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Broadly speaking, the term "narrative" is defined as any account of connected events and experiences. Narrative is used in several therapeutic interventions within behavioral health. Narrative approaches can be an affirming process for the patient and can increase a therapist's understanding of their patients' perspectives.1 Unfortunately, there is a lack of medical education and training on narrative approaches, and these remain underutilized in clinical settings. Comics are an accessible medium of expression that can empower the voices of underrepresented individuals and communities.

The diagnostic value of imaging Aβ plaques in Alzheimer's disease (AD) has accelerated the development of fluorine-18 labeled radiotracers with a longer half-life for easier translation to clinical use. We have developed [18F]flotaza, which shows high binding to Aβ plaques in postmortem human AD brain slices with low white matter binding. We report the binding of [18F]flotaza in postmortem AD hippocampus compared to cognitively normal (CN) brains and the evaluation of [18F]flotaza in transgenic 5xFAD mice expressing Aβ plaques. [18F]Flotaza binding was assessed in well-characterized human postmortem brain tissue sections consisting of HP CA1-subiculum (HP CA1-SUB) regions in AD (n = 28; 13 male and 15 female) and CN subjects (n = 32; 16 male and 16 female). Adjacent slices were immunostained with anti-Aβ and analyzed using QuPath. In vitro and in vivo [18F]flotaza PET/CT studies were carried out in 5xFAD mice. Post-mortem human brain slices from all AD subjects were positively IHC stained with anti-Aβ. High [18F]flotaza binding was measured in the HP CA1-SUB grey matter (GM) regions compared to white matter (WM) of AD subjects with GM/WM > 100 in some subjects. The majority of CN subjects had no decipherable binding. Male AD exhibited greater WM than AD females (AD WM♂/WM♀ > 5; p < 0.001) but no difference amongst CN WM. In vitro studies in 5xFAD mice brain slices exhibited high binding [18F]flotaza ratios (>50 versus cerebellum) in the cortex, HP, and thalamus. In vivo, PET [18F]flotaza exhibited binding to Aβ plaques in 5xFAD mice with SUVR~1.4. [18F]Flotaza is a new Aβ plaque PET imaging agent that exhibited high binding to Aβ plaques in postmortem human AD. Along with the promising results in 5xFAD mice, the translation of [18F]flotaza to human PET studies may be worthwhile.

Therapeutic antibodies for reducing Aβ plaque load in Alzheimer’s disease (AD) is currently making rapid progress. The diagnostic imaging of Aβ plaque load in AD has been underway and is now used in clinical studies. Here, we report our preliminary findings on imaging a therapeutic antibody, Lecanemab, in a postmortem AD brain anterior cingulate. [125I]5-iodo-3-pyridinecarboxamido-Lecanemab ([125I]IPC-Lecanemab) was prepared by coupling N-succinimidyl-5-([125I]iodo)-3-pyridinecarboxylate with Lecanemab in modest yields. The distinct binding of [125I]IPC-Lecanemab to Aβ-rich regions in postmortem human AD brains was higher in grey matter (GM) containing Aβ plaques compared to white matter (WM) (GM/WM was 1.6). Anti-Aβ immunostaining was correlated with [125I]IPC-Lecanemab regional binding in the postmortem AD human brains. [125I]IPC-Lecanemab binding was consistent with the binding of Aβ small molecules, [18F]flotaza and [125I]IBETA, in the same subjects. [18F]Flotaza and [125I]IBETA, however, exhibited significantly higher GM/WM ratios (>20) compared to [125I]IPC-Lecanemab. Our results suggest that radiolabeled [125I]IPC-Lecanemab retains the ability to bind to Aβ in human AD and may therefore be useful as a PET imaging radiotracer when labeled as [124I]IPC-Lecanemab. The ability to directly visualize in vivo a promising therapeutic antibody for AD may be useful in treatment planning and dosing and could be complimentary to small-molecule diagnostic imaging to assess outcomes of therapeutic interventions.

Postural instability is a detrimental and often treatment-refractory symptom of Parkinsons disease. While many existing studies quantify the biomechanical deficits among various postural domains (static, anticipatory, and reactive) in this population, less is known regarding the neural network dysfunctions underlying these phenomena. This review will summarize current studies on the cortical and subcortical neural activities during postural responses in healthy subjects and those with Parkinsons disease. We will also review the effects of current therapies, including neuromodulation and feedback-based wearable devices, on postural instability symptoms. With recent advances in implantable devices that allow chronic, ambulatory neural data collection from patients with Parkinsons disease, combined with sensors that can quantify biomechanical measurements of postural responses, future work using these devices will enable better understanding of the neural mechanisms of postural control. Bridging this knowledge gap will be the critical first step towards developing novel neuromodulatory interventions to enhance the treatment of postural instability in Parkinsons disease.

BACKGROUND: The effect of transdermal glyceryl trinitrate (GTN, a nitrovasodilator) on clinical outcome when administered before hospital admission in suspected stroke patients is unclear. Here, we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2). METHODS: RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4 hours of onset. The primary outcome was a shift in scores on the modified Rankin scale (mRS) at day 90. Secondary outcomes included death; a global analysis (Wei-Lachin test) containing Barthel Index, EuroQol-5D, mRS, telephone interview for cognitive status-modified and Zung depression scale; and neuroimaging-determined brain frailty markers. Data were reported as n (%), mean (SD), median [IQR], adjusted common OR (acOR), mean difference or Mann-Whitney difference (MWD) with 95% CI. RESULTS: 597 of 1149 (52%) patients had a final diagnosis of ischaemic stroke; age 75 (12) years, premorbid mRS>2 107 (18%), Glasgow Coma Scale 14 (2) and time from onset to randomisation 67 [45, 108] min. Neuroimaging brain frailty was common: median score 2 [2, 3] (range 0-3). At day 90, GTN did not influence the primary outcome (acOR for increased disability 1.15, 95% CI 0.85 to 1.54), death or global analysis (MWD 0.00, 95% CI -0.10 to 0.09). In subgroup analyses, there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1 hour of symptom onset and in those with more severe stroke. CONCLUSIONS: In patients who had an ischaemic stroke, ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital trials.

A growing body of literature has documented high rates of adverse childhood experiences (ACEs) and their effects on behavioral health among adolescents impacted by the juvenile legal system. Most research with justice-impacted youth assesses the ten standard ACEs, encompassing abuse, neglect, and household dysfunction. This body of work has largely ignored the five expanded ACEs which assess social and community level adversity. Justice-impacted youth commonly experience expanded ACEs (racial discrimination, placement in foster care, living in a disadvantaged neighborhood, witnessing violence, bullying), and inclusion of these adversities may enhance predictive utility of the commonly used ACEs score. The current study examined the prospective impact of total ACEs (standard and expanded) on alcohol and cannabis use, substance-related consequences, and psychiatric symptoms during the year following first ever contact with the juvenile court. Results indicate justice-impacted youth experience multiple expanded ACEs prior to first court contact. The expanded ACEs did not predict any of the behavioral health outcomes assessed, over and above the standard ACEs. Inclusion of expanded ACEs in the standard ACEs score may not increase utility in identifying prospective behavioral health outcomes among youth in first time contact with the juvenile legal system.

Abstract African pangolins are hunted for their meat and for use in local traditional medicine, as well as for their scales, which are trafficked internationally, especially to growing Asian markets. Pangolin’s population genetic structure can be used to trace the geographic origins of trafficked scales, but substantial sampling gaps across pangolins’ ranges hinder these efforts. In this study, we documented population structure and dynamics in the two species of African pangolin, the white-bellied pangolin (Phataginus tricuspis) and the giant pangolin (Smutsia gigantea) in the underexplored Republic of Congo. Using the mitochondrial control region and two nuclear markers (beta-fibrinogen and titin), we identified high genetic diversity in both species. We document a distinct mitochondrial lineage of the white-bellied pangolin, which was most likely shaped by river barriers together with dynamics of forest refugia related to the climatic shifts during the Pleistocene. We detected population growth in the white-bellied pangolin coinciding with a dry period during the Pleistocene, suggesting some ability for this typically forest-dwelling species to persist under diverse environmental conditions. Using landscape genetics, we found all but one of the pangolins we sampled at bush meat markets originated locally. A single individual appeared to have been imported to Congo from Cameroon. These findings significantly contribute to our understanding of pangolin population biology and local trade dynamics. In addition, our data from a previously unstudied part of pangolins’ ranges will help us to better understand international wildlife trafficking patterns and to target conservation and protection strategies for these highly vulnerable species.

As an important source of sub-micrometer particles, atmospheric new particle formation (NPF) has been observed in various environments. However, most studies provide little more than snapshots of the NPF process due to their underlying observations being limited in space and time. To obtain statistically relevant evidence on NPF across various environments, we investigated the characteristics of NPF based on a 5-year dataset of the German Ultrafine Aerosol Network (GUAN). The results were also compared with observations in previous studies, with the aim to depict a relatively complete picture of NPF in central Europe. The highest NPF occurrence frequency was observed in regional background sites, with an average of about 19 %, followed by urban background (15 %), low-mountain-range (7 %), and high Alpine (3 %) sites. The annual mean growth rate between 10 and 25 nm varied from 3.7–4.7 nm h−1, while the formation rate with same size range 10–25 nm from 0.4 to 2.9 cm−3 s−1. The contribution of NPF to ultrafine particles (UFPs) was about 13 %, 21 %, and 7 % for the urban background, regional background, and low mountain range, respectively. The influence of NPF on cloud condensation nuclei (CCN) number concentration and the aerosol extinction coefficient for NPF days was the highest in mountainous areas. These findings underscore the importance of local environments when assessing the potential impact of NPF on regional climate in models, and they also emphasize the usefulness of a long-term aerosol measurement network for understanding the variation in NPF features and their influencing factors over a regional scale.

Abstract Failure to appropriately predict and titrate reactivity to threat is a core feature of fear and anxiety-related disorders and is common following early life adversity (ELA). A population of neurons in the lateral central amygdala (CeAL) expressing corticotropin releasing factor (CRF) have been proposed to be key in processing threat of different intensities to mediate active fear expression. Here, we use in vivo fiber photometry to show that ELA results in sex-specific changes in the activity of CeAL CRF+ neurons, yielding divergent mechanisms underlying the augmented startle in ELA mice, a translationally relevant behavior indicative of heightened threat reactivity and hypervigilance. Further, chemogenic inhibition of CeAL CRF+ neurons selectively diminishes startle and produces a long-lasting suppression of threat reactivity. These findings identify a mechanism for sex-differences in susceptibility for anxiety following ELA and have broad implications for understanding the neural circuitry that encodes and gates the behavioral expression of fear.

To the Editor: Streptococcus pneumoniae (Spn) is a common member of the human nasopharyngeal microflora; yet, this same bacterium inflicts tissue damage and considerable mortality worldwide (1). Identifying host mechanisms [...]

Nationwide efforts to enhance services for adolescents experiencing commercial sexual exploitation (CSE) in the judicial system have led to the emergence of specialty courts, including human trafficking and girls' courts. Given that prior research has documented competing stances on the effectiveness of specialty courts for CSE-impacted populations, we conducted a systematic review of the literature to identify key characteristics of programming, profiles of adolescents served, and effectiveness of these courts. To identify relevant research and information, we systematically searched scholarly databases and information sources, conducted reference harvesting, and forwarded citation chaining. Articles presenting primary data with quantitative, qualitative, or mixed methodologies or programmatic descriptions of specialty courts serving adolescents at risk or with confirmed histories of CSE that were published after 2004 were included. We identified 39 articles on 21 specialty courts serving adolescents at risk or with confirmed histories of CSE, including seven specialty courts with evaluation or outcome data. Across specialty courts, adolescents benefited from an increase in linkage to specialized services, improved residential placement stability, and reduction in recidivism-measured by new criminal charges. Specialty court participation was also associated with improved educational outcomes and decreased instances of running away. A lack of empirical data, specifically of evaluation studies, emerged as a weakness in the literature. Still, findings support that specialty courts can be an integral judicial system response to CSE. Multidisciplinary collaboration can help target and respond to the multifaceted needs of adolescents, encourage healthy behaviors, and promote their overall wellness.