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Background: The global longevity revolution increased the older adult population, posing unique health and economic challenges with implications for healthcare, especially substance use disorders (SUD)., Methods: This was a retrospective cohort study of United States older adults, Hispanic and non-Hispanic, who got at least one mental and/or behavioral disorder diagnosis between 2017 and 2021 at age 65 or older. SUD prevalence, prescription frequency changes over time, and comorbidities associated with each medication were compared., Results: Electronic health records for 356,133 older adults (110,236 Hispanics and 245,897 non-Hispanics) were analyzed. Notably, 79 % of Hispanics fell below the 100 % federal poverty level, compared to 60 % of non-Hispanics (P<.001). Non-Hispanics also had significantly more average encounters (P=.003) and diagnoses (P<.001). Regression analysis on alcohol-related disorders indicated that the odd ratios of being male (OR=2.93, P<.000), and having low income (OR=1.62, P<.000), increase the odds for this SUD, while being Hispanic and primarily speaking Spanish decreases the odds for all SUDs considered in this study., Conclusions: This cohort study revealed significant disparities related to social determinants of health between Hispanic and non-Hispanic older adults and emphasizes the need for continuous surveillance of older adults as with SUDs. Differences in comorbidity patterns imply distinct risk factors within each population, influenced by demographic-specific elements. Recognizing these variations is essential for tailoring culturally sensitive prevention, intervention, and treatment strategies to each population's unique needs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Jonathan Hernandez-Agosto reports financial support was provided by the Artificial Intelligence/ Machine Learning Consortium to Advance Health Equity and Researcher Diversity (AIM-AHEAD) and the AIM-AHEAD Coordinating Center, funded by the Office of the Director, National Institutes of Health Common Fund under award number 1OT2OD032581-01. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Declaration of interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Spastic paraparesis has been described to occur in 13.7% of PSEN1 mutations and can be the presenting feature in 7.5%. In this paper, we describe a family with a particularly young onset of spastic paraparesis due to a novel mutation in PSEN1 (F388S). Three affected brothers underwent comprehensive imaging protocols, two underwent ophthalmological evaluations and one underwent neuropathological examination after his death at age 29. Age of onset was consistently at age 23 with spastic paraparesis, dysarthria and bradyphrenia. Pseudobulbar affect followed with progressive gait problems leading to loss of ambulation in the late 20s. Cerebrospinal fluid levels of amyloid-β, tau and phosphorylated tau and florbetaben PET were consistent with Alzheimer's disease. Flortaucipir PET showed an uptake pattern atypical for Alzheimer's disease, with disproportionate signal in posterior brain areas. Diffusion tensor imaging showed decreased mean diffusivity in widespread areas of white matter but particularly in areas underlying the peri-Rolandic cortex and in the corticospinal tracts. These changes were more severe than those found in carriers of another PSEN1 mutation, which can cause spastic paraparesis at a later age (A431E), which were in turn more severe than among persons carrying autosomal dominant Alzheimer's disease mutations not causing spastic paraparesis. Neuropathological examination confirmed the presence of cotton wool plaques previously described in association with spastic parapresis and pallor and microgliosis in the corticospinal tract with severe amyloid-β pathology in motor cortex but without unequivocal disproportionate neuronal loss or tau pathology. In vitro modelling of the effects of the mutation demonstrated increased production of longer length amyloid-β peptides relative to shorter that predicted the young age of onset. In this paper, we provide imaging and neuropathological characterization of an extreme form of spastic paraparesis occurring in association with autosomal dominant Alzheimer's disease, demonstrating robust diffusion and pathological abnormalities in white matter. That the amyloid-β profiles produced predicted the young age of onset suggests an amyloid-driven aetiology though the link between this and the white matter pathology remains undefined., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Crouzon Syndrome is a genetic craniosynostosis disorder associated with a high risk of ophthalmologic sequelae secondary to structural causes. However, ophthalmologic disorders due to intrinsic nerve aberrations in Crouzon Syndrome have not been described. Optic pathway gliomas (OPGs) are low grade gliomas that are intrinsic to the visual pathway, frequently associated with Neurofibromatosis type 1 (NF-1). OPGs involving both optic nerves without affecting the optic chiasm are rarely seen outside of NF-1. We report an unusual case of bilateral optic nerve glioma without chiasmatic involvement in a 17-month-old male patient with Crouzon Syndrome without any clinical or genetic findings of NF-1. This case suggests that close ophthalmologic follow up and orbital MRIs may benefit patients with Crouzon Syndrome.

The NCCN Guidelines for Wilms Tumor focus on the screening, diagnosis, staging, treatment, and management of Wilms tumor (WT, also known as nephroblastoma). WT is the most common primary renal tumor in children. Five-year survival is more than 90% for children with all stages of favorable histology WT who receive appropriate treatment. All patients with WT should be managed by a multidisciplinary team with experience in managing renal tumors; consulting a pediatric oncologist is strongly encouraged. Treatment of WT includes surgery, neoadjuvant or adjuvant chemotherapy, and radiation therapy (RT) if needed. Careful use of available therapies is necessary to maximize cure and minimize long-term toxicities. This article discusses the NCCN Guidelines recommendations for favorable histology WT.

Background: Resources within the Undiagnosed Diseases Network (UDN), such as genome sequencing (GS) and model organisms aid in diagnosis and identification of new disease genes, but are currently difficult to access by clinical providers. While these resources do contribute to diagnoses in many cases, they are not always necessary to reach diagnostic resolution. The UDN experience has been that participants can also receive diagnoses through the thoughtful and customized application of approaches and resources that are readily available in clinical settings., Methods: The UDN Genetic Counseling and Testing Working Group collected case vignettes that illustrated how clinically available methods resulted in diagnoses. The case vignettes were classified into three themes; phenotypic considerations, selection of genetic testing, and evaluating exome/GS variants and data., Results: We present 12 participants that illustrate how clinical practices such as phenotype-driven genomic investigations, consideration of variable expressivity, selecting the relevant tissue of interest for testing, utilizing updated testing platforms, and recognition of alternate transcript nomenclature resulted in diagnoses., Conclusion: These examples demonstrate that when a diagnosis is elusive, an iterative patient-specific approach utilizing assessment options available to clinical providers may solve a portion of cases. However, this does require increased provider time commitment, a particular challenge in the current practice of genomics., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

The objective of this study was to develop an assessment instrument to measure the effects of a continuing education intervention on 3 domains in pharmacists' knowledge needed to provide pharmaceutical care for transgender patients: (1) foundations of gender-affirming care, (2) health disparities and the specific needs of transgender patients, and (3) hormone treatments for transgender patients. Multiple-choice questions were developed, and an initial item bank of 47 items was drafted. Item bank revision was conducted by content matter experts, while feedback from 8 practicing pharmacists was provided for face validity and further insights. A preliminary test, containing 42 items was administered to 64 pharmacists before and after a three-hour continuing education intervention. Cronbach's alpha coefficient yielded a value of 0.65 as a pre-test and 0.77 as a post-test. Items were less difficult to answer by participants after taking the three-hour continuing education, showing better discrimination among high and low performers in the instrument administration as post-test, as well as better correlation when comparing participants' performance in the overall score against item-level performance. Psychometric evidence supports further instrument examination, which can improve this tool to measure gains in pharmacists' knowledge related to the care of transgender patients.

Background: Most pharmacists have not received formal training or education in the provision of care for transgender patients. Nonetheless, pharmacists have the potential to be valuable partners in the care of transgender patients, and a continuing education course might be valuable in addressing this knowledge gap., Objective: The aim of this study was to examine the impact of a three-hour continuing education course in improving the knowledge of pharmacists to provide pharmaceutical care for transgender patients., Methods: A quasi-experimental, one-group pre-test/post-test study design was used to measure the impact of a three-hour continuing pharmacy education course on the knowledge of pharmacists on transgender care. The course was divided into three units: (1) Transgender Patient Care Introduction, (2) General Health Issues of Transgender Patients, and (3) Gender Affirming Hormone Therapy. A total of 68 pharmacists participated in the study, of which 54 completed both the pre- and post-test. An ANOVA was used to compare differences in knowledge in the group before and after the educational intervention., Results: The majority of the participating pharmacists were cisgender, heterosexual women who had not received any formal training related to transgender care. Participants demonstrated the largest increase in execution score in the third unit, with a percent improvement of 25.22% (pre-test 45.06%, post-test 70.28%; p<0.001). The average total execution score was 52.15% in the pre-test and 72.89% (p< 0.001) in the post-test., Conclusions: Pharmacists benefited from a three-hour continuing education course with an increase in knowledge regarding transgender patient care and hormone therapy for gender affirmation. As this study only evaluated the effect in short term memory, further studies are needed to assess long term impact of the continuing education course on transgender care knowledge., Competing Interests: CONFLICT OF INTEREST The authors have no affiliation or significant financial involvement in any organizations or entity with a direct financial interest in the materials or subject matter discussed in the manuscript to disclose., (Copyright: © Pharmacy Practice and the Authors.)

Purpose: Intellectual disability (ID) and autism spectrum disorder (ASD) are genetically heterogeneous neurodevelopmental disorders. We sought to delineate the clinical, molecular, and neuroimaging spectrum of a novel neurodevelopmental disorder caused by variants in the zinc finger protein 292 gene (ZNF292)., Methods: We ascertained a cohort of 28 families with ID due to putatively pathogenic ZNF292 variants that were identified via targeted and exome sequencing. Available data were analyzed to characterize the canonical phenotype and examine genotype-phenotype relationships., Results: Probands presented with ID as well as a spectrum of neurodevelopmental features including ASD, among others. All ZNF292 variants were de novo, except in one family with dominant inheritance. ZNF292 encodes a highly conserved zinc finger protein that acts as a transcription factor and is highly expressed in the developing human brain supporting its critical role in neurodevelopment., Conclusion: De novo and dominantly inherited variants in ZNF292 are associated with a range of neurodevelopmental features including ID and ASD. The clinical spectrum is broad, and most individuals present with mild to moderate ID with or without other syndromic features. Our results suggest that variants in ZNF292 are likely a recurrent cause of a neurodevelopmental disorder manifesting as ID with or without ASD.

Objectives: The objectives of this study were (1) to assess pharmacist readiness to provide pharmaceutical care for transgender patients through measuring both pharmacists' knowledge and attitudes towards transgender patients, (2) to assess transgender patients' perception of pharmacist readiness to provide them pharmaceutical care through measuring both pharmacists' knowledge and attitudes toward them, and (3) to compare pharmacist readiness to provide pharmaceutical care for transgender patients and patient perception of this readiness., Design: The study used a descriptive, cross-sectional design. The pharmacist's readiness and the transgender patient's perception of their readiness, defined as a combination of knowledge and attitude, were evaluated. Two separate, validated questionnaires with dichotomous, multiple choice, and open-ended questions were used to measure both constructs among both populations., Setting: Community-based research., Participants: Pharmacists practicing in Puerto Rico were provided the questionnaire by e-mail or in person. Transgender participants in Puerto Rico were recruited through health clinics and community partners and were surveyed in person. The analysis included responses from 96 pharmacists and 31 transgender participants., Results: The majority of the pharmacists' knowledge scores (90%) were found in the low (0-5) and moderate (6-10) ranges, with a mean score of 7.23 out of a total possible score of 16 (SD ±2.36). For the attitude construct, most of the scores (81%) were found in the high (18-26) range, with a mean score of 19.63 out of a total possible score of 26 (SD ±3.65). For both constructs, transgender patient perceptions echoed the results of the pharmacists, indicating several perceived knowledge deficits in combination with mostly positive attitudes., Conclusion: The majority of pharmacists demonstrated positive attitudes toward caring for transgender patients, and transgender patients also perceived these positive attitudes from pharmacists. However, the measured and perceived knowledge deficits observed in this study suggest the need for educational interventions to improve pharmacist readiness to provide care for transgender patients., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Gastric adenocarcinoma is a rare diagnosis in childhood. A 14-year-old male patient presented with metastatic gastric adenocarcinoma, and a strong family history of colon cancer. Clinical sequencing of CDH1 and APC were negative. Whole exome sequencing was therefore applied to capture the majority of protein-coding regions for the identification of single-nucleotide variants, small insertion/deletions, and copy number abnormalities in the patient's germline as well as primary tumor., Materials and Methods: DNA was extracted from the patient's blood, primary tumor, and the unaffected mother's blood. DNA libraries were constructed and sequenced on Illumina HiSeq2000. Data were post-processed using Picard and Samtools, then analyzed with the Genome Analysis Toolkit. Variants were annotated using an in-house Ensembl-based program. Copy number was assessed using ExomeCNV., Results: Each sample was sequenced to a mean depth of coverage of greater than 120×. A rare non-synonymous coding single-nucleotide variant (SNV) in TP53 was identified in the germline. There were 10 somatic cancer protein-damaging variants that were not observed in the unaffected mother genome. ExomeCNV comparing tumor to the patient's germline, identified abnormal copy number, spanning 6,946 genes., Conclusion: We present an unusual case of Li-Fraumeni detected by whole exome sequencing. There were also likely driver somatic mutations in the gastric adenocarcinoma. These results highlight the need for more thorough and broad scale germline and cancer analyses to accurately inform patients of inherited risk to cancer and to identify somatic mutations., (Copyright © 2012 Wiley Periodicals, Inc.)

Daily sleep cycles in humans are driven by a complex circuit within which GABAergic sleep-promoting neurons oppose arousal. Drosophila sleep has recently been shown to be controlled by GABA, which acts on unknown cells expressing the Rdl GABAA receptor. We identify here the relevant Rdl-containing cells as PDF-expressing small and large ventral lateral neurons (LNvs) of the circadian clock. LNv activity regulates total sleep as well as the rate of sleep onset; both large and small LNvs are part of the sleep circuit. Flies mutant for pdf or its receptor are hypersomnolent, and PDF acts on the LNvs themselves to control sleep. These features of the Drosophila sleep circuit, GABAergic control of onset and maintenance as well as peptidergic control of arousal, support the idea that features of sleep-circuit architecture as well as the mechanisms governing the behavioral transitions between sleep and wake are conserved between mammals and insects.

Many lines of evidence indicate that GABA and GABA(A) receptors make important contributions to human sleep regulation. Pharmacological manipulation of these receptors has differential effects on sleep onset and sleep maintenance insomnia. Here we show that sleep is regulated by GABA in Drosophila and that a mutant GABA(A) receptor, Rdl(A302S), specifically decreases sleep latency. The drug carbamazepine (CBZ) has the opposite effect on sleep; it increases sleep latency as well as decreasing sleep. Behavioral and physiological experiments indicated that Rdl(A302S) mutant flies are resistant to the effects of CBZ on sleep latency and that mutant RDL(A302S) channels are resistant to the effects of CBZ on desensitization, respectively. These results suggest that this biophysical property of the channel, specifically channel desensitization, underlies the regulation of sleep latency in flies. These experiments uncouple the regulation of sleep latency from that of sleep duration and suggest that the kinetics of GABA(A) receptor signaling dictate sleep latency.

Daily rhythms of physiology and behaviour are precisely timed by an endogenous circadian clock. These include separate bouts of morning and evening activity, characteristic of Drosophila melanogaster and many other taxa, including mammals. Whereas multiple oscillators have long been proposed to orchestrate such complex behavioural programmes, their nature and interplay have remained elusive. By using cell-specific ablation, we show that the timing of morning and evening activity in Drosophila derives from two distinct groups of circadian neurons: morning activity from the ventral lateral neurons that express the neuropeptide PDF, and evening activity from another group of cells, including the dorsal lateral neurons. Although the two oscillators can function autonomously, cell-specific rescue experiments with circadian clock mutants indicate that they are functionally coupled.