Early neonatal inflammation affects adult pain reactivity and anxiety related traits in mice: genetic background counts

Protracted or recurrent pain and inflammation in the early neonatal period may cause long-lasting changes in central neural function. However, more research is necessary to better characterize the long-term behavioral sequelae of such exposure in the neonatal period. Objectives: (1) to study whether timing of postnatal exposure to persistent inflammation alters responsiveness to thermal pain in the adult animal; (2) to assess whether animals experiencing early postnatal chronic inflammation display altered anxiety related behavior; (3) to study the importance of genetic background. Newborn mice (outbred strain, CD1 and F1 hybrid strain, B6C3F1) received an injection of Complete Freund's Adjuvant (CFA) or saline on either postnatal day 1 or 14 (PND1; PND14) into the left hind paw. Pain to radiant heat and anxiety were examined in 12-week-old adult animals. Adult baseline PWL was significantly decreased in CD1 mice exposed to CFA on PND 1 and 14 as compared to their saline treated counterparts. B6C3F1 mice exposed to CFA on PND14 showed markedly reduced baseline PWL compared to the PND14 saline group. Persistent inflammation experienced by B6C3F1 mice on PND1 failed to affect baseline adult thermal responsiveness. Adult mice, CD1 and B6C3F1, displayed low anxiety traits only if they had been exposed to persistent inflammation on PND1 and not on PND14. Our research suggests a role for genetic background in modulating long-term behavioral consequences of neonatal persistent inflammation: the data support the hypothesis that pain experienced very early in life differentially affects adult behavioral and emotional responsiveness in outbred (CD1) and hybrid mice (B6C3F1).     

Comparative Evaluation of Ligation-Mediated PCR and Spoligotyping as Screening Methods for Genotyping of Mycobacterium tuberculosis Strains

Spoligotyping has been suggested as a screening test in multistep genotyping of Mycobacterium tuberculosis strains. Relying on restriction fragment length polymorphism (RFLP) analysis with IS6110 (IS6110 RFLP analysis) as a "gold standard," we performed a comparative evaluation of spoligotyping and ligation-mediated PCR (LMPCR), a recently described PCR-based typing method, as rapid screening tests for fingerprinting of 158 M. tuberculosis strains collected in Verona, Italy. LMPCR seemed to be comparable to spoligotyping in terms both of feasibility with rapidly extracted DNA and of generation of software-analyzable images. Moreover, LMPCR grouped considerably fewer strains than spoligotyping (38 versus 67%) and was found to reduce the cluster overestimation rate (26.3 versus 58%) and to give a better discriminatory index (0.992 versus 0.970) compared to spoligotyping. In our geographical region, where there was no evidence of clustered strains carrying fewer than six IS6110 copies, LMPCR was found to be more discriminatory than spoligotyping. We also evaluated two models of three-step typing strategies, involving the use of spoligotyping and LMPCR as screening methods and IS6110 RFLP analysis as a further supporting test. LMPCR proved to be a more effective first-step test than spoligotyping, significantly reducing the need for subtyping. LMPCR should be considered an alternative to spoligotyping as a rapid screening method for M. tuberculosis fingerprinting, particularly in areas with a low prevalence of M. tuberculosis strains carrying few copies of IS6110.     

Attitudes and knowledge about transplantation in dialyzed patients requesting a cadaveric kidney graft

AIM: Eighty-two patients answered a multiple choice questionnaire aimed at identifying their presumed and actual knowledge regarding transplantation, given immediately before evaluation by our transplant team for inclusion on our kidney transplant waiting list. SUBJECTS, METHODS AND RESULTS: A total of 78% stated that they had no or incomplete knowledge of transplantation and 22% were very well informed. The mean score for technical knowledge of transplantation (duration, requirement for removal of native kidneys, possibility of obtaining a second transplant, duration of immunosuppressive therapy and duration of the risk of rejection) was 3.1 +/- 0.15 SEM (maximal possible score 5), that for risk knowledge (risks of infections, unpleasant side effects, hypertension, diabetes mellitus, viral infections and cancer) was 1.4 +/- 0.15 (maximal possible score 6). A total of 23% knew that the spouse could donate a kidney, 74% stated that only a blood relative could and 3% that living donation was impossible. CONCLUSIONS: There is scarce knowledge about transplantation, especially with regard to the risks and living donation.     

Prognostic value of CD40 in adult soft tissue sarcomas.

PURPOSE: The purpose is to evaluate the expression of CD40, a membrane protein predominantly expressed on B cells, dendritic cells, and macrophages, in a series of adult soft tissue sarcomas and to test its possible prognostic value. EXPERIMENTAL DESIGN: CD40 expression was studied by immunohistochemistry. Correlations with other baseline characteristics of patients and tumors were analyzed with chi(2) test. The prognostic value was studied with univariable and multivariable analysis adjusted by age, sex, tumor size, grade, location, and distant metastases. RESULTS: Eighty-two patients, between January 1994 and May 2001, were analyzed. Membrane or cytoplasmic staining for CD40 protein was absent in 30% of the tumors but present in <10% of cells in 22 (27%), in 10% to 50% in 23 (28%), and in >50% of cells in 12 (15%) tumors. There was no correlation between CD40 expression and age, sex, size, grade, and location of the primary tumor and distant metastases. With 61 patients (74.4%) progressed and 31 (37.8%) dead, CD40 expression was a significant prognostic factor for disease-free and overall survival at univariable and multivariable analysis. Patients with tumors expressing CD40 in >50% of cells had a dramatically unfavorable prognosis with median disease-free and overall survival of 7 and 17 months, respectively, and hazard ratios of relapse and death as compared with patients with CD40-negative tumors of 2.89 (95% confidence interval: 1.26-6.60) and 6.92 (95% confidence interval: 2.18-22.0), respectively. CONCLUSIONS: These data suggest that expression of CD40 protein in >50% of cells might indicate an unfavorable prognosis in adult soft tissue sarcomas.     

Trichoderma species fungemia after high‐dose chemotherapy and autologous stem cell transplantation: a case report

We present a case of Trichoderma fungemia with pulmonary involvement in a multiple myeloma patient, who was severely immunocompromised and heavily treated with high‐dose melphalan, and underwent autologous hematopoietic cell transplantation. This is the first report, to our knowledge, of proven Trichoderma fungemia, defined by published criteria, successfully treated with voriconazole.     

West Nile virus transmission through organ transplantation in north-eastern Italy: a case report and implications for pre-procurement screening

Purpose

West Nile virus (WNV) transmission through organ transplantation occurs rarely and screening of organ donors for WNV infection remains controversial. This report describes the case of WNV encephalitis in a kidney recipient and the case of asymptomatic WNV infection in the organ donor, both observed at Treviso Hospital, northeastern Italy. After briefly reviewing the literature, we discuss the implications for WNV screening.

Methods

We reviewed medical, laboratory and epidemiological records at our hospital, and the literature concerning cases of organ-transmitted WNV infections and WNV screening of organ donors in Italy and worldwide.

Results

The kidney recipient was the first confirmed case of WNV infection notified in northeastern Italy in 2011, and the first case of WNV infection in a cluster of four transplant recipients who acquired the infection from a common organ donor. The organ donor, whose WNV infection was only retrospectively diagnosed by IgM detection, represents the index case of a WNV outbreak in the Treviso Province. Screening of her blood prior to organ recovery did not show detectable levels of WNV nucleic acid with the use of quantitative real-time polymerase chain reaction.

Conclusions

This report emphasizes that transplant-acquired WNV neuroinvasive disease can be particularly severe. We suggest that pre-procurement screening of organ donors by testing blood with both WNV IgM capture ELISA and a sensitive nucleic acid testing should be adopted during the transmission season in the present Italian epidemiological setting.     

Role of relaxation and specific suggestions in hypnotic emotional numbing.

The cognitive characteristics of highly hypnotizable subjects (Highs) allow them to easily modify their cognitive and autonomic state. Under hypnosis, Highs receiving cognitive, fear-like stimulation exhibit the cardiovascular changes typical of fear/stress, but also show an EEG pattern indicating a balance between fear-induced arousal and hypnotic relaxation. Indeed, hypnosis is effective in the attenuation of both emotional experience and behaviour (emotional numbing). The aim of the present experiment was to investigate the possible different role of relaxation and suggestion in hypnotic emotional numbing. Tonic skin conductance, respirogram, heart rate, systolic and diastolic blood pressure were recorded in 3 groups of hypnotized subjects: Group 1 received a fearful guided imagery associated with threat suggestions (Threat) followed by the same fearful suggestion associated with numbing instructions (relaxation and "No-Threat"); Group 2 received the same instructions in the opposite order of presentation; Group 3 received the fearful suggestion with threat instructions twice. The numbing suggestion reduced fear-related emotional experience and autonomic responses; if No-Threat preceded Threat, the heart rate, heart rate variability and blood pressure were also reduced during Threat, in spite of self reports of high negative emotion. Thus, 1) the subjective experience and the autonomic response to fear can be dissociated; 2) the efficacy of numbing suggestion is extended to a subsequent Threat stimulation; 3) habituation does not contribute to the numbing effect. The results indicate that the specific numbing suggestion is the main factor in hypnotic modulation of the experience of fear.     

Electrochemotherapy Treatment of Locally Advanced and Metastatic Soft Tissue Sarcomas: Results of a Non-Comparative Phase II Study

Aims

Our aim was to evaluate the activity, toxicity, and feasibility of electrochemotherapy (ECT) in patients with soft-tissue sarcomas (STS).

Methods

A two-stage phase II trial was conducted between October 2006 and March 2012. Patients (N = 34) with locally advanced or metastatic STS, unsuitable for standard oncological treatments and with maximum 3-cm deep tumors, received an intravenous bolus of bleomycin (15,000 IU/m²), followed by tumor electroporation according to the European Standard Operating Procedures of ECT. Outcome measures included local response according to response evaluation criteria in solid tumors (RECIST), toxicity and tumor control. Feasibility measures included the accuracy of electrode placement and the intensity of electric current flowing in tumor tissue.

Results

Median tumor size was 4.0 cm (range 2–12). Objective response, assessed on 71 target lesions, was 92.2 % (complete 32.3, 95 % CI 28–64). A total of 15 patients received up to four cycles due to incomplete response, but re-treatment did not significantly improve outcome (p = 0.205). After a median follow-up of 19.3 months, 2-year local control rate was 72.5 %. Median time to local failure (N = 11 patients) was 5.1 months. Tumor response (p = 0.041) and control (p = 0.047) correlated with histological grading. Relevant toxicity consisted of G3 skin ulceration and soft tissue necrosis (35 and 23 % of patients, respectively), although this was manageable on an outpatient basis. The accuracy of electrode placement was 47.1 %, and the adequacy of electroporative current 85.3 %.

Conclusions

ECT may represent an active and safe treatment to achieve local control in advanced STS patients with symptomatic disease. Future research challenges include the improvement of electrode placement and voltage delivery together with the containment of soft tissue toxicity.