Removing Barriers and Honoring Autonomy: Rethinking Mental Health Professional Assessments in Adolescent Gender-Affirming Medical Care.

ABSTRACT: Adolescents seeking gender-affirming medical care (GAMC) face numerous barriers that may delay or inhibit their access to these services. Such obstacles include mental health professional (MHP) assessment requirements prior to initiating GAMC. MHP letters ultimately carry little benefit for patients. Their formulaic nature discourages nuance, reduces likelihood of capturing gender embodiment goals (beyond a narrow definition of gender dysphoria), and may cause clinicians to overlook presenting mental health concerns. MHP assessment requirements also reinforce the conception of gender dysphoria as a mental health disorder. Moreover, studies have not shown that requiring MHP assessment letters effectively reduces regret among patients. Fortunately, primary clinicians who provide GAMC are most often capable of assessing patients without additional input from an MHP. In this article, we provide an ethical framework for clinicians that prioritizes patient autonomy through an informed assent approach. We discuss Appelbaum's criteria and its application, and contexts in which MHP consultation is appropriate. We also address common questions about informed assent among clinicians, patients, and families. Finally, we advocate for bolstering multidisciplinary support teams involved in GAMC to facilitate the informed assent process. This approach upholds patient autonomy, expands access to GAMC, and utilizes the mental health workforce more effectively.

Nonlinear beamforming for intracardiac echocardiography: a comparative study.

Intracardiac echocardiography (ICE) enables cardiac imaging with a wide field of view, deep imaging depth, and high frame rate during surgery. However, strong sidelobe and grating lobe artifacts created by the ultra-compact transducer degrade its image quality, making diagnosis and monitoring of treatment difficult. Conventionally, aperture apodization algorithms are often used to suppress sidelobe and grating lobe artifacts at the expense of lateral resolution, which is undesirable in ICE. In this study, we present comparative results of the beamforming methods specifically in ICE application. We demonstrate and compare five nonlinear beamforming algorithms in ICE: nonlinear pth root delay and sum (NL-p-DAS), nonlinear pth root spectral magnitude scaling (NL-p-SMS), delay-and-sum with coherence factors (DAS + SCF), delay and sum with apodization (DAS + apodization) and delay and sum (DAS). Phantom and ex-vivo experiment compare the performance of each algorithm in static and dynamic conditions. DAS + SCF shows the best lateral resolution, and all four algorithms improve the image contrast and sidelobe suppression over conventional DAS. NL-p-SMS stands out for the best axial resolution and suppression of grating lobe artifacts. For motion tracking, NL-p-SMS shows better temporal resolution than other methods. Overall, all the beamforming algorithms other than DAS showed improved image quality. Among them, NL-p-SMS, which has a high temporal resolution, showed the potential for providing more accurate information regards movement tracking. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-024-00352-9.

Gamma-Aminobutyric Acid in Rice Bran Extract Exerts Antistress Effects in Mouse Models with Depressive-Like Behaviors.

Various neurotransmitters are involved in regulating stress systems. In this study, we investigated the effects of gamma-aminobutyric acid-rich rice bran extract (GRBe) in mice stressed by forced swimming and tail suspension tests. Four weeks of oral administration of GRBe (500-2000 mg/kg) reduced the levels of dopamine and corticosterone in the blood and brain while increasing serotonin levels. GRBe was involved not only in stress but also in regulating sleep and obesity-related genes. Modern society experiences diverse and tense lives because of urbanization and informatization, which cause excessive stress due to complicated interpersonal relationships, heavy work burden, and fatigue from the organized society. High levels of stress cause psychological instability and disrupt the balance in the autonomic nervous system, which maintains the body's equilibrium, resulting in cardiovascular and cerebrovascular diseases, hormonal imbalances, and sleep disorders. Therefore, our results suggest that GRBe is a useful substance that can relieve tension by ultimately influencing a depressive-like state by lowering the levels of neuronal substances, hormones, and cytokines involved in stress and sleep disorders.

Video-rate endocavity photoacoustic/harmonic ultrasound imaging with miniaturized light delivery.

Significance: Endocavity ultrasound (US) imaging is a frequently employed diagnostic technique in gynecology and urology for the assessment of male and female genital diseases that present challenges for conventional transabdominal imaging. The integration of photoacoustic (PA) imaging with clinical US imaging has displayed promising outcomes in clinical research. Nonetheless, its application has been constrained due to size limitations, restricting it to spatially confined locations such as vaginal or rectal canals. Aim: This study presents the development of a video-rate (20 Hz) endocavity PA/harmonic US imaging (EPAUSI) system. Approach: The approach incorporates a commercially available endocavity US probe with a miniaturized laser delivery unit, comprised of a single large-core fiber and a line beamshaping engineered diffuser. The system facilitates real-time image display and subsequent processing, including angular energy density correction and spectral unmixing, in offline mode. Results: The spatial resolutions of the concurrently acquired PA and harmonic US images were measured at 318 µm and 291 µm in the radial direction, respectively, and 1.22 deg and 1.50 deg in the angular direction, respectively. Furthermore, the system demonstrated its capability in multispectral PA imaging by successfully distinguishing two clinical dyes in a tissue-mimicking phantom. Its rapid temporal resolution enabled the capture of kinetic dye perfusion into an ex vivo porcine ovary through the depth of porcine uterine tissue. EPAUSI proved its clinical viability by detecting pulsating hemodynamics in the male rat's prostate in vivo and accurately classifying human blood vessels into arteries and veins based on sO2 measurements. Conclusions: Our proposed EPAUSI system holds the potential to unveil previously overlooked indicators of vascular alterations in genital cancers or endometriosis, addressing pressing requirements in the fields of gynecology and urology.

X-ray free-electron laser induced acoustic microscopy (XFELAM).

The X-ray free-electron laser (XFEL) has remarkably advanced X-ray imaging technology and enabled important scientific achievements. The XFEL's extremely high power, short pulse width, low emittance, and high coherence make possible such diverse imaging techniques as absorption/emission spectroscopy, diffraction imaging, and scattering imaging. Here, we demonstrate a novel XFEL-based imaging modality that uses the X-ray induced acoustic (XA) effect, which we call X-ray free-electron laser induced acoustic microscopy (XFELAM). Initially, we verified the XA effect by detecting XA signals from various materials, then we validated the experimental results with simulation outcomes. Next, in resolution experiments, we successfully imaged a patterned tungsten target with drilled various-sized circles at a spatial resolution of 7.8 ± 5.1 µm, which is the first micron-scale resolution achieved by XA imaging. Our results suggest that the novel XFELAM can expand the usability of XFEL in various areas of fundamental scientific research.

Neuroepithelial tumor with EWSR1::PATZ1 fusion: A literature review.

We present the clinicopathological and molecular genetic characteristics of a neuroepithelial tumor (NET), EWSR1::PATZ1 fusion-positive with a literature review. This fusion has recently been discovered in rare central nervous system tumors and soft tissue sarcomas and was not included in the fifth edition of the WHO classifications. We identified this fusion in 2 NETs. The first case involved a 7-year-old girl and the second case occurred in a 53-year-old man; both presented with headaches and vomiting. The pediatric case initially showed an intermediate grade of the tumor, but upon recurrences, it transformed into a high-grade tumor with 2 relapses in 8.3 years. This case exhibited high mitotic activity (20/10 high-power fields), and a high Ki-67 index (21%). The TERT promoter (TERTp) mutation was present in both initial and recurrent tumors. In contrast, the adult case was a low-grade tumor with no mitotic activity or recurrence over 13.5 months after subtotal resection and gamma knife surgery. Interestingly, the pediatric case demonstrated a longer survival time compared to conventional glioblastoma. The TERTp mutation, similar to being a molecular signature in adult-type glioblastoma, could also be an indicator of high-grade behavior in PATZ1 fusion NET.

Psychopharmacological Considerations for Gender-Affirming Hormone Therapy.

ABSTRACT: The field of transgender health has grown exponentially since the early 2010s. While this increased visibility has not been without controversy, there is growing acknowledgement of the needs of transgender, nonbinary, and gender expansive (TNG) patients and the health disparities they experience compared to the cisgender population. There is also increased interest among clinicians and trainees in providing gender-affirming care in all medical specialties. This is particularly relevant in psychiatry as mental health disparities in TNG patients have been well-documented. TNG patients experience significant minority stress and higher rates of psychiatric illness, self-harm, suicidality, and psychiatric hospitalization compared to their cisgender peers. In this review, we will cover potential interactions and side effects relevant to psychiatric medication management for the three most common medication classes prescribed as part of gender-affirming hormone therapy (GAHT): gonadotropin-releasing hormone receptor agonists, estradiol, and testosterone. Although no studies directly examining the efficacy of psychiatric medications or their interactions with GAHT for TNG patients have been published yet, we have synthesized the existing literature from both cisgender and TNG patients to shed light on health care disparities seen in TNG patients. Since clinicians' lack of comfort and familiarity with gender-affirming care contributes significantly to these disparities, we hope this narrative review will help psychiatric prescribers provide TNG patients with the same quality of care that cisgender patients receive.

Yuja Juice and Concentrate Enhance Immunomodulating Effects via Increasing Immune-Related Cytokines in RAW264.7 Cells and Mouse Splenocytes.

Good immunity is highly valued in modern society. Although yuja's efficacy in immunity enhancement has been elucidated, there have been few studies on its role. In this study, we investigate the immune enhancement activity of yuja juice extracts (YJEs) and yuja concentrate extracts (YCEs). The immunoregulatory potencies of YJE and YCE were examined by determining cell viability and the expression of cytokines and immune-related molecules in RAW264.7 cells and mouse primary splenocytes. YJE and YCE induced the production of inducible nitric oxide synthase and cytokines (IL-10, IL-4, IL-6, and IFN-γ) at 1000 µg/mL concentration in RAW 264.7 cells. In addition, in mice that were orally administered 3000 or 2000 mg/kg concentrations of YJE or YCE, immune-related cytokines in splenocytes were boosted to levels higher than those in control mice. Importantly, no liver toxicity was observed at all doses. Thus, our results suggest that compounds present in YJEs and YCEs represent novel natural immune-modulatory substances.

Impact of biologic agents on body weight and obesity-related disorders in patients with psoriasis: A nationwide population-based cohort study.

OBJECTIVE: This large-scale population-based study aimed to analyze the effects of biologic agents on body weight and obesity-related disorders in patients with psoriasis for 10 years (January 2010 to December 2019), using the customized database provided by the Korean National Health Insurance Service. METHODS: The demographic data and health charts of 620,885 psoriasis patients, divided into three groups according to their treatment modalities (biologics, non-biologic systemic agents, and other agents), were analyzed. RESULTS: Patients with severe psoriasis who were prescribed biologic agents had a higher rate of comorbidities, such as diabetes, dyslipidemia, fatty liver, increased body weight, body mass index, and waist circumference than those in the other treatment groups. We found that the use of biologic agents was a significant independent risk factor for gaining weight after correcting for age, sex, initial weight, total prescription period, duration between the weight measurements before and after psoriasis treatment, exercise, smoking, drinking and presence of comorbidities. In contrast, the use of non-biologic systemic agents was not a significant independent risk factor for weight change. Gender-stratified regression analysis found that biologics were an independent variable affecting weight change for men, but not for women. CONCLUSIONS: Patients with severe psoriasis who are prescribed biologic agents tend to have a higher body weight and a higher prevalence of obesity-related disorders than those in other treatment groups. Caution must be exercised when using biologics, as they may cause additional weight gain, especially in men.

Temperature Matters: Bacterial Response to Temperature Change.

Temperature is one of the most important factors in all living organisms for survival. Being a unicellular organism, bacterium requires sensitive sensing and defense mechanisms to tolerate changes in temperature. During a temperature shift, the structure and composition of various cellular molecules including nucleic acids, proteins, and membranes are affected. In addition, numerous genes are induced during heat or cold shocks to overcome the cellular stresses, which are known as heat- and cold-shock proteins. In this review, we describe the cellular phenomena that occur with temperature change and bacterial responses from a molecular perspective, mainly in Escherichia coli.

Epigenetic Alteration of H3K27me3 as a Possible Oncogenic Mechanism of Central Neurocytoma.

Central neurocytoma (CN) is a low-grade neuronal tumor that mainly arises from the lateral ventricle (LV). This tumor remains poorly understood in the sense that no driver gene aberrations have been identified thus far. We investigated immunomarkers in fetal and adult brains and 45 supratentorial periventricular tumors to characterize the biomarkers, cell of origin, and tumorigenesis of CN. All CNs occurred in the LV. A minority involved the third ventricle, but none involved the fourth ventricle. As expected, next-generation sequencing performed using a brain-tumor-targeted gene panel in 7 CNs and whole exome sequencing in 5 CNs showed no driver mutations. Immunohistochemically, CNs were robustly positive for FGFR3 (100%), SSTR2 (92%), TTF-1 (Nkx2.1) (88%), GLUT-1 (84%), and L1CAM (76%), in addition to the well-known markers of CN, synaptophysin (100%) and NeuN (96%). TTF-1 was also positive in subependymal giant cell astrocytomas (100%, 5/5) and the pituicyte tumor family, including pituicytoma and spindle cell oncocytoma (100%, 5/5). Interestingly, 1 case of LV subependymoma (20%, 1/5) was positive for TTF-1, but all LV ependymomas were negative (0/5 positive). Because TTF-1-positive cells were detected in the medial ganglionic eminence around the foramen of Monro of the fetal brain and in the subventricular zone of the LV of the adult brain, CN may arise from subventricular TTF-1-positive cells undergoing neuronal differentiation. H3K27me3 loss was observed in all CNs and one case (20%) of LV subependymoma, suggesting that chromatin remodeling complexes or epigenetic alterations may be involved in the tumorigenesis of all CNs and some ST-subependymomas. Further studies are required to determine the exact tumorigenic mechanism of CN.

ZBTB7A suppresses glioblastoma tumorigenesis through the transcriptional repression of EPB41L5.

Glioblastoma multiforme (GBM), the most aggressive and malignant glioma, has a poor prognosis. Although patients with GBM are treated with surgery, chemotherapy, and radiation therapy, GBM is highly resistant to treatment, making it difficult and expensive to treat. In this study, we analyzed the Gene Expression Profiling Interactive Analysis dataset, the Cancer Genome Atlas dataset, and Gene Expression Omnibus array data. ZBTB7A (also called FBI1/POKEMON/LRF) was found to be highly expressed in low-grade glioma but significantly downregulated in patients with GBM. ZBTB7A is a transcription factor that plays an important role in many developmental stages, including cell proliferation. The activation of epithelial-mesenchymal transition (EMT) is a key process in cancer progression and metastasis. Erythrocyte membrane protein band 4.1 like 5 (EPB41L5) is an essential protein for EMT progression and metastasis in various types of cancer. We found that ZBTB7A depletion in U87 cells induced GBM progression and metastasis. Based on RNA sequencing data, ZBTB7A directly binds to the promoter of the EPB41L5 gene, reducing its expression and inhibiting GBM progression. We demonstrated that ZBTB7A dramatically inhibits GBM tumor growth through transcriptional repression of EPB41L5. Thus, both ZBTB7A and EPB41L5 may be potential biomarkers and novel therapeutic targets for GBM treatment. Overall, we discovered the role of a novel tumor suppressor that directly inhibits GBM progression (ZBTB7A) and identified EPB41L5 as a therapeutic target protein for patients with GBM.

A Method to Study α-Synuclein Toxicity and Aggregation Using a Humanized Yeast Model.

Parkinson's disease is the second most common neurodegenerative disorder and is characterized by progressive cell death caused by the formation of Lewy bodies containing misfolded and aggregated α-synuclein. α-synuclein is an abundant presynaptic protein that regulates synaptic vesicle trafficking, but the accumulation of its proteinaceous inclusions results in neurotoxicity. Recent studies have revealed that various genetic factors, including bacterial chaperones, could reduce the formation of α-synuclein aggregates in vitro. However, it is also important to monitor the anti-aggregation effect in the cell to apply this as a potential treatment for the patients. It would be ideal to use neuronal cells, but these cells are difficult to handle and take a long time to exhibit the anti-aggregation phenotype. Therefore, a quick and effective in vivo tool is required for the further evaluation of in vivo anti-aggregation activity. The method described here was used to monitor and analyze the anti-aggregation phenotype in the humanized yeast Saccharomyces cerevisiae, which expressed human α-synuclein. This protocol demonstrates in vivo tools that could be used for monitoring α-synuclein-induced cellular toxicity, as well as the formation of α-synuclein aggregates in cells.

Cytoplasmic molecular chaperones in Pseudomonas species.

Pseudomonas is widespread in various environmental and host niches. To promote rejuvenation, cellular protein homeostasis must be finely tuned in response to diverse stresses, such as extremely high and low temperatures, oxidative stress, and desiccation, which can result in protein homeostasis imbalance. Molecular chaperones function as key components that aid protein folding and prevent protein denaturation. Pseudomonas, an ecologically important bacterial genus, includes human and plant pathogens as well as growth-promoting symbionts and species useful for bioremediation. In this review, we focus on protein quality control systems, particularly molecular chaperones, in ecologically diverse species of Pseudomonas, including the opportunistic human pathogen Pseudomonas aeruginosa, the plant pathogen Pseudomonas syringae, the soil species Pseudomonas putida, and the psychrophilic Pseudomonas antarctica.

LUHMES Dopaminergic Neurons Are Uniquely Susceptible to Ferroptosis.

Ferroptosis is a necrotic cell death caused by lipid oxidation that may be responsible for neural degeneration in Parkinson's disease. We assessed whether three neuronal cell lines are sensitive to killing by ferroptosis. Ferroptosis inducer erastin killed LUHMES neurons at sub-micromolar concentrations, whereas neuronal cells derived from SH-SY5Y cells or neural stem cells were at least 50-fold less sensitive. LUHMES differentiated neurons were likewise sensitive to killing by RSL3 or ML210, inhibitors of the glutathione peroxidase 4 enzyme (GPX4) that consumes GSH to detoxify lipid peroxides. Additional assays showed that erastin, RSL3, and ML210 increased lipid peroxide levels, and that LUHMES neurons were protected from both peroxide accumulation and cell death by ferrostatin-1. A possible role of iron was assessed by evaluating the effects of five metal chelators on cytotoxicity of erastin and RSL3. LUHMES neurons were protected from RSL3 by three of the chelators, 2,3-dimercapto-1-propanesulfonic acid (DMPS), deferoxiprone (DFX), and deferiprone (DFP). Collectively, these results demonstrate the vulnerability of LUHMES neurons to ferroptosis by chemical treatments that disrupt glutathione synthesis, lipid peroxide detoxification, or iron metabolism. The same vulnerabilities may occur in CNS neurons, which reportedly generate low levels of GSH and metallothioneins, limiting their ability to neutralize oxidative stresses and toxic metals. These results suggest a rationale and methods to search for environmental toxicants that may exploit these vulnerabilities and promote neurodegenerative diseases.

Toxic leukoencephalopathy with axonal spheroids caused by chemotherapeutic drugs other than methotrexate.

BACKGROUND: The objective of this report is to share the clinicopathological features of chemotherapy-induced toxic leukoencephalopathy, which is a rare and under-recognized disease, clinically characterized by rapidly progressive cognitive loss that often leads to sudden death. CASE PRESENTATION: A 64-year-old woman and a 63-year-old man, who had both suffered from a rapid deterioration of consciousness, were autopsied under the clinical impressions of either the central nervous system graft versus host disease (CNS-GVHD), infectious encephalitis, or autoimmune encephalitis. Both patients had been treated with multiple chemotherapy regimens, including adriamycin, cytarabine arabinoside, daunorubicin, fludarabine, azacitidine, and allogeneic peripheral blood stem cell transplantation to treat hematological malignancies (acute myelogenous leukemia and myelodysplastic syndrome). Neuropathological findings at autopsy revealed rarefaction and vacuolar changes of the white matter with axonal spheroids, reactive gliosis, and foamy macrophage infiltration, predominantly in the visual pathways of the occipital and temporal lobes. Damaged axons exhibited immunoreactivity to beta-amyloid, consistent with axonopathy. However, there was no lymphocyte infiltration that suggested CNS-GVHD or any type of encephalitis. CONCLUSION: The neuropathology found in the presented cases had the characteristic features of toxic leukoencephalopathy (chemobrain). Our cases showed that toxic leukoencephalopathy can also be caused by chemotherapy drugs other than methotrexate.

PAAN/MIF nuclease inhibition prevents neurodegeneration in Parkinson's disease.

Parthanatos-associated apoptosis-inducing factor (AIF) nuclease (PAAN), also known as macrophage migration inhibitor factor (MIF), is a member of the PD-D/E(X)K nucleases that acts as a final executioner in parthanatos. PAAN's role in Parkinson's disease (PD) and whether it is amenable to chemical inhibition is not known. Here, we show that neurodegeneration induced by pathologic α-synuclein (α-syn) occurs via PAAN/MIF nuclease activity. Genetic depletion of PAAN/MIF and a mutant lacking nuclease activity prevent the loss of dopaminergic neurons and behavioral deficits in the α-syn preformed fibril (PFF) mouse model of sporadic PD. Compound screening led to the identification of PAANIB-1, a brain-penetrant PAAN/MIF nuclease inhibitor that prevents neurodegeneration induced by α-syn PFF, AAV-α-syn overexpression, or MPTP intoxication in vivo. Our findings could have broad relevance in human pathologies where parthanatos plays a role in the development of cell death inhibitors targeting the druggable PAAN/MIF nuclease.