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To prevent cardiotoxicity while digging the unique value of AC in cardiac pharmacology, there exists a huge urge to better know the characteristic of AC being a cardiotoxic agent or a potential heart drug. Here, this article reviews the advances of AC metabolism and focuses on the latest mechanistic findings of cardiac efficacy and toxicity of this aconite alkaloid or its metabolites. We also discuss how to prevent AC-related cardiotoxicity, as well as the issues before the development of AC-based medicines that should be solved, to provide new insight into the paradoxical nature of this ancient poison.A detailed knowledge on the exact morphology of pelvic injuries provided crucial information in understanding the mechanisms of injury and has influence on the natural course and subsequent mortality. Rabusertib ic50 However, forensic medical literature investigating pelvic fractures in detail is scarce to date. This case series aims to compare the accuracy in detecting pelvic injuries using autopsy and ante mortem computed tomography (CT). Nineteen deceased patients with CT scans of pelvic fractures were included retrospectively. Pelvic injuries were independently assessed by a board-certified radiologist (R) and a board-certified trauma surgeon (T), both using the ante mortem CT scans, and by a board-certified forensic pathologist using autopsy (A) results without knowledge of the CT scan findings. No patient had died causatively from a pelvic fracture. Most injuries of the pelvis were present in the pubic rami (16/18) and sacral bone (13/18), followed by the sacroiliac joint (9/18) and iliac bone fractures (8/18). Ilium fractures (A100%;R67%;T67%) and injuries of the sacroiliac joint (A83%;R50%;T42%) were best detected via autopsy. The diagnosis of sacral fractures (A19%;R94%;T88%) and fractures of the pubic rami (A67%;R96%;T96%) were most often missed in autopsy. The results show deficits in the assessment of the pelvic injury for both CT and autopsy. Autopsy was superior in detecting injuries of the sacroiliac joint, but inferior in detecting sacral and pubic bone fractures. For an encompassing evaluation of ligamento-skeletal pelvic injuries, the complementary use of both CT and autopsy is recommended.The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the main target for antiviral and vaccine development. Despite its relevance, e information is scarse about its evolutionary traces. The aim of this study was to investigate the diversification patterns of the spike for each clade of SARS-CoV-2 through different approaches. Two thousand and one hundred sequences representing the seven clades of the SARS-CoV-2 were included. Patterns of genetic diversifications and nucleotide evolutionary rate were estimated for the spike genomic region. The haplotype networks showed a star shape, where multiple haplotypes with few nucleotide differences diverge from a common ancestor. Four hundred seventy-nine different haplotypes were defined in the seven analyzed clades. The main haplotype, named Hap-1, was the most frequent for clades G (54%), GH (54%), and GR (56%) and a different haplotype (named Hap-252) was the most important for clades L (63.3%), O (39.7%), S (51.7%), and V (70%). The evolutionary rate for the spike protein was estimated as 1.08 × 10-3 nucleotide substitutions/site/year. Moreover, the nucleotide evolutionary rate after nine months of the pandemic was similar for each clade. In conclusion, the present evolutionary analysis is relevant as the spike protein of SARS-CoV-2 is the target for most therapeutic candidates; besides, changes in this protein could have consequences on viral transmission, response to antivirals and efficacy of vaccines. Moreover, the evolutionary characterization of clades improves knowledge of SARS-CoV-2 and deserves to be assessed in more detail as re-infection by different phylogenetic clades has been reported.

There is growing evidence that exposure to organic solvents can play a role in the etiology of rheumatoid arthritis (RA). This prospective cohort study aimed to investigate the association between RA and toluene exposure.

The study cohort consisted of Korea Occupational Safety and Health Agency data from male workers exposed to toluene who had undergone a toluene-associated special medical examination at least once between January 1, 2000 and December 31, 2004 (n = 148,870). The morbidity from RA based on hospital admission records was estimated from 2000 to 2005 using National Health Insurance Claim Data. The standardized admission ratio (SAR) for RA was calculated with reference to the general population. Levels of urinary hippuric acid (HA), a metabolite of toluene, were measured and used for exposure assessment.

Toluene-exposed workers were at an elevated risk of seropositive rheumatoid arthritis (ICD-10 code M05) with an SAR of 2.38 (95% confidence interval [CI] 1.14-4.37) and other rheumatoid arthritis (M06) with an SAR of 1.22 (95% CI 0.91-1.59). When data were stratified according to the duration of toluene exposure and by tertiles of urinary HA level, no significant difference was apparent.

SARs of the toluene-exposed workers are higher than that of the general reference population, indicating that exposure to toluene may contribute to an increased risk of RA. Further studies of toluene-exposed workers with longer follow-up are needed.

SARs of the toluene-exposed workers are higher than that of the general reference population, indicating that exposure to toluene may contribute to an increased risk of RA. Further studies of toluene-exposed workers with longer follow-up are needed.The paper presents a method for the determination of methadone, EDDP, and EMDP in postmortem biological materials using liquid-liquid extraction with ethyl acetate (pH9) and UHPLC-MS/MS technique. Methadone-d9 and EDDP-d3 were used as the internal standards. The method validation results for blood and urine were as follows linearity 0.5-1000 ng/ml; R2 > 0.9993 for methadone, EDDP and R2 > 0.9944 for EMDP. Intra- and inter-day precision 0.1%-7.5% and 0.3%-8.6%, respectively; intra- and inter-day accuracy -11.8% to 13.9% and -9.3 to 14.8%, respectively; recovery 91.5%-123.0%; matrix effect 83.5%-123.9%. This study also describes 18 postmortem cases, where methadone concentrations ranged 2.3-1180 ng/ml in blood (n = 17), from 11.0 to >10,000 ng/ml in urine (n = 13) and 135.2-409.0 in vitreous humor (VH, n = 3). EDDP concentrations ranged from not detectable to 180 ng/mL in blood, from 42.4 to >10,000 ng/ml in urine and 18.3-36.5 in VH. EMDP concentrations were found in four cases in blood from below LLOQ to 1.8 ng/ml and in seven cases in urine, ranged 2.