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/ .

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.

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.

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.

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.

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.

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.

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.

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.

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.

Antibiotic lock-technique for the treatment of catheter-related bloodstream infections.

The management of central venous catheter-related bloodstream infections (CRBSI), though still debated, requires the removal of the line in most cases: we investigated the efficacy of an alternative approach, based on higher concentrations of antibiotics locked within the catheter lumen, in an open, pilot study aimed at preserving the line in place and at eradicating the infection. Thirty consecutive patients carrying a central line over 10 days and who fulfilled criteria for ascertained diagnosis of bacterial CRBSI, had the catheter "locked" with antimicrobials therein; all patients also received systemic antibiotic therapy within the first 48 hours. Subsequently, 15 patients underwent locks alone, and 15 locks plus systemic therapy. Twenty-eight out of 30 (93.3%) patients retained the catheter in place, appearing to be cleared of infection and no treatment-related untoward events were observed. Locks should be considered as effective as line removal in the management of bacterial CRBSI in unselected patients, and could thus provide advantages in terms of resource sparing and lowered antibiotic pressure in the hospital setting.

[Vertical trasmission of human immunodeficiency virus (HIV) and other sexually transmitted infections (STI)]. / Trasmissione materno-fetale di HIV e di altri agenti di malattie a trasmissione sessuale.

Infectious agents which are sexually transmitted determine considerable morbidity in women during the gestational period. Connatal and perinatal infection of the newborn, miscarriage, and low birthweight have all been described. Vertical transmission of HIV and other STD may occur via the placenta during gestation (the major mechanism for syphilis) or at birth during the passage through the cervico-vaginal channel (the major mechanism for HIV, HBV, HSV, gonorrhoea and chlamydia). High serum viral loads of HIV significantly increase the likelihood of newborn infection, while the presence of lesions in the genital tract at birth increases the odd for transmission for HSV. Breast feeding is a well described route of transmission for HIV infection, but it is irrelevant to the transmission of HBV. Cutaneous lesions of the breast and nipples carry a risk of transmission of syphilis and HSV through breast-feeding. Treatment of the etiologic agent is considered an effective means for the prevention of vertical transmission and is recommended for all STI agents except for HBV. HIV infected women on antiretroviral therapy should continue the same treatment regimen if they become pregnant (with the exception of indinavir and efavirenz, which should be replaced as soon as possible); women who did not assume antiretroviral drugs at the time they became pregnant, should start treatment as soon as they reach the second trimester of gestation. Delivery should be performed by elective cesarian section in all HIV infected women. Delivery should also be performed by cesarian section in women who develop a primary HSV infection and have cervico-vaginal lesions. Recurrent episodes of genital herpes are associated to a much lower risk of vertical transmission and do not represent a criterium for cesarian section. Women with documented cervical chlamydia infection should receive a full treatment regimen at the 36th week of gestation. Women with chronic HBV infection do not require etiologic treatment; however, their newborns should receive concomitant doses of HBV immunoglobulins and HBV vaccine soon after birth. Standard practices of prevention of vertical transmission of STI agents applies to women regardless their native country. However, the feasibility of implementation of the guidelines in poor resource countries is a matter of great concern: an unresolved debate is ongoing on optimal strategies for the prevention of vertical transmission of HIV in such countries.

Pharmacokinetic evaluation of oral levofloxacin in human immunodeficiency virus-infected subjects receiving concomitant antiretroviral therapy.

The purpose of this study was to evaluate the pharmacokinetics (PK) profile of oral levofloxacin in human immunodeficiency virus-positive patients in steady-state treatment with nelfinavir (NFV) or with efavirenz (EFV) and to determine the effects of levofloxacin on the PK parameters of these two antiretroviral agents. For levofloxacin, plasma samples were obtained at steady state during a 24-h dosing interval. Plasma NFV and EFV concentrations were evaluated before and after 4 days of levofloxacin treatment. Levofloxacin PK do not seem affected by NFV and EFV. There was no significant difference between NFV and EFV plasma levels obtained with and without levofloxacin.