BackgroundTo identify metabolic biomarkers that can be used to differentiate sepsis from systemic inflammatory response syndrome (SIRS), assess severity and predict outcomes.Methods65 patients were involved in this study, including 35 patients with sepsis, 15 patients with SIRS and 15 normal patients. Small metabolites that were present in patient serum samples were measured by liquid chromatography mass spectrometry techniques and analysed using multivariate statistical methods.ResultsThe metabolic profiling of normal patients and patients with SIRS or sepsis was markedly different. A significant decrease in the levels of lactitol dehydrate and S-phenyl-d-cysteine and an increase in the levels of S-(3-methylbutanoyl)-dihydrolipoamide-E and N-nonanoyl glycine were observed in patients with sepsis in comparison to patients with SIRS (p<0.05). Patients with severe sepsis and septic shock displayed lower levels of glyceryl-phosphoryl-ethanolamine, Ne, Ne dimethyllysine, phenylacetamide and d-cysteine (p<0.05) in their sera. The profiles of patients with sepsis 48 h before death illustrated an obvious state of metabolic disorder, such that S-(3-methylbutanoyl)-dihydrolipoamide-E, phosphatidylglycerol (22:2 (13Z, 16Z)/0:0), glycerophosphocholine and S-succinyl glutathione were significantly decreased (p<0.05). The receiver operating characteristic curve of the differential expression of these metabolites was also performed.ConclusionsThe body produces significant evidence of metabolic disorder during SIRS or sepsis. Seven metabolites may potentially be used to diagnose sepsis.Trial registration numberClinicalTrial.gov identifier NCT01649440.

Combination of surgical curettage and topical PDT has been proven to be a safe and effective procedure, and may offer a wide clinical application for the treatment of perianal condyloma acuminata.

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Introduction: Many acutely ill children in low- and middle-income settings have a high risk of mortality both during and after hospitalisation despite guideline-based care. Understanding the biological mechanisms underpinning mortality may suggest optimal pathways to target for interventions to further reduce mortality. The Childhood Acute Illness and Nutrition (CHAIN) Network (www.chainnnetwork.org) Nested Case-Cohort Study (CNCC) aims to investigate biological mechanisms leading to inpatient and post-discharge mortality through an integrated multi-omic approach. Methods and analysis; The CNCC comprises a subset of participants from the CHAIN cohort (1278/3101 hospitalised participants, including 350 children who died and 658 survivors, and 270/1140 well community children of similar age and household location) from nine sites in six countries across sub-Saharan Africa and South Asia. Systemic proteome, metabolome, lipidome, lipopolysaccharides, haemoglobin variants, toxins, pathogens, intestinal microbiome and biomarkers of enteropathy will be determined. Computational systems biology analysis will include machine learning and multivariate predictive modelling with stacked generalization approaches accounting for the different characteristics of each biological modality. This systems approach is anticipated to yield mechanistic insights, show interactions and behaviours of the components of biological entities, and help develop interventions to reduce mortality among acutely ill children. Ethics and dissemination. The CHAIN Network cohort and CNCC was approved by institutional review boards of all partner sites. Results will be published in open access, peer reviewed scientific journals and presented to academic and policy stakeholders. Data will be made publicly available, including uploading to recognised omics databases. Trial registration NCT03208725.

There are limited data on exposure to mycotoxins in Pakistan. Here, we measured exposure to deoxynivalenol (DON), a common contaminant of wheat, and aflatoxin B1 (AFB1), a known contaminant of rice, using biomarkers of exposure. Wheat (n = 195) and rice (n = 62) samples were analyzed for AFB1 and DON levels, and the corresponding urinary biomarkers were analyzed in urine samples from a rural population (n = 264, aged 4–80 years, male 58%) using ultra-sensitive liquid chromatography–tandem mass spectrometry. AFB1 was detected in 66% of rice (5.04 ± 11.94 µg/kg) and 3% of wheat samples. AFM1 (hydroxylated form of AFB1)was detected in 69% of urine samples, mean 0.023 ± 0.048 ng/mL and DON was detected in 20% of urine samples, mean 0.170 ± 0.129 ng/mL. The maximum probable daily intake for DON derived from the urinary biomarker was 59.8 ng/kg b.w./day, which is below the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives’ tolerable daily intake (1000 ng/kg b.w./day). However, for aflatoxin, the derived margin of exposure (MoE) of (13.2) was well below the safe MoE (10,000) suggested by the European Food Safety Authority. The calculated aflatoxin-associated cancer risk of 0.514/105 individuals/year suggests that measures should be taken to reduce the AFB1 contamination in food, particularly rice, in Pakistan.

Background Liver cirrhosis is a global health problem due to a large number of disability-associated life years and mortality. However, evidence is scarce on its causes in Eastern-Ethiopia, a place where there is a high prevalence of liver cirrhosis of unknown etiology. This study attempted to identify the risk factors related to liver cirrhosis in the area. Methods A case-control study was conducted at a tertiary care hospital from January 2020 to July 2021. Following diagnoses using an ultrasound-based cirrhosis scale, a total of 127 cases were identified and compared with 253 control patients. A structured questionnaire and data abstraction form were used to collect demographic, lifestyle, and clinical information. A blood sample was also taken from each participant for clinical chemistry, hepatitis B virus (HBV), and hepatitis C virus tests as well as for an aflatoxin B 1 (AFB 1 ) albumin adduct (AF-alb) assay. Binary logistic regression analysis was used to determine predictors of liver cirrhosis. Results AF-alb levels were detected in 75% of the cases and 64% of the controls, with a median (IQR) level of 11 pg/mg (5.5–25) and 7.0 pg/mg (4.3–20.5), respectively (p<0.05). Moreover, the number of subjects with high AF-alb levels (≥8.6 pg/mg) was greater in cases (45%, p<0.05)) than controls (28%). Age ≥55 years (adjusted odds ratio (AOR)=0.4; 95% CI: 0.2, 0.8), being a farmer (AOR= 3.0; 95% CI: 1.5, 6.0), family history of liver disease (AOR= 2.9; 95% CI: 1.1, 7.9), HBV seropositivity (AOR=4.0; 95% CI: 1.9, 8.8), and exposure to high levels of AF-alb (AOR=2.0; 95% CI: 1.1, 3.7) were significantly associated with liver cirrhosis. Conclusion This study found a strong link between AFB 1 exposure and liver cirrhosis. Mitigation of aflatoxin exposure and a better understanding of additional environmental risk factors like pesticides may be necessary to reduce the disease burden in Ethiopia.

High levels of mycotoxin contamination have been reported in various food commodities in Pakistan, however, there has been no exposure assessment study using multiple mycotoxins’ biomarkers. This study aimed to simultaneously assess the exposure to the five major mycotoxins: aflatoxin B1 (AFB1), deoxynivalenol (DON), fumonisin B1 (FB1), ochratoxin A (OTA) and zearalenone (ZEN) in a Pakistani population using an integrated approach of human biomonitoring. Human urine samples (n = 292) were analyzed by a super-sensitive liquid-chromatography tandem mass spectrometry (LC-MS/MS) method. Rice and wheat were also collected and analyzed for mycotoxins by the LC-MS/MS method. Food consumption data were collected using a 24 h recall method. A high prevalence of urinary AFM1 (66%, mean ± SD 20.8 ± 41.3 pg/mL) and OTA (99%, 134.7 ± 312.0 pg/mL) were found, whilst urinary DON, FB1 and ZEN levels were low. The probable daily intake (PDI) derived from the urinary biomarkers revealed that 89% of the participants had exposure to OTA exceeding the established tolerable daily intake (TDI = 17 ng/kg bw/day). The average PDI of AFB1 for the studied population was 43 ng/kg bw/day, with rice as the main source of AFB1 exposure. In summary, exposure to AFB1 and OTA are of health concern and require further management.

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