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Quantitative photoacoustic tomography aims to recover maps of the local concentrations of tissue chromophores from multispectral images. While model-based inversion schemes are promising approaches, major challenges to their practical implementation include the unknown fluence distribution and the scale of the inverse problem. We describe an inversion scheme based on a radiance Monte Carlo model and an adjoint-assisted gradient optimization that incorporates fluence-dependent step sizes and adaptive moment estimation. The inversion is shown to recover absolute chromophore concentrations, blood oxygen saturation, and the Grüneisen parameter from in silico three-dimensional phantom images for different radiance approximations. The scattering coefficient is assumed to be homogeneous and known a priori.

Dopaminergic neurons are critical to movement, mood, addiction, and stress. Current techniques for generating dopaminergic neurons from human induced pluripotent stem cells (hiPSCs) yield heterogenous cell populations with variable purity and inconsistent reproducibility between donors, hiPSC clones, and experiments. Here, we report the rapid (5 weeks) and efficient (~90%) induction of induced dopaminergic neurons (iDANs) through transient overexpression of lineage-promoting transcription factors combined with stringent selection across five donors. We observe maturation-dependent increase in dopamine synthesis and electrophysiological properties consistent with midbrain dopaminergic neuron identity, such as slow-rising after- hyperpolarization potentials, an action potential duration of ~3 ms, tonic sub-threshold oscillatory activity, and spontaneous burst firing at a frequency of ~1.0–1.75 Hz. Transcriptome analysis reveals robust expression of genes involved in fetal midbrain dopaminergic neuron identity. Specifically expressed genes in iDANs, as well as those from isogenic induced GABAergic and glutamatergic neurons, were enriched in loci conferring heritability for cannabis use disorder, schizophrenia, and bipolar disorder; however, each neuronal subtype demonstrated subtype-specific heritability enrichments in biologically relevant pathways, and iDANs alone were uniquely enriched in autism spectrum disorder risk loci. Therefore, iDANs provide a critical tool for modeling midbrain dopaminergic neuron development and dysfunction in psychiatric disease.

•First demonstration of a wearable, HD-DOT technology, in the infant population.•Advances in system and head-gear design, ergonomics, registration approaches.•Technology is very well tolerated by infant participants.•Production of 3D images of brain function outside the scanner environment.•HD-DOT yields dramatic improvements in spatial specificity and SNR relative to fNIRS. Studies of cortical function in the awake infant are extremely challenging to undertake with traditional neuroimaging approaches. Partly in response to this challenge, functional near-infrared spectroscopy (fNIRS) has become increasingly common in developmental neuroscience, but has significant limitations including resolution, spatial specificity and ergonomics. In adults, high-density arrays of near-infrared sources and detectors have recently been shown to yield dramatic improvements in spatial resolution and specificity when compared to typical fNIRS approaches. However, most existing fNIRS devices only permit the acquisition of ~20–100 sparsely distributed fNIRS channels, and increasing the number of optodes presents significant mechanical challenges, particularly for infant applications. A new generation of wearable, modular, high-density diffuse optical tomography (HD-DOT) technologies has recently emerged that overcomes many of the limitations of traditional, fibre-based and low-density fNIRS measurements. Driven by the development of this new technology, we have undertaken the first study of the infant brain using wearable HD-DOT. Using a well-established social stimulus paradigm, and combining this new imaging technology with advances in cap design and spatial registration, we show that it is now possible to obtain high-quality, functional images of the infant brain with minimal constraints on either the environment or on the infant participants. Our results are consistent with prior low-density fNIRS measures based on similar paradigms, but demonstrate superior spatial localization, improved depth specificity, higher SNR and a dramatic improvement in the consistency of the responses across participants. Our data retention rates also demonstrate that this new generation of wearable technology is well tolerated by the infant population.

Human major depressive disorder (MDD), along with related mood disorders, is among the world’s greatest public health concerns; however, its pathophysiology remains poorly understood. Persistent changes in gene expression are known to promote physiological aberrations implicated in MDD. More recently, histone mechanisms affecting cell type- and regional-specific chromatin structures have also been shown to contribute to transcriptional programs related to depressive behaviors, as well as responses to antidepressants. Although much emphasis has been placed in recent years on roles for histone posttranslational modifications and chromatin-remodeling events in the etiology of MDD, it has become increasingly clear that replication-independent histone variants (e.g., H3.3), which differ in primary amino acid sequence from their canonical counterparts, similarly play critical roles in the regulation of activity-dependent neuronal transcription, synaptic connectivity, and behavioral plasticity. Here, we demonstrate a role for increased H3.3 dynamics in the nucleus accumbens (NAc)—a key limbic brain reward region—in the regulation of aberrant social stress-mediated gene expression and the precipitation of depressive-like behaviors in mice. We find that molecular blockade of these dynamics promotes resilience to chronic social stress and results in a partial renormalization of stress-associated transcriptional patterns in the NAc. In sum, our findings establish H3.3 dynamics as a critical, and previously undocumented, regulator of mood and suggest that future therapies aimed at modulating striatal histone dynamics may potentiate beneficial behavioral adaptations to negative emotional stimuli.

Background Safety-net clinics are an important source of low-cost or free mental healthcare to those with limited financial resources. Such clinics are often staffed by trainees in early stages of their career. Only limited data exist on best practices in treatment-implementation and on clinical outcomes attained in such clinics. The primary purpose of this article is to describe the design of an outpatient psychiatry student-run free clinic (SRFC) serving uninsured individuals in New York City’s East Harlem neighborhood and to analyze the quality of services provided and the clinical outcomes attained. Methods The authors conducted a retrospective chart review of n  = 69 patients treated in the EHHOP Mental Health Clinic (E-MHC) to describe the demographic and clinical characteristics of the study population. Utilizing Health Effectiveness Data and Information Set metrics, they estimated the likelihoods of patients meeting metric quality criteria compared to those in other New York State (NYS) insurance groups. The authors derived linear mixed effect and logistic regression models to ascertain factors associated with clinical outcomes. Finally, the authors collected patient feedback on the clinical services received using a customized survey. Results Almost all patients were of Hispanic ethnicity, and about half of patients had more than one psychiatric disorder. The clinical service performance of the E-MHC was non-inferior on most measures examined. Factors associated with symptom improvement were the number of treatment sessions and certain demographic and clinical variables. Patients provided highly positive feedback on the mental healthcare services they received. Conclusions SRFCs can provide quality care to vulnerable patients that leads to clinically meaningful reductions in psychiatric symptoms and is well-received by patients.

Objective The purpose of the article is to evaluate an innovative education program in which medical students were trained in cognitive behavior therapy (CBT) and provided CBT treatments under supervision to uninsured individuals with depressive, anxiety, adjustment, and trauma-based disorders. Methods The authors assessed improvements in trainees’ CBT knowledge using the Cognitive Therapy Awareness Scale before and after their didactic training. CBT supervisors rated trainees’ clinical competencies utilizing standardized checklist evaluations based upon supervision reports. The authors employed mixed effects ANOVA and regression modeling to test the association between the addition of CBT to treatment as usual (TAU) and improvements in patients’ depressive and anxious symptom severity. The authors collected feedback and self-assessment of functioning with a Psychotherapy Feedback Questionnaire. Results Medical students showed increases in CBT knowledge that were maintained six months later and demonstrated satisfactory competency in CBT techniques. The addition of CBT to TAU was associated with greater improvements in depressive, but not anxious, symptom severity. However, among the TAU + CBT group, there was an association between the number of CBT sessions received and the magnitude of improvement in anxious symptoms from baseline. Patients gave positive feedback to medical student CBT providers and reported improvements in broad domains of psychosocial functioning. Conclusions Medical students can provide competent and clinically beneficial CBT treatments for depression and anxiety disorders. These findings have implications for medical training and support the use of medical students to deliver care for individuals with limited access to psychotherapy.

Premature infants exhibit widespread insults and delays in white matter maturation that can be sensitively detected early using diffusion tensor imaging. Diffusion tensor tractography facilitates in vivo visualization of white matter tracts and has the potential to be more sensitive than simpler two-dimensional DTI-based measures. However, the reliability and reproducibility of performing tractography for major white matter tracts in preterm infants is not known. The main objective of our study was to develop highly reliable and repeatable methods for ten white matter tracts in extremely low birth weight infants (birth weight ≤ 1000 g) at term-equivalent age. To demonstrate clinical utility, we also compared fiber microstructural and macrostructural parameters between preterm and healthy term controls. Twenty-nine ELBW infants and a control group of 15 healthy term newborns were studied. A team of researchers experienced in neuroanatomy/neuroimaging established the manual segmentation protocol based on a priori anatomical knowledge and an extensive training period to identify sources of variability. Intra- and inter-rater reliability and repeatability was tested using intra-class correlation coefficient, within-subject standard deviation (SD), repeatability, and Dice similarity index. Our results support our primary goal of developing highly reliable and reproducible comprehensive methods for manual segmentation of 10 white matter tracts in ELBW infants. The within-subject SD was within 1-2% and repeatability within 3-7% of the mean values for all 10 tracts. The intra-rater Dice index was excellent with a range of 0.97 to 0.99, and as expected, the inter-rater Dice index was lower (range: 0.80 to 0.91), but still within a very good reliability range. ELBW infants exhibited fewer fiber numbers and/or abnormal microstructure in a majority of the ten quantified tracts, consistent with injury/delayed development. This protocol could serve as a valuable tool for prompt evaluation of the impact of neuroprotective therapies and as a prognostic biomarker for neurodevelopmental impairments.

The Starr–Edwards ball and cage valves were among the first and most commonly used mechanical valve devices. These valves offered a novel design that would become one of the mainstays for replacement of severely diseased heart valves in the early second half of the twentieth century. We describe the case of a patient with a Starr–Edwards ball and cage valve in the aortic position that was replaced 40 years earlier who was admitted with concerns for symptoms of new volume overload. Transthoracic and transesophageal echocardiography demonstrated a functional mechanical aortic valve with no evidence of compromise. The patient was treated with diuretics for congestive heart failure exacerbation and on 3 years follow-up was doing well. This is one of the few cases reported of a patient with Starr–Edwards ball and cage aortic valve functioning normally extending into the fifth decade without signs of significant instability.

The successful treatment of depressive disorders critically depends on adherence to prescribed treatment regimens. Despite increasing rates of antidepressant medication prescription, adherence to the full treatment course remains poor. Rates of antidepressant non-adherence are higher for uninsured patients and members of some marginalized racial and ethnic communities due to factors such as inequities in healthcare and access to insurance. Among patients treated in a free, student-run and faculty-supervised clinic serving uninsured patients in a majority Hispanic community in East Harlem, adherence rates are lower than those observed in patients with private or public New York State health insurance coverage. A prior study of adherence in these patients revealed that difficulty in obtaining medications from an off-site hospital pharmacy was a leading factor that patients cited for non-adherence. To alleviate this barrier to obtaining prescriptions, we tested the effectiveness of on-site, in-clinic medication dispensing for improving antidepressant medication adherence rates among uninsured patients. We found that dispensing medications directly to patients in clinic was associated with increased visits at which patients self-reported proper adherence and increased overall adherence rates. Furthermore, we found evidence that higher rates of antidepressant medication adherence were associated with more favorable treatment outcomes. All patients interviewed reported increased satisfaction with on-site dispensing. Overall, this study provides promising evidence that on-site antidepressant dispensing in a resource-limited setting improves medication adherence rates and leads to more favorable treatment outcomes with enhanced patient satisfaction.

Significance: Indirect imaging problems in biomedical optics generally require repeated evaluation of forward models of radiative transport, for which Monte Carlo is accurate yet computationally costly. We develop an approach to reduce this bottleneck, which has significant implications for quantitative tomographic imaging in a variety of medical and industrial applications. Aim: Our aim is to enable computationally efficient image reconstruction in (hybrid) diffuse optical modalities using stochastic forward models. Approach: Using Monte Carlo, we compute a fully stochastic gradient of an objective function for a given imaging problem. Leveraging techniques from the machine learning community, we then adaptively control the accuracy of this gradient throughout the iterative inversion scheme to substantially reduce computational resources at each step. Results: For example problems of quantitative photoacoustic tomography and ultrasound-modulated optical tomography, we demonstrate that solutions are attainable using a total computational expense that is comparable to (or less than) that which is required for a single high-accuracy forward run of the same Monte Carlo model. Conclusions: This approach demonstrates significant computational savings when approaching the full nonlinear inverse problem of optical property estimation using stochastic methods.