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BACKGROUND: The epidemiological, prognostic, and therapeutic features of child and adolescent meningioma are poorly defined. Clinical knowledge has been drawn from small case series and extrapolation from adult studies. This study was done to pool and analyse the clinical evidence on child and adolescent meningioma. METHODS: Searches of PubMed, Medline, and Embase identified 35 case series of child and adolescent meningioma completed over the past 21 years. Individual patient data were obtained from 30 studies via direct communication with investigators. Primary outcomes were relapse-free survival (RFS) and overall survival. Prognostic variables were extent of initial surgery, use of upfront radiotherapy, age, sex, presence of neurofibromatosis, tumour location, and tumour grade. RFS and overall survival were analysed using Kaplan-Meier survival curves and multivariable Cox regression models. FINDINGS: From a total of 677 children and adolescents with meningioma, 518 were eligible for RFS analysis and 547 for overall survival analysis. Multivariable analysis showed that patients who underwent initial gross-total resection had better RFS (hazard ratio 0·16, 95% CI 0·10-0·25; p<0·0001) and overall survival (0·21, 0·11-0·39; p<0·0001) than those who had subtotal resection. No significant benefit was seen for upfront radiotherapy in terms of RFS (0·59, 0·30-1·16; p=0·128) or overall survival (1·10, 0·53-2·28; p=0·791). Patients with neurofibromatosis type 2 (NF2) had worse RFS than those without neurofibromatosis (2·36, 1·23-4·51; p=0·010). There was a significant change in overall survival with time between patients with NF2 compared with those without neurofibromatosis (1·45, 1·09-1·92; p=0·011); although overall survival was initially better for patients with NF2 than for those without neurofibromatosis, overall survival at 10 years was worse for patients with NF2. Patients with WHO grade III tumours had worse RFS than those with WHO grade I (3·90, 2·10-7·26; p<0·0001) and grade II tumours (2·49, 1·11-5·56; p=0·027). INTERPRETATION: Extent of initial surgical resection is the strongest independent prognostic factor for child and adolescent meningioma. No benefit for upfront radiotherapy was noted. Hence, aggressive surgical management, to achieve gross-total resection, is the initial treatment of choice. In the event of a subtotal resection, repeat resection is recommended to achieve maximum extirpation. Close observation is warranted for patients who have a subtotal resection or who have WHO grade III tumours. Patients without neurofibromatosis should have a minimum 10-year follow-up, whereas patients with NF2 should be considered a special risk category, necessitating life-long follow-up. FUNDING: None. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) aims to reduce new leprosy cases by 70% by 2030, necessitating advancements in leprosy diagnostics. Here we discuss the development of two WHO's target product profiles for such diagnostics. These profiles define criteria for product use, design, performance, configuration and distribution, with a focus on accessibility and affordability. The first target product profile outlines requirements for tests to confirm diagnosis of leprosy in individuals with clinical signs and symptoms, to guide multidrug treatment initiation. The second target product profile outlines requirements for tests to detect Mycobacterium leprae or M. lepromatosis infection among asymptomatic contacts of leprosy patients, aiding prophylactic interventions and prevention. Statistical modelling was used to assess sensitivity and specificity requirements for these diagnostic tests. The paper highlights challenges in achieving high specificity, given the varying endemicity of M. leprae, and identifying target analytes with robust performance across leprosy phenotypes. We conclude that diagnostics with appropriate product design and performance characteristics are crucial for early detection and preventive intervention, advocating for the transition from leprosy management to prevention., ((c) 2024 The authors; licensee World Health Organization.)

Background: Suicide rates in the United States have increased recently among Black men. To address this public health crisis, smartphone-based ecological momentary assessment (EMA) platforms are a promising way to collect dynamic, real-time data that can help improve suicide prevention efforts. Despite the promise of this methodology, little is known about its suitability in detecting experiences related to suicidal thoughts and behavior (STB) among Black men., Objective: This study aims to clarify the acceptability and feasibility of using smartphone-based EMA through a pilot study that assesses the user experience among Black men., Methods: We recruited Black men aged 18 years and older using the MyChart patient portal messaging (the patient-facing side of the Epic electronic medical record system) or outpatient provider referrals. Eligible participants self-identified as Black men with a previous history of STB and ownership of an Android or iOS smartphone. Eligible participants completed a 7-day smartphone-based EMA study. They received a prompt 4 times per day to complete a brief survey detailing their STB, as well as proximal risk factors, such as depression, social isolation, and feeling like a burden to others. At the conclusion of each day, participants also received a daily diary survey detailing their sleep quality and their daily experiences of everyday discrimination. Participants completed a semistructured exit interview of 60-90 minutes at the study's conclusion., Results: In total, 10 participants completed 166 EMA surveys and 39 daily diary entries. A total of 4 of the 10 participants completed 75% (21/28) or more of the EMA surveys, while 9 (90%) out of 10 completed 25% (7/28) or more. The average completion rate of all surveys was 58% (20.3/35), with a minimum of 17% (6/35) and maximum of 100% (35/35). A total of 4 (40%) out of 10 participants completed daily diary entries for the full pilot study. No safety-related incidents were reported. On average, participants took 2.08 minutes to complete EMA prompts and 2.72 minutes for daily diary surveys. Our qualitative results generally affirm the acceptability and feasibility of the study procedures, but the participants noted difficulties with the technology and the redundancy of the survey questions. Emerging themes also addressed issues such as reduced EMA survey compliance and diminished mood related to deficit-framed questions related to suicide., Conclusions: Findings from this study will be used to clarify the suitability of EMA for Black men. Overall, our EMA pilot study demonstrated mixed feasibility and acceptability when delivered through smartphone-based apps to Black men. Specific recommendations are provided for managing safety within these study designs and for refinements in future intervention and implementation science research., International Registered Report Identifier (irrid): RR2-10.2196/31241., (©Leslie B Adams, Thomasina Watts, Aubrey DeVinney, Emily E Haroz, Johannes Thrul, Jasmin Brooks Stephens, Mia N Campbell, Denis Antoine, Benjamin Lê Cook, Sean Joe, Roland J Thorpe Jr. Originally published in JMIR Formative Research (https://formative.jmir.org), 22.01.2024.)

Genetic and environmental variation are key contributors during organism development, but the influence of minor perturbations or noise is difficult to assess. This study focuses on the stochastic variation in allele-specific expression that persists through cell divisions in the nine-banded armadillo (Dasypus novemcinctus). We investigated the blood transcriptome of five wild monozygotic quadruplets over time to explore the influence of developmental stochasticity on gene expression. We identify an enduring signal of autosomal allelic variability that distinguishes individuals within a quadruplet despite their genetic similarity. This stochastic allelic variation, akin to X-inactivation but broader, provides insight into non-genetic influences on phenotype. The presence of stochastically canalized allelic signatures represents a novel axis for characterizing organismal variability, complementing traditional approaches based on genetic and environmental factors. We also developed a model to explain the inconsistent penetrance associated with these stochastically canalized allelic expressions. By elucidating mechanisms underlying the persistence of allele-specific expression, we enhance understanding of development's role in shaping organismal diversity., (© 2023. The Author(s).)

Objective: Suicide among Black adolescent youth has steadily increased in recent years, yet few studies describe how facets of social identity shape suicidal thoughts and behaviors (STBs) during this critical stage of development. Ethnic identity represents an underexplored, yet important element of social identity among Black youth that may contribute to differential associations with STBs. This study examined the association between ethnic identity and self-reported suicidal ideation, planning, and attempts., Methods: Data were drawn from 1,170 African American ( n  = 810) and Caribbean Black ( n  = 368) adolescents aged 13-17 (Mean age = 15) that participated in the National Survey of American Life Adolescent supplement study., Results: Using latent profile analyses, three patterns of ethnic identity were identified: Undifferentiated, Low Ethnic Identification, and Alienated. Caribbean Black adolescents were more likely to be in the Low Ethnic Identification class relative to the Undifferentiated class. Adolescents in the Undifferentiated group reported higher proportions of suicidal ideation, planning, and attempts compared to the remaining latent profile groups., Conclusion: Findings demonstrate that ethnic identity is an important aspect of social identity that can influence STBs among Black adolescents. Considering increased suicide attempts and death rates among Black youth, findings underscore the importance of examining culturally relevant developmental processes that may shape suicidal beliefs and behaviors.

Despite widespread evidence that neighborhood conditions impact health, few studies apply theory to clarify the physical and social factors in communities that drive health outcomes. Latent class analysis (LCA) addresses such gaps by identifying distinct neighborhood typologies and the joint influence that neighborhood-level factors play in health promotion. In the current study, we conducted a theory-driven investigation to describe Maryland neighborhood typologies and examined differences in area-level self-rated poor mental and physical health across typologies. We conducted an LCA of Maryland census tracts (n = 1384) using 21 indicators of physical and social characteristics. We estimated differences in tract-level self-rated physical and mental health across neighborhood typologies using global Wald tests and pairwise comparisons. Five neighborhood classes emerged: Suburban Resourced (n = 410, 29.6%), Rural Resourced (n = 313, 22.6%), Urban Underserved (n = 283, 20.4%), Urban Transient (n = 226, 16.3%), Rural Health Shortage (n = 152, 11.0%). Prevalence of self-rated poor physical and mental health varied significantly (p < 0.0001) by neighborhood typology, with the Suburban Resourced neighborhood class demonstrating the lowest prevalence of poor health and the Urban Underserved neighborhoods demonstrating the poorest health. Our results highlight the complexity of defining "healthy" neighborhoods and areas of focus to mitigate community-level health disparities to achieve health equity., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Globally, suicide is a leading cause of death among adolescents, with the highest burden of suicide occurring in Africa. Despite this, little is known about the epidemiology of suicide among adolescents in West Africa. In this study, we explore suicidality among West African adolescents., Methods: Using pooled data from the Global School-Based Student Health Survey in four West African countries (Ghana, Benin, Liberia, and Sierra Leone), we investigated the prevalence of suicidal ideation and suicide attempt and examined associations with 15 covariates using univariate and multivariable logistic regression., Results: Overall, 18.6% of adolescents in the pooled sample (N = 9,726) had considered suicide, while 24.7% reported attempting suicide. Significant correlates of suicide attempt included older age (16+ years; odds ratio [OR]: 1.70, confidence interval [CI]: 1.09-2.63), difficulty sleeping due to worry (OR: 1.27, CI: 1.04-1.56), loneliness (OR: 1.65, CI: 1.39-1.96), truancy (OR: 1.38. CI: 1.05-1.82), being a target of bullying (OR: 1.53, CI: 1.26-1.85), getting physically attacked (OR: 1.73, CI: 1.42-2.11), physical fighting (OR: 1.47, CI: 1.21-1.79), current cigarette use (OR: 2.71, CI: 1.88-3.89), and initiation of drug use (OR: 2.19, CI: 1.71-2.81). Conversely, having close friends was associated with lower odds of suicide attempt (OR: 0.67, CI: 0.48-0.93). Several covariates were also significantly associated with suicidal ideation., Discussion: Suicidal ideation and attempts are highly prevalent among school-going adolescents in these West African countries. Multiple modifiable risk and protective factors were identified. Programs, interventions, and policies aimed at addressing these factors may play a significant role in preventing suicides in these countries., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To explore demographic predictors of Emergency Department (ED) utilization among youth with a history of suicidality (i.e., ideation or behaviors)., Methods: Electronic health records were extracted from 2017 to 2021 for 3094 8-22 year-old patients with a history of suicidality at an urban academic medical center ED in the Mid-Atlantic. Logistic regression analyses were used to assess for demographic predictors of ED utilization frequency, timing of subsequent visits, and reasons for subsequent visits over a 24-month follow-up period., Results: Black race (OR = 1.45, 95% CI = 1.11-1.92), Female sex (OR = 1.59, 95% CI = 1.26-2.03), and having Medicaid insurance (OR = 1.71, 95% CI = 1.37-2.14) were associated with increased utilization, while being under 18 was associated with lower utilization (<12: OR = 0.38, 95% CI = 0.26-0.56; 12-18: OR = 0.47, 95% CI = 0.35-0.63). These demographics were also associated with ED readmission within 90 days, while being under 18 was associated with a lower odds of readmission., Conclusions: Among patients with a history of suicidality, those who identify as Black, young adults, patients with Medicaid, and female patients were more likely to be frequent utilizers of the ED within the 2 years following their initial visit. This pattern may suggest inadequate health care access for these groups, and a need to develop better care coordination with an intersectional focus to facilitate utilization of other health services., (© 2023 American Association of Suicidology.)

Background: Depression is a global mental health challenge. We assessed the prevalence of depressive symptoms and their association with age, chronic conditions, and health status among middle-aged and elderly people in peri-urban Dar es Salaam, Tanzania., Methods: Depressive symptoms were measured in 2,220 adults aged over 40 years from two wards of Dar es Salaam using the ten-item version of the Center of Epidemiologic Studies Depression Scale (CES-D-10) and a cut-off score of 10 or higher. The associations of depressive symptoms with age, 13 common chronic conditions, multimorbidity, self-rated health and any limitation in six activities of daily living were examined in univariable and multivariable logistic regressions., Results: The estimated prevalence of depressive symptoms was 30.7% (95% CI 28.5-32.9). In univariable regressions, belonging to age groups 45-49 years (OR 1.35 [95% CI 1.04-1.75]) and over 70 years (OR 2.35 [95% CI 1.66-3.33]), chronic conditions, including ischemic heart disease (OR 3.43 [95% CI 2.64-4.46]), tuberculosis (OR 2.42 [95% CI 1.64-3.57]), signs of cognitive problems (OR 1.90 [95% CI 1.35-2.67]), stroke (OR 1.56 [95% CI 1.05-2.32]) and anemia (OR 1.32 [95% CI 1.01-1.71]) and limitations in activities of daily living (OR 1.35 [95% CI 1.07-1.70]) increased the odds of depressive symptoms. Reporting good or very good health was associated with lower odds of depressive symptoms (OR 0.48 [95% CI 0.35-0.66]). Ischemic heart disease and tuberculosis remained independent predictors of depressive symptoms in multivariable regressions., Conclusion: Depressive symptoms affected almost one in three people aged over 40 years. Their prevalence differed across age groups and was moderated by chronic conditions, health status and socioeconomic factors., Competing Interests: The authors declare that they have no competing interests., (© The Author(s) 2023.)

Despite a steady decrease in suicide rates in the United States, the rate among Black males has increased in recent decades. Moreover, suicide is now positioned as the third leading cause of death in this population, signaling a public health crisis. Enhancing the ability for future suicide prevention scholars to fully characterize and intervene on suicide risk factors is an emerging health equity priority, yet there is little empirical evidence to robustly investigate the alarming trends in Black male suicide. We present fundamental areas of expansion in suicide prevention research focused on establishing culturally responsive strategies to achieve mental health equity. Notably, we identify gaps in existing research and offer future recommendation to reduce suicide death among Black males. Our perspective aims to present important and innovative solutions for ensuring the inclusion of Black males in need of suicide prevention and intervention efforts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Adams and Thorpe.)

This is the life story of Dr. Lucy B. Rorke-Adams, who was raised in the rural Midwest of the United States by Armenian immigrant parents during the Depression. The youngest in a family of five girls, she was lovingly nurtured by her parents and sisters. She was encouraged to become educated in order to lead a worthwhile life and contribute to society. She chose medicine, specifically the specialty of pediatric neuropathology, and over her long career succeeded in advancing the field. In particular, she made major contributions to understanding childhood brain tumors, central nervous system (CNS) malformations, and pathophysiology of abusive CNS injury in infants and children.

The risk of developing cancer is correlated with body size and lifespan within species, but there is no correlation between cancer and either body size or lifespan between species indicating that large, long-lived species have evolved enhanced cancer protection mechanisms. Previously we showed that several large bodied Afrotherian lineages evolved reduced intrinsic cancer risk, particularly elephants and their extinct relatives ( Proboscideans ), coincident with pervasive duplication of tumor suppressor genes (Vazquez and Lynch, 2021). Unexpectedly, we also found that Xenarthrans (sloths, armadillos, and anteaters) evolved very low intrinsic cancer risk. Here, we show that: (1) several Xenarthran lineages independently evolved large bodies, long lifespans, and reduced intrinsic cancer risk; (2) the reduced cancer risk in the stem lineages of Xenarthra and Pilosa coincided with bursts of tumor suppressor gene duplications; (3) cells from sloths proliferate extremely slowly while Xenarthran cells induce apoptosis at very low doses of DNA damaging agents; and (4) the prevalence of cancer is extremely low Xenarthrans , and cancer is nearly absent from armadillos. These data implicate the duplication of tumor suppressor genes in the evolution of remarkably large body sizes and decreased cancer risk in Xenarthrans and suggest they are a remarkably cancer-resistant group of mammals., Competing Interests: JV, MP, BM, MK, LA, VL No competing interests declared

Background: Discrimination is experienced across demographic attributes (e.g., race and gender) and vantage points (e.g., personal and vicarious), yet few studies have classified these different experiences of discrimination within healthcare systems. Moreover, which discriminatory experiences have greater influence on patient-reported quality outcomes remains poorly understood. To address these gaps, we used latent class analysis (LCA) to identify typologies of past experiences with healthcare discrimination among adults with depression-who experience more frequent and stigmatizing healthcare interactions than the general population-and assess the relationship between class membership and current ratings of patient-reported quality outcomes., Methods: We surveyed a nationally representative sample of adults with depression (n = 803) to assess past experiences of discrimination by medical providers in terms of both the characteristics targeted for discrimination and whether healthcare discrimination was experienced personally or by friends and family members. We conducted an LCA to identify discrimination-exposure classes and a modified Poisson regression to identify associations between class membership and patient-reported quality outcomes (e.g., overall medical provider quality, respect, clear communication, and careful listening), while adjusting for covariates., Results: We identified four latent classes of healthcare discrimination: low discrimination (LD; referent class: 72.2% of total sample), vicarious linguistic discrimination (VL; 13.9%), elevated personal and vicarious racial discrimination (EPVR; 10.5%), and high racial/ethnic discrimination (HRE; 3.4%). Compared to those in the LD class, individuals in the EPVR class had higher rates of reporting their current medical provider's respect and careful listening skills as sometimes or never, (Respect aIRR: 1.90, 95% CI: 1.05-3.42; Listening aIRR: 2.18, 95% CI: 1.29-3.66). Those in the HRE class reported higher rates of reporting their medical provider's quality and communication as poor or fair and lower ratings of careful listening (Quality aIRR: 2.06, 95% CI: 1.08-3.93; Communication aIRR: 1.97, 95% CI: 1.00-3.63; Listening aIRR: 2.41, 95% CI: 1.27-4.59), compared to those in the LD class. Those in the VL class had higher rates of reporting that their medical provider never or sometimes respected or carefully listened to them (Respect aIRR: 2.12, 95% CI: 1.20-3.72; Listening aIRR:1.67, 95% CI:1.03-2.71) than those in, the LD class., Conclusions: Healthcare organizations committed to providing equitable patient care should establish more robust quality improvement approaches to prevent discrimination at the medical provider level as well as structures of accountability to reconcile previously embedded social inequities within the healthcare system., Competing Interests: Declaration of competing interests The authors declare that they have no competing interests for this study.

The Center for Epidemiological Studies Depression Scale (CES-D) is widely used to assess depressive symptoms in the general population. It lacks validation for widespread use within the American Indian population, however. To address this gap, we explored and confirmed the factor structure of the CES-D among a community sample of southeastern American Indian women. We analyzed data from a sample of 150 American Indian women ages 18-50 from a southeastern tribe who had complete responses on the CES-D as part of a larger cross-sectional, community-engaged study. We performed exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to assess the measure's validity. We examined EFA models ranging from one to five factors, with the four-factor structure yielding the best overall model fit (CFI = 1.00, TLI = 0.99, RMSEA = 0.03). Differences between the four-factor EFA-retained structure from our sample and Radloff's four-factor structure emerged. Only the interpersonal factor was common to both factor structures. Our study findings confirm the validity of the original four-factor structure of the CES-D for younger adult American Indian women in the southeast. Contrasting findings with the EFA-retained structure, however, provide a more nuanced interpretation of our results., (© 2022 Wiley Periodicals LLC.)

Objective: Little is known about the factors African American parents consider when seeking care for their child after emotional and behavioral difficulties emerge. This study aimed to examine factors associated with seeking professional care within 30 days after identifying a child's need (i.e., rapid care seeking) and with deferring care for ≥1 year., Methods: This cross-sectional study surveyed African American parents raising a child with emotional or developmental challenges (N=289). Logistic regression was used to examine associations of parent activation, medical mistrust, and care-seeking barriers with two outcomes: rapidly seeking care and deferring care seeking., Results: About 22% of parents rapidly sought care, and 49% deferred care for 1 year or longer. Parents were more likely to rapidly seek care if they had higher parent activation scores; lived with other adults with mental health challenges; or, contrary to the authors' hypothesis, mistrusted doctors. Parents were less likely to rapidly seek care if the challenge did not initially bother them much or if their health insurance would not cover the service. Parents were more likely to defer care if they feared involuntary hospitalization for their child or if their health insurance would not cover the service. Parents were less likely to defer care if they had at least some college education or lived with other adults with mental health challenges., Conclusions: Community-based pediatric and child welfare professionals should be informed about facilitators and barriers to mental health care seeking as part of efforts to develop interventions that support African American families.

Objectives: To assess the relationship between an Area Deprivation Index (ADI) and a Social Determinant of Health (SDoH) measure within a diverse sample. A prescreening tool based on routinely collected information could reduce clinical burden by identifying patients impacted by SDoH for comprehensive assessment., Study Design: In total, 499 consented pediatric patient-families who spoke English, Spanish, or Arabic and had a child ≤12 years receiving primary care at a large academic institution were enrolled. Participants completed the Health Leads Social Needs (HLSN) survey. Residential address was extracted from the electronic health record to calculate Brokamp ADI at the census-tract level. The main outcome was the correlations between the total HLSN score and Brokamp ADI, overall and in each language subgroup. ADI distributions were also compared between participants with/without need for each of the 8 HLSN survey SDoH domains, using 2-sample t-tests and Pearson χ 2 tests., Results: In total, 54.9% of participants were English-speaking, 30.9% were Spanish-speaking, and 14.2% were Arabic-speaking. Spearman correlations between Brokamp ADI and total HLSN score were overall (r s  = 0.15; P = .001), English (r s  = 0.12; P = .04), Spanish (r s  = 0.03; P = .7), and Arabic (r s  = 0.24; P = .04). SDoH domain analyses found significant ADI differences between those with/without need in housing instability, childcare, transportation, and health literacy., Conclusions: There were small but statistically significant associations between the Brokamp ADI and total HLSN score and SDoH domains of housing instability, childcare, transportation, and health literacy. These findings support testing the Brokamp ADI as a prescreening tool to help identify patients with social needs in an outpatient clinical setting., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Although many psychometric assessments are used extensively in population-based research to determine psychopathology, these tools have not been thoroughly validated or appropriately adapted for use in diverse populations. Indeed, depression measurement studies among American Indian and female populations are scarce, omitting key opportunities to tailor psychological measurement for this population. To build psychometric evidence of measures in this population, we used a procedural method to examine a standard psychological instrument-the Center for Epidemiological Studies Depression Scale (CES-D)-with a community sample of southeast American Indian women. Our results showed strong psychometric reliability of the 20-item CES-D. The "effort" item presented diminished validity, as demonstrated by a negative counter-intuitive item-to-total correlation (ITC) value. Dropping the "effort" item resulted in a 19-item scale with a better fit in the within-group examination of community-based American Indian women. Compared to the 20-item CES-D scale, the revised 19-item measure ("effort" item removed) resulted in minimal changes to women's depression categories. However, we did detect patterns in shifts such that the 19-item scale generally underestimated (i.e., placed women in a lower category) depressive symptoms compared to the 20-item scale. Depending on their study goals, researchers engaging in population-based research should carefully weigh the use of original scales that allow for consistency in reporting with refined scales that fit psychometrically. We present the outlined method as a tool that expands on current approaches in scale refinement, and aids researchers in making more informed decisions regarding refined scales with diverse populations.

Mycobacterium leprae infection of peripheral nerves and the subsequent nerve function impairment (NFI), especially in response to reactional episodes, are hallmarks of leprosy. Improved treatments for M. leprae -induced nerve injury are needed, as most if not all of the disability and stigma associated with leprosy arises from the direct or indirect effects of NFI. Nine-banded armadillos ( Dasypus novemcinctus ), like humans, exhibit the full clinical spectrum of leprosy and extensive involvement of the peripheral nerves. In this study, state-of-the-art technology was used to compare nerve function between uninfected and M. leprae -infected armadillos. Motor nerve conduction velocity (MNCV) and compound muscle action potential (cMAP), which measure changes in the rate of impulse conduction velocity and amplitude, revealed a progression of impairment that was directly correlated with the duration of M. leprae infection and enabled development of an objective nerve impairment scoring system. Ultrasonography accompanied by color Doppler imaging detected enlargement of the M. leprae -infected nerves and increased vascularity, possibly due to inflammation. Assessment of epidermal nerve fiber density (ENFD), which shows a length-dependent innervation in armadillos that is similar to humans, identified small fiber degeneration early after M. leprae infection. Staining for neuromuscular junction (NMJ) integrity, which is an indicator of signal transduction efficiency into skeletal muscle, discerned a markedly lower number and structural integrity of NMJ in M. leprae -infected armadillo footpads. These tools for assessing nerve injury were used to monitor the effects of intervention therapy. Two potential neuro-protective drugs, ethoxyquin (EQ) and 4-aminopyridine (4-AP), were tested for their ability to ameliorate peripheral nerve injury in M. leprae -infected armadillos. 4-AP treatment improved MNCV, cMAP, and EFND compared to untreated animals, while EQ had less effect. These results support the armadillo as a model for M. leprae -induced peripheral nerve injury that can provide insights toward the understanding of NFI progression and contribute to the preclinical investigation of the safety and efficacy of neuro-preventive and neuro-therapeutic interventions for leprosy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pena, Lahiri, Ebenezer, Wheat, Figarola, Truman and Adams.)

Despite well-documented evidence illustrating the relationship between discrimination and health, less is known about the influence of unfair treatment when receiving medical care. Moreover, our current knowledge of cross-national and racial variations in healthcare discrimination is limited in aging populations. This article addresses these gaps using two harmonized data sets of aging populations to clarify the relationship between healthcare discrimination and health in the United States and Brazil. We use nationally representative, harmonized data from the Health and Retirement Study in the United States and the Brazilian Longitudinal Study of Aging to examine and compare perceived discrimination in the healthcare setting and its relationship to self-rated health, depression diagnosis, and depressive symptoms across national contexts. Using Poisson regression models and population attributable risk percent estimates, we found that aging adults reporting healthcare discrimination were at higher risk of poor self-rated health, diagnosed depression, and depressive symptoms. Our results also suggest that reducing perceived healthcare discrimination may contribute to improved self-rated health and mental well-being in later life across racialized societies. In two comparative settings, we highlight the differential impact of healthcare discrimination on self-rated health and depression. We describe the implications of our study's findings for national public health strategies focused on eliminating discrimination in the healthcare setting, particularly among aging countries., Competing Interests: The authors declare that they have no competing interests for this study., (© 2022 The Authors.)

Leprosy is a granulomatous infection caused by infection with Mycobacterium leprae or M. lepromatosis. We evaluated skin biopsy and slit skin smear samples from 92 leprosy patients in Colombia by quantitative PCR. Five (5.4%) patients tested positive for M. lepromatosis, providing evidence of the presence of this pathogen in Colombia.

The treatment of leprosy is long and complex, benefiting from the development of sterilizing, rapidly-acting drugs. Reductive evolution made Mycobacterium leprae exquisitely sensitive to Telacebec, a phase 2 drug candidate for tuberculosis . The unprecedented potency of Telacebec against M. leprae warrants further validation in clinical trials.

Objective: Black young adults with serious mental illnesses (SMI) have low rates of employment and school completion. Racial disparities exist in the delivery of vocational services, with Black people less likely to be screened in, and if screened in less likely to receive job training. This qualitative exploratory study examined how Black young adults with SMI perceive the barriers and facilitators to achieving their vocational goals., Method: Our conceptual model for this study is the Social-Ecological Model (SEM), which contains four domains of analysis (intrapersonal, interpersonal, community, and societal), informed by Critical Race Theory (CRT). We completed semistructured, qualitative interviews with 28 Black young adults with SMI. We analyzed data using qualitative content and inductive analyses., Results: Numerous respondents were experiencing racial discrimination in their vocational pursuits and their lives overall, and expressed doubts about achieving vocational success in racially imbalanced environments. Facilitating their vocational growth was trusting relationships with nonjudgmental and understanding vocational counselors (VC) who provided supports reflecting client preferences. As college students, respondents benefited from the presence and accessibility of Black faculty and students. As employees, they valued workplace supervisors who provided direct support and feedback., Conclusions and Implications for Practice: Black young adults with SMI face high and racialized barriers to pursuing work and education at multiple socioecological levels. The field of psychiatric rehabilitation should prepare VCs to understand and address the needs and expressed preferences of Black young adults with SMI. Also called for is research, centered on and directed by Black communities, on the effectiveness of race-conscious vocational practices. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Mycobacterium leprae, the etiologic agent of leprosy, cannot be cultured on artificial media. This characteristic, coupled with its long generation time, presents a number of unique challenges to studying this pathogen. One of the difficulties facing both researchers and clinicians is the absence of a rapid test to measure the viability of M. leprae in clinical or experimental specimens. The lack of such a tool limits the understanding of M. leprae immunopathogenesis and makes determining the efficacy of drug treatments difficult. With this in mind, we developed a robust two-step molecular viability assay (MVA) that first enumerates the M. leprae in the tissue; then, this data is used to normalize bacterial RNA quantities for the second step, in which the expression of M. leprae esxA and hsp18 are measured. This assay is specific and sensitive enough to be used on most clinical samples. This protocol describes the steps required to extract DNA and RNA from M. leprae-infected tissue, enumerate M. leprae, and measure M. leprae viability based on the normalized expression of two M. leprae-specific genes (hsp18 and esxA). This protocol also outlines an optimal laboratory design and workflow for performing this assay. © 2022 The Leprosy Mission Nepal. Current Protocols published by Wiley Periodicals LLC. This article has been contributed to by US Government employees and their work is in the public domain in the USA. Basic Protocol 1: DNA and RNA P purification from M. leprae-infected tissue Basic Protocol 2: Enumeration of M. leprae by RLEP qPCR on the DNA fraction Basic Protocol 3: Calculation of M. leprae per tissue and normalization of RNA Basic Protocol 4: Reverse-transcription of normalized RNA to generate cDNA Basic Protocol 5: Determination of M. leprae viability using HSP18 and ESXA qPCR on the cDNA Support Protocol 1: M. leprae qPCR primer/probe stock preparation Support Protocol 2: Preparation of plasmid stocks and standard curves., (© 2022 The Leprosy Mission Nepal. Current Protocols published by Wiley Periodicals LLC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Mycobacterium leprae , the causative agent of leprosy, is an obligate intracellular pathogen primarily residing within host macrophages and Schwann cells. Whole genome sequencing predicts a highly degraded genome with approximately one third of the coding capacity resulting in the loss of many catabolic pathways. Therefore, it can be assumed that M. leprae obtains many of the necessary metabolites for intracellular survival and growth from the host cells. In this study, global transcriptomic analyses were done on freshly harvested M. leprae growing in athymic mouse footpads for five months (MFP5) and compared to those held in axenic medium for 48 (ML48) and 96 (ML96) hours. Results show that all of the genes and pseudogenes were transcribed under both in vivo and in vitro conditions. 24% and 33% of gene transcript levels were significantly altered in ML48 and ML96 respectively, compared to MFP5. Approximately 45% (39/86) of lipid metabolism genes were significantly downregulated in ML96 compared to MFP5, majority of which are in the β-oxidation pathway. Cholesterol oxidase, acyl-CoA dehydrogenase, and coenzyme F420-dependent oxidoreductase, were significantly upregulated in both ML48 and ML96 compared to MFP5. 30% of cell wall and cell processes functional category genes had altered gene transcription at 96hr compared to MFP5. 40% of 57 genes associated with mycobacterial virulence showed significantly altered transcript levels with 52% significantly downregulated in ML96, including most of the Pro-Glu/Pro-Pro-Glu genes. All 111 hypothetical protein genes with unknown function were expressed. Adenosine triphosphate (ATP) synthesis in M. leprae appears to be significantly downregulated under ex vivo conditions. This is the first study comparing M. leprae global gene expression during in vivo growth and ex vivo stationery phase in axenic medium confirming that during the growth phase in the footpads of experimentally infected mice, M. leprae is metabolically active and its primary source of energy production is probably lipids., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ojo, Williams, Adams and Lahiri.)

Importance: The prevalence of internalizing problems among US adolescents has risen in the past decade. The extent to which concerns about school violence or shootings are associated with risk of internalizing problems is unknown., Objective: To examine the prospective association of concern, worry, and stress related to school violence or shootings with internalizing problems and to examine sex and racial and ethnic differences in the magnitude of the associations., Design, Setting, and Participants: This longitudinal cohort study involved 3 surveys administered 6 months apart (fall of grade 11 [prebaseline]; spring of grade 11 [baseline]; and fall of grade 12 [follow-up]) from 2015 to 2016. Participants included 2263 students from 10 high schools in Los Angeles, California. Analyses were performed from April 29, 2020, to April 8, 2021., Exposures: Baseline self-reported level of concern, worry, and stress about shootings or violence at the student's school or other schools, each rated on 5-point scales (ranging from not at all [0] to extremely [4]) with a mean score calculated as a 3-item composite index rescaled into z-score standard deviation units., Main Outcomes and Measures: Surpassing clinically significant or borderline significant thresholds for major depressive disorder, generalized anxiety disorder, or panic disorder based on symptom ratings on the Revised Children's Anxiety and Depression Scale at 6-month follow-up., Results: Of the 2263 students included in the analyses (1250 [55.2%] girls; mean [SD] age, 16.5 [0.4] years), appreciable proportions reported being very or extremely concerned (850 0f 2226 [38.2%]), worried (703 of 2209 [31.8%]), or stressed (332 of 2183 [15.2%]) about shootings or violence at their school or other schools. After adjusting for prebaseline covariates, concerns about school violence or shootings were associated with clinically significant generalized anxiety symptoms (odds ratio [OR], 1.31; 95% CI, 1.15-1.50) and panic symptoms (OR, 1.18; 95% CI, 1.05-1.32), but not depressive symptoms (OR, 1.13; 95% CI, 0.99-1.30) at the 6-month follow-up. There was a significant association between concern with school violence or shootings and depressive symptoms for Black youth (OR, 3.15; 95% CI, 1.38-7.19) and non-Hispanic/Latinx White youth (OR, 1.62 [95% CI, 1.25-2.09]) but not for youth of other races and ethnicities (OR for Asian, 1.26 [95% CI, 0.86-1.85]; OR for Hispanic/Latinx, 0.94 [95% CI, 0.76-1.16]; OR for other, 0.93 [95% CI, 0.54-1.61]). Sex did not moderate these associations., Conclusions and Relevance: The findings of this study suggest that concern, worry, and stress related to school violence or shootings may be risk factors for internalizing problems among adolescents, with variation in the strength of the association by race/ethnicity.

Leprosy is a zoonosis in the southern United States involving humans and wild armadillos. The majority of patients presenting with zoonotic strains of Mycobacterium leprae note extensive outdoor activity but only rarely report any history of direct contact with wild armadillos. Whether M. leprae is transmitted to new vertebrate hosts through the environment independently or with the aid of other organisms, e.g., arthropod vectors, is a fundamental question in leprosy transmission. The objectives of this study were to assess the potential for ticks to transmit M. leprae and to test if viable M. leprae can be maintained in tick-derived cells. To evaluate tick transmission, nymphal Amblyomma maculatum ticks were injected with isolated M. leprae. Infection and transmission were assessed by qPCR. Ticks infected as nymphs harbored M. leprae through vertical transmission events (nymph to adult and adult to progeny); and, horizontal transmission of M. leprae to a vertebrate host was observed. Mycobacterium leprae DNA was detected in multiple tick life cycle stages. Likewise, freshly isolated M. leprae (Thai-53) was used to infect a tick-derived cell line, and enumeration and bacterial viability were assessed at individual time points for up to 49 days. Evaluations of the viability of long-term cultured M. leprae (Thai-53 and Br4923) were also assessed in a mouse model. Tick-derived cells were able to maintain viable M. leprae over the 49-day course of infection and M. leprae remained infectious within tick cells for at least 300 days. The results of this study suggest that ticks themselves might serve as a vector for the transmission of M. leprae and that tick cells are suitable for maintenance of viable M. leprae for an extended period of time., Competing Interests: RS participated in this study while working in the National Hansen’s Disease Program and is currently employed by Retrobiotech LLC., United States. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tongluan, Shelton, Collins, Ingraffia, McCormick, Pena, Sharma, Lahiri, Adams, Truman and Macaluso.)

In recent years, community health workers (CHWs) have emerged as key stakeholders in implementing community-based public health interventions in racially diverse contexts. Yet little is known about the extent to which CHW training curriculums influence intervention effectiveness in marginalized racial and ethnic minority communities. This review summarizes evidence on the relationship between CHW training curricula and intervention outcomes conducted among African American and Latinx populations. We conducted a literature search of intervention studies that focused on CHW public health interventions in African American and Latinx populations using PubMed, PsycINFO, ERIC, CINAHL, EMBASE, and Web of Science databases. Included studies were quantitative, qualitative, and mixed methods studies employed to conduct outcome (e.g., blood pressure and HbA1c) and process evaluations (e.g., knowledge and self-efficacy) of CHW-led interventions. Out of 3,295 articles from the database search, 36 articles met our inclusion criteria. Overall, the strength of evidence linking specific CHW training curricula components to primary intervention health outcomes was weak, and no studies directly linked outcomes to specific characteristics of CHW training. Studies that described training related to didactic sessions or classified as high intensity reported higher percentages of positive outcomes compared to other CHW training features. These findings suggest that CHW training may positively influence intervention effectiveness but additional research using more robust methodological approaches is needed to clarify these relationships.

Background: Despite cumulative socioeconomic disadvantage and risk factors, Black Americans have a lower prevalence of depression than whites. Given the emerging focus of depression as a public mental health crisis, culturally informed depression measures and scale development techniques are needed to better alleviate the mental health burden of socially marginalized populations. Yet, for Black men, race- and gender-related factors that position emotional vulnerability as a sign of weakness, may potentially mask the timely identification of mental health needs in this population. Thus, we address these gaps by employing a stakeholder-driven, community-engaged process for understanding Black men's depression experience., Methods: We use concept mapping, a structured mixed methods approach, to determine how stakeholders of Black men's health conceptualize their depressive symptoms. Thirty-six stakeholders participated in a three-phase concept mapping study conducted in 2018. Three separate stakeholder groups were engaged for this study, including Black men, Black women, and primary care providers., Results: Participants generated 68 characteristics of Black men's depression which were reflected within five conceptual clusters: (1) physical states; (2) emotional states; (3) diminished drive; (4) internal conflicts; (5) communication with others; and (6) social pressures. Using a content analysis approach, we found that items comprising the "social pressures" cluster were not reflected in any common depression scales., Conclusions: Findings from this study illustrate the similar and divergent pathways in which Black men express depressed mood. Furthermore, concept mapping results also yield a novel opportunity for culturally informed scale development in future research.

Leprosy is a chronic granulomatous infectious disease caused by the pathogen, Mycobacterium leprae, and the more recently discovered, M. lepromatosis. Described in 1873, M. leprae was among the first microorganisms to be proposed as a cause of a human infectious disease. As an obligate intracellular bacterium, it has still not thus far been reproducibly cultivated in axenic medium or cell cultures. Shepard's mouse footpad assay, therefore, was truly a breakthrough in leprosy research. The generation of immunosuppressed and genetically engineered mice, along with advances in molecular and cellular techniques, has since offered more tools for the study of the M. leprae-induced granuloma. While far from perfect, these new mouse models have provided insights into the immunoregulatory mechanisms responsible for the spectrum of this complex disease., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA. Immunological Reviews published by John Wiley & Sons Ltd.)

Background: Psychological responses to potentially traumatic events tend to be heterogeneous, with some individuals displaying resilience. Longitudinal associations between resilience and mental distress during the COVID-19 pandemic, however, are poorly understood. The objective of this study was to examine the association between resilience and trajectories of mental distress during the COVID-19 pandemic., Methods: Participants were 6,008 adults from the Understanding America Study, a probability-based Internet-panel representative of the US adult population. Baseline data were collected between March 10 and March 31, 2020, with nine follow-up waves conducted between April 1 and August 4. Mixed-effects logistic regression was used to examine the association between date and mental distress, stratified by resilience level (low, normal, or high)., Results: In contrast to the high resilience group, participants in the low and normal resilience groups experienced increases in mental distress in the early months of the pandemic (low: OR=2.94, 95% CI=1.93-4.46; normal: OR=1.91, 95% CI=1.55-2.35). Men, middle-aged and older adults, Black adults, and adults with a graduate degree were more likely to report high resilience, whereas adults living below the poverty line were less likely to report high resilience., Limitations: These associations should not be interpreted as causal, and resilience was measured at only one time-point., Conclusions: Trajectories of mental distress varied markedly by resilience level during the early months of the COVID-19 pandemic, with low-resilience adults reporting the largest increases in mental distress during this crisis. Activities that foster resilience should be included in broader strategies to support mental health throughout the pandemic., (Copyright © 2020. Published by Elsevier B.V.)

Background: The Center for Epidemiologic Studies-Depression (CES-D) scale is a widely used measure of depressive symptoms, but its construct validity has not been adequately assessed in sub-Saharan Africa. This study validates the CES-D among an aging Shangaan-speaking and predominantly Black African sample in rural South Africa, with a special emphasis on gender differences., Methods: An 8-item CES-D scale was administered in Shangaan to 5059 respondents, aged 40+ years, residing in Agincourt, South Africa. We used Cronbach's alpha and exploratory and confirmatory factor analysis to examine and confirm dimensionality of the CES-D scale. Differential endorsement of CES-D items by gender were assessed using the Mantel-Haenszel (MH) odds ratio test., Results: Reliability of the CES-D scale differed by gender with women reporting higher internal consistency on items than men. A two-factor solution was retained and confirmed representing two latent factors: (1) Negative Affect (six items) and (2) Diminished Positive Affect (two items). MH results showed that men exhibited significantly higher odds of putting an effort in everything that they did (OR: 1.33, 95% CI: 1.15-1.54) and lower odds of feeling depressed (OR: 0.71, 95% CI: 0.56-0.89) and having restless sleep (OR: 0.67, 95% CI:0.58-0.77) than women., Limitations: Analyses were limited to a dichotomous, short form of the CES-D, a self-reported population-based measure., Conclusion: Aging Black Africans differ in endorsing affective and somatic items on the CES-D scale by gender, which may lead to skewed population-level estimates of depression in key subpopulations. These findings highlight the importance of continued research disentangling cross-cultural and gendered nuances of depression measurements., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: 1) To describe activation skills of African American parents on behalf of their children with mental health needs. 2) To assess the association between parent activation skills and child mental health service use., Methods: Data obtained in 2010 and 2011 from African American parents in North Carolina raising a child with mental health needs (n = 325) were used to identify child mental health service use from a medical provider, counselor, therapist, or any of the above or if the child had ever been hospitalized. Logistic regression was used to model the association between parent activation and child mental health service use controlling for predisposing, enabling, and need characteristics of the family and child., Results: Mean parent activation was 65.5%. Over two-thirds (68%) of children had seen a medical provider, 45% had seen a therapist, and 36% had seen a counselor in the past year. A quarter (25%) had been hospitalized. A 10-unit increase in parent activation was associated with a 31% higher odds that a child had seen any outpatient provider for their mental health needs (odds ratio = 1.31, confidence interval = 1.03-1.67, p = 0.03). The association varied by type of provider. Parent activation was not associated with seeing a counselor or a therapist or with being hospitalized., Conclusion: African American families with activation skills are engaged and initiate child mental health service use. Findings provide a rationale for investing in the development and implementation of interventions that teach parent activation skills and facilitate their use by practices in order to help reduce disparities in child mental health service use., (Copyright © 2020 The Permanente Press. All rights reserved.)

Background: Mycobacterium leprae was thought to be the exclusive causative agent of leprosy until Mycobacterium lepromatosis was identified in a rare form of leprosy known as diffuse lepromatous leprosy (DLL)., Methods: We isolated M. lepromatosis from a patient with DLL and propagated it in athymic nude mouse footpads. Genomic analysis of this strain (NHDP-385) identified a unique repetitive element, RLPM, on which a specific real-time quantitative polymerase chain reaction assay was developed. The RLPM assay, and a previously developed RLEP quantitative polymerase chain reaction assay for M. leprae, were validated as clinical diagnostic assays according to Clinical Laboratory Improvement Amendments guidelines. We tested DNA from archived histological sections, patient specimens from the United States, Philippines, and Mexico, and US wild armadillos., Results: The limit of detection for the RLEP and RLPM assays is 30 M. leprae per specimen (0.76 bacilli per reaction; coefficient of variation, 0.65%-2.44%) and 122 M. lepromatosis per specimen (3.05 bacilli per reaction; 0.84%-2.9%), respectively. In histological sections (n = 10), 1 lepromatous leprosy (LL), 1 DLL, and 3 Lucio reactions contained M. lepromatosis; 2 LL and 2 Lucio reactions contained M. leprae; and 1 LL reaction contained both species. M. lepromatosis was detected in 3 of 218 US biopsy specimens (1.38%). All Philippines specimens (n = 180) were M. lepromatosis negative and M. leprae positive. Conversely, 15 of 47 Mexican specimens (31.91%) were positive for M. lepromatosis, 19 of 47 (40.43%) were positive for M. leprae, and 2 of 47 (4.26%) contained both organisms. All armadillos were M. lepromatosis negative., Conclusions: The RLPM and RLEP assays will aid healthcare providers in the clinical diagnosis and surveillance of leprosy., (© Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

As a part of a larger, mixed-methods research study, we conducted semi-structured interviews with 21 adults with depressive symptoms to understand the role that past health care discrimination plays in shaping help-seeking for depression treatment and receiving preferred treatment modalities. We recruited to achieve heterogeneity of racial/ethnic backgrounds and history of health care discrimination in our participant sample. Participants were Hispanic/Latino ( n = 4), non-Hispanic/Latino Black ( n = 8), or non-Hispanic/Latino White ( n = 9). Twelve reported health care discrimination due to race/ethnicity, language, perceived social class, and/or mental health diagnosis. Health care discrimination exacerbated barriers to initiating and continuing depression treatment among patients from diverse backgrounds or with stigmatized mental health conditions. Treatment preferences emerged as fluid and shaped by shared decisions made within a trustworthy patient-provider relationship. However, patients who had experienced health care discrimination faced greater challenges to forming trusting relationships with providers and thus engaging in shared decision-making processes.

Background: Subclinical infection with Mycobacterium leprae is one potential source of leprosy transmission, and post-exposure prophylaxis (PEP) regimens have been proposed to control this source. Because PEP trials require considerable investment, we applied a sensitive variation of the kinetic mouse footpad (MFP) screening assay to aid in the choice of drugs and regimens for clinical trials., Methodology/principal Findings: Athymic nude mice were inoculated in the footpad (FP) with 6 x 103 viable M. leprae and treated by gastric gavage with a single dose of Rifampin (SDR), Rifampin + Ofloxacin + Minocycline (SD-ROM), or Rifapentine + Minocycline + Moxifloxacin (SD-PMM) or with the proposed PEP++ regimen of three once-monthly doses of Rifampin + Moxifloxacin (RM), Rifampin + Clarithromycin (RC), Rifapentine + Moxifloxacin (PM), or Rifapentine + Clarithromycin (PC). At various times post-treatment, DNA was purified from the FP, and M. leprae were enumerated by RLEP quantitative PCR. A regression analysis was calculated to determine the expected RLEP value if 99.9% of the bacilli were killed after the administration of each regimen. SDR and SD-ROM induced little growth delay in this highly susceptible murine model of subclinical infection. In contrast, SD-PMM delayed measurable M. leprae growth above the inoculum by 8 months. The four multi-dose regimens delayed bacterial growth for >9months post-treatment cessation., Conclusions/significance: The delay in discernable M. leprae growth post-treatment was an excellent indicator of drug efficacy for both early (3-4 months) and late (8-9 months) drug efficacy. Our data indicates that multi-dose PEP may be required to control infection in highly susceptible individuals with subclinical leprosy to prevent disease and decrease transmission., Competing Interests: The authors have declared that no competing interests exist.

Far from being an equalizer, as some have claimed, the COVID-19 pandemic has exposed just how vulnerable many of our social, health, and political systems are in the face of major public health shocks. Rapid responses by health systems to meet increased demand for hospital beds while continuing to provide health services, largely via a shift to telehealth services, are critical adaptations. However, these actions are not sufficient to mitigate the impact of coronavirus for people from marginalized communities, particularly those with behavioral health conditions, who are experiencing disproportional health, economic, and social impacts from the evolving pandemic. Helping these communities weather this storm requires partnering with existing community-based organizations and local governments to rapidly and flexibly meet the needs of vulnerable populations., (© 2020 Policy Studies Organization.)

The persistence of new leprosy cases in endemic areas such as India, Brazil, Bangladesh, and the Philippines has encouraged studies of chemoprophylaxis among contacts of patients. Epidemiological screening tools to enable early detection of infected individuals in endemic populations would be critical to target individuals most in need of intervention. Despite decades of attempts, however, there still are no tests available for the early detection of low-level infection with Mycobacterium leprae. In this report, we describe the development of a leprosy skin test using M. leprae-specific antigens. We selected the chimeric LID-1 fusion protein, formulated to achieve maximum performance at a minimal dose, as a skin test candidate based on its ability to elicit delayed-type hypersensitivity (DTH) reactions in M. leprae immune guinea pigs in a sensitive and specific manner, i.e., with no cross-reactivity observed with other mycobacterial species. Importantly, evaluations in armadillos indicated that intradermal inoculation of formulated LID-1 could distinguish uninfected from M. leprae-infected animals manifesting with symptoms distinctly similar to the PB presentation of patients. Together, our data provide strong proof-of-concept for developing an antigen-specific skin test to detect low-level M. leprae infection. Such a test could, when applied with appropriate use of chemo- and/or immunoprophylaxis, be instrumental in altering the evolution of clinical disease and M. leprae transmission, thus furthering the objective of zero leprosy.

Mycobacteria are important causes of disease in human and animal hosts. Diseases caused by mycobacteria include leprosy, tuberculosis (TB), nontuberculous mycobacteria (NTM) infections and Buruli Ulcer. To better understand and treat mycobacterial disease, clinicians, veterinarians and scientists use a range of discipline-specific approaches to conduct basic and applied research, including conducting epidemiological surveys, patient studies, wildlife sampling, animal models, genetic studies and computational simulations. To foster the exchange of knowledge and collaboration across disciplines, the Many Hosts of Mycobacteria (MHM) conference series brings together clinical, veterinary and basic scientists who are dedicated to advancing mycobacterial disease research. Started in 2007, the MHM series recently held its 8th conference at the Albert Einstein College of Medicine (Bronx, NY). Here, we review the diseases discussed at MHM8 and summarize the presentations on research advances in leprosy, NTM and Buruli Ulcer, human and animal TB, mycobacterial disease comorbidities, mycobacterial genetics and 'omics, and animal models. A mouse models workshop, which was held immediately after MHM8, is also summarized. In addition to being a resource for those who were unable to attend MHM8, we anticipate this review will provide a benchmark to gauge the progress of future research concerning mycobacteria and their many hosts., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The Center for Epidemiologic Studies Depression (CES-D) scale is one of the most widely used measures for assessing depression in population-based research. Little is known about the varying range of symptomatology expressed by Black men, who report higher chronicity and disability of their depressive symptoms compared to men of other racial and ethnic backgrounds. This study assessed the dimensional structure of the CES-D 12-item scale using exploratory and confirmatory factor analysis in a community-based sample of Black men ( n = 683). Two latent factors emerged from the scale that best fit the data: interpersonal negative affect (INA) and diminished positive affect (DPA). The item "I felt like everything I did was an effort" was removed from the final measure, resulting in an 11-item scale. The total score for the revised CES-D-11 displayed acceptable internal consistency on both latent factors (Cronbach's α = 0.83 [INA] and 0.73 [DPA]) and model fit (χ 2 = 165.58, TLI = 0.967, CFI = 0.974, RMSEA = 0.065). Results differ from CES-D factor analyses in other demographic groups, including studies with other male subpopulations, such that depressed mood and interpersonal problems factors are merged as a unidimensional construct. Findings suggest that the "effort" item from the CES-D 12 should be interpreted with caution among Black men. Future studies should continue to disentangle the divergent pathways in which Black men express depressed mood.

Objectives: This study investigates whether quantitative image analysis of pretreatment CT scans can predict volumetric response to chemotherapy for patients with colorectal liver metastases (CRLM)., Methods: Patients treated with chemotherapy for CRLM (hepatic artery infusion (HAI) combined with systemic or systemic alone) were included in the study. Patients were imaged at baseline and approximately 8 weeks after treatment. Response was measured as the percentage change in tumour volume from baseline. Quantitative imaging features were derived from the index hepatic tumour on pretreatment CT, and features statistically significant on univariate analysis were included in a linear regression model to predict volumetric response. The regression model was constructed from 70% of data, while 30% were reserved for testing. Test data were input into the trained model. Model performance was evaluated with mean absolute prediction error (MAPE) and R 2 . Clinicopatholologic factors were assessed for correlation with response., Results: 157 patients were included, split into training (n = 110) and validation (n = 47) sets. MAPE from the multivariate linear regression model was 16.5% (R 2 = 0.774) and 21.5% in the training and validation sets, respectively. Stratified by HAI utilisation, MAPE in the validation set was 19.6% for HAI and 25.1% for systemic chemotherapy alone. Clinical factors associated with differences in median tumour response were treatment strategy, systemic chemotherapy regimen, age and KRAS mutation status (p < 0.05)., Conclusion: Quantitative imaging features extracted from pretreatment CT are promising predictors of volumetric response to chemotherapy in patients with CRLM. Pretreatment predictors of response have the potential to better select patients for specific therapies., Key Points: • Colorectal liver metastases (CRLM) are downsized with chemotherapy but predicting the patients that will respond to chemotherapy is currently not possible. • Heterogeneity and enhancement patterns of CRLM can be measured with quantitative imaging. • Prediction model constructed that predicts volumetric response with 20% error suggesting that quantitative imaging holds promise to better select patients for specific treatments.

Leprosy (Hansen's Disease) has occurred throughout human history, and persists today at a low prevalence in most populations. Caused by Mycobacterium leprae, the infection primarily involves the skin, mucosa and peripheral nerves. The susceptible host range for Mycobacterium leprae is quite narrow. Besides humans, nine banded armadillos (Dasypus novemcinctus) and red squirrels (Sciurus vulgaris) are the only other natural hosts for M. leprae, but only armadillos recapitulate the disease as seen in humans. Armadillos across the Southern United States harbor a single predominant genotypic strain (SNP Type-3I) of M. leprae, which is also implicated in the zoonotic transmission of leprosy. We investigated, whether the zoonotic strain (3I) has any notable growth advantages in armadillos over another genetically distant strain-type (SNP Type-4P) of M. leprae, and if M. leprae strains manifest any notably different pathology among armadillos. We co-infected armadillos (n = 6) with 2 × 10 9 highly viable M. leprae of both strains and assessed the relative growth and dissemination of each strain in the animals. We also analyzed 12 additional armadillos, 6 each individually infected with the same quantity of either strain. The infections were allowed to fulminate and the clinical manifestations of the disease were noted. Animals were humanely sacrificed at the terminal stage of infection and the number of bacilli per gram of liver, spleen and lymph node tissue were enumerated by Q-PCR assay. The growth of M. leprae strain 4P was significantly higher (P < 0.05) than 3I when each strain was propagated individually in armadillos. Significantly (P < 0.0001) higher growth of the 4P strain also was confirmed among animals co-infected with both 3I and 4P strain types using whole genome sequencing. Interestingly, the zoonotic strain does not exhibit any growth advantage in these non-human hosts, but the varied proliferation of the two M. leprae strains within armadillos suggest there are notable pathological variations between M. leprae strain-types., (Published by Elsevier B.V.)

Chromosome abnormalities detected during cytogenetic investigations for B-cell malignancy offer prognostic information that can have wide ranging clinical impacts on patients. These impacts may include monitoring frequency, treatment type, and disease staging level. The use of the synthetic oligonucleotide DSP30 combined with interleukin 2 (IL2) has been described as an effective mitotic stimulant in B-cell disorders, not only in chronic lymphocytic leukemia (CLL) but also in a range of other B-cell malignancies. Here, we describe the comparison of two B-cell mitogens, lipopolysaccharide (LPS), and DSP30 combined with IL2 as mitogens in a range of common B-cell disorders excluding CLL. The results showed that DSP30/IL2 was an effective mitogen in mature B-cell disorders, revealing abnormal cytogenetic results in a range of B-cell malignancies. The abnormality rate increased when compared to the use of LPS to 64% (DSP30/IL2) from 14% (LPS). In a number of cases the disease burden was proportionally very low, less than 10% of white cells. In 37% of these cases, the DSP30 culture revealed abnormal results. Importantly, we also obtained abnormal conventional cytogenetics results in 3 bone marrow cases in which immunophenotyping showed an absence of an abnormal B-cell clone. In these cases, the cytogenetics results correlated with the provisional diagnosis and altered their staging level. The use of DSP30 and IL2 is recommended for use in many B-cell malignancies as an effective mitogen and their use has been shown to enable successful culture of the malignant clone, even at very low levels of disease., (© 2018 Wiley Periodicals, Inc.)