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Youth with epilepsy (YWE) are at elevated risk for anxiety, yet anxiety is often undetected and understudied in this population. Most research on anxiety in YWE is based on parent proxy-report and broad-band measures with limited sensitivity. The aim of the current study was to: 1) examine rates of anxiety symptoms in YWE using a diagnosis-specific, self-report measure of anxiety symptoms, 2) assess differences in anxiety symptoms by sociodemographic and medical variables, and 3) evaluate changes in anxiety symptoms following a brief behavioral health intervention delivered within an interdisciplinary epilepsy clinic visit. As part of routine clinical care, 317 YWE [M age =13.4+2.5 years (range 7-19 years); 54% female; 84% White: Non-Hispanic] completed the Multidimensional Anxiety Scale for Children, self-report (MASC-10), with a subset completing the MASC-10 at a second timepoint (n=139). A retrospective chart review was completed and sociodemographic, medical variables and behavioral health interventions were collected. Thirty percent of YWE endorsed elevated anxiety symptoms, with higher rates in those who were younger. YWE who received a behavioral health intervention for anxiety (n=21) demonstrated greater decreases in anxiety symptoms from Time 1 to Time 2 compared to those who did not receive a behavioral intervention (n=108). The integration of psychologists into pediatric epilepsy clinics may have allowed for early identification of anxiety symptoms, as well behavioral interventions to address these symptoms, which has the potential to decrease the need for more intensive services., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The COVID-19 vaccine has become available to children ages 5-12, yet vaccine uptake is suboptimal. Political ideology is a correlate of COVID-related beliefs and vaccine likelihood among US adults. However, since political ideology is not easily modifiable, attention to modifiable mechanisms that may explain links between political ideology and vaccine hesitancy is important in addressing this public health crisis. Caregiver attitudes around vaccine safety and efficacy have been related to vaccine uptake in other populations and warrant additional study in the context of COVID-19. The current study examined whether caregiver's attitudes regarding the safety and efficacy of the COVID-19 vaccine mediated the relationship between caregiver political ideology and likelihood of having their child vaccinated., Methods: 144 US caregivers of children (6-12 years) completed an online survey in summer 2021 to assess political ideology, vaccine-related beliefs, and likelihood of having their child vaccinated against COVID-19., Results: Caregivers with more liberal political views reported higher likelihood of eventual child vaccination compared to caregivers who reported a more conservative views (t(81) = 6.08, BCa CI [2.97, 5.67]). Moreover, parallel mediation models indicated caregiver?s perceptions of risks (BCa CI [-.98, -.10]) and efficacy (BCa CI [-3.16, -2.15]) of the vaccine each mediated the aforementioned relationship, with perceived efficacy explaining significantly more variance than risks., Conclusions: Findings extend knowledge by identifying social cognitive factors that impact caregiver vaccine hesitancy. Interventions to address caregiver's hesitancy to have their child vaccinated through modifying caregiver's inaccurate beliefs regarding vaccines or enhancing perceptions of vaccine efficacy is warranted., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Genetic code expansion has proven invaluable to the elucidation of functions of defined protein modifications through the site-specific incorporation of noncanonical amino acids. The use of nonhydrolyzable derivatives of post-translational modifications can greatly increase site stoichiometry and half-life. Investigating acetyllysine reader domain (bromodomain) interactions with acetylated nonhistone proteins is challenging due to the limited tools available and dynamic nature of this post-translational modification. Here, we demonstrate that bromodomains bind acetyllysine peptides and those substituted with an acetyllysine derivative, trifluoroacetyllysine, with similar affinity and selectivity. Importantly, both trifluoroacetyllysine and acetyllysine can be site-specifically incorporated into proteins expressed in bacterial and mammalian cells, and the strong electron-withdrawing trifluoro substituent makes the latter resistant to deacetylation by sirtuins (SIRTs). The controlled expression of SIRT-resistant, site-specifically acetylated transcription factors expands the set of available tools for determining the function of acetylation, and it serves as a template for investigating bromodomain interactions with acetylated transcription factors.

The biological functions of the dual bromodomains of human transcription-initiation-factor TFIID subunit 1 (TAF1(1,2)) remain unknown, although TAF1 has been identified as a potential target for oncology research. Here, we describe the discovery of a potent and selective in vitro tool compound for TAF1(2), starting from a previously reported lead. A cocrystal structure of lead compound 2 bound to TAF1(2) enabled structure-based design and structure-activity-relationship studies that ultimately led to our in vitro tool compound, 27 (GNE-371). Compound 27 binds TAF1(2) with an IC 50 of 10 nM while maintaining excellent selectivity over other bromodomain-family members. Compound 27 is also active in a cellular-TAF1(2) target-engagement assay (IC 50 = 38 nM) and exhibits antiproliferative synergy with the BET inhibitor JQ1, suggesting engagement of endogenous TAF1 by 27 and further supporting the use of 27 in mechanistic and target-validation studies.

Acetylation of histone H3 at lysine 27 is a well-defined marker of enhancer activity. However, the functional impact of this modification at enhancers is poorly understood. Here, we use a chemical genetics approach to acutely block the function of the cAMP response element binding protein (CREB) binding protein (CBP)/P300 bromodomain in models of hematological malignancies and describe a consequent loss of H3K27Ac specifically from enhancers, despite the continued presence of CBP/P300 at chromatin. Using this approach to dissect the role of H3K27Ac at enhancers, we identify a critical role for this modification in the production of enhancer RNAs and transcription of enhancer-regulated gene networks., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: To determine key worries about hypoglycaemia among insulin-using adults with Type 2 diabetes using a focus group approach., Methods: Thirteen focus groups were conducted in three diabetes outpatient care units and one peer support group was set up, in Germany. A total of 64 insulin-dependent adults with Type 2 diabetes (36.5% women, mean age 65.2 ± 11.0 years) discussed their worries about hypoglycaemia. The qualitative results were assigned into thematic categories using a bottom-up coding procedure. Participants completed the Hypoglycaemia Fear Survey and demographic measures were recorded. The results of the Hypoglycaemia Fear Survey were contrasted with the focus group findings to evaluate how accurately the Hypoglycaemia Fear Survey comprehensively captures features of fear of hypoglycaemia in Type 2 diabetes., Results: Eight themes were identified: 'unconsciousness/death'; 'aloneness/ helplessness', 'fear of hurting somebody'; 'shame'; 'loss of physical control'; 'long-term complications'; 'diabetes self-management issues'; and 'impaired awareness'. A total of 30 participants (46.9%) scored ≥3 on at least one item of the Hypoglycaemia Fear Survey worry subscale, indicating elevated worries. The Hypoglycaemia Fear Survey comprehensively captured all identified themes. Self-efficacy with regard to diabetes self-management seemed to play an important role in fear of hypoglycaemia in Type 2 diabetes., Conclusions: Given that even subclinical worries can have negative effects on quality of life and diabetes self-management, emphasis should be placed on diabetes education; in particular, to help patients to develop self-efficacy concerning diabetes self-management. The Hypoglycaemia Fear Survey comprehensively captures hypoglycaemia worries in Type 2 diabetes. Additional assessment of self-efficacy might be beneficial to identify people at risk of developing hypoglycaemia worries., (© 2017 Diabetes UK.)

Members of the ISWI family of chromatin remodelers mobilize nucleosomes to control DNA accessibility and, in some cases, are required for recovery from DNA damage. However, it remains poorly understood how the non-catalytic ISWI subunits BAZ1A and BAZ1B might contact chromatin to direct the ATPase SMARCA5. Here, we find that the plant homeodomain of BAZ1A, but not that of BAZ1B, has the unusual function of binding DNA. Furthermore, the BAZ1A bromodomain has a non-canonical gatekeeper residue and binds relatively weakly to acetylated histone peptides. Using CRISPR-Cas9-mediated genome editing we find that BAZ1A and BAZ1B each recruit SMARCA5 to sites of damaged chromatin and promote survival. Genetic engineering of structure-designed bromodomain and plant homeodomain mutants reveals that reader modules of BAZ1A and BAZ1B, even when non-standard, are critical for DNA damage recovery in part by regulating ISWI factors loading at DNA lesions and supporting transcriptional programs required for survival.ISWI chromatin remodelers regulate DNA accessibility and have been implicated in DNA damage repair. Here, the authors uncover functions, in response to DNA damage, for the bromodomain of the ISWI subunit BAZ1B and for the non-canonical PHD and bromodomain modules of the paralog BAZ1A.

Bromodomain-containing protein 9 (BRD9), an epigenetic "reader" of acetylated lysines on post-translationally modified histone proteins, is upregulated in multiple cancer cell lines. To assess the functional role of BRD9 in cancer cell lines, we identified a small-molecule inhibitor of the BRD9 bromodomain. Starting from a pyrrolopyridone lead, we used structure-based drug design to identify a potent and highly selective in vitro tool compound 11, (GNE-375). While this compound showed minimal effects in cell viability or gene expression assays, it showed remarkable potency in preventing the emergence of a drug tolerant population in EGFR mutant PC9 cells treated with EGFR inhibitors. Such tolerance has been linked to an altered epigenetic state, and 11 decreased BRD9 binding to chromatin, and this was associated with decreased expression of ALDH1A1, a gene previously shown to be important in drug tolerance. BRD9 inhibitors may therefore show utility in preventing epigenetically-defined drug resistance., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Mycobacterium tuberculosis protein Rv0577 is a prominent antigen in tuberculosis patients, the component responsible for neutral red staining of virulent strains of M. tuberculosis, a putative component in a methylglyoxal detoxification pathway, and an agonist of toll-like receptor 2. It also has an amino acid sequence that is 36% identical to that of Streptomyces coelicolor AfsK-binding protein A (KbpA), a component in the complex secondary metabolite pathways in the Streptomyces genus. To gain insight into the biological function of Rv0577 and the family of KpbA kinase regulators, the crystal structure for Rv0577 was determined to a resolution of 1.75 Å, binding properties with neutral red and deoxyadenosine were surveyed, backbone dynamics were measured, and thermal stability was assayed by circular dichroism spectroscopy. The protein is composed of four approximate repeats with a βαβββ topology arranged radially in consecutive pairs to form two continuous eight-strand β-sheets capped on both ends with an α-helix. The two β-sheets intersect in the center at roughly a right angle and form two asymmetric deep "saddles" that may serve to bind ligands. Nuclear magnetic resonance chemical shift perturbation experiments show that neutral red and deoxyadenosine bind to Rv0577. Binding to deoxyadenosine is weaker with an estimated dissociation constants of 4.1 ± 0.3 mM for saddle 1. Heteronuclear steady-state { 1 H}- 15 N nuclear Overhauser effect, T 1 , and T 2 values were generally uniform throughout the sequence with only a few modest pockets of differences. Circular dichroism spectroscopy characterization of the thermal stability of Rv0577 indicated irreversible unfolding upon heating with an estimated melting temperature of 56 °C.

The biological function of bromodomains, epigenetic readers of acetylated lysine residues, remains largely unknown. Herein we report our efforts to discover a potent and selective inhibitor of the bromodomain of cat eye syndrome chromosome region candidate 2 (CECR2). Screening of our internal medicinal chemistry collection led to the identification of a pyrrolopyridone chemical lead, and subsequent structure-based drug design led to a potent and selective CECR2 bromodomain inhibitor (GNE-886) suitable for use as an in vitro tool compound.

The KDM5 family of histone demethylases catalyzes the demethylation of histone H3 on lysine 4 (H3K4) and is required for the survival of drug-tolerant persister cancer cells (DTPs). Here we report the discovery and characterization of the specific KDM5 inhibitor CPI-455. The crystal structure of KDM5A revealed the mechanism of inhibition of CPI-455 as well as the topological arrangements of protein domains that influence substrate binding. CPI-455 mediated KDM5 inhibition, elevated global levels of H3K4 trimethylation (H3K4me3) and decreased the number of DTPs in multiple cancer cell line models treated with standard chemotherapy or targeted agents. These findings show that pretreatment of cancer cells with a KDM5-specific inhibitor results in the ablation of a subpopulation of cancer cells that can serve as the founders for therapeutic relapse.

The biological role played by non-BET bromodomains remains poorly understood, and it is therefore imperative to identify potent and highly selective inhibitors to effectively explore the biology of individual bromodomain proteins. A ligand-efficient nonselective bromodomain inhibitor was identified from a 6-methyl pyrrolopyridone fragment. Small hydrophobic substituents replacing the N-methyl group were designed directing toward the conserved bromodomain water pocket, and two distinct binding conformations were then observed. The substituents either directly displaced and rearranged the conserved solvent network, as in BRD4(1) and TAF1(2), or induced a narrow hydrophobic channel adjacent to the lipophilic shelf, as in BRD9 and CECR2. The preference of distinct substituents for individual bromodomains provided selectivity handles useful for future lead optimization efforts for selective BRD9, CECR2, and TAF1(2) inhibitors.

CBP and EP300 are highly homologous, bromodomain-containing transcription coactivators involved in numerous cellular pathways relevant to oncology. As part of our effort to explore the potential therapeutic implications of selectively targeting bromodomains, we set out to identify a CBP/EP300 bromodomain inhibitor that was potent both in vitro and in cellular target engagement assays and was selective over the other members of the bromodomain family. Reported here is a series of cell-potent and selective probes of the CBP/EP300 bromodomains, derived from the fragment screening hit 4-methyl-1,3,4,5-tetrahydro-2H-benzo[b][1,4]diazepin-2-one.

Bromodomains are epigenetic readers that are recruited to acetyllysine residues in histone tails. Recent studies have identified non-acetyl acyllysine modifications, raising the possibility that these might be read by bromodomains. Profiling the nearly complete human bromodomain family revealed that while most human bromodomains bind only the shorter acetyl and propionyl marks, the bromodomains of BRD9, CECR2, and the second bromodomain of TAF1 also recognize the longer butyryl mark. In addition, the TAF1 second bromodomain is capable of binding crotonyl marks. None of the human bromodomains tested binds succinyl marks. We characterized structurally and biochemically the binding to different acyl groups, identifying bromodomain residues and structural attributes that contribute to specificity. These studies demonstrate a surprising degree of plasticity in some human bromodomains but no single factor controlling specificity across the family. The identification of candidate butyryl- and crotonyllysine readers supports the idea that these marks could have specific physiological functions., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Professionalism is fundamental to good medical practice but is multifaceted so observing that a person is professional in some areas will not guarantee that person would be professional in others. Most definitions of professionalism include a commitment to self-monitor and to improve; some personal virtues; and effective relationships with colleagues, patients and people who are important to those patients. In addition, it is suggested that expectations of professionalism may alter depending on context, both of time and place. Societal expectations relating to professionalism are likely to change over time and our expectations of individuals may alter according to the stage of training. The environment (the workplace, one's colleagues, the work tasks) is also highly influential on the manifestation of professional behaviours. The medical profession's social contract in relation to professionalism will always need to be updated. The effect of time and place means that searching for innate or stable elements of professionalism, in order to predict subsequent behaviours, is therefore difficult. This has implications for the selection, education and assessment of medical students. The focus should be on how to build adaptability and resilience to contextual influences; to identify those elements of professionalism that can be learnt; and build systems of assessment that reflect professionalism's multifaceted and contextual aspects.

Selection processes for medical schools need to be unbiased, valid, and psychometrically reliable, as well as evidence-based and transparent to all stakeholders. A range of academic and non-academic criteria are used for selection, including matriculation scores, aptitude tests and interviews. Research into selection is fraught with methodological difficulties; however, it shows positive benefits for structured selection processes. Pretest coaching and "faking good" are potential limitations of current selection procedures. Developments in medical school selection include the use of personality tests, centralised selection centres and programs to increase participation by socially disadvantaged students.

Genomic copy number alterations (CNA) are common in breast cancer. Identifying characteristic CNAs associated with specific breast cancer subtypes is a critical step in defining potential mechanisms of disease initiation and progression. We used genome-wide array comparative genomic hybridization to identify distinctive CNAs in breast cancer subtypes from 259 young (diagnosed with breast cancer at <55 years) African American (AA) and Caucasian American (CA) women originally enrolled in a larger population-based study. We compared the average frequency of CNAs across the whole genome for each breast tumor subtype and found that estrogen receptor (ER)-negative tumors had a higher average frequency of genome-wide gain (P < 0.0001) and loss (P = 0.02) compared to ER-positive tumors. Triple-negative (TN) tumors had a higher average frequency of genome-wide gain (P < 0.0001) and loss (P = 0.003) than non-TN tumors. No significant difference in CNA frequency was observed between HER2-positive and -negative tumors. We also identified previously unreported recurrent CNAs (frequency >40%) for TN breast tumors at 10q, 11p, 11q, 16q, 20p, and 20q. In addition, we report CNAs that differ in frequency between TN breast tumors of AA and CA women. This is of particular relevance because TN breast cancer is associated with higher mortality and young AA women have higher rates of TN breast tumors compared to CA women. These data support the possibility that higher overall frequency of genomic alteration events as well as specific focal CNAs in TN breast tumors might contribute in part to the poor breast cancer prognosis for young AA women.

The Mycobacterium tuberculosis protein tyrosine phosphatase PtpB shows resistance to the oxidative conditions that prevail within an infected host macrophage, but the mechanism of this molecular adaptation is unknown. Crystal structures of PtpB revealed previously that a closed, two-helix lid covers the active site. By measuring single-molecule Forster-type resonance energy transfer to probe the dynamics of two helices that constitute the lid, we obtained direct evidence for large, spontaneous opening transitions of PtpB with the closed form of both helices favored approximately 3:1. Despite similar populations of conformers, the two helices move asynchronously as demonstrated by different opening and closing rates under our experimental conditions. Assuming that lid closure excludes oxidant, the rates of opening and closing quantitatively accounted for the slow observed rate of oxidative inactivation. Increasing solvent viscosity using glycerol but not PEG8000 resulted in higher rates of oxidative inactivation due to an increase in the population of open conformers. These results establish that the rapid conformational gating of the PtpB lid constitutes a reversible physical blockade that transiently masks the active site and retards oxidative inactivation.

Myc oncoproteins are essential regulators of the growth and proliferation of mammalian cells. In Drosophila the single ortholog of Myc (dMyc), encoded by the dm gene, influences organismal size and the growth of both mitotic and endoreplicating cells. A null mutation in dm results in attenuated endoreplication and growth arrest early in larval development. Drosophila also contains a single ortholog of the mammalian Mad/Mnt transcriptional repressor proteins (dMnt), which is thought to antagonize dMyc function. Here we show that animals lacking both dMyc and dMnt display increased viability and grow significantly larger and develop further than dMyc single mutants. We observe increased endoreplication and growth of larval tissues in these double mutants and disproportionate growth of the imaginal discs. Gene expression analysis indicates that loss of dMyc leads to decreased expression of genes required for ribosome biogenesis and protein synthesis. The additional loss of dMnt partially rescues expression of a small number of dMyc and dMnt genes that are primarily involved in rRNA synthesis and processing. Our results indicate that dMnt repression is normally overridden by dMyc activation during larval development. Therefore the severity of the dm null phenotype is likely due to unopposed repression by dMnt on a subset of genes critical for cell and organismal growth. Surprisingly, considerable growth and development can occur in the absence of both dMyc and dMnt.

Processive versus distributive methyl group transfer was assessed for pea Rubisco large subunit methyltransferase, a SET domain protein lysine methyltransferase catalyzing the formation of trimethyllysine-14 in the large subunit of Rubisco. Catalytically competent complexes between an immobilized form of des(methyl) Rubisco and Rubisco large subunit methyltransferase were used to demonstrate enzyme release that was co-incident with and dependent on formation of trimethyllysine. Catalytic rate constants determined for formation of trimethyllysine were considerably lower ( approximately 10-fold) than rate constants determined for total radiolabel incorporation from [3H-methyl]-S-adenosylmethionine. Double-reciprocal velocity plots under catalytic conditions favoring monomethyllysine indicated a random or ordered reaction mechanism, while conditions favoring trimethyllysine suggested a hybrid ping-pong mechanism. These results were compared with double-reciprocal velocity plots and product analyses obtained for HsSET7/9 (a monomethyltransferase) and SpCLR4 (a dimethyltransferase) and suggest a predictive ability of double-reciprocal velocity plots for single versus multiple methyl group transfers by SET domain protein lysine methyltransferases. A model is proposed for SET domain protein lysine methyltransferases in which initial binding of polypeptide substrate and S-adenosylmethionine is random, with polypeptide binding followed by deprotonation of the epsilon-amine of the target lysyl residue and subsequent methylation. Following methyl group transfer, S-adenosylhomocysteine and monomethylated polypeptide dissociate from monomethyltransferases, but di- and trimethyltransferases begin a successive and catalytically obligatory deprotonation of enzyme-bound methylated lysyl intermediates, which along with binding and release of S-adenosylmethionine and S-adenosylhomocysteine is manifested as a hybrid ping-pong-like reaction mechanism.

The Myc-Max-Mad/Mnt network of transcription factors has been implicated in oncogenesis and the regulation of proliferation in vertebrate cells. The identification of Myc and Max homologs in Drosophila melanogaster has demonstrated a critical role for dMyc in cell growth control. In this report, we identify and characterize the third member of this network, dMnt, the sole fly homolog of the mammalian Mnt and Mad family of transcriptional repressors. dMnt possesses two regions characteristic of Mad and Mnt proteins: a basic helix-loop-helix-zipper domain, through which it dimerizes with dMax to form a sequence-specific DNA binding complex, and a Sin-interacting domain, which mediates interaction with the dSin3 corepressor. Using the upstream activation sequence/GAL4 system, we show that expression of dMnt results in an inhibition of cellular growth and proliferation. Furthermore, we have generated a dMnt null allele, which results in flies with larger cells, increased weight, and decreased life span compared to wild-type flies. Our results demonstrate that dMnt is a transcriptional repressor that regulates D. melanogaster body size.

Members of the Myc family of proto-oncogenes have long been implicated in regulating proliferation, apoptosis and oncogenesis. Recently, transcriptional and biological studies have suggested a direct role for Myc in regulating growth. We have used dm(4), a new null allele of the Drosophila diminutive (dm) gene, which encodes dMyc on the X chromosome, to investigate a role for dMyc in larval endoreplicating tissues, where cellular growth and DNA replication occur in the absence of cell division. Hemizygous dm(4)/Y mutants arrest as second instar larvae, and fat body nuclei of dm(4)/Y mutants fail to attain normal size and normal levels of DNA, resulting from a reduced frequency of S-phase. Thus, dMyc is required for endoreplication and larval growth. In support of this, dMyc, as well as its antagonist dMnt, are expressed in larval tissues in a pattern consistent with their involvement in regulating endoreplication. Overexpression of dMyc in endoreplicating cells results in dramatic increases in nuclear DNA content and cell and nucleolar size, whereas dMnt overexpression has the opposite effect. BrdU incorporation and Cyclin E protein levels continue to oscillate in dMyc-overexpressing cells, indicating that the normal cell cycle control mechanisms are not disrupted. dMyc driven growth and endoreplication are strongly attenuated when the endocycle is blocked with Cyclin E or the cdk inhibitor p21. By contrast, the ability of dMyc to promote growth and endoreplication is only partly reduced when PI3K activity is blocked, suggesting that they influence distinct growth pathways. Our results indicate that larval growth and endoreplication are coupled processes that, although linked to cell cycle control mechanisms, are regulated by dMyc and dMnt.

SET domain protein methyltransferases catalyze the transfer of methyl groups from the cofactor S-adenosylmethionine (AdoMet) to specific lysine residues of protein substrates, such as the N-terminal tails of histones H3 and H4 and the large subunit of the Rubisco holoenzyme complex. The crystal structures of pea Rubisco large subunit methyltransferase (LSMT) in ternary complexes with either lysine or epsilon-N-methyllysine (MeLys) and the product S-adenosylhomocysteine (AdoHcy) were determined to resolutions of 2.65 and 2.55 A, respectively. The zeta-methyl group of MeLys is bound to the enzyme via carbon-oxygen hydrogen bonds that play a key role in catalysis. The methyl donor and acceptor are aligned in a linear geometry for S(N)2 nucleophilic transfer of the methyl group during catalysis. Differences in hydrogen bonding between the MeLys epsilon-amino group and Rubisco LSMT and SET7/9 explain why Rubisco LSMT generates multiply methylated Lys, wheras SET7/9 generates only MeLys.

Childhood sexual-abuse occurrences are life-altering events. Children are remarkably successful at keeping the facts of sustained abuse hidden. This results in delayed therapeutic intervention, or none at all. Traditionally, evaluating the symptoms of physical and emotional trauma has been the basis of screening for sexual abuse. This article presents an alternative method. The evaluation of some basic components of psychosexual development will make more evident a child's vulnerability to and/or experience with sexual abuse. A guide to parent-child education based on these same components of psychosexual maturity is also presented as a means of prevention. Screening and education are recognized as interdependent activities within this model of care.