A MRSA mystery: how PBP4 and cyclic-di-AMP join forces against ß-lactam antibiotics.

The high-level resistance to next-generation ß-lactams frequently found in Staphylococcus aureus isolates lacking mec, which encodes the transpeptidase PBP2a traditionally associated with methicillin-resistant Staphylococcus aureus (MRSA), has remained incompletely understood for decades. A new study by Lai et al. found that the co-occurrence of mutations in pbp4 and gdpP, which respectively cause increased PBP4-mediated cell wall crosslinking and elevated cyclic-di-AMP levels, produces synergistic ß-lactam resistance rivaling that of PBP2a-producing MRSA (L.-Y. Lai, N. Satishkumar, S. Cardozo, V. Hemmadi, et al., mBio 15:e02889-23. 2024, https://doi.org/10.1128/mbio.02889-23). The combined mutations are sufficient to explain the high-level ß-lactam resistance of some mec-lacking strains, but the mechanism of synergy remains elusive and an avenue for further research. Importantly, the authors establish that co-occurrence of these mutations leads to antibiotic therapy failure in a Caenorhabditis elegans infection model. These results underscore the need to consider this unique and novel ß-lactam resistance mechanism during the clinical diagnosis of MRSA, rather than relying on mec as a diagnostic.

Forensic odontology in DVI-A path forward.

Dental identification is a pillar of disaster victim identification (DVI). Dental identification is accurate, efficient, inexpensive, and accepted in courts of law. The (known) antemortem (AM) dental charts and radiographic images acquired from the dentist of the missing person are evaluated, processed, and compared to post mortem (PM) findings present in the dentition or fragments of the dentition of the deceased individual. These comparisons evaluate and assess individuating restorative dental work, dental anatomical areas of concordance, spatial relationships of teeth one to another, and occasionally calculate the degree of "uniqueness" of either or both of the AM and PM dentition compared to known population databases. In a multiple fatality incident, odontologists may utilize age stratification to assist other means of identification. Computer comparison algorithms using recorded data can indicate possible matches between AM and PM data sets. Following clinical assessment, collection of post mortem tooth specimens for DNA profiling generation may be undertaken. This paper will highlight modern and efficient use of these tools. The framework for how dental identification in these incidents is currently managed is presented. The authors propose a change to this approach that moves away from interpretive subjective assessment toward comparisons based largely on objective data. The aim of this paper is to highlight the benefits of minimizing subjective decisions and maximizing objective data in the dental DVI process while simultaneously reducing risk to clinical personnel and minimizing costs by reducing the number of clinicians required onsite.

A pilot randomized control trial of online exposure for eating disorders and mechanisms of change delivered after discharge from intensive eating disorder care: A registered report.

More than 50% of individuals with an eating disorder (ED) will readmit to treatment within 6 months of treatment discharge and often due to persistent cognitive ED pathology. Interventions addressing unremitted cognitive ED pathology following discharge from intensive treatment are crucial to prevent readmission. Imaginal exposure therapy facilitates the approach of feared stimuli not accessible in everyday life (e.g., rapidly gaining weight). In the current pilot randomized control trial (RCT), participants will be randomly assigned to a five-session online imaginal exposure condition (n = 65) or a control online writing and thinking intervention (n = 65) within a month of discharge from intensive treatment. Exposure participants write about and imagine an ED fear and control participants will write about their ED generally. We will examine the feasibility and acceptability of the treatment conditions and whether imaginal exposure is more effective in preventing readmission than the control condition. We will test the efficacy of the imaginal exposure treatment in reducing ED symptoms and fears of food and weight gain, and whether fear learning is a mechanism of change related to ED pathology. Ultimately, this research will lead to the development of an easily deployable readmission prevention treatment based on fear conditioning targets.

The Renfrew Unified Treatment for Eating Disorders and Comorbidity: Long-Term Effects of an Evidence-Based Practice Implementation in Residential Treatment.

Background: The Renfrew Unified Treatment for Eating Disorders and Comorbidity (UT) is a transdiagnostic, emotion-focused treatment adapted for use in residential group treatment. This study examined the effect of UT implementation across five years of treatment delivery. Methods: Data were collected by questionnaire at admission, discharge (DC), and 6-month follow-up (6MFU). Patient outcomes were measured by the Eating Disorder Examination-Questionnaire, Center for Epidemiologic Studies-Depression Scale, Brief Experiential Avoidance Questionnaire (BEAQ), Anxiety Sensitivity Index, and Southampton Mindfulness Scale. Data were analyzed for N = 345 patients treated with treatment-as-usual (TAU), and N = 2,763 treated with the UT in subsequent years. Results: Results from multilevel models demonstrated a significant interaction between implementation status (TAU vs. UT) and time, both linear and quadratic, for the depression, experiential avoidance, anxiety sensitivity, and mindfulness variables. Patients treated with the UT showed more improvement in these variables on average, as well as more rebound between DC and 6MFU. Results from multilevel models examining eating disorder outcome showed no significant difference between the TAU and UT for the full sample, but a significant three-way interaction indicated that the UT produced more improvement in the EDE-Q relative to the TAU particularly for patients who entered treatment with high levels of experiential avoidance (BEAQ score). Conclusion: This long-term study of a transdiagnostic, evidence-based treatment in residential care for eating disorders and comorbidity suggests implementation was associated with beneficial effects on depression and emotion function outcomes, as well as eating disorder severity for patients with high levels of baseline emotion regulation problems. These effects did not appear to diminish in the 5 years following initial implementation.

Use of dental CBCT software for evaluation of medical CT-acquired images in a multiple fatality incident: Proof of principles.

Comparison of post-mortem dental findings to ante mortem dental records is a well-established, frequently used scientific means of human identification. Dentistry has adapted a form of CT scanning that uses a cone-shaped beam and is thus termed cone beam computed tomography (CBCT). CBCT is presently being used in many aspects of dentistry including osseointegrated implant planning, orthodontics, endodontics, investigation of pathology, and assessment prior to complex dental extractions. The identification of seven individuals from multiple fatality incident was undertaken using a simple technique for completing comparative radiographic dental identifications using post-mortem medical computed tomographic (CT) image-acquisition techniques and commercially available dental software normally used in clinical care. The authors will show the means by which the harvesting of anatomically important data from medical CTs and conversion of these files was undertaken to provide crisp, clear post-mortem dental images for forensic comparison to assist in the identification of two adults and provide age stratification of three juveniles. The use of this technique has shown to be beneficial for expediting efficient identification of deceased individuals, helping to isolate which cases may need additional scientific methods of identification, saving time and money to the organization and eliminating biological/body substance or radiation exposure to the operator. The application of this software for use in forensic dental identification cases is presented, and the methodology to create post-mortem images suitable for comparison is detailed.

Marijuana Use in the Elderly: Implications and Considerations.

OBJECTIVE: This article reviews the literature on the use of marijuana in the elderly. Pharmacists play an important role in the management of medications including drug use of potentially illegal drugs, including marijuana. The use of both recreational and medical marijuana has grown exponentially in the general population, including in older adults. As of 2017, marijuana for medical use is legal in 26 states and the District of Columbia. DATA SOURCES: PubMed and Internet search using the following terms: marijuana, cannabis, delta-9-tetrhydrocannabinol (THC), cannabidiol, cannabinoid, elderly, geriatric, and pharmacology. Findings are based on data collected from older adults (65 years of age and older) through August 2016. STUDY SELECTION: Because of the lack of research and funding, reputable literature on the impact of marijuana on older adults is scarce. The available evidence suggests that elderly individuals should be cautious when consuming marijuana, especially those who have certain comorbid conditions. DATA EXTRACTION: The geriatric population has a higher likelihood of having multiple comorbidities and is subject to polypharmacy. Marijuana use, medicinal or recreational, complicates the picture with additive central nervous system side effects. DATA SYNTHESIS: This article reviews the growing information on marijuana use and discusses issues to consider and cautions in usage that can apply to day-to-day clinical practice and geriatric care. The role of the pharmacist in educating patients, caregivers, and health care providers is expanding with the growing number of states that have legalized medical marijuana (26 states and the District of Columbia, as of 2017). Important education points including drug-drug interactions, drug-disease interactions, and signs and symptoms of acute overdose should be considered. CONCLUSION: With this review, pharmacists will be informed on recommendations on the use of marijuana in the older adult. Monitoring of therapy, as well as adverse effects, will be reviewed, including some legal issues and challenges.

Fatal laryngeal angioedema: a case report and a workup of angioedema in a forensic setting.

Angioedema is an episodic swelling of the deep dermis, subcutis, and/or submucosal tissue due to an increase in local vascular permeability. Swelling may involve skin, respiratory, and gastrointestinal tracts. The most commonly involved areas are the periorbital region and the lips. Here we report a case of a fatal laryngeal obstruction due to angioedema likely caused by an angiotensin-converting-enzyme inhibitor. The decedent, a 58-year-old man, was witnessed developing sudden facial swelling and acute respiratory difficulties quickly followed by unresponsiveness. His past medical history suggested that this was his second episode of angioedema without urticaria. Postmortem examination revealed a complete laryngeal obstruction in the absence of infection, neoplasm, or autoimmune disease. Postmortem computed tomography of the head and neck showed a complete obstruction of the upper airway. Based on the current understanding of the pathophysiology of different types of angioedema, we will suggest a workup of angioedema without urticaria in the forensic setting and offer readers resources they can use in their practice.