Oxidative modification of cytoplasmic RNA in vulnerable neurons is an important, well documented feature of the pathophysiology of Alzheimer disease. Here we report that RNA-bound iron plays a pivotal role for RNA oxidation in vulnerable neurons in Alzheimer disease brain. The cytoplasm of hippocampal neurons showed significantly higher redox activity and iron(II) staining than age-matched controls. Notably, both were susceptible to RNase, suggesting a physical association of iron(II) with RNA. Ultrastructural analysis further suggested an endoplasmic reticulum association. Both rRNA and mRNA showed twice the iron binding as tRNA. rRNA, extremely abundant in neurons, was considered to provide the greatest number of iron binding sites among cytoplasmic RNA species. Interestingly, the difference of iron binding capacity disappeared after denaturation of RNA, suggesting that the higher order structure may contribute to the greater iron binding of rRNA. Reflecting the difference of iron binding capacity, oxidation of rRNA by the Fenton reaction formed 13 times more 8-hydroxyguanosine than tRNA. Consistent with in situ findings, ribosomes purified from Alzheimer hippocampus contained significantly higher levels of RNase-sensitive iron(II) and redox activity than control. Furthermore, only Alzheimer rRNA contains 8-hydroxyguanosine in reverse transcriptase-PCR. Addressing the biological significance of ribosome oxidation by redox-active iron, in vitro translation with oxidized ribosomes from rabbit reticulocyte showed a significant reduction of protein synthesis. In conclusion these results suggest that rRNA provides a binding site for redoxactive iron and serves as a redox center within the cytoplasm of vulnerable neurons in Alzheimer disease in advance of the appearance of morphological change indicating neurodegeneration.

3,4-Methylenedioxypyrovalerone (MDPV) is a psychoactive, synthetic analog of the central nervous system stimulant cathinone. Its recent popularity as a recreational drug in the United States has led to numerous reports to poison control centers across the country. As with other synthetic cathinones, the recreational use of MDPV has resulted in death. MDPV is thought to exert its pharmacologic effects by inhibiting the reuptake of dopamine and norepinephrine. This report describes the case of an exposure of a 39-year-old male to MDPV, which resulted in his death. Postmortem concentrations of MDPV in various tissues were measured. The detection of MDPV in tissues and fluids was accomplished using gas chromatography-mass spectrometry analysis after solid-phase extraction. Blood analysis also demonstrated therapeutic levels of lamotrigine, fluoxetine, risperidone, benztropine, pseudoephedrine and ibuprofen. The detection of cathinones in hair was conducted using high-performance liquid chromatography-tandem mass spectrometry after solid-phase extraction. MDPV was uniformly distributed among multiple tissues (blood, brain, muscle, cerebrospinal fluid and lung) at concentrations of approximately 0.4 to 0.6 µg/mL. Tissue and fluids responsible for detoxification/excretion had higher concentrations of MDPV (kidney, liver and bile > 0.8 µg/mL). A blood concentration ≥ 0.4 µg/mL was judged sufficient to cause death. The cause of death was ruled MDPV intoxication resulting in cardiac arrhythmia.

Sudden unexpected death is typically diagnosed in infants, children, teenagers, and young adults following completion of an autopsy that fails to identify a cause of death or when autopsy suggests a potentially genetic cause of death in an individual less than 40, such as cardiomyopathy or aneurysm. Such deaths may be a result of genetic abnormalities that are unable to be diagnosed by gross or microscopic inspection, but may be detectable by molecular studies. Unfortunately, the ability to perform postmortem genetic testing is frequently hindered by lack of an appropriate specimen following completion of an autopsy. This paper provides recommendations developed by the National Association of Medical Examiners with the assistance of genetic counselors. The recommendations establish procedures to facilitate postmortem genetic testing and DNA banking by health care professionals assisting families who have experienced sudden death in young relatives by clarifying proper sample acquisition and storage. Additionally, recommendations for discussion with surviving family members and test planning are provided. The objective of these recommendations is to ensure that postmortem samples suitable for DNA banking are retained, allowing at risk family members improved detection of potentially treatable genetic diseases.

Two cases of suicidal electrocution are presented: one using a household lamp, the other using a homemade electrocution machine. The mechanisms of death and the histologic changes in electrocution are discussed.

This pilot and feasibility study evaluated wrist-worn accelerometers to measure recovery from day-case surgery in comparison with daily quality of recovery-15 scores. The protocol was designed with extensive patient and public involvement and engagement, and delivered by a research network of anaesthesia trainees. Forty-eight patients recruited through pre-operative assessment clinics wore wrist accelerometers for 7 days before (pre-operative) and immediately after elective surgery (early postoperative), and again at 3 months (late postoperative). Validated activity and quality of recovery questionnaires were administered. Raw accelerometry data were archived and analysed using open source software. The mean (SD) number of valid days of accelerometer wear per participant in the pre-operative, early and late postoperative periods were 5.4 (1.7), 6.6 (1.1) and 6.6 (1.0) days, respectively. On the day after surgery, Euclidian norm minus one (a summary measure of raw accelerations), step count, light physical activity and moderate/vigorous physical activity decreased to 57%, 47%, 59% and 35% of baseline values, respectively. Activity increased progressively on a daily basis but had not returned to baseline values by 7 days. Patient questionnaires suggested subjective recovery by postoperative day 3 to 4; however, accelerometry data showed that activity levels had not returned to baseline at this point. All activity measures had returned to baseline by 3 months. Wrist-worn accelerometery is acceptable to patients and feasible as a surrogate measure for monitoring postoperative recovery from day-case surgery. Our results suggest that patients may overestimate their rate of recovery from day-case surgery, which has important implications for future research.