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Postmortem toxicology is an ever-changing landscape presenting challenges for toxicologists and medical examiners. Trends can vary for certain benzodiazepines. While diazepam use tends to remain constant, alprazolam and clonazepam ebb and flow depending on prescription trends and street popularity. Novel benzodiazepines like etizolam vary in casework depending on legal restrictions and black market availability. In May 2022, the first case of the designer benzodiazepine, bromazolam, was detected in Jefferson County Coroner/Medical Examiner's Office casework. Between then and December 2023, an additional nine cases have been observed. Bromazolam is the brominated analog of the low-dose benzodiazepine, alprazolam, and is likely similar in potency. As bromazolam is a potent benzodiazepine, low concentrations of this novel drug are likely to contribute to central nervous system depression in opioid overdose cases. We present 10 cases in which bromazolam was detected in postmortem samples at the University of Alabama at Birmingham toxicology laboratory. The decedents ranged in age from 20 to 41 years. Most of the decedents were White (n  = 8; 80%) and male (n = 7; 70%). Bromazolam concentrations ranged from 21 to 3220 ng/mL (mean 401 ng/mL). All but one case were polydrug, and all deaths were related to drug toxicity. Fentanyl was detected in 8 of the 10 decedents, with concentrations ranging from <2.5 to 97 ng/mL (mean 30 ng/mL). Additional drugs detected were methamphetamine, ethanol, oxycodone, methadone, cocaine, amphetamine, morphine, and diphenhydramine. While all manners of death were ruled as accidental, bromazolam was included in the cause of death statements in 9 of the 10 cases. Capturing important emerging drug trends in the death certificate is critical to help inform public health and medical colleagues for preventive measures and treatment in the continued drug epidemic. [ABSTRACT FROM AUTHOR]

Progressive supranuclear palsy (PSP) is an incurable neurodegenerative disease characterized by 4-repeat (0N/4R)-Tau protein accumulation in CNS neurons. We generated transgenic zebrafish expressing human 0N/4R-Tau to investigate PSP pathophysiology. Tau zebrafish replicated multiple features of PSP, including: decreased survival; hypokinesia; impaired optokinetic responses; neurodegeneration; neuroinflammation; synapse loss; and Tau hyperphosphorylation, misfolding, mislocalization, insolubility, truncation, and oligomerization. Using automated assays, we screened 147 small molecules for activity in rescuing neurological deficits in Tau zebrafish. (+)JQ1, a bromodomain inhibitor, improved hypokinesia, survival, microgliosis, and brain synapse elimination. A heterozygous brd4+/− mutant reducing expression of the bromodomain protein Brd4 similarly rescued these phenotypes. Microglial phagocytosis of synaptic material was decreased by (+)JQ1 in both Tau zebrafish and rat primary cortical cultures. Microglia in human PSP brains expressed Brd4. Our findings implicate Brd4 as a regulator of microglial synaptic elimination in tauopathy and provide an unbiased approach for identifying mechanisms and therapeutic targets in PSP. Progressive supranuclear palsy (PSP) is an incurable neurodegenerative disease characterised by accumulation of 4R-Tau protein in the brain. Transgenic zebrafish overexpressing human 4R-Tau showed rapid PSP-like phenotypes, allowing an unbiased small molecule screen coupled with reverse genetics to identify Brd4-dependent microglial synapse removal as a mechanism mediating neurological phenotypes. [ABSTRACT FROM AUTHOR]

The global rise of new psychoactive substances (NPSs) poses challenges for their analysis in biological matrices due to their complex chemistries and short market lifespan. A comparative study for the simultaneous extraction, separation, and detection of 19 NPSs was conducted. Six solid-phase extraction (SPE) methods and one supported liquid extraction method (SLE) were compared for the extraction of analytes from blood, serum, plasma, and urine. Comparisons of four derivatization agents were conducted, at four temperatures and two incubation times. Extraction methods were assessed by precision, sensitivity, and extraction efficiency. Derivatizing agents were assessed on their selectivity and sensitivity, and a three-way ANOVA was conducted to determine statistical significance. CSDAU SPE cartridges were shown to be the most efficient when extracting analytes from blood, serum, and plasma, whereas Xcel I cartridges performed the strongest when extracting analytes from urine. SPE extraction efficiencies, when utilizing the best-performing cartridges, ranged from 49 to 119%. SLE successfully extracted all analytes from all matrices (ranging from 22 to 120%). Pentafluoropropionic anhydride: ethyl acetate was the most successful derivatizing agent, allowing all analytes to be detected, with the highest peak area responses and more unique spectra. The optimum temperature for incubation was 37 °C, with no statistical difference found between the two incubation times. [ABSTRACT FROM AUTHOR]

Long outpatient waiting times pose a significant global challenge in healthcare, impacting children and families with implications for health outcomes. This paper presents the eHealth system called eADVICE (electronic Advice and Diagnosis Via the Internet following Computerised Evaluation) that is designed to address waiting list challenges for paediatricians. Initially designed for children's incontinence, the system's success in terms of health goals and user experience led to its adaptation for paediatric sleep problems. This paper focuses on user experiences and the development of a working alliance with the virtual doctor, alongside health outcomes based on a randomised controlled trial (N = 239) for incontinence. When reengineering eADVICE to sleep disorders, the promising results regarding the reciprocal relationship between user experience and building a working alliance encouraged a focus on the further development of the embodied conversational agent (ECA) component. This involved tailoring the ECA discussion to patient cognition (i.e., beliefs and goals) to further improve engagement and outcomes. The proposed eADVICE framework facilitates adaptation across paediatric conditions, offering a scalable model to enhance access and self-efficacy during care delays. [ABSTRACT FROM AUTHOR]

Ethanol is the psychoactive substance identified most frequently in post-mortem specimens. Unfortunately, interpreting post-mortem ethanol concentrations can be difficult because of post-mortem alcohol redistribution and the possibility of postmortem alcohol neogenesis. Indeed, in the time interval between death and sample collection, the decedent may be exposed to non-controlled environments for an extended period, promoting microbial colonization. Many authors report that in the presence of carbohydrates and other biomolecules, various species of bacteria, yeast, and fungi can synthesize ethanol and other volatile substances in vitro and in vivo. The aim of this study was to study the impact of several variables on microbial ethanol production as well as develop a mathematical model that could estimate the microbial-produced ethanol in correlation with the most significant consensual produced higher alcohol, 1-propanol. An experimental setup was developed using human blood samples and cadaveric fragments incubated under strictly anaerobic conditions to produce a novel substrate, "cadaveric putrefactive blood" mimicking post-mortem corpse conditions. The samples were analyzed daily for ethanol and 1-propanol using an HS-GC-FID validated method. The formation of ethanol was evaluated considering different parameters such as putrefactive stage, blood glucose concentration, storage temperature, and storage time. Statistical analysis was performed using the Mann-Whitney non-parametric test and simple linear regression. The results indicate that the early putrefactive stage, high blood glucose concentration, high temperature, and time of incubation increase microbial ethanol production. In addition, the developed mathematical equation confirms the feasibility of using 1-propanol as a marker of post-mortem ethanol production. [ABSTRACT FROM AUTHOR]

Background: Volunteering is a form of prosocial behaviour that has a been recognised as having positive benefits for medical students. However, there is a lack of research on what influences students to volunteer during and after weather‐related disasters. Our study (1) explores factors related to medical students' willingness and readiness to volunteer, and (2) describes mental health impacts of the flood events on students. Methods: We conducted a mixed‐methods study of medical students on rural clinical placements in a regional area of Australia, 2 to 6 weeks after two major flooding events in 2022. Data were collected through survey and focus groups. Summary statistics were generated from the survey data, and Fisher's exact test was used to determine associations between student experience of the flood and self‐rated well‐being. Qualitative data were deductively analysed using Byrne and colleagues' theory of prosocial behaviour during an emergency. Results: The 36 students who participated in focus groups (including the 34 who completed the survey) (response rates 84% and 79%, respectively) demonstrated high levels of prosocial behaviours and were willing to volunteer. A sense of moral obligation was the primary reason for volunteering, whereas concerns for their physical and psychological safety, and missing key aspects of their training, were the strongest reasons for not continuing to volunteer. Students reported personal stress, anxiety and trauma during this period, with significant associations between self‐rated impacts on their well‐being and feelings of being terrified, helpless and hopeless during the flooding events and of still being distressed weeks later (p <.05). Conclusions: This study expands on prosocial behaviour theory by applying Byrne and colleagues elaborated model in the context of medical student volunteering during the 2022 major flooding events in Australia. Modifiable barriers to prosocial behaviour are identified along with proposed strategies to address these barriers. As the climate warms, we can expect an increase in the intensity and frequency of weather‐related disasters. Here @JodieBailie1 et al. explore how medical students are well placed to support communities in their response to such events. [ABSTRACT FROM AUTHOR]

Purpose: Children referred to specialist outpatient clinics by primary care providers often have long waiting times before being seen. We assessed whether an individualized, web-based, evidence-informed management support for children with urinary incontinence while waiting reduced requests for specialist appointments. Materials and Methods: A multicenter, waitlisted randomized controlled trial was conducted for children (5-18 years) with urinary incontinence referred to tertiary pediatric continence clinics. Participants were randomized to the web-based eHealth program electronic Advice and Diagnosis Via the Internet following Computerized Evaluation (eADVICE), which used an embodied conversational agent to engage with the child at the time of referral (intervention) or 6 months later (control). The primary outcome was the proportion of participants requesting a clinic appointment at 6 months. Secondary outcomes included persistent incontinence, and the Paediatric incontinence Questionnaire (PinQ) score. Results: From 2018 to 2020, 239 children enrolled, with 120 randomized to eADVICE and 119 to the control arm. At baseline, participants' mean age was 8.8 years (SD 2.2), 62% were males, mean PinQ score was 5.3 (SD 2.2), 36% had daytime incontinence, and 97% had nocturnal enuresis. At 6 months, 78% of eADVICE participants vs 84% of controls requested a clinic visit (relative risk 0.92, 95% CI 0.79, 1.06, P = .3), and 23% eADVICE participants vs 10% controls were completely dry (relative risk 2.23, 95% CI 1.10, 4.50, P [.03). The adjusted mean PinQ score was 3.5 for eADVICE and 3.9 for controls (MD -0.37, 95% CI -0.71, -0.03, P = .03). Conclusions: The eADVICE eHealth program for children awaiting specialist appointments doubled the proportion who were dry at 6 months and improved quality of life but did not reduce clinic appointment requests. [ABSTRACT FROM AUTHOR]

Background: Systematic reviews provide the highest level of evidence about a topic. Ten‐week workshops in conducting systematic reviews were held with hospital doctors in 2019 and 2020. Aim: This study analysed participants' feedback about the systematic review workshops to improve how we teach clinicians about conducting systematic reviews. Methods: Attendees completed a post‐workshop survey (with multiple‐choice and free‐text items) to assess knowledge and skills gained. We compared the responses of senior and junior doctors. We used descriptive statistics for the quantitative data and compared groups using Χ2 testing. Qualitative data were analysed using conceptual content analysis. Results: Of 81 attendees, 52% completed the survey. Of those, 69% had no prior experience with systematic reviews, 93% reported increased knowledge and ability to conduct research and 69% reported increased ability to conduct systematic reviews. More senior than junior clinicians reported gaining knowledge about writing and publishing (37% vs 11%, P = 0.047) and making greater use of skills gained to conduct research (56% vs 23%, P = 0.029). Five themes were identified: learning through course structure; learning through course organisation; teaching style; flexible learning; and suggestions for progression and improvement. Respondents suggested running the workshops during protected teaching time, more time for some sessions, conducting the workshop series more often and making clinicians aware of the workshop series at hospital orientation. Conclusion: The skills learnt from the systematic review workshop series impacted not only participants' research knowledge and skills, and plans to conduct future research, but also facilitated looking up medical literature in daily clinical work, supporting evidence‐based clinical practice. [ABSTRACT FROM AUTHOR]