Reducing adult cardiac surgical site infections and the economic impact of using multidisciplinary collaboration.

BACKGROUND: Cardiac surgical site infections (SSIs) have devastating consequences and present several challenges for patients and healthcare providers. Adult cardiac SSI surveillance commenced in 2009 at our hospitals, Guy's & St Thomas' NHS Foundation Trust, London, as a patient safety initiative amid reported increased incidence of SSIs. Before this time, infection incidence was unclear because data collection was not standardized. AIM: To standardize SSI data collection and establish baseline SSI rates to facilitate deployment of evidence-based targeted interventions within clinical governance structures to improve quality, safety, and efficiency in line with our organizational targets. METHODS: We standardized local data collection protocols in line with Public Health England recommendations and identified local champions. We undertook prospective SSI surveillance collaboratively to enable us to identify potential practice concerns and address them more effectively through a series of initiatives. Clinical staff completed dedicated surveillance forms intraoperatively and postoperatively. FINDINGS: Overall adult cardiac SSI rates fell from 5.4% in 2009 to 1.2% in 2016 and coronary artery bypass graft rates from 6.5% in 2009 to 1.7% in 2016 (P < 0.001). Gram-negative bacteria were recognized as important SSI causative organisms and were better controlled after introducing stringent infection control measures. CONCLUSION: Comprehensive, evidence-based infection control practices were successfully implemented through a multidisciplinary collaborative approach, which may have great potential to reduce Gram-negative, Staphylococcus aureus, polymicrobial and overall SSI burden and/or associated costs. We now investigate all SSIs using an established SSI detailed investigation protocol to promote continual quality improvement that aligns us perfectly with global efforts to fight antimicrobial resistance.

Developing an anti-Campylobacter jejuni vaccine.

The proteomics era allows for the definition of biological organisms at the protein level, offering new opportunities for delimiting the self- and non-self boundaries between microbes and the human host. Here, we apply proteomics to design a vaccine against the major pathogenic factor of Campylobacter jejuni, i.e. cytolethal distending toxin (CDT). We used the scientific rationale that only peptide sequences not represented in the host proteome have the potential to evoke powerful, non-cross-reactive immune responses, thereby guaranteeing effectiveness and safety.

Sub-epitopic dissection of HCV E1315-328HRMAWDMMMNWSPT sequence by similarity analysis.

Our labs are focused on identifying amino acid sequences having the ability to react specifically with the functional binding site of a complementary antibody. Our epitopic definition is based on the analysis of the similarity level of antigenic amino acid sequences to the host proteome. Here, the similarity profile to the human proteome of an HCV E1 immunodominant epitope, i.e. the HCV E1(315-328)HRMAWDMMMNWSPT sequence, led to i) characterizing the immunoreactive HCV E1 315-328 region as a sequence endowed with a low level of similarity to human proteins; ii) defining 2 contiguous immunodominant linear determinants respectively located at the NH(2) and COOH terminus of the conserved viral antigenic sequence. This study supports the hypothesis that low sequence similarity to the host's proteome modulates the pool of epitopic amino acid sequences in a viral antigen, and appears of potential value in defining immunogenic viral peptide sequences to be used in immunotherapeutic approaches for HCV treatment.

Peptidology: short amino acid modules in cell biology and immunology.

Short amino acid motifs, either linear sequences or discontinuous amino acid groupings, can interact with specific protein domains, so exerting a central role in cell adhesion, signal transduction, hormone activity, regulation of transcript expression, enzyme activity, and antigen-antibody interaction. Here, we analyze the literature for such critical short amino acid motifs to determine the minimal peptide length involved in biologically important interactions. We report the pentapeptide unit as a common minimal amino acid sequence critically involved in peptide-protein interaction and immune recognition. The present survey may have implications in defining the dimensional module for peptide-based therapeutical approaches such as the development of novel antibiotics, enzyme inhibitors/activators, mimetic agonists/antagonists of neuropeptides, thrombolitic agents, specific anti-viral agents, etc. In such a therapeutical context, it is of considerable interest that low molecular weight peptides can easily cross biological barriers, are less susceptible to protease attacks, and can be administered at high concentrations. In addition, small peptides are a rational target for strategies aimed at antigen-specific immunotherapeutical intervention. As an example, specific short peptide fragments might be used to elicit antibodies capable of reacting with the full-length proteins containing the peptide fragment's amino acid sequence, so abolishing the risk of cross-reactivity.

Flow cytometry DNA content and morphobiological characteristics in chronic and neoplastic human liver disease.

In the search for parameters that can indicate changes in the behaviour of liver tissue from normal to chronic to neoplastic disease, DNA content by FCM (ploidy and percent of 4N cells) and morphobiological characteristics were investigated in fresh liver specimens of 16 patients with normal liver, 21 with persistent hepatitis (CPH), 23 with chronic active hepatitis (CAH), 17 with cirrhosis, and 13 with hepatocellular carcinoma (HCC). Aneuploidy was mostly found in HCC specimens (54%), whereas the percentage of 4N peak decreased in chronic hepatitis and cirrhosis patients but increased to 11.09% in HCC samples (r = -0.02; p = 0.05). Finally, the binuclearity rate decreased gradually from normal to flogistic to HCC specimens. The 4N peak and the binuclearity rate were closely correlated in non-HCC (p = 0.0006, by T-test) but not in HCC samples. Only DNA ploidy and the binuclearity rate have been confirmed as being significantly and independently related to the histology of liver tissue by multivariate regression analysis.

[Can alpha-interferon exacerbate a case of mixed cryoglobulinemia?]. / Può l'alfa interferone esacerbare una crioglobulinemia mista tipo II latente?

We describe a case of exacerbated mixed cryoglobulinemia in a patient previously treated with alpha-interferon, for chronic active hepatitis. The possible pathogenesis of this exacerbated mixed cryoglobulinemia and the relationship between cytokines, hepatitis viral infections and immune reactions is discussed.

Production processes of recombinant IL-1 beta from Bacillus subtilis: comparison between intracellular and exocellular expression.

The human IL-1 beta coding sequence derived from a cDNA library was inserted into two different plasmid expression vectors, pSM214 and pSM308, which promote the synthesis of recombinant products intracellularly and exocellularly, respectively. The hybrid constructs pSM261 and pSM320 were obtained. Bacillus subtilis SMS118 was transformed with these plasmids and the recombinant strains were grown in 1 litre bioreactors. Different growth conditions were analyzed to optimize yields both in terms of biomass and IL-1 beta production. In the pSM261-harbouring strain, IL-1 beta was synthesized in the cytoplasm to levels ranging from 1 to 2.7 mg g-1 of cells, corresponding to up to 40 mg l-1 of the culture. In contrast, SMS118(pSM320) was able to secrete 0.27 mg of natural IL-1 beta per g of cells (6.7 mg l-1 of culture). Processes for the purification of IL-1 beta from the supernatant and the biomass of the two cultures were also developed and compared in terms of yield and simplicity of the purification schemes. From our data it turns out that the route of intracellular expression is very efficient and superior to the one which results in secretion of IL-1 beta. This indicates that the use of B. subtilis as a recombinant host in biotechnology is not strictly dependent on its ability to secrete proteins into the culture medium.

Cloning and nucleotide sequence of the isoamylase gene from a strain of Pseudomonas sp.

A strain of Pseudomonas sp., SMP1, isolated from a soil sample collected in the Monterotondo area (Rome), secreted isoamylase activity into the culture medium. The enzyme was purified and optimal reaction and stability conditions were determined by varying pH and temperature. The chemico-physical properties of the enzyme were similar to those of the isoamylase purified in Japan more than 20 years ago from 'Pseudomonas amyloderamosa' strain SB15. A genomic library of SMP1 was prepared in Escherichia coli using pUC12 as vector. Two isoamylase-producing colonies were identified out of 6300 screened. The hybrid plasmids isolated from the two clones showed common restriction patterns. The chromosomal portion of one of these plasmids (pSM257) was completely sequenced. Comparison between the deduced amino acid sequence of the isoamylase and the published sequences of other amylolytic enzymes showed the presence of conserved domains.

Ceensp: A Europeização das Políticas de Saúde - Geraldo Lucchese

Exposição de Geraldo Lucchese, farmacêutico e sanitarista. Mestre e doutor em saúde pública pela ENSP/Fiocruz. Trabalhou na Secretaria de Vigilância Sanitária do Ministério da Saúde, quando exerceu a coordenação dos trabalhos de harmonização da legislação sanitária no Mercosul. Colaborou na Coordenação do Subgrupo de Trabalho nº 11 - Saúde, do Mercosul. Atualmente, é consultor legislativo da Câmara dos Deputados - área de Saúde Pública. Arquivos disponíveis para leitura, audição e/ou download nos ícones ao lado.