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Hypomorphic mutations are a valuable tool for analysing gene function, but current methods have difficult to predict effects on gene expression and are organism specific. Here the authors present a pan-species approach using variable polyA tracks to modulate expression of a target protein.

Nature Communications 8: Article number: 14112 (2017); Published: 20 January 2017; Updated: 16 February 2017 The original version of this Article contained a typographical error in the spelling of the Author Preetam Janakirama, which was incorrectly given as Preetam Jankirama. This has now been corrected in both the PDF and HTML versions of the Article.

Plasmodium falciparum is a causative agent of human malaria. Sixty percent of mRNAs from its extremely AT-rich (81%) genome harbor long polyadenosine (polyA) runs within their ORFs, distinguishing the parasite from its hosts and other sequenced organisms. Recent studies indicate polyA runs cause ribosome stalling and frameshifting, triggering mRNA surveillance pathways and attenuating protein synthesis. Here, we show that P. falciparum is an exception to this rule. We demonstrate that both endogenous genes and reporter sequences containing long polyA runs are efficiently and accurately translated in P. falciparum cells. We show that polyA runs do not elicit any response from No Go Decay (NGD) or result in the production of frameshifted proteins. This is in stark contrast to what we observe in human cells or T. thermophila, an organism with similar AT-content. Finally, using stalling reporters we show that Plasmodium cells evolved not to have a fully functional NGD pathway.

Purpose: To determine factors that put US veterans with active tuberculosis at risk for extrapulmonary tuberculosis (EPTB) compared with pulmonary tuberculosis., Methods: We included veterans with laboratory-confirmed tuberculosis from 1990-2022 in our retrospective cohort study. Multivariable logistic regression was used to estimate the association of demographic and clinical risk factors with EPTB., Results: Of 7493 veterans aged 20-100 years (median, 58 years) with laboratory-confirmed tuberculosis, 1397 (19%) had EPTB. The most common EPTB infection among veterans was pleural (31.4%), while meningitis carried the highest mortality risk at 90 days. Factors independently associated with EPTB among veterans were non-Hispanic black race/ethnicity, diabetes mellitus, human immunodeficiency virus infection, severe kidney disease, and all-cause mortality within 90 days after tuberculosis diagnosis., Conclusions: Our study demonstrated several risk factors for EPTB among US veterans. Healthcare providers should be educated regarding patient populations at risk for EPTB, especially given the challenges in diagnosing this disease and the importance of instituting early treatment to prevent severe illness and death., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

We applied lymphogranuloma venereum (LGV) clinical case criteria to a cohort of 1381 Veterans positive for HIV and Chlamydia trachomatis (CT) from 2016 from 2023 and analyzed variables to ascertain risk factors for LGV and factors associated with the use of standard treatment regimens. In total, 284/1381 (20.6%) met the criteria for LGV. A total of 179/284 (63%) were probable cases, and 105/284 (37%) were possible cases (those meeting clinical criteria but with concurrent sexually transmitted infections (STI) associated with LGV-like symptoms). None had confirmatory CT L1-L3 testing. A total of 230 LGV cases (81%) presented with proctitis, 71 (25%) with ulcers, and 57 (20.1%) with lymphadenopathy. In total, 66 (23.2%) patients had >1 symptom of LGV. A total of 43 (15%) LGV cases were hospitalized. Primary risk factors for LGV were male birth sex ( p = 0.004), men who have sex with men ( p < 0.001), and the presence of STIs other than gonorrhea or syphilis ( p = 0.011). In total, 124/284 (43.7%) LGV cases received standard recommended treatment regimens. Probable cases were more likely to receive standard treatment than possible cases ( p = 0.003). We report that 20.6% of CT cases met clinical criteria for LGV among HIV-infected Veterans and that less than half of cases received recommended treatment regimens, indicating that LGV is likely underestimated and inadequately treated among this US population.

Background: Bariatric surgery affects the absorption of medications including antidepressants, but data regarding these effects are limited., Objectives: Our objectives were to review publicly available data regarding changes in antidepressant serum concentration following bariatric surgery in order to develop medication dosing recommendations in this patient population., Methods: A comprehensive literature review was performed utilizing key search terms in Pubmed. Additional data were retrieved from the Food and Drug Administration and DrugBank Online resources., Results: A total of twelve published articles were included in addition to the publicly available data from the Food and Drug Administration and DrugBank. The serum concentration of antidepressants following bariatric surgery demonstrated considerable variability between and within drug classes due to unique pharmacokinetic features, drug preparation, and formulation. Recommendations were developed from published data regarding changes in serum concentration and drug-specific pharmacokinetic data., Conclusions: To our knowledge, this is the first study to propose medication dose-adjustment recommendations for patients on antidepressants undergoing bariatric surgery. We were limited by the relatively small amount of data available and recommend monitoring patients and use of clinical judgment along with this guidance., (Copyright © 2024. Published by Elsevier Inc.)

The COVID-19 pandemic increased already high rates of student mental health concerns and further underscored inequities and disparities in access to services and care. As schools continue to address the effects of the pandemic, they must prioritize student mental health and well-being. In this commentary, using feedback from the Maryland School Health Council, we present the connection between mental health in school and the Whole School, Whole Community, Whole Child (WSCC) model, a school health model commonly employed by schools and school districts. In doing so, we aim to highlight how school districts can use this model to address child mental health needs across a multi-tiered system of support., (© 2023, American School Health Association.)

Background: Health care providers and health-related researchers face significant challenges when applying sentiment analysis tools to health-related free-text survey data. Most state-of-the-art applications were developed in domains such as social media, and their performance in the health care context remains relatively unknown. Moreover, existing studies indicate that these tools often lack accuracy and produce inconsistent results., Objective: This study aims to address the lack of comparative analysis on sentiment analysis tools applied to health-related free-text survey data in the context of COVID-19. The objective was to automatically predict sentence sentiment for 2 independent COVID-19 survey data sets from the National Institutes of Health and Stanford University., Methods: Gold standard labels were created for a subset of each data set using a panel of human raters. We compared 8 state-of-the-art sentiment analysis tools on both data sets to evaluate variability and disagreement across tools. In addition, few-shot learning was explored by fine-tuning Open Pre-Trained Transformers (OPT; a large language model [LLM] with publicly available weights) using a small annotated subset and zero-shot learning using ChatGPT (an LLM without available weights)., Results: The comparison of sentiment analysis tools revealed high variability and disagreement across the evaluated tools when applied to health-related survey data. OPT and ChatGPT demonstrated superior performance, outperforming all other sentiment analysis tools. Moreover, ChatGPT outperformed OPT, exhibited higher accuracy by 6% and higher F-measure by 4% to 7%., Conclusions: This study demonstrates the effectiveness of LLMs, particularly the few-shot learning and zero-shot learning approaches, in the sentiment analysis of health-related survey data. These results have implications for saving human labor and improving efficiency in sentiment analysis tasks, contributing to advancements in the field of automated sentiment analysis., (©Juan Antonio Lossio-Ventura, Rachel Weger, Angela Y Lee, Emily P Guinee, Joyce Chung, Lauren Atlas, Eleni Linos, Francisco Pereira. Originally published in JMIR Mental Health (https://mental.jmir.org), 25.01.2024.)

Background: U.S. Special Operations Forces (SOF) are at increased risk of multiple mild traumatic brain injury (mmTBI). Testosterone was prescribed for several participants in a VA program designed to address sequelae of mmTBI for SOF., Objective: To determine testosterone prevalence in the Palo Alto VA Intensive Evaluation and Treatment Program (IETP) and observe for association between testosterone and neurobehavioral outcomes., Methods: A retrospective cohort study included patients in the Palo Alto VA IETP. Sociodemographic data, testosterone blood levels, and neurobehavioral outcomes were collected from medical records., Results: 55 IETP participants were included: six were testosterone users; the rest were classified as non-users. Testosterone use in this population is 11%, higher than reported national averages in the U.S. Of the 6 testosterone users, 2 (33%) had a formal diagnosis of hypogonadism prior to initiation of testosterone. Neurobehavioral outcome scores between testosterone users and non-users failed to show statistically significant differences, except for the PROMIS pain score, which was higher in the testosterone user population., Conclusion: The current study did not find an association between mmTBI, testosterone use, or testosterone level and neurobehavioral outcomes. This study highlights a need to further examine the relationship between hypogonadism, mmTBI, SOF culture around testosterone, and the effects of testosterone use in this population.

Background: Among nearly 400,000 children in US foster care, an estimated 10 % are medically complex. Yet, population-level data about children with medical complexity (CMC) served by the child welfare system, both for prevention and foster care services, are largely unavailable., Objective: To understand how US child welfare agencies define, identify, and track CMC., Participants and Setting: Child welfare agencies across the US., Methods: Agencies were recruited to complete a survey as part of a larger study exploring how CMC are served by the child welfare system. Survey responses related to defining, identifying, and tracking CMC were included in analysis. Descriptive statistical analysis was conducted with Stata. Qualitative content and thematic analysis were applied to free text responses., Results: Surveys were completed by agencies from 28 states and 2 major cities. Nearly half of the agencies did not have a clear definition to identify CMC; those that did have a definition often lacked standardization. The majority of agencies could not easily identify CMC or access CMC-related data within data systems. Agencies described lack of a clear definition as a barrier to collecting population level data., Conclusions: Many US child welfare agencies lack a clear definition to identify and track CMC, impacting the ability to tailor care and service delivery to meet their unique needs. To address this, a clear definition for CMC should be developed and consistently applied within child welfare data systems. Once CMC are identifiable, future research can collect population-level data and provide recommendations for best practices and policies., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To compare barriers and facilitators to accessing health care services among service members and veterans (SMVs) by traumatic brain injury (TBI) severity groups., Design: Qualitative descriptive study guided by an access to health care services conceptual framework., Setting: Five Veterans Affairs (VA) polytrauma rehabilitation centers., Participants: SMVs (N=55, including 10 caregivers as proxies) ≥2 years post-TBI recruited from the VA TBI Model Systems and grouped by TBI severity (mild/moderate, severe)., Main Outcome Measures: Barriers and facilitators accessing care., Results: The main facilitators included ease of communicating with providers to help SMVs identify and utilize appropriate health care, family advocates who promoted engagement in health care, ability to use government and community facilities, and online resources or equipment. Distance to services was uniformly identified as a main barrier for both patient groups. However, facilitators and barriers to health care access differed by TBI severity. SMVs with severe TBI highlighted the role of nonprofit organizations in promoting health care engagement and the availability of VA specialty residential programs in meeting health care needs. Having unrecognized health care needs in chronic stages and communication difficulties with providers were more commonplace for those with greater TBI severity and affected quality of care. Those with mild/moderate TBI highlighted challenges associated with paying for services in the community and scheduling of services., Conclusions: Barriers and facilitators exist across multiple dimensions of a health care access framework and vary by TBI severity. Results suggest possible mechanistic links between health care access and SMV health outcomes. Findings support current policy and practice efforts to facilitate health care access for SMVs with TBI but highlight the need for tailored approaches for those with greater disability., (Published by Elsevier Inc.)

The NIMH Healthy Research Volunteer Dataset is a collection of phenotypic data characterizing healthy research volunteers using clinical assessments such as assays of blood and urine, mental health assessments, diagnostic and dimensional measures of mental health, cognitive and neuropsychological functioning, structural and functional magnetic resonance imaging (MRI), along with diffusion tensor imaging (DTI), and a comprehensive magnetoencephalography battery (MEG). In addition, blood samples of healthy volunteers are banked for future analyses. All data collected in this protocol are broadly shared in the OpenNeuro repository, in the Brain Imaging Data Structure (BIDS) format. In addition, task paradigms and basic pre-processing scripts are shared on GitHub. There are currently few open access MEG datasets, and multimodal neuroimaging datasets are even more rare. Due to its depth of characterization of a healthy population in terms of brain health, this dataset may contribute to a wide array of secondary investigations of non-clinical and clinical research questions., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: To identify predictors of driving status in service members and veterans 1 year following a traumatic brain injury (TBI)., Setting: The 5 Department of Veterans Affairs (VA) Polytrauma Rehabilitation Centers (PRCs)., Participants: A total of 471 service members and veterans (128 with mild/complicated mild TBI and 343 with moderate/severe TBI) who received TBI-focused inpatient rehabilitation at one of the VA PRCs and who participated in a 1-year postinjury follow-up assessment., Design: Secondary analysis from the Department of Veterans Affairs Polytrauma Rehabilitation Centers Traumatic Brain Injury Model Systems (VA PRC TBIMS) national database., Main Measures: Primary outcome was a single item that assessed driving status at 1 year postinjury. Predictor variables included demographics; sensory impairment, substance use, and employment status at time of injury; PTSD symptoms reported at study enrollment; and functional impairment rated at rehabilitation discharge., Results: In unadjusted bivariate analyses, among those with a mild/complicated mild TBI, older age and greater functional impairment were associated with lower likelihood of driving. Among those with a moderate/severe TBI, discharge to a nonprivate residence, greater functional impairment, and higher PTSD symptoms were linked to lower likelihood of driving. Adjusted multivariate analyses indicated that functional impairment was uniquely associated with driving status in both TBI severity groups. After controlling for other predictors, self-reported PTSD symptoms, particularly dysphoria symptoms, were associated with lower likelihood of driving in both severity groups., Conclusion: Given the significance of clinician-rated functional impairment and self-reported PTSD symptoms to the prediction of driving status 1 year post-TBI among service members and veterans, rehabilitation efforts to improve functioning and reduce negative affect may have a positive impact on driving and community integration., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Circadian rhythms regulate adaptive alterations in mammalian physiology and are maximally entrained by the short wavelength blue spectrum; cataracts block the transmission of light, particularly blue light. Cataract surgery is performed with two types of intraocular lenses (IOL): (1) conventional IOL that transmit the entire visible spectrum and (2) blue-light-filtering (BF) IOL that block the short wavelength blue spectrum. We hypothesized that the transmission properties of IOL are associated with long-term survival. This retrospective cohort study of a 15-hospital healthcare system identified 9,108 participants who underwent bilateral cataract surgery; 3,087 were implanted with conventional IOL and 6,021 received BF-IOL. Multivariable Cox proportional hazards models that included several a priori determined subgroup and sensitivity analyses yielded estimates supporting that conventional IOL compared with BF-IOL may be associated with significantly reduced risk of long-term death. Confirming these differences and identifying any potential causal mechanisms await the conduct of appropriately controlled prospective translational trials., Competing Interests: All authors declare no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work; no other relationships or activities that could appear to have influenced the submitted work., (© 2020 The Authors.)

McCune-Albright syndrome (MAS) is a mosaic disorder arising from gain-of-function mutations in the GNAS gene, which encodes the 3',5'-cyclic adenosine monophosphate (cAMP) pathway-associated G-protein, G s α. Clinical manifestations of MAS in a given individual, including fibrous dysplasia, are determined by the timing and location of the GNAS mutation during embryogenesis, the tissues involved, and the role of G s α in the affected tissues. The G s α mutation results in dysregulation of the cAMP signaling cascade, leading to upregulation of phosphodiesterase type 4 (PDE4), which catalyzes the hydrolysis of cAMP. Increased cAMP levels have been found in vitro in both animal models of fibrous dysplasia and in cultured cells from individuals with MAS but not in humans with fibrous dysplasia. PET imaging of PDE4 with 11 C-( R )-rolipram has been used successfully to study the in vivo activity of the cAMP cascade. To date, it remains unknown whether fibrous dysplasia and other symptoms of MAS, including neuropsychiatric impairments, are associated with increased PDE4 activity in humans. Methods: 11 C-( R )-rolipram whole-body and brain PET scans were performed on 6 individuals with MAS (3 for brain scans and 6 for whole-body scans) and 9 healthy controls (7 for brain scans and 6 for whole-body scans). Results: 11 C-( R )-rolipram binding correlated with known locations of fibrous dysplasia in the periphery of individuals with MAS; no uptake was observed in the bones of healthy controls. In peripheral organs and the brain, no difference in 11 C-( R )-rolipram uptake was noted between participants with MAS and healthy controls. Conclusion: This study is the first to find evidence for increased cAMP activity in areas of fibrous dysplasia in vivo. No differences in brain uptake between MAS participants and controls were detected-a finding that could be due to several reasons, including the limited anatomic resolution of PET. Nevertheless, the results confirm the usefulness of PET scans with 11 C-( R )-rolipram to indirectly measure increased cAMP pathway activation in human disease., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Traumatic brain injury (TBI) is associated with increased risk for psychological and substance use disorders. The study aim is to determine incidence and risk factors for persistent opioid prescription after hospitalization for TBI. Electronic medical records of patients age ≥ 18 admitted to a neuroscience intensive care unit between January 2013 and February 2017 for an intracranial injury were retrospectively reviewed. Primary outcome was opioid use through 12 months post-hospital discharge. A total of 298 patients with complete data were included in the analysis. The prevalence of opioid use among preadmission opioid users was 48 (87%), 36 (69%) and 22 (56%) at 1, 6 and 12-months post-discharge, respectively. In the opioid naïve group, 69 (41%), 24 (23%) and 17 (19%) were prescribed opioids at 1, 6 and 12 months, respectively. Preadmission opioid use (OR 324.8, 95% CI 23.1-16907.5, p = 0.0004) and higher opioid requirements during hospitalization (OR 4.5, 95% CI 1.8-16.3, p = 0.006) were independently associated with an increased risk of being prescribed opioids 12 months post-discharge. These factors may be used to identify and target at-risk patients for intervention., Competing Interests: The authors have declared that no competing interests exist.

Objective: This longitudinal qualitative study explores the impact of natural disasters on religious attachment (perceived relationship with God). We sought to validate and conceptually extend the religion-as-attachment model in a postdisaster context., Method: At 4 weeks (T1; n = 36) and 6 months postdisaster (T2; n = 29), survivors of the 2016 Louisiana flood completed a disaster-adapted version of the Religious Attachment Interview (Granqvist & Main, 2017)., Results: At T1 and T2, survivors emphasized God being a safe haven (source of protection, comfort, or nurturance). This emphasis was especially pronounced for survivors who were directly affected (their home or business flooded) or had previous disaster exposure to Hurricane Katrina. Overall, survivors consistently emphasized God serving as a stronger and wiser attachment figure, and it was rare for them to report experiencing perceived separation or loss of intimacy from God. At T1 and T2, around 85% of survivors described their current religious attachment as either having a positive affective quality (e.g., closer, stronger) or as no different from before the disaster; around 15% said it had a negative affective quality (e.g., disappointed, strained). In describing their postdisaster religion/spirituality, survivors highlighted (a) God being a source of love, comfort, strength, and hope; (b) actively putting trust/faith in God; and (c) experiencing God through family/community., Conclusion: Results support and conceptually extend the religion-as-attachment model in a postdisaster context. Findings suggest disasters activate the attachment system, and survivors commonly view and relate with God as an attachment figure, especially one who serves as a safe haven. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Objective: To determine the effect of the established polytrauma/traumatic brain injury (TBI) infrastructure on immediate posttreatment functional gains, the long-term sustainability of any gains, and participation-related community reintegration outcomes in a baseline cohort of patients 8 years postadmission., Design: Retrospective review and prospective repeated measures of an inception cohort., Setting: Polytrauma rehabilitation center (PRC)., Participants: Patients consecutively admitted to the PRC inpatient rehabilitation unit during its first full fiscal year, 2006 (N=44)., Interventions: The PRC infrastructure and formalized rehabilitation for polytrauma/TBI., Main Outcome Measures: FIM scores at admission, discharge, 3 months, and 8 years postdischarge; participation-related socioeconomic factors reflecting community reintegration 8 years after admission., Results: Functional gains were statistically significantly increased from admission to discharge. Improvements were maintained at both 3 months postdischarge and 8 years postdischarge. The socioeconomic data collected at 8-year follow-up showed >50% either competitively employed or continuing their education and 100% living in a noninstitutionalized setting., Conclusions: This study addresses a concern regarding the long-term functional outcomes of rehabilitation patients treated by the established infrastructure of the Polytrauma System of Care inpatient rehabilitation centers. The results suggest that polytrauma/TBI rehabilitation care using a comprehensive, integrated approach is effective and durable in achieving functional gains and successful community reintegration within our initial PRC cohort. Follow-up of subsequent fiscal year cohorts would add to the validity of these outcome findings., (Published by Elsevier Inc.)

Neuropathic pain symptoms respond poorly to available therapeutics, with most treated patients reporting unrelieved pain and significant impairment in daily life. Here, we show that Pannexin 1 (Panx1) in hematopoietic cells is required for pain-like responses following nerve injury in mice, and a potential therapeutic target. Panx1 knockout mice (Panx1 -/- ) were protected from hypersensitivity in two sciatic nerve injury models. Bone marrow transplantation studies show that expression of functional Panx1 in hematopoietic cells is necessary for mechanical hypersensitivity following nerve injury. Reconstitution of irradiated Panx1 knockout mice with hematopoietic Panx1 -/- cells engineered to re-express Panx1 was sufficient to recover hypersensitivity after nerve injury; this rescue required expression of a Panx1 variant that can be activated by G protein-coupled receptors (GPCRs). Finally, chemically distinct Panx1 inhibitors blocked development of nerve injury-induced hypersensitivity and partially relieved this hypersensitivity after it was established. These studies indicate that Panx1 expressed in immune cells is critical for pain-like effects following nerve injury in mice, perhaps via a GPCR-mediated activation mechanism, and suggest that inhibition of Panx1 may be useful in treating neuropathic pain., Competing Interests: The authors declare no competing financial interests.

The causes of homelessness are complex and poorly understood. This paper describes the homeless population in Santa Clara County, California in terms of Adverse Childhood Events, Traumatic Brain Injuries (TBIs), and family breakdown. Respondents reported severely traumatic childhoods; 78.7% grew up in a household with a person with drug or alcohol dependence and 64.6% endured psychological abuse as a child. Seventy-six percent of subjects recalled at least one TBI, 58.4% with loss of consciousness. Nineteen percent were in foster care as children and 40.2% reported having someone other than a parent as a primary caregiver. Fifty-three percent felt they had moved too much as children, and 37.5% had experienced homelessness as children. Santa Clara County has both the highest median income and the highest rate of unsheltered homelessness in the nation. Leaders and community members should work together to improve the lives of the home-less and to prevent another generation of homeless people.

There has been intensive interest to ensure equitable and appropriate access to the specialized rehabilitative services of the VA Polytrauma System of Care (PSC) for patients sustaining polytrauma and traumatic brain injuries (TBI). A retrospective cohort study with prospective data acquisition was conducted to assess validity and objectivity of the acceptance decision algorithm to the VA Palo Alto Health Care System (VAPAHCS) PSC. Our hypotheses are (1) VAPAHCS PSC referral decisions were appropriate and without bias and (2) the identified needs of redirected referrals were addressed. This analysis included 1,025 referrals (906 patients); 813 patients (89.7%) were accepted, and 93 (10.3%) were redirected. Redirected cases were older, were more often active duty service members, and were not from the West Coast. There were more females redirected due to concomitant spinal cord injury. These are rationale differences. In redirected patients, the most commonly identified rehabilitation needs were psychological support, mobility/physical therapy, and communication/speech services; >75% of patients had these services offered elsewhere outside of the PSC resources. While balancing financial stewardship and meeting our mission to provide outstanding rehabilitative care to veterans and service members, we demonstrated that acceptance decisions were valid and without bias, and redirected patients received appropriate alternate resources.

Advances in areas of neuroscience are highly relevant to psychiatric disorders but there exists a gap between discoveries in neuroscience and the practice of clinical psychiatry. Psychiatry is a field in need of high impact research conducted by physician-scientists who have first-hand experience treating patients with mental illness and who use this clinical knowledge to improve and discover better or novel interventions. This paper focuses primarily on the training of psychiatry residents for successful scientific research careers and what residency programmes and others can do to help them succeed. Changes also need to be made at a regulatory level to enhance the research training and literacy of psychiatry residents. The shortage of psychiatrists who are well trained in basic and translational research can only be remedied if the path to becoming an independent investigator is lined with stepping stones that support success, including during the residency years. Partnerships among funding agencies, professional societies and training institutions can lay the groundwork for our psychiatric trainees to stay on the path to rewarding scientific research careers.

Background: Ingested inorganic arsenic (InAs) is methylated to monomethylated (MMA) and dimethylated metabolites (DMA). Methylation may have an important role in arsenic toxicity, because the monomethylated trivalent metabolite [MMA(III)] is highly toxic., Objectives: We assessed the relationship of creatinine and nutrition--using dietary intake and blood concentrations of micronutrients--with arsenic metabolism, as reflected in the proportions of InAS, MMA, and DMA in urine, in the first study that incorporated both dietary and micronutrient data., Methods: We studied methylation patterns and nutritional factors in 405 persons who were selected from a cross-sectional survey of 7,638 people in an arsenic-exposed population in West Bengal, India. We assessed associations of urine creatinine and nutritional factors (19 dietary intake variables and 16 blood micronutrients) with arsenic metabolites in urine., Results: Urinary creatinine had the strongest relationship with overall arsenic methylation to DMA. Those with the highest urinary creatinine concentrations had 7.2% more arsenic as DMA compared with those with low creatinine (p < 0.001). Animal fat intake had the strongest relationship with MMA% (highest tertile animal fat intake had 2.3% more arsenic as MMA, p < 0.001). Low serum selenium and low folate were also associated with increased MMA%., Conclusions: Urine creatinine concentration was the strongest biological marker of arsenic methylation efficiency, and therefore should not be used to adjust for urine concentration in arsenic studies. The new finding that animal fat intake has a positive relationship with MMA% warrants further assessment in other studies. Increased MMA% was also associated, to a lesser extent, with low serum selenium and folate.

The present study identifies a broad taxonomy of motives underlying the desire to regulate prejudice and assess the impact of motivation to regulate prejudice on levels of explicit and implicit prejudice. Using self-determination theory as the foundation, six forms of motivation to regulate prejudice are proposed. In Study 1 (N = 257), an exploratory factor analysis reveals evidence for the six proposed dimensions. In Study 2 (N = 198), the six-factor taxonomy of motivation to regulate prejudice is further validated using a confirmatory factor analysis, and construct validity is obtained. In Study 3 (N = 62), motivation to regulate prejudice is manipulated before participants complete the Implicit Association Test (IAT) and explicit measures of prejudice. Results reveal that those with highly self-determined regulation of prejudice demonstrate lower implicit and explicit prejudice than their less self-determined counterparts. Results are discussed in terms of an increased understanding of the motivation to control prejudice.

Low-income African American, Latino, and White women were screened and recruited for a depression treatment trial in social service and family planning settings. Those meeting full criteria for major depression (MDD; N = 267) were randomized to cognitive-behavior therapy (CBT), antidepressant medication, or community mental health referral. All randomly assigned participants were evaluated by baseline telephone and clinical interview, and followed by telephone for one year. Posttraumatic stress disorder (PTSD) comorbidity was assessed at baseline and one-year follow-up in a clinical interview. At baseline, 33% of the depressed women had current comorbid PTSD. These participants had more exposure to assaultive violence, had higher levels of depression and anxiety, and were more functionally impaired than women with depression alone. Depression in both groups improved over the course of one year, but the PTSD subgroup remained more impaired throughout the one-year follow-up period. Thus, evidence-based treatments (antidepressant medication or structured psychotherapy) decrease depression regardless of PTSD comorbidity, but women with PTSD were more distressed and impaired throughout. Including direct treatment of PTSD associated with interpersonal violence may be more effective in alleviating depression in those with both diagnoses.

This study examines 1-year depressive symptom and functional outcomes of 267 predominantly lowincome, young minority women randomly assigned to antidepressant medication, group or individual cognitive- behavioral therapy (CBT), or community referral. Seventy-six percent assigned to medications received 9 or more weeks of guideline-concordant doses of medications; 36% assigned to psychotherapy received 6 or more CBT sessions. Intent-to-treat, repeated measures analyses revealed that medication (p=.001) and CBT (p=.02) were superior to community referral in lowering depressive symptoms across 1-year follow-up. At Month 12, 50.9% assigned to antidepressants, 56.9% assigned to CBT, and 37.1% assigned to community referral were no longer clinically depressed. These findings suggest that both antidepressant medications and CBT result in clinically significant decreases in depression for low-income minority women., (Copyright (c) 2006 APA, all rights reserved.)

Anorexia nervosa (AN) is a disorder that is increasing in frequency in adolescents, and the age of onset is often in the prepubertal years, potentially affecting the development of peak bone mass and linear growth. The GH-IGF-I axis plays an important role in bone formation, and alterations in GH secretory patterns have been described in adult women with AN. However, GH secretory dynamics in adolescents with AN have not been described, and the effects of alterations in GH secretory patterns and GH concentration on bone metabolism in AN are not known. We examined patterns of GH secretion by deconvolutional analysis, and GH concentration by Cluster analysis, in adolescent girls with AN (n = 22) and controls (n = 20) of comparable bone age and pubertal stage. We also examined the roles of cortisol, leptin, and estradiol in the regulation of GH secretion and concentration, and the relationship of GH secretory patterns and concentration to bone metabolism. Basal GH secretion and secretory pulse number in adolescent girls with AN were increased compared with control values (P = 0.03 and 0.007, respectively), and increased disorderliness of GH secretion (approximate entropy) was found in AN (P = 0.004). Mean and nadir GH concentrations and total area under the concentration curve were increased (P = 0.03, 0.002, and 0.03, respectively), and IGF-I levels were decreased (P = 0.0002) in girls with AN compared with healthy adolescent girls. IGF-I levels correlated negatively with nadir GH concentrations (r = -0.35; P = 0.02). Serum cortisol levels were higher in girls with AN than in controls (P < 0.0001) and correlated inversely with IGF-I (r = -0.58; P = 0.0001) and weakly with GH concentration (area under the concentration curve; r = -0.43; P = 0.05). A strong inverse relationship between markers of nutritional status (body mass index, fat mass, and leptin) and basal and pulsatile GH secretion, and mean and nadir GH concentrations was observed. GH concentration predicted levels of all markers of bone formation and a marker of bone resorption (N-telopeptide) in healthy controls, but not in AN. We demonstrate increases in basal GH secretion, number of secretory bursts, and GH concentration in adolescents with AN compared with controls, accompanied by low IGF-I levels. These data are consistent with the hypothesis that an acquired GH resistance occurs in this undernourished group. We also demonstrate that GH secretion and concentration are nutritionally regulated, and that the effects of nutrition exceed the effects of cortisol on GH concentration. Acquired GH resistance may play a role in the osteopenia and decreased peak bone mass frequently associated with AN.

Epidemiologic studies in human populations have identified a broad spectrum of risk factors for cancer. Gene-damaging agents have been a primary focus of cancer epidemiology; however, all xenobiotics do not interact with DNA directly. Some exogenous agents induce epigenetic changes. In view of this, markers that measure changes to the epigenome must also be incorporated into molecular epidemiologic studies. We review the current understanding of the impact of exogenous agents including: micronutrients, chemotherapeutic agents, metals, and others, on DNA methylation. Two categories of genes are described: (1) genes that can alter susceptibility to aberrant DNA methylation and (2) genes that increase susceptibility to cancer when they are silenced through DNA methylation. Methods for incorporating markers of DNA methylation status into etiologic investigations of the impact of environmental exposures on disease (e.g., cancer) are discussed.