Architecture of a server application for use in environmental patient monitoring

W celu poprawnego zaimplementowania systemu telemedycznego konieczne jest stworzenie i wdrożenie odpowiednio przygotowanej centralnej aplikacji serwerowej. Aplikacja taka została opisana w poniższym artykule. Powinna ona zapewniać odpowiednią funkcjonalność i udostępniać wymagany zakres danych zarówno dla pacjentów jak i operatorów i personelu medycznego. Konieczne jest wykorzystanie odpowiednio dostosowanego protokołu komunikacyjnego w celu jednoczesnego zapewnienia kompletności informacji i zminimalizowania obciążenia dla terminali mobilnych. Jednocześnie wymagane jest podzielenie aplikacji na odpowiednie warstwy w celu ułatwienia integracji w istniejących systemach i wdrażania. Konieczne jest również zapewnienie bezbłędnej komunikacji i wysokiego poziomu bezpieczeństwa podczas uzyskiwania dostępu do chronionych danych medycznych.Proper telemedical system implementation requires a central server application for storing and managing data and diagnostics messages. Such an application is described in the presented article below. It should provide sufficient functionality and allow for appropriate access privileges for different groups of users, including patients, operators and medical staff. A properly designed protocol must be used to simultaneously provide complete and safe information and minimize load on mobile terminals. At the same time it is necessary to divide the application into proper layers to be easily integrated into existing medical systems and make implementation easier. It is also of utmost importance to provide a high level of safety during access to protected, sensitive data

Nucleotide excision repair of oxidised genomic DNA is not a source of urinary 8-oxo-7,8-dihydro-2’-deoxyguanosine.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Urinary 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodGuo) is a widely measured biomarker of oxidative stress. It has been commonly assumed to be a product of DNA repair, and therefore reflective of DNA oxidation. However, the source of urinary 8-oxodGuo is not understood, although potential confounding contributions from cell turnover and diet have been ruled out. Clearly it is critical to understand the precise biological origins of this important biomarker, so that the target molecule that is oxidised can be identified, and the significance of its excretion can be interpreted fully. In the present study we aimed to assess the contributions of nucleotide excision repair (NER), by both the global genome NER (GG-NER) and transcription-coupled NER (TC-NER) pathways, and sanitisation of the dGTP pool (e.g. via the activity of the MTH1 protein), on the production of 8-oxodGuo, using selected genetically-modified mice. In xeroderma pigmentosum A (XPA) mice, in which GG-NER and TC-NER are both defective, the urinary 8-oxodGuo data were unequivocal in ruling out a contribution from NER. In line with the XPA data, the production of urinary 8-oxodGuo was not affected in the xeroderma pigmentosum C mice, specifically excluding a role of the GG-NER pathway. The bulk of the literature supports the mechanism that the NER proteins are responsible for removing damage to the transcribed strand of DNA via TC-NER, and on this basis we also examined Cockayne Syndrome mice, which have a functional loss of TC-NER. These mice showed no difference in urinary 8-oxodGuo excretion, compared to wild type, demonstrating that TC-NER does not contribute to urinary 8-oxodGuo levels. These findings call into question whether genomic DNA is the primary source of urinary 8-oxodGuo, which would largely exclude it as a biomarker of DNA oxidation. The urinary 8-oxodGuo levels from the MTH1 mice (both knock-out and hMTH1-Tg) were not significantly different to the wild-type mice. We suggest that these findings are due to redundancy in the process, and that other enzymes substitute for the lack of MTH1, however the present study cannot determine whether or not the 2’-deoxyribonucleotide pool is the source of urinary 8-oxodGuo. On the basis of the above, urinary 8-oxodGuo is most accurately defined as a non-invasive biomarker of oxidative stress, derived from oxidatively generated damage to 2’-deoxyguanosine

Human complement activation by smooth and rough Proteus mirabilis lipopolysaccharides

Proteus mirabilis bacilli play an important role in human urinary tract infections, bacteremia, and rheumatoid arthritis. The authors previously studied human complement C3 conversion by smooth-form P. mirabilis O10, O23, O30, and O43 lipopolysaccharides (LPSs) and showed that smooth Proteus LPSs fragmented C3 in a dose- and time-dependent manner. In the present study, one smooth P. mirabilis S1959 and its two polysaccharide-truncated LPSs isolated from an R mutant strain were used to study the C3 conversion. The conversion of C3 to C3c by smooth and rough P. mirabilis LPSs was studied by capture ELISA and crossed immunoelectrophoresis. Proteins isolated from the outer membrane were analyzed by discontinuous sodium dodecyl sulfate gel electrophoresis. The smooth P. mirabilis S1959 (O3) strain was resistant to the bactericidal activity of human serum, in contrast to the Ra and Re mutant strains. The presence of an exposed core oligosaccharide in R110 LPS was not sufficient to protect the strain from serum-dependent killing. In addition to LPS structure, the outer-membrane proteins may also play roles in protecting the smooth P. mirabilis S1959 (O3) strain from the bactericidal action of serum. It was shown that the Ra P. mirabilis R110 and the Re P. mirabilis R45 mutants possess very different OMP compositions from that of the P. mirabilis S 1959 strain. Regardless of the complement resistance of the P. mirabilis strains, the S1959, R110, and R45 LPSs fragmented C3 and induced C3c neo-antigen exposure. The use of complement-deficient human serum allows the conclusion that the Re-type P. mirabilis R45 LPS fragmented C3 by the antibody-independent classical pathway