Microbiota and microRNAs in lung diseases: mutual influence and role insights.

Trillions of microbial cells colonize human body both internally and externally. The prevalent amount of these reside in the gastrointestinal tract (gut microbiome). Gut microflora support the transformation of food nutrients. The products of this modification processes both modulate gastro-intestinal immunity, and influence other organs such as lung and brain. Recently, it was reported the role of micro-RNAs (miRNAs) as regulators in different pathways of the innate and/or adaptive immune responses. Latest studies discussed the aptitude of probiotics strains to balance the host immune response at a post-transcriptional level by controlling miRNAs expression. We speculated a model of lung immune regulation driven by the axis microbiota-microRNAs, involving asthma, acute injury, cancer and COPD. Based on this axis, we propose a novel approach based on the modification of microRNAs expression centered not exclusively on antagomiRs but also on microbiota modification in order to further potentiate their therapeutic effects.

Biodegradation ability of two selected microbial autochthonous consortia from a chronically polluted marine coastal area (Priolo Gargallo, Italy).

The aims of this study were: (i) the characterization of the structure of the indigenous microbial community associated with the sediments under study; (ii) the isolation and characterization of microbial consortia able to degrade the aged hydrocarbons contaminating the sediments, and (iii) the assessment of related biodegradation capability of selected consortia. Samples of surface sediments were collected in Priolo Gargallo harbour (Sicily, Italy). The samples were analysed for physical, chemical (GC-FID analysis) and microbiological characteristics (qualitative (16S rDNA clone library) and quantitative (DAPI, CFU and MPN count) analysis). The sediment samples were used for the selection of two microbial consortia (indicated as PSO and PSM) with high biodegradation capacity for crude oil (∼95%) and PAHs (∼63%) respectively. Genetic analysis showed that Alcanivorax and Cycloclasticus were the dominant genera in both the PSO and PSM consortia. Oil-polluted environments naturally develop an elevated biorecovery potential. The presence of a highly specialized microbial flora (adapted to support the contamination) and their stimulation through favourable induced conditions provides a promising recovery strategy. The chance to identify and select indigenous bacteria and/or consortia with a high biodegradation capacity is fundamental for the development and optimization of bioaugmentation strategies especially for those concerning in situ applications.

Lack of clear and univocal genotype-phenotype correlation in familial Mediterranean fever patients: A systematic review.

Familial Mediterranean fever (FMF) is the most common autosomal recessive autoinflammatory disease. To date, following the isolation of more than 280 MEFV sequence variants, the genotype-phenotype correlation in FMF patients has been intensively investigated; however, an univocal and clear consensus has not been yet reached. Thus, the aim of this systematic review was to analyze the available literature findings in order to provide to scientific community an indirect estimation of the impact of genetic factors on the phenotypic variability of FMF. This systematic review has been conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. The p.M694V mutation was reported to have a relatively severe clinical course, similarly, patients homozygous for M694I and M680I, or carrying a combination of both at codons 694 and 680, have a severe disease. Also, patients homozygous for M694V and V726A variants experienced more severe clinical picture. Conversely, heterozygous p.V726A and p.E148Q genotypes have been correlated with a milder disease course. At present, doubts remain on the potential pathogenic role of E148Q variant. The heterogenity in clinical FMF manifestations reflects the changes occuring in repertoire of mutations. We believe that clinical criteria and gene tests, enhancing each other, could better support the diagnosis of FMF.

TGFBI expression is an independent predictor of survival in adjuvant-treated lung squamous cell carcinoma patients.

BACKGROUND: Transforming growth factor ß-induced protein (TGFBI) is a secreted protein that mediates cell anchoring to the extracellular matrix. This protein is downregulated in lung cancer, and when overexpressed, contributes to apoptotic cell death. Using a small series of stage IV non-small cell lung cancer (NSCLC) patients, we previously suggested the usefulness of TGFBI as a prognostic and predictive factor in chemotherapy-treated late-stage NSCLC. In order to validate and extend these results, we broaden the analysis and studied TGFBI expression in a large series of samples obtained from stage I-IV NSCLC patients. METHODS: TGFBI expression was assessed by immunohistochemistry in 364 completely resected primary NSCLC samples: 242 adenocarcinomas (ADCs) and 122 squamous cell carcinomas (SCCs). Kaplan-Meier curves, log-rank tests and the Cox proportional hazards model were used to analyse the association between TGFBI expression and survival. RESULTS: High TGFBI levels were associated with longer overall survival (OS, P<0.001) and progression-free survival (PFS, P<0.001) in SCC patients who received adjuvant platinium-based chemotherapy. Moreover, multivariate analysis demonstrated that high TGFBI expression is an independent predictor of better survival in patients (OS: P=0.030 and PFS: P=0.026). CONCLUSIONS: TGFBI may be useful for the identification of a subset of NSCLC who may benefit from adjuvant therapy.

Beneficial effects of fibrin glue (Quixil) versus Lichtenstein conventional technique in inguinal hernia repair: a randomized clinical trial.

INTRODUCTION: In inguinal hernia repair, many complications are due to mesh fixation technique. Therefore, new types of atraumatic methods of fixation have been proposed. In this article, we present the results of a prospective multicentric parallel randomized controlled trial aiming to compare two mesh fixation techniques: fibrin sealant (QUIXIL(®), Omrix Biopharmaceuticals S.A., Belgium) and Lichtenstein technique. METHOD: Adult patients with primary uncomplicated inguinal hernia were randomized in two groups: fibrin sealant group (FSG) and Lichtenstein group (LTG). The two groups underwent a follow-up of 15 months. Operative time is the primary outcome. Intraoperative and postoperative outcomes were analyzed. Moreover, a differential cost analysis was performed. Patients and evaluators (with exception of the surgeon who treated the patient) were blinded. RESULTS: A total of 102 patients, 50 in FSG and 52 in LTG, were enrolled from January 2009 to June 2010, and two patients were lost to follow-up at the twelfth month. No significant differences in baseline and clinical characteristics were observed in the two groups. Operative time was longer in LTG (median/ interquartile range: 35 min/30-42.5 min vs. 31 min/28-35 min; effect size: 0.65/95% CI 0.50-0.91; p < 0.05). No differences in intraoperative complications were observed. No significant differences were observed in early complication rate (RR = 0.62; p > 0.05). Numbness rate was lower in the FSG at 1 week (RR = 0.43; p < 0.01) and at 1 month (RR = 0.17; p < 0.05). No significant differences were observed after 6 months. Postoperative pain was lower in the FSG at 1 week (0/0-1 vs. 1/0-2; p < 0.05) and at 1 month (0/0-0 vs. 0/0-1; p < 0.05). Pain disappeared in all patients after 6 months. Analgesic assumption rate was lower in the FSG (RR = 0.42; p < 0.05). Twenty per cent of FSG and 9.62% of LTG patients were discharged within 12 h; 78% of FSG and 90.38% of LTG patients were discharged within 24 h. The only one recurrence we observed was in FSG group. About costs, although fibrin sealant needed for one mesh fixation is about 10 times more costly than the needed sutures, the total costs of the two procedures did not change significantly. This was mainly due to reduction in operative time. CONCLUSIONS: The use of fibrin sealant determined a significant reduction in short-term numbness rate and postoperative pain. There was no relevant difference in total costs per patient between the two procedures.

Temperature dependence of denitrification in phototrophic river biofilms.

Denitrification is an ecosystem service of nitrogen load regulation along the terrestrial-freshwater-marine continuum. The present study documents the short-term temperature sensitivity of denitrification enzyme activity in phototrophic river biofilms as a typical microbial assemblage of this continuum. Denitrification measurements were performed using the acetylene inhibition method at four incubation temperatures: 1.1, 12.1, 21.2 and 30.9°C. For this range of temperature, N(2)O production could be fitted to an exponential function of incubation temperature, yielding mean (±standard error) activation energy of 1.42 (±0.24) eV and Q(10) of 7.0 (±1.4). This first quantification of denitrification enzyme activity temperature dependence in phototrophic river biofilms compares with previous studies performed in soils and sediments. This demonstrates the high temperature dependence of denitrification as compared to other community-level metabolisms such as respiration or photosynthesis. This result suggests that global warming can unbalance natural community metabolisms in phototrophic river biofilms and affect their biogeochemical budget.

TGFbeta-induced protein mediates lymphatic endothelial cell adhesion to the extracellular matrix under low oxygen conditions.

TGFbeta-induced protein (TGFBI) is an extracellular protein that mediates cell adhesion to collagen, laminin and fibronectin through its interaction with different beta integrins. We had previously reported that hypoxia-induced TGFBI mRNA expression in lymphatic endothelial cells (LEC). Here, we demonstrate that TGFBI can contribute to hypoxia-induced increases in LEC adhesion to the ECM. We show that while there are no changes in alpha1, alpha4, alphav, beta1, beta2, beta3, alpha5beta1, alphavbeta3, alphavbeta5 integrin expression on the LEC surface after hypoxia exposure, there exists an accumulation of TGFBI adaptor protein in LEC supernatants. We also demonstrate that hypoxia driven TGBFI expression is dependent on TGFbeta production by LEC. Furthermore, we show that TGFBI mediated LEC adhesion and migration through the ECM by its binding to the beta3 integrin. The identification of the specific mechanisms regulating LEC-ECM interactions may help us design new therapeutic applications for diseases in which lymphatic vessel function is compromised.

Prevalence and management of pain in Italian patients with advanced non-small-cell lung cancer.

Pain is a highly distressing symptom for patients with advanced cancer. WHO analgesic ladder is widely accepted as a guideline for its treatment. Our aim was to describe pain prevalence among patients diagnosed with advanced non-small-cell lung cancer (NSCLC), impact of pain on quality of life (QoL) and adequacy of pain management. Data of 1021 Italian patients enrolled in three randomised trials of chemotherapy for NSCLC were pooled. QoL was assessed by EORTC QLQ-C30 and LC-13. Analgesic consumption during the 3 weeks following QoL assessment was recorded. Adequacy of pain management was evaluated by the Pain Management Index (PMI). Some pain was reported by 74% of patients (42% mild, 24% moderate and 7% severe); 50% stated pain was affecting daily activities (30% a little, 16% quite a bit, 3% very much). Bone metastases strongly affected presence of pain. Mean global QoL linearly decreased from 64.9 to 36.4 from patients without pain to those with severe pain (P<0.001). According to PMI, 616 out of 752 patients reporting pain (82%) received inadequate analgesic treatment. Bone metastases were associated with improved adequacy and worst pain with reduced adequacy at multivariate analysis. In conclusion, pain is common in patients with advanced NSCLC, significantly affects QoL, and is frequently undertreated. We recommend that: (i). pain self-assessment should be part of oncological clinical practice; (ii). pain control should be a primary goal in clinical practice and in clinical trials; (iii). physicians should receive more training in pain management; (iv). analgesic treatment deserves greater attention in protocols of anticancer treatment.

Experimental model of human body louse infection using green fluorescent protein-expressing Bartonella quintana.

A laboratory colony of human body lice was experimentally infected by feeding on rabbits made artificially bacteremic with a green fluorescent protein-expressing Bartonella quintana. B. quintana was detected in the gut and feces until death but not in the eggs. The life span of the lice was not modified. The rabbit model should provide valuable clues to the role of lice in the transmission of B. quintana.

Diagnosis of granulocytic ehrlichiosis in humans by immunofluorescence assay.

Serodiagnostic tests are widely available for tick-borne diseases. We evaluated a cell-free antigen of the human granulocytic ehrlichiosis agent. Immunofluorescence assay (IFA) with this antigen is as efficient as with the MRL kit and allows a one-step IFA with other cell-free antigens that is useful when testing sera from patients bitten by ticks.

Neurological deficit following spinal anaesthesia: MRI and CT evidence of spinal cord gas embolism.

A 62-year-old diabetic woman developed permanent neurological deficits in the legs following spinal anaesthesia. MRI showed oedema in the spinal cord and a small intramedullary focus of signal void at the T10 level, with negative density at CT. Intramedullary gas bubbles have not been reported previously among the possible neurological complications of spinal anaesthesia; a combined ischaemic/embolic mechanism is hypothesised.

Use of viscoelastics post-trabeculectomy: a survey of members of the American Glaucoma Society.

BACKGROUND AND OBJECTIVE: American Glaucoma Society members were surveyed to determine the pattern of use of viscoelastics for anterior chamber reformation at the slit-lamp in the post-operative clinical management of patients who have undergone trabeculectomy in order to give ophthalmologists an indication of how these materials are being used by their colleagues. MATERIALS AND METHODS: We surveyed 196 members of the American Glaucoma Society regarding the following; (1) whether they inject viscoelastic post-operatively at the slit-lamp as an in-office procedure, (2) the type of viscoelastic used most often, (3) the criteria for injection of viscoelastic, (4) the time to first follow-up, (5) the average number of injections, and (6) the occurrence of post-injection endophthalmitis. RESULTS: One hundred twenty-five (64%) of the 196 mailed surveys were answered and returned. Ninety-four (75%) of the respondents reported injecting viscoelastics in the postoperative period at the slit-lamp as an in-office procedure. Healon (60%) (Pharmacia & Upjohn Co, Kalamazoo, MI), Viscoat (17%) (Alcon, Ft. Worth, TX), and Healon GV (7%) (Pharmacia & Upjohn Co, Kalamazoo, MI) were the three most often used viscoelastics. Hypotony, iriscornea touch, and lens-cornea touch were given as criteria for injection 19%, 47%, and 88% of the time, respectively. Range of time to first follow-up was 1 hour to 7 days, with a mean time of 1 day. Range of average number of injections was 1 to 3 with a mean of 2 injections for patients requiring injection. Only one respondent reported an incidence of endophthalmitis. CONCLUSIONS: The use of viscoelastic materials in the postoperative trabeculectomy patient in the office at the slit-lamp for anterior chamber reformation is a prevalent practice. Healon is the most commonly used viscoelastic postoperatively and lens-corneal touch is the most common criterion for injection. The average number of injections is 2, with a mean and mode follow-up time of 1 day. Endophthalmitis is a rare complication.

Ausência de anticorpos contra o vírus da doença de Aujeszky em suínos no Estado do Rio Grande do Sul / Absence of antibodies to Aujeszky virus in swine in the State of Rio Grande do Sul, Brazil

A serological survey was carried out on 16.305 swine sera collected over a eight year period (1987-1994) from various municipalities of the State of Rio Grande do Sul, Brazil, in search for antibodies to Aujeszky's disease virus (ADV), using ELISA and serum neutraliozation tests. All sera examined were negative for ADV antibodies. These results suggest that ADV is not present in an enzootic form in swine in that State

[Monitoring of hepatocyte xenotransplantation. Usefulness of various laboratory parameters]. / Monitoraggio dello xenotrapianto di epatociti. Utilità di alcuni parametri di laboratorio.

The authors report a study in which they evaluate the efficacy of some laboratory parameters for monitoring intrasplenic hepatocyte xenotransplantation (mouse to rat) as an alternative to 99Tc-HIDA dynamic scan and histologic exam. Swiss mouse and wistar rat hepatocytes were obtained with collagenase digestion. Wistar male rats were used as recipient and were allocated into three groups: A) omotransplanted rats; B) xenotransplanted rats; C) xenotransplanted and immunosuppressed (Cyclosporin A: 20 mg/kg/daily orally) rats. All rats underwent > 70% hepatectomy. Blood samples were obtained daily from a femoral vein and AST, ALT, ALP, bilirubin, albumin and urea were measured. No statistical differences were observed among groups and the laboratory parameters tested can't be considered a valid technique to xenotransplant rejection monitoring.

Combined cyclosporine and corticosteroid therapy for sight-threatening uveitis in Behçet's disease.

Behçet's disease is a multisystem disorder that may cause profound ocular inflammation and blindness. We reviewed 19 patients with severe ocular Behçet's disease treated with combined cyclosporine and corticosteroid therapy. Previous treatment with corticosteroids alone failed to control the uveitis in all patients. Ten patients were given cyclosporine therapy alone (mean dosage, 8.6 mg/kg of body weight per day), and nine patients were given lower dosages of cyclosporine (mean dosage, 6.2 mg/kg of body weight per day) in combination with prednisone (mean dosage, 29.4 mg per day). The mean follow-up on therapy was 51 months. After three months of therapy, a trend toward greater improvement in visual acuity was noted in patients treated with combined cyclosporine and prednisone compared to those receiving cyclosporine alone (17.8 letters vs 10.2 letters, P = .2379), but after one year little difference was observed in the improvement between the two groups (5.8 letters vs 3.3 letters, P = .7984). However, a trend toward greater renal toxicity was seen in patients treated with cyclosporine alone after both three months and one year of therapy. Because of either a suboptimal therapeutic response or adverse effects, all patients treated with cyclosporine alone at baseline had prednisone added to their regimen after a mean time of 23.5 months. Overall, visual acuity remained stable or improved in 28 of 37 eyes (75.7%) over the course of therapy. These data suggest that combined cyclosporine and prednisone therapy is an effective treatment for Behçet's uveitis and may be less toxic than therapy with cyclosporine alone. A prospective, randomized trial with a larger sample size is needed to provide definitive data.

[Anhepatic rat, technic for reconstruction of venous circulation]. / Ratto anepatico, tecnica di ricostruzione della circolazione venosa.

Authors report an experimental model of total hepatectomy in the rat. In this model whole liver was replaced by an autologous vascular prosthesis. On the contrary as reported in other experiences, in this model is maintained the cavo-caval flow, with absence of cavo-caval and porta-caval shunts. Anhepatic rats survival not exceeded two hours from surgery.

[Hepatocyte transplantation. From experimentation to therapeutic attempts in man]. / II trapianto di epatociti. Dalla sperimentazione ai tentativi terapeutici nell'uomo.

Recently, hepatocyte transplantation has widely increased its interest. This technique can be perspectively considered as an attractive alternative to orthotopic liver transplantation to support liver function in acute, chronic and genetic metabolic hepatic diseases. The authors review the most significant steps in the field of hepatocyte transplantation with particular reference to its clinical experimental application in genetic metabolic disorders and acute liver failure.