Sepsis and meningitis caused by serogroup B meningococcus are devastating diseases of infants and young adults, which cannot yet be prevented by vaccination. By genome mining, we discovered GNA1870, a new surface-exposed lipoprotein of Neisseria meningitidis that induces high levels of bactericidal antibodies. The antigen is expressed by all strains of N. meningitidis tested. Sequencing of the gene in 71 strains representative of the genetic and geographic diversity of the N. meningitidis population, showed that the protein can be divided into three variants. Conservation within each variant ranges between 91.6 to 100%, while between the variants the conservation can be as low as 62.8%. The level of expression varies between strains, which can be classified as high, intermediate, and low expressors. Antibodies against a recombinant form of the protein elicit complement-mediated killing of the strains that carry the same variant and induce passive protection in the infant rat model. Bactericidal titers are highest against those strains expressing high yields of the protein; however, even the very low expressors are efficiently killed. The novel antigen is a top candidate for the development of a new vaccine against meningococcus.
Study design: Prospective clinical trial. Objectives: To evaluate the e cacy of a speci®c protocol for prevention of thrombo-embolic disease occurring during the acute stage of spinal cord lesions, based on the simultaneous use of pharmacological plus mechanical procedures. Setting: Regional Spinal Unit of Florence, Italy. Introduction: Deep venous thrombosis (DVT) is a dangerous pathology whose ®rst clinical sign can be represented by unexpected pulmonary embolism (PE). Its incidence in acute spinal cord injured (SCI) patients is reported to range between 9% and 90%. Its prevention represents one of the major challenges for the clinicians involved in the care of such patients. Method: Two hundred and seventy-®ve SCI patients consecutively admitted to our Centre were investigated by colour doppler ultrasonography of lower limbs and pelvis on admission, after 30 ± 45 days and whenever clinically requested. Subcutaneous Nadroparine, a low molecular weight heparin (LMWH), plus early mobilisation, permanently dressed gradient elastic stockings (PGES), and external sequential pneumatic compression (ESPC) of the lower limbs, applied during the ®rst 30 days after injury, were given to all of them. Colour doppler ultrasonography (CDUS) complete investigations of the lower limbs and pelvis were performed on admission, after 30 ± 45 days and whenever clinically requested. The patients were divided into two groups according to their time interval from injury to the admission to our Centre. Results: The incidence of detected DVT was 2% in those patients (99) admitted early to our centre (within 72 h from the trauma), who immediately received our prophylactic protocol. No PE was reported. The other group of patients (176), all admitted between 8 and 28 days (mean 12 days) developed DVT in 26% of cases. None of these patients received ESPC before being admitted to our Centre. No patient had been admitted between 3 and 8 days interval time post injury. Conclusion: Early application of pharmacological plus mechanical treatment for DVT prevention produces a marked reduction in such complications. It also reduces the risks of morbidity and mortality in our patients, and, not least, reduces the hospitalization costs during the early period of rehabilitation.
Natural resistance-associated substitutions (RASs) are reported with highly variable prevalence across different HCV genotypes (GTs). Frequency of natural RASs in a large Italian real-life cohort of patients infected with the 4 main HCV-GTs was investigated. NS3, NS5A and NS5B sequences were analysed in 1445 HCV-infected DAA-naïve patients. Sanger-sequencing was performed by home-made protocols on 464 GT1a, 585 GT1b, 92 GT2c, 199 GT3a, 16 GT4a and 99 GT4d samples. Overall, 20.7% (301/1455) of patients showed natural RASs, and the prevalence of multiclass-resistance was 7.3% (29/372 patients analysed). NS3-RASs were particularly common in GT1a and GT1b (45.2-10.8%, respectively), mainly due to 80K presence in GT1a (17%). Almost all GTs showed high prevalence of NS5A-RASs (range: 10.2–45.4%), and especially of 93H (5.1%). NS5A-RASs with fold-change >100x were detected in 6.8% GT1a (30H/R-31M-93C/H), 10.3% GT1b (31V-93H), 28.4% GT2c (28C-31M-93H), 8.5% GT3a (30K-93H), 45.5% GT4a (28M-30R-93H) and 3.8% GT4d (28V-30S-93H). Sofosbuvir RAS 282T was never detected, while the 159F and 316N RASs were found in GT1b (13.4–19.1%, respectively). Natural RASs are common in Italian patients infected with HCV-GTs 1–4. High prevalence of clinically-relevant RASs (such as Y93H) supports the appropriateness of HCV resistance-test to properly guide DAA-based therapy.
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