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Objectives: Possible immunomodulatory effect of amantadine in patients treated in intensive care unit (ICU), mostly among patients with brain injuries or vascular diseases was observed in several studies. The potential antiviral effect of amantadine against SARS-CoV-2 was discarded in clinical trials; however, immunomodulatory potential was not studied. The aim of the study was to investigate the effect of immunomodulatory amantadine therapy on mortality in patients with respiratory insufficiency due to COVID-19 requiring mechanical ventilation in ICU., Methods: Retrospective analysis of 241 cases of 141 (58.5%) receiving intravenous amantadine sulfate vs 100 (41.5%) controls on standard of care only was performed., Results: Overall mortality was 72.6%, being notably lower among amantadine treated patients (59.5%, n = 84) compared with controls (91%, n = 91), P-value = 0.001. In multivariate models administration of amantadine was independently associated with lower mortality rate (hazard ratio: 0.220, CI: 0.146-0.333 P-value = 0.001). Furthermore, survival was improved in patients who received amantadine; late administration of amantadine after 5th day was independently associated with lower mortality (hazard ratio: 0.560, CI: 0.313-0.999, P-value = 0.050)., Conclusion: In patients treated in ICU with severe respiratory failure, administration of amantadine is associated with lower mortality, which may be associated with the potential anti-inflammatory and immunomodulatory effects of this agent., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Human head hair shape, commonly classified as straight, wavy, curly or frizzy, is an attractive target for Forensic DNA Phenotyping and other applications of human appearance prediction from DNA such as in paleogenetics. The genetic knowledge underlying head hair shape variation was recently improved by the outcome of a series of genome-wide association and replication studies in a total of 26,964 subjects, highlighting 12 loci of which 8 were novel and introducing a prediction model for Europeans based on 14 SNPs. In the present study, we evaluated the capacity of DNA-based head hair shape prediction by investigating an extended set of candidate SNP predictors and by using an independent set of samples for model validation. Prediction model building was carried out in 9674 subjects (6068 from Europe, 2899 from Asia and 707 of admixed European and Asian ancestries), used previously, by considering a novel list of 90 candidate SNPs. For model validation, genotype and phenotype data were newly collected in 2415 independent subjects (2138 Europeans and 277 non-Europeans) by applying two targeted massively parallel sequencing platforms, Ion Torrent PGM and MiSeq, or the MassARRAY platform. A binomial model was developed to predict straight vs. non-straight hair based on 32 SNPs from 26 genetic loci we identified as significantly contributing to the model. This model achieved prediction accuracies, expressed as AUC, of 0.664 in Europeans and 0.789 in non-Europeans; the statistically significant difference was explained mostly by the effect of one EDAR SNP in non-Europeans. Considering sex and age, in addition to the SNPs, slightly and insignificantly increased the prediction accuracies (AUC of 0.680 and 0.800, respectively). Based on the sample size and candidate DNA markers investigated, this study provides the most robust, validated, and accurate statistical prediction models and SNP predictor marker sets currently available for predicting head hair shape from DNA, providing the next step towards broadening Forensic DNA Phenotyping beyond pigmentation traits., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Chromatographic studies on breath composition are aimed at finding volatile markers useful for medical diagnostics or in screening investigations. Studies leading to the development of screening breath tests are especially important for the diagnostics of chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). The aim of the presented study was to confirm diagnostic usefulness of chosen volatile compounds detected in breath, which are suggested as potential biomarkers of renal dysfunction and diabetes. Breath analysis were carried out in three groups: 10 healthy volunteers, 10 patients with CKD and 10 patients with CKD and T2DM. All exhaled air samples were analyzed using gas chromatograph (Agilent 6890GC) coupled with mass spectrometer (5975MSD). Thermal desorption was applied as the enrichment method. TMA was detected only in CKD patients. Higher breath concentrations of methanethiol (MeSH) were observed in CKD patients with coexisting diabetes than in patients with renal dysfunction only or in the healthy group. There was a tendency of increasing MeSH concentration in breath with increasing total glutathione in plasma (r=0.53, p=0.0026). Also, a trend of increasing dimethylsulfide (DMS) levels detected in breath was noticed with an increase of hydrogen sulfide concentration in plasma (r=0.74; p=0.00001) as well as with aspartate aminotransferase (AST), (r=0.61; p=0.001). The presented results suggest the possibility of applying TMA, MeSH, and DMS detection in breath as diagnostic methods., (Copyright © 2017 Elsevier B.V. All rights reserved.)

DNA-based prediction of hair morphology, defined as straight, curly or wavy hair, could contribute to an improved description of an unknown offender and allow more accurate forensic reconstructions of physical appearance in the field of forensic DNA phenotyping. Differences in scalp hair morphology are significant at the worldwide scale and within Europe. The only genome-wide association study made to date revealed the Trichohyalin gene (TCHH) to be significantly associated with hair morphology in Europeans and reported weaker associations for WNT10A and FRAS1 genes. We conducted a study that centered on six SNPs located in these three genes with a sample of 528 individuals from Poland. The predictive capacity of the candidate DNA variants was evaluated using logistic regression; classification and regression trees; and neural networks, by applying a 10-fold cross validation procedure. Additionally, an independent test set of 142 males from six European populations was used to verify performance of the developed prediction models. Our study confirmed association of rs11803731 (TCHH), rs7349332 (WNT10A) and rs1268789 (FRAS1) SNPs with hair morphology. The combined genotype risk score for straight hair had an odds ratio of 2.7 and these predictors explained ∼ 8.2% of the total variance. The selected three SNPs were found to predict straight hair with a high sensitivity but low specificity when a 10-fold cross validation procedure was applied and the best results were obtained using the neural networks approach (AUC=0.688, sensitivity=91.2%, specificity=23.0%). Application of the neural networks model with 65% probability threshold on an additional test set gave high sensitivity (81.4%) and improved specificity (50.0%) with a total of 78.7% correct calls, but a high non-classification rate (66.9%). The combined TTGGGG SNP genotype for rs11803731, rs7349332, rs1268789 (European frequency=4.5%) of all six straight hair-associated alleles was identified as the best predictor, giving >80% probability of straight hair. Finally, association testing of 44 SNPs previously identified to be associated with male pattern baldness revealed a suggestive association with hair morphology for rs4679955 on 3q25.1. The study results reported provide the starting point for the development of a predictive test for hair morphology in Europeans. More studies are now needed to discover additional determinants of hair morphology to improve the predictive accuracy of this trait in forensic analysis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The role of epistatic effects in the determination of complex traits is often underlined but its significance in the prediction of pigmentation phenotypes has not been evaluated so far. The prediction of pigmentation from genetic data can be useful in forensic science to describe the physical appearance of an unknown offender, victim, or missing person who cannot be identified via conventional DNA profiling. Available forensic DNA prediction systems enable the reliable prediction of several eye and hair colour categories. However, there is still space for improvement. Here we verified the association of 38 candidate DNA polymorphisms from 13 genes and explored the extent to which interactions between them may be involved in human pigmentation and their impact on forensic DNA prediction in particular. The model-building set included 718 Polish samples and the model-verification set included 307 independent Polish samples and additional 72 samples from Japan. In total, 29 significant SNP-SNP interactions were found with 5 of them showing an effect on phenotype prediction. For predicting green eye colour, interactions between HERC2 rs12913832 and OCA2 rs1800407 as well as TYRP1 rs1408799 raised the prediction accuracy expressed by AUC from 0.667 to 0.697 and increased the prediction sensitivity by >3%. Interaction between MC1R 'R' variants and VDR rs731236 increased the sensitivity for light skin by >1% and by almost 3% for dark skin colour prediction. Interactions between VDR rs1544410 and TYR rs1042602 as well as between MC1R 'R' variants and HERC2 rs12913832 provided an increase in red/non-red hair prediction accuracy from an AUC of 0.902-0.930. Our results thus underline epistasis as a common phenomenon in human pigmentation genetics and demonstrate that considering SNP-SNP interactions in forensic DNA phenotyping has little impact on eye, hair and skin colour prediction., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The analytical potential of chromatographic breath analysis towards detection of compounds suggested as markers of chronic kidney disease (CKD) was tested. Until now, trimethylamine (TMA) considered as a potential marker of renal disorder was detected mainly in plasma. Detection of TMA in breath was rarely undertaken due to analytical difficulties associated with amines' properties. The results of our investigations confirmed that an application of thermal desorption (TD) and gas chromatography with mass-spectral detection (GC/MS) allows direct detection of TMA in breath. The preliminary studies allowed to determine the breath composition in case of patients suffering from CKD and to compare the obtained results to a control group. Breath samples were collected from 14 patients and 9 healthy volunteers. TMA was detected in all patients suffering from CKD in the range 1.76-38.02ppb, but not in the control group. Acetone and isoprene were present in the exhaled air of all examined persons. The concentration of acetone was in the range of 26.52-329.46ppb in the patient group and 73.11-437.14ppb in the control group. Isoprene was detected in the range 57.17-329.8ppb among CKD patients and 27.99-143.77ppb in healthy volunteers. Additionally aliphatic hydrocarbons and sulfur compounds were determined in breath as compounds which could be essential in case of diseases coexisting with CKD. Apart from TMA and pentane no statistically significant differences were found using our analytical technique. TMA was detected in the breath of all patients with CKD and in none of breath samples in control group. TMA seems to be a promising marker of CKD., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) represents a sensitive and efficient technique to determine expression levels of target genes in multiple samples and is increasingly used in clinical oncology to evaluate the patient's outcome or to detect minimal residual disease. Normalization of raw data are required to obtain comparable results between different specimens and is usually achieved by correlating transcript abundances of target genes with those of a single control gene with putatively stable expression levels. In this study, expression stability of six supposed control genes was evaluated in 64 samples of primary neuroblastoma and HPRT1 and SDHA mRNA levels were shown to exhibit the least expression variability among the samples. Because application of more than one control gene may enhance reliability of real-time RT-PCR results, various normalization factors consisting of the geometrical mean of multiple control gene expression values were calculated and evaluated by mRNA quantification of 14 target genes. Comparison with transcript levels determined by oligonucleotide-array expression analysis revealed that target gene mRNA quantification became most consistent after normalization to averaged expression levels of HPRT1 and SDHA. This normalization factor was in addition demonstrated to be not associated with stage of disease or MYCN amplification status of the tumor. Thus, these data indicate that the geometrical mean of HPRT1 and SDHA transcript levels represents a suitable internal control for biological and clinical studies investigating differential gene expression in primary neuroblastoma by real-time RT-PCR.

A new method of analytical determination of some thiolo (PS) and thiono (PS) group containing phosphorus insecticides using a coulometric titration with the anodically generated chlorine and biamperometric end-point detection was described. The method worked well for compounds containing one (methamidophos) or two PS bonds (iso-malathion) or one PS bond (fenitrothion) but failed for compounds containing both PS and PS bonds (malathion, dimethoate) or additional sterically hindered CSC bond (fenthion). Based on the found number z of electrons transferred per mol of oxidized compounds, mechanistic pathways for chlorination of PS and PS containing thiophosphorus insecticides with molecular chlorine in aqueous, acidic medium were proposed.