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BackgroundGoogle Glass is a promising premarket device that includes an optical head-mounted display. Several proof of concept reports exist, but there is little scientific evidence regarding its use in a medical setting. ObjectiveThe objective of this study was to empirically determine the feasibility of deploying Glass in a forensics setting. MethodsGlass was used in combination with a self-developed app that allowed for hands-free operation during autopsy and postmortem examinations of 4 decedents performed by 2 physicians. A digital single-lens reflex (DSLR) camera was used for image comparison. In addition, 6 forensic examiners (3 male, 3 female; age range 23-48 years, age mean 32.8 years, SD 9.6; mean work experience 6.2 years, SD 8.5) were asked to evaluate 159 images for image quality on a 5-point Likert scale, specifically color discrimination, brightness, sharpness, and their satisfaction with the acquired region of interest. Statistical evaluations were performed to determine how Glass compares with conventionally acquired digital images. ResultsAll images received good (median 4) and very good ratings (median 5) for all 4 categories. Autopsy images taken by Glass (n=32) received significantly lower ratings than those acquired by DSLR camera (n=17) (region of interest: z=–5.154, P

Background: Sudden infant death syndrome (SIDS) is the leading cause of death among infants aged between one month and one year. Altered enzyme activities or expression of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have been observed in SIDS patients that might lead to disturbed autonomic function and, together with other risk factors, might trigger SIDS. To explore the contribution of AChE and BChE from a genomic viewpoint, we sought to investigate the association between SIDS and selected single nucleotide polymorphisms (SNPs) in the ACHE and BCHE genes. Methods: In this case-control study, 13 potentially regulatory SNPs were selected from ACHE and BCHE and were genotyped in 201 SIDS cases and 338 controls. The association of SIDS with the 11 successfully genotyped candidate variants was examined using statistical analyses of overall or stratified cases and haplotype analyses. Results: No significant overall associations were observed between SIDS and ACHE and BCHE variants in allele, genotype, and haplotype analyses. In subgroup analyses, eight variants were found to be nominally associated with SIDS, though these associations did not remain statistically significant after correction for multiple comparisons. One haplotype (T-C-G-C-C in rs3495-rs1803274-rs1355538-rs2048493-rs1126680) of BCHE was associated with the female SIDS subgroup (57.3% in controls vs. 46.3% in female SIDS cases, p = 0.010). Conclusions: The selected variants in ACHE and BCHE were not overall associated with SIDS in this study, and thus cannot generally explain the previously reported dysregulation of enzyme activities in SIDS. However, some evidence of association in subgroups and a possible contribution of variants other than those tested here would need to be explored in larger studies. [ABSTRACT FROM AUTHOR]

An analytical strategy for identification by an LC–MS/MS multitarget screening method and a suitable LC–MS/MS based quantification were developed for the psychotropic drug phenibut. The samples analyzed were collected during traffic control and were associated with driving under the influence of drugs. A positive sample for phenibut was identified in a single case of driving under the influence. The quantification revealed a drug concentration of 1.9 μg/mL. An interaction with blood alcohol (BAC = 0.10%) was discussed as the explanation of the way of driving and deficit manifestations observed (swaying, nystagmus, quivering of the eyelid, and reddened eyes). According to the available information, the quantified phenibut concentration could be explained by an intake of four tablets (self‐reported) during the day containing 250 mg of the drug. Chromatography was performed with a Luna 5 μm C18 (2) 100 A, 150 mm × 2 mm analytical column, and a buffer system consisted of 10 mM ammonium acetate and 0.1% acetic acid (v/v) included in mobile phases marked as A (H2O/methanol = 95/5, v/v) and B (H2O/methanol = 3/97, v/v). An effective limit of detection (LOD = 0.002 μg/mL) could be achieved for the multitarget screening method. The quantification of phenibut was performed on a second LC–MS/MS system with LOD/LOQ values of 0.22/0.40 μg/mL. Since phenibut quantification data are rare, the presented information can be used with caution for evaluation of positive cases in the future. [ABSTRACT FROM AUTHOR]

Aims Heart failure (HF) after myocardial infarction (MI) is a major cause of morbidity and mortality. We sought to investigate the functional importance of cardiac iron status after MI and the potential of pre-emptive iron supplementation in preventing cardiac iron deficiency (ID) and attenuating left ventricular (LV) remodelling. Methods and results MI was induced in C57BL/6J male mice by left anterior descending coronary artery ligation. Cardiac iron status in the non-infarcted LV myocardium was dynamically regulated after MI: non-haem iron and ferritin increased at 4 weeks but decreased at 24 weeks after MI. Cardiac ID at 24 weeks was associated with reduced expression of iron-dependent electron transport chain (ETC) Complex I compared with sham-operated mice. Hepcidin expression in the non-infarcted LV myocardium was elevated at 4 weeks and suppressed at 24 weeks. Hepcidin suppression at 24 weeks was accompanied by more abundant expression of membrane-localized ferroportin, the iron exporter, in the non-infarcted LV myocardium. Notably, similarly dysregulated iron homeostasis was observed in LV myocardium from failing human hearts, which displayed lower iron content, reduced hepcidin expression, and increased membrane-bound ferroportin. Injecting ferric carboxymaltose (15 µg/g body weight) intravenously at 12, 16, and 20 weeks after MI preserved cardiac iron content and attenuated LV remodelling and dysfunction at 24 weeks compared with saline-injected mice. Conclusion We demonstrate, for the first time, that dynamic changes in cardiac iron status after MI are associated with local hepcidin suppression, leading to cardiac ID long term after MI. Pre-emptive iron supplementation maintained cardiac iron content and attenuated adverse remodelling after MI. Our results identify the spontaneous development of cardiac ID as a novel disease mechanism and therapeutic target in post-infarction LV remodelling and HF. [ABSTRACT FROM AUTHOR]

Aim: Impaired resilience to stress may be a factor in sudden infant death syndrome (SIDS). However, no comprehensive studies have been performed on polymorphisms that are relevant to the hypothalamic–pituitary–adrenal (HPA) axis, which regulates the stress hormone cortisol. Methods: We analysed 22 relevant single nucleotide polymorphisms (SNPs) in 206 anonymised SIDS cases who died at a mean of 131 days (range: 5–343) and 256 adult controls who were recruited from paternity testing cases. Additional stratified analyses were performed for sex, age and season of death. Both the cases and the controls were Caucasian. Results: Variants for rs2235543 (HSD11B1) and rs3779250 (CRHR2) were associated with SIDS in the overall analysis, and borderline for rs2446432 (CRH), at least before corrections for multiple testing. A combination of these three variants was observed in 52.9% of SIDS cases but only 43.0% of controls (p = 0.039). Five or more variants showed an association in the subgroups. Conclusion: Our findings suggest that the HPA axis influences SIDS and supports the hypothesis that an inadequate stress response may add to the risk. The associated variants for rs2235543, rs3779250 and rs2446432 appeared to decrease the cortisol concentration and impair an appropriate stress response. [ABSTRACT FROM AUTHOR]

Aims Alcohol use alters the reward signaling processes contributing to the development of addiction. We studied the effects of alcohol use disorder (AUD) on brain regions and blood of deceased women and men to examine sex-dependent differences in epigenetic changes associated with AUD. We investigated the effects of alcohol use on the gene promoter methylation of GABBR1 coding for GABAB receptor subunit 1 in blood and brain. Methods We chose six brain regions associated with addiction and the reward pathway (nucleus arcuatus, nucleus accumbens, the mamillary bodies, amygdala, hippocampus and anterior temporal cortex) and performed epigenetic profiling of the proximal promoter of the GABBR1 gene of post-mortem brain and blood samples of 17 individuals with AUD pathology (4 female, 13 male) and 31 healthy controls (10 female, 21 male). Results Our results show sex-specific effects of AUD on GABBR1 promoter methylation. Especially, CpG −4 showed significant tissue-independent changes and significantly decreased methylation levels for the AUD group in the amygdala and the mammillary bodies of men. We saw prominent and consistent change in CpG-4 across all investigated tissues. For women, no significant loci were observed. Conclusion We found sex-dependent differences in GABBR1 promoter methylation in relation to AUD. CpG-4 hypomethylation in male individuals with AUD is consistent for most brain regions. Blood shows similar results without reaching significance, potentially serving as a peripheral marker for addiction-associated neuronal adaptations. Further research is needed to discover more contributing factors in the pathological alterations of alcohol addiction to offer sex-specific biomarkers and treatment. [ABSTRACT FROM AUTHOR]

Aims The dopamine receptor D2 (DRD2) is substantially involved in several forms of addiction. In addition to genetic polymorphisms, epigenetic mechanisms have emerged as an important means of regulation. Previously, DRD2 hypo- and hyper-methylation have been observed in alcohol use disorder (AUD). Blood samples are commonly used as a surrogate marker of epigenetic alterations in epigenetic research, but few specific comparisons between blood and brain tissue samples in AUD exist. Methods We used post-mortem brain tissue samples of 17 deceased patients with AUD and 31 deceased controls to investigate the relationship between blood and brain methylation of the DRD2 promoter. Results When investigating individual cytosine methylation sites (CpG), several significant differences were found in the nucleus accumbens and hippocampus in the study population. Investigating binding sites with significant differences in methylation levels revealed hypomethylated CpGs targeting mainly activating transcription factors. Conclusion These findings support an altered transcription of the DRD2 gene in AUD specimens with a consecutively changed reward response in the brain. While methylation between specific brain regions and blood is comparable, our study further suggests that blood methylation cannot provide meaningful perspectives on DRD2 promoter methylation in the brain. [ABSTRACT FROM AUTHOR]

The aim of the work was the development and validation of a liquid chromatography – tandem mass spectrometry (LC–MS-MS) γ-hydroxybutyrate (GHB) quantification method in urine and human serum by the use of the analyte adduct ion formation strategy. A combined detection with a conventional precursor ion in the negative electrospray mode and additionally GHB adduct ions with both sodium acetate and lithium acetate was in focus. Therefore, GHB quantification was based on separated MS-MS signals. Two tandem mass spectrometers representing different MS-MS generations (Sciex API 4000 QTrap and Sciex API 5500 QTrap) were used for method validation and comparison. Shimadzu HPLC systems equipped with a Luna 5-µm C18 (2) 100 A, 150-mm × 2-mm analytical column were successfully applied for sample analyses. Infusion experiments were performed for adduct identification and analyte detection optimization. Sample preparation could be limited to a simple and fast protein precipitation/sample dilution. An effective signal-separated GHB quantification with three independent precursor ions representing separated areas of the mass spectrum was developed, validated according to forensic guidelines and applied in the routine. The developed and applied strategy resulted in a higher safety factor for the analyte quantification performed in the forensic toxicology. A relevant analytical improvement could be achieved with this alternative adduct-based GHB analysis since a good correlation of analyte concentrations calculated on the basis of separated signals was stated as useful analytical information. [ABSTRACT FROM AUTHOR]

Since rodenticides represent a substance group relevant in toxicological analyses, the aim of this work was the development of a complex multi‐target screening strategy for the identification with liquid chromatography–tandem mass spectrometry. A simple protein precipitation was used as the sample preparation strategy. Further, a Luna 5 μm C18 (2) 100 Å, 150 × 2 mm analytical column was applied for the separation of relevant analytes with a Shimadzu HPLC. Signal detection was performed with a SCIEX API 5500 QTrap MS/MS system. The rodenticides investigated (α‐chloralose, brodifacoum, bromadiolone, coumatetralyl, difenacoum, and warfarin) could be incorporated effectively into a multi‐target screening strategy covering about 250 substances representing different groups with a limit of detection appropriate for substance identification. The strategy can easily be modified to perform semi‐quantitative measurements for this substance group and could be supplemented by quantification based on standard addition. [ABSTRACT FROM AUTHOR]

Both age-dependent and age-independent alteration of DNA methylation in human tissues are functionally associated with the development of many malignant and non-malignant human diseases. TCGA-KIRC data were biometrically analyzed to identify new loci with age-dependent DNA methylation that may contribute to tumor risk in normal kidney tissue. ANKRD34B and ZIC1 were evaluated as candidate genes by pyrosequencing of 539 tissues, including 239 normal autopsy, 157 histopathologically tumor-adjacent normal, and 143 paired tumor kidney samples. All candidate CpG loci demonstrated a strong correlation between relative methylation levels and age (R = 0.70–0.88, p < 2 × 10−16) and seven out of 10 loci were capable of predicting chronological age in normal kidney tissues, explaining 84% of the variance (R = 0.92). Moreover, significantly increased age-independent methylation was found for 9 out of 10 CpG loci in tumor-adjacent tissues, compared to normal autopsy tissues (p = 0.001–0.028). Comparing tumor and paired tumor-adjacent tissues revealed two patient clusters showing hypermethylation, one cluster without significant changes in methylation, and a smaller cluster demonstrating hypomethylation in the tumors (p < 1 × 10−10). Taken together, our results show the presence of additional methylation risk factors besides age for renal cancer in normal kidney tissue. Concurrent tumor-specific hypermethylation suggests a subset of these loci are candidates for epigenetic renal cancer susceptibility. [ABSTRACT FROM AUTHOR]

Dirty Sprite, also known as "lean" or "purple drank", is a preparation associated with the presence of codeine and promethazine. These drinks, predominantly used by young people, are mixtures of, for example, soft drinks, prescription medicines, and prescription cough syrups. The use of these illicit preparations started in Texas in the 1960s and become popularized in the 1990s. However, the misuse of these cocktails has become more common in other countries to date, for example, in Thailand. Given the illicit nature of these preparations and the lack of information available on the composition of these products, there is a need to identify and quantify the drugs that may be present. Three samples of Dirty Sprite were analyzed using GC–MS after liquid/liquid‐extraction under acidic and basic conditions. Since the acidic extraction did not show the detection of relevant substances, samples were alkalized to pH ≥ 9, followed by extraction with 1‐chlorobutane. GC–MS screening revealed the identification of codeine, dihydrocodeine, promethazine and impurities of cocaine. A selected ion monitoring method was developed for the quantification of these compounds using lemonade as a calibration matrix. Quantitative analysis showed concentrations of 130‐mg/L codeine, 75‐mg/L promethazine, and 3.4‐mg/L cocaine in sample 1; 74‐mg/L promethazine and 91‐mg/L dihydrocodeine in sample 2; and 130‐mg/L codeine combined with 68‐mg/L promethazine in sample 3. The results also illustrate that the consumption of drugs detected in Dirty Sprite samples could lead to health risks given that these prescription medicines are consumed outside the medical environment. [ABSTRACT FROM AUTHOR]