzylhydrazine [Morpurgo, L., Agostinelli, E., Muccigrosso, J., Martini, F., Mondovi, B., & Avigliano, L. (1989) Biochem. J. 260, 19-25] was rewritten. All examined electronic transitions, though highly sensitive to cofactor ionization and hydrogen bonding, could be accounted for without introducing perturbations due to copper. This confirms that copper is not within bonding distance of the oxidized cofactor.

In-vitro studies of two 5-nitroimidazole derivatives.

This paper reports the findings obtained using two new compounds belonging to the 5-nitroimidazole family: sulphuridazole (V1) and sulphonidazole (V2). We first assessed their antimicrobial activity on Clostridia spp. and then extended the study to Gram-positive and Gram-negative aerobic microorganisms and to Candida albicans. Their MICs were compared with those of metronidazole. The findings show that the antibacterial and antimycotic activity of sulphonidazole is greater than that of sulphuridazole, while metronidazole is not active against any aerobic organism. It also emerges that the NO2 group is indispensable for all the microorganisms assayed and that sulphuridazole and sulphonidazole are the first two 5-nitroimidazoles active against C. albicans. The redox potentials of the 5-nitroimidozoles studied suggest that their action mechanism is mainly based on redox processes.