ANAT 3.0: a framework for elucidating functional protein subnetworks using graph-theoretic and machine learning approaches.

BACKGROUND: ANAT is a Cytoscape plugin for the inference of functional protein-protein interaction networks in yeast and human. It is a flexible graphical tool for scientists to explore and elucidate the protein-protein interaction pathways of a process under study. RESULTS: Here we present ANAT3.0, which comes with updated PPI network databases of 544,455 (human) and 155,504 (yeast) interactions, and a new machine-learning layer for refined network elucidation. Together they improve network reconstruction to more than twofold increase in the quality of reconstructing known signaling pathways from KEGG. CONCLUSIONS: ANAT3.0 includes improved network reconstruction algorithms and more comprehensive protein-protein interaction networks than previous versions. ANAT is available for download on the Cytoscape Appstore and at https://www.cs.tau.ac.il/~bnet/ANAT/ .

A survey of methicillin-resistant Staphylococcus aureus control strategies in Italy.

PURPOSE: Data regarding the implementation of state-of-the-art methicillin-resistant Staphylococcus aureus (MRSA) control procedures in Italy are lacking. There is a need to evaluate compliance with MRSA recommendations (CR) in Italian hospitals. METHODS: A 67-question closed-answer survey was sent to all Italian hospitals, in order to analyze and evaluate program consistency with CR [hand hygiene (HH), contact precautions, screening of high-risk patients, decolonization, feedback on surveillance data, and antimicrobial guidelines and education programs]. RESULTS: 205 hospitals, which account for 42 % of national admissions, returned questionnaires. 131 hospitals (64 %) did not have written MRSA control guidelines. Hospitals reported the following levels of compliance with CR: (1) HH: 67 hospitals (33 %); (2) contact precautions: 33 (16 %); (3) MRSA screening: 66 (32 %); (4) MRSA decolonization: 42 (20 %); (5) surveillance data feedback: 87 (43 %); and (6) antimicrobial guidelines and education programs: 41 (20 %). One hospital (0.5 % of responses) had implemented all recommendations and 28 hospitals (14 %) had implemented four or five recommendations. 31 % of hospitals surveyed had implemented none. Multivariate analysis showed that the only factor identified as being associated with the implementation of MRSA control recommendations was the number of meetings/year of the infection control team (ICT) (p = 0.004). CONCLUSIONS: Written MRSA control guidelines are available in only one-third of Italian facilities. An organized system, with ≥4 interventions, has been implemented in just 1 out of 7 hospitals. HH programs and ICT activity are related to better MRSA control. In Italy, there is significant opportunity for improvement in MRSA control.

Association between facial measurements and polymorphisms in human epidermal growth factor and transforming growth factor ß1.

The aim of the study was to evaluate the association between genetic polymorphisms in human epidermal growth factor (EGF) (rs4444903) and transforming growth factor ß1 - (TGF-ß1) (rs1800470) with facial measurements in patients with dentofacial deformities. A total of 144 adult patients with dentofacial deformities were included. Facial linear and angular measurements were traced in lateral cephalometric radiographs used Dolphin 2D software. Cells from oral mucosa were collected for DNA to be extracted. The polymorphisms were genotyped using real-time polymerase chain reaction (PCR). Probabilites of less than 0.05 were accepted as significant. The rs4444903 heterozygous patients had a decrease in the mandibular length (p=0.043) and the length of the mandibular base (p=0.008), and homozygous A patients also had a reduction in the length of the mandibular base (p=0.013) compared with homozygous G patients. Patients AG had an increase in measurement of the anterior facial height (p=0.032) and in ANS-Me distance (p=0.022) when compared with homozygous A. To the rs1800470, heterozygous patients had an increase in the length of the mandibular base (p=0.043) when compared with homozygous A. Heterozygous AG patients had an increase in angular measurements in TGF-ß1 polymorphism for the upper gonial angle, when compared with the homozygous AA (p=0.032). Genetic polymorphisms in EGF and TGF-ß1 are associated with facial measurements in a Brazilian population of patients with dentofacial deformities.

Adherence to surgical site infection guidelines in Italian cardiac surgery units.

BACKGROUND: Data on the adherence to surgical site infection (SSI) prevention guidelines in Italian cardiac surgery units are lacking. METHODS: A multiple-choice questionnaire, structured into eight sections following the Centers for Disease Control 1999 (CDC) guidelines, was prepared and sent to 24 surgical units participating in a national study group (GIS-InCard); this units perform over 20% of all cardiac surgical procedures in Italy. Answers were stratified based upon the evidence of the recommendations: grade IA (ten questions), grade IB (52 questions), grade II (11 questions), and no recommendation (seven questions). RESULTS: 17 of the 24 units (72%) returned the questionnaire. Adherence to grade IA recommendations was 69 +/- 34%, with five units (29%) showing a > or =80% adherence. Adherence to grade IB and II was 65 +/- 26% and 71 +/- 28%, respectively. Adherence did not vary significantly depending on the evidence of the recommendation, i.e., grade IA, IB or II (p = 0.72). Low adherence levels to grade I recommendations were observed on hair removal: (1) it was performed systematically in all male patients (0% adherence), (2) it was performed on the morning of the intervention in 29% of centers, and (3) the method of hair removal was adequate in 41% of cases. Despite 94% of units having written guidelines on antibiotic prophylaxis, only 65% administered antibiotic prophylaxis with the correct timing - i.e., on anesthesia induction. CONCLUSIONS: Adherence to CDC SSI guidelines in Italy is fair. The evidence of the recommendation does not influence adherence. Organizational improvements, especially those regarding hair removal and the timing of antibiotic prophylaxis, should be implemented in most hospitals.

Risk factors and clinical characteristics associated with hospitalization for community-acquired bacterial pneumonia in HIV-positive patients according to the presence of liver cirrhosis.

BACKGROUND: Community-acquired bacterial pneumonia (CABP) represents an important cause of morbidity and mortality for cirrhotic and HIV-infected patients, respectively. However, little is known on CABP in HIV-positive patients with cirrhosis. A study was performed to describe the clinical features and factors predictive of mortality and prolonged hospitalization in cirrhotic HIV-infected patients with a diagnosis of CABP. METHODS: Demographic and clinical characteristics of cirrhotic HIV-positive subjects, hospitalized for CABP in our department from June 2000 to December 2006, were compared with those of non-cirrhotic HIV-infected patients with the same diagnosis hospitalized from June 2000 to November 2001. Variables with p < 0.10 in univariate analysis were tested for their predictive value for mortality and length of hospitalization with uni- and multivariate logistic regression analysis. RESULTS: Twenty-nine cirrhotic and 73 non-cirrhotic HIV-positive patients with CABP were compared. Age and alcohol abuse were significantly higher in cirrhotics. At hospital admission, cirrhotic patients had more frequently mental status alterations (7.26 [2.21-23.82], p = 0.001) and milder symptoms and signs (temperature > 37.5 C: 0.27 [0.10-0.75], p = 0.01; respiratory rate > 20: 0.34 [0.13-0.92], p = 0.033; systemic inflammatory response syndrome (SIRS): 0.39 [0.16-0.95], p = 0.038). Adjusting for age, cirrhosis was associated with a higher mortality (5.96 [1.05-33.57]; p = 0.043). Adjusting for age, gender, and concomitant antiretroviral treatment, cirrhosis was also associated with a prolonged hospitalization (> 7 days: 9.30 [1.84-46.82]; p = 0.007). CONCLUSION: The diagnosis of CABP can be difficult in cirrhotic HIV-positive patients because clinical presentation is milder. However, CABP needs to be promptly recognized because mortality is higher in these patients.

Recent changes in bacterial epidemiology and the emergence of fluoroquinolone-resistant Escherichia coli among patients with haematological malignancies: results of a prospective study on 823 patients at a single institution.

BACKGROUND: Regular monitoring of bacterial epidemiology allows evaluation of antibacterial strategies adopted. The aim of this study was to disclose evolving trends in the epidemiology of infections and emerging antibiotic resistance in unselected inpatients with haematological cancers. METHODS: Febrile/infectious episodes occurring in 823 patients consecutively admitted to a single institution during a 16 month period were analysed. Levofloxacin prophylaxis was used in patients with >7 days expected neutropenia. RESULTS: Fever developed in 364 patients (44.2%) and an infection was documented in 187 (22.7%), either clinically (6.1%) or microbiologically (16.6%). Levofloxacin prophylaxis, used in 39.4% of cases, caused a reduction in febrile episodes only among neutropenic patients and no difference in the frequency of documented infections. Among 164 pathogens isolated, gram-negative (49.4%) outweighed gram-positive bacteria (40.9%), Escherichia coli being most frequent (23.2%). Fluoroquinolone resistance and methicillin resistance were the most frequent types of antibiotic resistance, occurring in 56.1% of bacterial isolates and in 66.7% of staphylococci, respectively. Fluoroquinolone-resistant E. coli accounted for 20.1% of all isolates and for 86.8% of E. coli. Multivariate analysis of risk factors for fluoroquinolone resistance identified prophylaxis (P < 0.001) and neutropenia >7 days (P = 0.02) as independent. Methicillin resistance was independently associated with prophylaxis (P = 0.041) and central venous catheters (P = 0.036). Infections by fluoroquinolone-resistant strains did not show a worse outcome. CONCLUSIONS: A shift towards gram-negative bacteria has been occurring in recent years in the bacterial epidemiology of haematological patients. Fluoroquinolone resistance is emerging as a major type of antibacterial resistance, particularly among E. coli strains. Further investigation is needed to explore the consequences of such epidemiological changes.

Hyper-reactive malarial splenomegaly in a patient with human immunodeficiency virus.

Both hyperreactive malarial splenomegaly (HMS) and HIV infection are highly prevalent in sub-Saharan Africa, but the inter-relationships between the two conditions are not clearly defined. Diagnosis of HMS is particularly difficult in HIV-infected patients, and detection of circulating malaria parasites by polymerase chain reaction (PCR) may represent a useful diagnostic tool.

Consumerism in prenatal diagnosis? A local Italian study.

AIM: To assess the causes of excessive use of prenatal diagnosis. MATERIAL AND METHODS: 304 questionnaires were completed anonymously by puerperae in a Siena (Italy) hospital in May-August 2006. The questionnaires contained 24 questions about the women, examinations performed during pregnancy and the reasons for them. RESULTS: The mean number of ultrasound examinations per woman was 6.5 +/- 2.5. Forty-two percent of the women in our sample (29.3% of women under 35 and 68.9% of women over 35 years of age) reported that amniocentesis/CVS had been performed; the mean age of these women was 34.1 +/- 4.5 years. Eighty-five percent of the women under 36 years of age who had amniocentesis declared that it was performed as a personal choice and 15% for the presence of risk factors. Among 131 women who performed amniocentesis, 32 performed it with a normal blood screening for Down syndrome (DS), and 76 declared to have performed no blood screening for DS. Only 45% of women stated that they thought age above 35 years was a risk factor for pregnancy, but most of them (75%) were aware that amniocentesis was performed to detect chromosomal anomalies. In 89% of the cases a source of information about prenatal testing was the woman's gynecologist. CONCLUSION: This study shows that the high use of prenatal examinations is often not justified by the presence of clinical risk factors and that both national health system and caregivers should find new strategies to inform women about the aims of prenatal tests, and promote a more serene approach to pregnancy. A broader study is needed to confirm these data.

Melatonin and IL-25 modulate apoptosis and angiogenesis mediators in metastatic (CF-41) and non-metastatic (CMT-U229) canine mammary tumour cells.

BACKGROUND: Melatonin has oncostatic actions and IL-25 is active in inflammatory processes that induce apoptosis in tumor cells AIM: The aim of this study was to evaluate melatonin and IL-25 in metastatic (CF-41) and non-metastatic (CMT-U229) canine mammary tumor cells cultured as monolayers and tridimensional structures. MATERIALS AND METHODS: The cells were treated with melatonin, IL-25 and IL-17B silencing gene and performed cell viability, gene and protein expression of caspase-3 and VEGFA (Vascular endothelial growth factor A) and an apoptosis membrane protein array. RESULTS: Treatment with 1 mM of melatonin reduced cell viability of both tumor cell lines, all treatments alone and combined significantly increased caspase-3 cleaved and proteins involved in the apoptotic pathway and reduced pro-angiogenic VEGFA, confirming the effectiveness of these potential promising treatments. CONCLUSION: This is the first study evaluating the potential use of these strategies in CF-41 and CMT-U229 cell lines and together encourages subsequent in vitro and in vivo studies for further exploration of clinical applications.

Benign paroxysmal positional vertigo (BPPV): it may occur after dental implantology. A mini topical review.

OBJECTIVE: Benign Paroxysmal Positional Vertigo (BPPV) is one of the most frequent vestibular disorders. BPPV as a complication of Osteotome Sinus Floor Elevation (OSFE) is a complication that rarely occurs. The aim of this paper is to better understand the mechanisms underlying the BPPV after SFE with the osteotomes. This could be important for all the dental and maxillofacial surgeons that should know and manage this clinical occurrence. DISCUSSION: The osteotome sinus floor elevation (OSFE), firstly described by Summers requires the use of a surgical mallet for striking the bone, until the optimal depth is reached. The surgical mallet develops a mechanical trauma, even if the striking is performed with a gentle percussion. The recent literature describes an average occurrence of OSFE-induced BPPV quite low, but the symptoms show to be unpleasant and severe, often able to alter the patient's daily life. CONCLUSIONS: A successful remission of BPPV following treatment with a particle repositioning maneuver will be necessary and relatively urgent for the surgeons who have experienced this clinical complication. The surgeons, therefore, must be aware of these complications and about the ways to manage them.

Clinical stability in human immunodeficiency virus-infected patients with community-acquired pneumonia.

Clinical stability (CS), defined as normalization of vital signs, is often used to manage inpatients with community-acquired pneumonia (CAP). The main objective of our study was to identify a reliable definition of CS for human immunodeficiency virus (HIV)-positive patients with CAP. During an 18-month period, 437 HIV-positive Italian inpatients with CAP were enrolled in the study. We used 3 definitions of CS (from a less conservative [definition 1] to a more conservative [definition 3] definition) based on combinations of different thresholds for vital signs. Assessments were performed at admission and daily during the hospital stay. For the 3 definitions, 14.9%, 8.0%, and 4.8% of patients were stable at baseline, with deterioration after reaching CS in 7.16%, 4.76%, and 2.05%, respectively. The 8 patients whose conditions deteriorated after reaching CS definition 3 (systolic blood pressure, >90 mm Hg; pulse, <90 beats/min; respiratory rate, <20 breaths/min; oxygen saturation, >90%; temperature, <37 degrees C; ability to eat; and normal mental status) survived and were discharged from the hospital. The more conservative definition of CS appears to be reliable for the management of HIV-infected patients with CAP.

Short report: primaquine-tolerant Plasmodium vivax in an Italian traveler from Guatemala.

Plasmodium vivax infections caused by strains with low sensitivity to primaquine are widespread in the Western Pacific and Southeast Asia, and have been recently reported from Central America as well. We report a case of primaquine failure in a P. vivax infection acquired in Guatemala. A 28-year-old Italian woman developed two months after returning from Guatemala a vivax malaria attack that was treated with a standard chloroquine course (1,500 mg over three days) combined with primaquine (15 mg/day for 14 days). Two months later, she had a relapse that was again treated with chloroquine and primaquine at the same doses. After two more months, a second relapse occurred: this time primaquine (30 mg/day for 14 days was administered; the patient remained well during a follow-up period of six months and all parasitologic examination results were negative. Doses of primaquine as high as 6 mg/kg total dose may be indicated in the treatment of vivax malaria cases from Central America.

Short report: Diagnosis of tick-borne relapsing fever by the quantitative buffy coat fluorescence method.

The quantitative buffy coat (QBC) parasite detection method is a sensitive and specific tool for the diagnosis of malaria parasites. It is also useful for the diagnoses of other hemoparasites, including Trypanosoma, Babesia, and Leptospira. We report a case of relapsing fever diagnosed by this technique in a short-term traveler from Senegal. The diagnosis was confirmed by the standard Giemsa hemoscopy and by the identification of significant titers of antibodies to Borrelia spp. of tick-borne relapsing fevers by specific immunofluorescence and Western blot tests. The QBC technique seems to be useful in the diagnosis of tick-borne relapsing fever in blood samples and should be included in the management of fever in the traveler returning from tropical regions.

Tuberculosis due to drug-resistant Mycobacterium bovis in pregnancy.

We describe the management practices adopted in a case of pulmonary and extra-pulmonary tuberculosis caused by an isoniazid/pyrazinamide resistant strain of Mycobacterium bovis in a 26-week pregnant woman. She was initially treated with rifampin, isoniazid and ethambutol, pre-term delivery was induced and streptomycin was then added to the regimen. Screening of the new-born revealed no signs of either disease or infection. Isoniazid prophylaxis was not administered and the new-born was vaccinated and isolated from the mother for two months; however she continued to be fed with her mother's milk for the whole period.

Tolerability of twice-weekly rifabutin-isoniazid combinations versus daily isoniazid for latent tuberculosis in HIV-infected subjects: a pilot study.

The tolerability of and adherence to intermittent short-term rifabutin-isoniazid preventive treatment was assessed in subjects dually infected with Mycobacterium tuberculosis and the human immunodeficiency virus (HIV). In a randomised, open-label, phase II pilot study, 44 subjects received either rifabutin 300 mg and isoniazid 750 mg twice weekly for 3 months (group A, n = 16) or the same regimen with rifabutin at 600 mg (group B, n = 14), or isoniazid 300 mg/day for 6 months (group C, n = 14). Three, two and four subjects in groups A, B, and C, respectively, did not complete their treatment (one case of flu-like syndrome in group B; one methadone withdrawal syndrome in group A; and patient decision in two cases in group A and four in group C). Overall, adverse events were reported by four, nine, and seven subjects in groups A, B and C, respectively. Intermittent combined rifabutin + isoniazid for 3 months had lower default rates than daily standard isoniazid for 6 months. The regimen with rifabutin at 300 mg dose compared favourably to standard isoniazid, and warrants larger efficacy studies to assess its role for the prevention of latent tuberculosis in HIV-infected subjects.

Incidence of tuberculosis in a community of Senegalese immigrants in Northern Italy.

SETTING: Tuberculosis is the world's foremost cause of death from a single infectious agent among adults. Although morbidity and mortality rates are highest in low income countries, industrialized countries have also faced a recent resurgence of the tuberculosis epidemic. In Europe and the United States increasing tuberculosis incidence rates are observed, particularly among persons with the human immunodeficiency virus infection and immigrants from highly endemic countries. OBJECTIVE: To measure the incidence of tuberculosis in a retrospective cohort of Senegalese immigrants in a closed community. DESIGN: During 1991, 721 of 794 (91%) community residents were actively screened using the tuberculin skin test and chest X-ray. In 1995 the out-patient clinical charts and the tuberculosis notification registers were reviewed to determine tuberculosis incidence. RESULTS AND CONCLUSION: A total of 328 subjects (45.4% of those screened) was retrospectively followed for a cumulative period of 10 147 months. Ten cases of active tuberculosis were detected. The annual incidence rate for tuberculosis was 11.8/1000, compared to 15.1/ 100 000 in the general population. Tuberculosis incidence was similar in subjects with a positive (12.3/1000), compared to a negative baseline tuberculin test (12.5/1000). Tuberculosis incidence is very high, and recent infections might account for a substantial proportion of cases among immigrants living in closed communities.

Pediatric migration and hepatitis A risk in host population.

Hepatitis A virus (HAV) circulation in a given area is closely related to socioeconomic standards. Following the improvement of living conditions, HAV seroprevalence rates in the population have decreased steadily during the last decades in many Western European countries, including Italy, thereby leading to a shift of risk of disease towards older age groups. Since the severity of the disease closely parallels age, a higher incidence of symptomatic cases in adults is now reported in Europe and the United States, being travel-related to a large extent. Intrafamilial person-to-person spread is also an important source of infection and transmission from children to parents may occur due to the lack of immunity in the general population. In the last two decades, Italy has been the destination of an increasing number of migrants from developing countries, where HAV is highly endemic. Furthermore, international adoption programmes cause pediatric populations from HAV endemic countries to increase in low endemic areas, possibly leading to secondary cases in close contacts.7 The aim of this paper is to report the epidemic HAV outbreak which occurred among the voluntary nursing staff of a pediatric Rwandan refugee community hosted in a village of the Brescia Province, in northern Italy.