Genome-wide identification, in silico characterization and expression analysis of ZIP-like genes from Trichomonas vaginalis in response to Zinc and Iron.

Trace elements such as Zinc and Iron are essential components of metalloproteins and serve as cofactors or structural elements for enzymes involved in several important biological processes in almost all organisms. Because either excess or insufficient levels of Zn and Fe can be harmful for the cells, the homeostatic levels of these trace minerals must be tightly regulated. The Zinc regulated transporter, Iron regulated transporter-like Proteins (ZIP) comprise a diverse family, with several paralogues in diverse organisms and are considered essential for the Zn and Fe uptake and homeostasis. Zn and Fe has been shown to regulate expression of proteins involved in metabolism and pathogenicity mechanisms in the protozoan pathogen Trichomonas vaginalis, in contrast high concentrations of these elements were also found to be toxic for T. vaginalis trophozoites. Nevertheless, Zn and Fe uptake and homeostasis mechanisms is not yet clear in this parasite. We performed a genome-wide analysis and localized the 8 members of the ZIP gene family in T. vaginalis (TvZIP1-8). The bioinformatic programs predicted that the TvZIP proteins are highly conserved and show similar properties to the reported in other ZIP orthologues. The expression patterns of TvZIP1, 3, 5 and 7 were diminished in presence of Zinc, while the rest of the TvZIP genes showed an unchanged profile in this condition. In addition, TvZIP2 and TvZIP4 showed a differential expression pattern in trophozoites growth under different Iron conditions. These results suggest that TvZIP genes encode membrane transporters that may be responsible for the Zn and Fe acquisition in T. vaginalis.

The sequential organ failure assessment (SOFA) score is an effective triage marker following staggered paracetamol (acetaminophen) overdose.

BACKGROUND: The sequential organ failure assessment (SOFA) score is an effective triage marker following single time point paracetamol (acetaminophen) overdose, but has not been evaluated following staggered (multiple supratherapeutic doses over >8 h, resulting in cumulative dose of >4 g/day) overdoses. AIM: To evaluate the prognostic accuracy of the SOFA score following staggered paracetamol overdose. METHODS: Time-course analysis of 50 staggered paracetamol overdoses admitted to a tertiary liver centre. Individual timed laboratory samples were correlated with corresponding clinical parameters and the daily SOFA scores were calculated. RESULTS: A total of 39/50 (78%) patients developed hepatic encephalopathy. The area under the SOFA receiver operator characteristic for death/liver transplantation was 87.4 (95% CI 73.2-95.7), 94.3 (95% CI 82.5-99.1), and 98.4 (95% CI 84.3-100.0) at 0, 24 and 48 h, respectively, postadmission. A SOFA score of <6 at tertiary care admission predicted survival with a sensitivity of 100.0% (95% CI 76.8-100.0) and specificity of 58.3% (95% CI 40.8-74.5), compared with 85.7% (95% CI 60.6-97.4) and 75.0% (95% CI 65.2-79.5) , respectively, for the modified Kings College criteria. Only 2/21 patients with an admission SOFA score <6 required renal replacement therapy or intracerebral pressure monitoring. SOFA significantly outperformed the Model for End-stage Liver Disease, but not APACHE II, at 0, 24-and 48-h following admission. CONCLUSIONS: A SOFA score <6 at tertiary care admission following a staggered paracetamol overdose, is associated with a good prognosis. Both the SOFA and APACHE II scores could improve triage of high-risk staggered paracetamol overdose patients.

The sequential organ failure assessment (SOFA) score is prognostically superior to the model for end-stage liver disease (MELD) and MELD variants following paracetamol (acetaminophen) overdose.

BACKGROUND: The prognostic value of the model for end-stage liver disease (MELD) and sodium-based MELD variants in predicting survival following paracetamol overdose remains unclear. AIM: To examine the prognostic accuracy of sodium-based MELD variants in paracetamol-induced acute liver injury compared with the sequential organ failure assessment (SOFA) score. METHODS: Retrospective analysis of 138 single time point paracetamol overdoses admitted to a tertiary liver centre. Individual laboratory samples were correlated with the corresponding clinical parameters in relation to time post-overdose, and the daily MELD, MELD-Na, MELDNa, MESO, iMELD, UKELD, updated MELD and SOFA scores were calculated. RESULTS: Sixty-six (47.8%) patients developed hepatic encephalopathy, of whom 7 were transplanted and 21 died without liver transplantation. SOFA had a significantly greater area under the receiver operator characteristic for the prediction of spontaneous survival compared with MELD at both 72 (P = 0.024) and 96 (P = 0.017) h post-overdose. None of the sodium-based MELD variants improved the prognostic accuracy of MELD. A SOFA score >6 by 72 h or >7 by 96 h, post-overdose predicted death/transplantation with a negative predictive value of 96.9 (95% CI 90.2-99.4) and 98.8 (95% CI 93.6-99.9) respectively. SOFA and MELD had similar accuracy for predicting the development of hepatic encephalopathy (P = 0.493). CONCLUSIONS: The SOFA score is superior to MELD in predicting spontaneous survival following paracetamol-induced acute liver injury. Modification of the MELD score to include serum sodium does not improve prognostic accuracy in this setting. SOFA may have potential as a quantitative triage marker following paracetamol overdose.

The systemic inflammatory response syndrome and sequential organ failure assessment scores are effective triage markers following paracetamol (acetaminophen) overdose.

BACKGROUND: The systemic inflammatory response syndrome (SIRS) and sequential organ failure assessment (SOFA) scores are widely used as prognostic markers in critical care settings and could improve triage of high-risk paracetamol (acetaminophen) overdose patients. AIM: To evaluate the prognostic accuracy of the SIRS and SOFA scores following single time point paracetamol overdose. METHODS: Analysis of 100 single time point paracetamol overdoses admitted to a tertiary liver centre, with subsequent prospective validation of identified thresholds. Individual laboratory samples were correlated with the corresponding clinical parameters in relation to time post-overdose, and the daily SOFA and SIRS scores calculated. RESULTS: A total of 74 (74%) patients developed the SIRS, which occurred significantly earlier in patients who died (n=21) compared with spontaneous survivors (n=53, P=0.05). The SIRS occurred in 70 (70%) patients by 96h post-overdose, with a 30% mortality rate; compared with 0% mortality in the 30 non-SIRS patients (P=0.001). Median SOFA scores were significantly higher in nonsurvivors at 48 (P=0.009), 72 (P<0.001), and 96h (P<0.001). A SOFA score >7 during the first 96h post-overdose predicted death/transplantation with a sensitivity of 95.0 (95% CI 78.5-99.1) and specificity of 70.5 (95% CI 66.3-71.6). A validation cohort of 38 single time point paracetamol overdoses confirmed the extremely high negative predictive value of both the SIRS and SOFA thresholds. CONCLUSIONS: The absence of either a SOFA score >7 or a SIRS response during the first 96 h following paracetamol overdose could improve triage and reduce transfers of lower risk patients to tertiary liver centres.