The ability to undergo apoptosis, previously thought to be exclusive to multicellular organisms, has been demonstrated in unicellular parasites. On the basis of an observation that Plasmodium "crisis forms" were seen in vitro after cultivation in media containing an antimalarial drug, we attempted to determine whether Plasmodium falciparum has the ability to undergo apoptosis. By use of either the apoptosis-inducer etoposide or the antimalarial chloroquine, apoptosis in Plasmodium asexual stages was evident by the observation of DNA fragmentation and disruption of transmembrane mitochondrial potential. Next, we sought to determine whether Plasmodium produces specific cysteine proteases that can induce apoptosis. We hypothesized that the 2 metacaspase-like proteins present in the Plasmodium genome contained features typical of downstream execution steps and upstream signaling pathways such caspase activation and domain recruitment. We report that one of the metacaspase genes, PF13_0289, in addition to a universally conserved catalytic cysteine and histidine dyad required for catalysis activity, contains a putative caspase recruitment domain in the N-terminal amino acid sequence. This putative P. falciparum metacaspase protein has been designated PfMCA1. Our findings offer important insights into parasite survival strategies that could open new ways for therapeutic alternatives to drug resistance.

Introduction:Pulmonary embolism (PE) is a life-threatening illness with high morbidity and mortality. Echocardiography (ECG) plays an important role in the early identification of right ventricular (RV) dysfunction, making it a helpful tool in identifying hemodynamically stable patients affected by PE with a higher mortality risk. The purpose of this study was to evaluate if one or more ECG indexes could predict a short-term evolution towards RV dysfunction.Methods:We selected all patients consecutively admitted to the Careggi Hospital Emergency Department with the clinical suspicion of PE, confirmed by computed tomography angiography prior to enrollment. Subsequently, properly trained emergency physicians acquired a complete ECG to measure RV morphological and functional indices. For each patient, we recorded if he or she received a fibrinolytic treatment, a surgical embolectomy or heparin therapy during the emergency department (ED) stay. Then, every patient was re-evaluated with ECG, by the same physician, after 1 week in our intensive observation unit and 1 month as outpatient in our ED regional referral center for PE.Results:From 2002 to 2007, 120 consecutive patients affected by PE were evaluated by echocardiography at the Careggi Hospital ED. Nine patients (8%) were treated with thrombolytic therapy. Six died within 1 week and 4 abandoned the study, while the remaining 110 survived and were re-evaluated by ECG after 1 week and 1 month. The majority of the echocardiographic RV indexes improve mostly in the first 7 days: Acceleration Time (AT) from 78±14 ms to 117±14 ms (p<0.001), Diameter of Inferior Vena Cava (DIVC) from 25±6 mm to 19±5 mm (p<0.001), Tricuspid Annular Plane Systolic Excursion (TAPSE) from 16±6 mm to 20±6 mm (p<0.001). Pulmonary Artery Systolic Pressure (PASP) showed a remarkable decrease from 59±26 mmHg to 37±9 mmHg, (p<0.001). The measurements of the transverse diameters of both ventricles and the respective ratio showed a progressive normalization with a reduction of RV diameter, an increase of Left Ventricular (LV) diameter and a decrease of RV/LV ratio over time. To evaluate the RV function, the study population was divided into 3 groups based on the TAPSE and PASP mean values at the admission: Group 1 (68 patients) (TAPSE+/ PASP−), Group 2 (12 patients) (TAPSE−/PASP−), and Group 3 (30 patients) (TAPSE−/PASP+). Greater values of AT, minor RV diameter, greater LV diameter and a lesser RV/LV ratio were associated with a short-term improvement of TAPSE in the Group 2. Instead, in Group 3 the only parameter associated with short-term improvement of TAPSE and PASP was the treatment with thrombolytic therapy (p<0.0001).Conclusion:Greater values of AT, minor RV diameter, greater LV diameter and a lesser RV/LV ratio were associated with a short-term improvement of TAPSE−/PASP− values. Patients with evidence of RV dysfunction (TAPSE−/PASP+), may benefit from thrombolytic therapy to improve a short- term RV function. After 1 month, also a decreased DIVC predicted improved RV function.

Antibiotic strategies against Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients should consider the natural history of the P. aeruginosa infection, ranging from the first isolation of the germ in the airways to isolation at every microbiological culture, and the patient's clinical condition. Antibiotic treatment against P. aeruginosa given at the time of first isolation may prevent or delay chronic infection. The period of intermittent colonization can be considered the time before the development of mucoid P. aeruginosa phenotype. The optimal treatment strategy in this stage remains unclear in terms of agents used and duration of treatment. To treat acute exacerbation, the authors suggest using intravenous administration of two different classes of antibiotics. Maintenance antibiotics are administered to slow the decline in pulmonary function for P. aeruginosa chronic infection. The meaning of maintenance therapy has changed over time, beginning from intravenous quarterly anti-Pseudomonas antibiotics, irrespective of symptoms, to other strategies such as oral macrolides, ciprofloxacin or inhaled antibiotics (tobramycin and colistin). Aerosol delivery can provide a high concentration at the desired site with minimal absorption and therefore low risk of toxicity. There is scientific evidence that antibiotics are clinically effective in CF patients. Antibiotic selection should be based on periodic isolation and identification of pathogens and antimicrobial susceptibility.

Background: Novel facilities such as an intensive observation unit and an outpatient clinic could result in improving management of patients presenting with atrial fibrillation (AF). Methods: This observational study enrolled 3475 patients. Group 1 (1120 patients; years [2004][2005] was managed with standard approach; group 2 (992 patients; years [2006][2007] was managed with additional intensive observation; group 3 (1363 patients; years 2008-2009) was managed with additional intensive observation and outpatient clinic. Primary end point was admission to hospital. Secondary end points included modalities of rhythm conversion and administration of class IC vs class III antiarrhythmic drugs in patients with AF lasting less than 48 hours. Results: Lack of rhythm control, comorbidities, diabetes, and age were independent predictors of hospitalization. Admissions significantly decreased from group 1 (50%) to 2 (38%) and to 3 (24%) (P b .001). Interestingly, more than a quarter of patients in group 3 were referred to the outpatient clinic for short-term follow-up, eventually avoiding admission. Patients with AF lasting less than 48 hours (n = 2189) and without structural heart disease (n = 1685) achieved sinus rhythm in 89% of cases and were discharged. In these patients, early administration of antiarrhythmic drugs of class IC and III gained sinus rhythm in 80% and 20%, respectively (P b .001). Spontaneous conversion occurred in 26%; electrical, 17%; and pharmacological, 57%. Conclusions: In patients with AF, beyond the standard approach, the novel organization with an additional intensive observation unit for early pharmacological interventions and an outpatient clinic for elective treatment and short-term follow-up significantly reduced admission irrespective of independent predictors of hospitalizations. Patients without structural heart disease treated with antiarrhythmic drugs achieved sinus rhythm in 89% of cases, mostly with class IC drugs.

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The aim of cystic fibrosis (CF) care is to improve both the life expectancy and quality of life of patients. However, rising costs and limited resources of health services must be taken into account. There are many different antibiotic strategies for therapy of Pseudomonas aeruginosa infection in CF patients. In this 5-year retrospective study we found that the cost of treatment of initial infection is considerably lower than the cost of treating chronic P. aeruginosa infections. The percentage distribution of costs of antibiotic treatment in relationship to the administration route was considerably different between outpatients and inpatients. We observed an increase in antibiotic costs with the age of the patient and the decrease in FEV(1)values. The implementation of early eradication treatment, in addition to decreasing the prevalence of patients chronically infected by P. aeruginosa, might also bring about a notable decrease in costs.

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