Single-Cell RNA Sequencing of Sox17-Expressing Lineages Reveals Distinct Gene Regulatory Networks and Dynamic Developmental Trajectories.

During early embryogenesis, the transcription factor SOX17 contributes to hepato-pancreato-biliary system formation and vascular-hematopoietic emergence. To better understand Sox17 function in the developing endoderm and endothelium, we developed a dual-color temporal lineage-tracing strategy in mice combined with single-cell RNA sequencing to analyze 6934 cells from Sox17-expressing lineages at embryonic days 9.0-9.5. Our analyses showed 19 distinct cellular clusters combined from all 3 germ layers. Differential gene expression, trajectory and RNA-velocity analyses of endothelial cells revealed a heterogenous population of uncommitted and specialized endothelial subtypes, including 2 hemogenic populations that arise from different origins. Similarly, analyses of posterior foregut endoderm revealed subsets of hepatic, pancreatic, and biliary progenitors with overlapping developmental potency. Calculated gene-regulatory networks predict gene regulons that are dominated by cell type-specific transcription factors unique to each lineage. Vastly different Sox17 regulons found in endoderm versus endothelial cells support the differential interactions of SOX17 with other regulatory factors thereby enabling lineage-specific regulatory actions.

Stringent specificity in the construction of a GABAergic presynaptic inhibitory circuit.

GABAergic interneurons are key elements in neural coding, but the mechanisms that assemble inhibitory circuits remain unclear. In the spinal cord, the transfer of sensory signals to motor neurons is filtered by GABAergic interneurons that act presynaptically to inhibit sensory transmitter release and postsynaptically to inhibit motor neuron excitability. We show here that the connectivity and synaptic differentiation of GABAergic interneurons that mediate presynaptic inhibition is directed by their sensory targets. In the absence of sensory terminals these GABAergic neurons shun other available targets, fail to undergo presynaptic differentiation, and withdraw axons from the ventral spinal cord. A sensory-specific source of brain derived neurotrophic factor induces synaptic expression of the GABA synthetic enzyme GAD65--a defining biochemical feature of this set of interneurons. The organization of a GABAergic circuit that mediates presynaptic inhibition in the mammalian CNS is therefore controlled by a stringent program of sensory recognition and signaling.

The Noncanonical Role of ULK/ATG1 in ER-to-Golgi Trafficking Is Essential for Cellular Homeostasis.

ULK1 and ULK2 are thought to be essential for initiating autophagy, and Ulk1/2-deficient mice die perinatally of autophagy-related defects. Therefore, we used a conditional knockout approach to investigate the roles of ULK1/2 in the brain. Although the mice showed neuronal degeneration, the neurons showed no accumulation of P62(+)/ubiquitin(+) inclusions or abnormal membranous structures, which are observed in mice lacking other autophagy genes. Rather, neuronal death was associated with activation of the unfolded protein response (UPR) pathway. An unbiased proteomics approach identified SEC16A as an ULK1/2 interaction partner. ULK-mediated phosphorylation of SEC16A regulated the assembly of endoplasmic reticulum (ER) exit sites and ER-to-Golgi trafficking of specific cargo, and did not require other autophagy proteins (e.g., ATG13). The defect in ER-to-Golgi trafficking activated the UPR pathway in ULK-deficient cells; both processes were reversed upon expression of SEC16A with a phosphomimetic substitution. Thus, the regulation of ER-to-Golgi trafficking by ULK1/2 is essential for cellular homeostasis.

Platelet transfusions in adult ICU patients with thrombocytopenia: A sub-study of the PLOT-ICU inception cohort study.

BACKGROUND: Platelet transfusions are frequently used in the intensive care unit (ICU), but current practices including used product types, volumes, doses and effects are unknown. STUDY DESIGN AND METHODS: Sub-study of the inception cohort study 'Thrombocytopenia and Platelet Transfusions in the ICU (PLOT-ICU)', including acutely admitted, adult ICU patients with thrombocytopenia (platelet count <150 × 109/L). The primary outcome was the number of patients receiving platelet transfusion in ICU by product type. Secondary outcomes included platelet transfusion details, platelet increments, bleeding, other transfusions and mortality. RESULTS: Amongst 504 patients with thrombocytopenia from 43 hospitals in 10 countries in Europe and the United States, 20.8% received 565 platelet transfusions; 61.0% received pooled products, 21.9% received apheresis products and 17.1% received both with a median of 2 (interquartile range 1-4) days from admission to first transfusion. The median volume per transfusion was 253 mL (180-308 mL) and pooled products accounted for 59.1% of transfusions, however, this varied across countries. Most centres (73.8%) used fixed dosing (medians ranging from 2.0 to 3.5 × 1011 platelets/transfusion) whilst some (mainly in France) used weight-based dosing (ranging from 0.5 to 0.7 × 1011 platelets per 10 kg body weight). The median platelet count increment for a single prophylactic platelet transfusion was 2 (-1 to 8) × 109/L. Outcomes of patients with thrombocytopenia who did and did not receive platelet transfusions varied. CONCLUSIONS: Among acutely admitted, adult ICU patients with thrombocytopenia, 20.8% received platelet transfusions in ICU of whom most received pooled products, but considerable variation was observed in product type, volumes and doses across countries. Prophylactic platelet transfusions were associated with limited increases in platelet counts.

Opioid Misuse and Associated Health Risks among Adults on Probation and Parole: Prevalence and Correlates 2015-2020.

BACKGROUND: As state legislatures work to reduce prison populations and increase the use of community-based alternatives, limited knowledge exists about the service needs of those under criminal justice supervision in the community. Preliminary research indicates unusually high rates of disease, disability, and death. Health risks for this population include opioid misuse, a form of substance misuse that has reached epidemic proportions in the U.S. Evidence indicates this may be one of multiple epidemics this population experiences, complicating intervention. METHODS: Our study included 5154 individuals on probation or parole. Using 2015-2020 data from the National Survey of Drug Use and Health (NSDUH), we conducted a series of logistic regressions examining associations between opioid misuse and a range of health risks, controlling for sociodemographic variables and survey year. RESULTS: Approximately 17% of those on probation or parole indicated past-year opioid misuse, a rate 4 times higher than in the general population. Compared to those on probation and parole who did not misuse opioids, it was associated with higher odds of other health risk behaviors and mental health problems. For example, the odds of marijuana and cocaine use were 4-6 times higher and the odds of substance use disorder were 10 times higher. Similarly, the odds of experiencing major depressive episodes and serious psychological distress were 2-3 times higher. CONCLUSIONS: Our findings reveal a markedly high risk for opioid misuse within this population along with associated risks for behavioral and mental health problems. The complex treatment needs of this population require greater policy attention and further research.

Experiences of cultural stress among U.S. citizen migrants: A mixed method approach.

On September 20, 2017, Hurricane Maria made landfall in Puerto Rico, devastating the archipelago and forcing thousands of Puerto Ricans to migrate to the U.S. mainland. Guided by a cultural stress theory framework, the present mixed method study examined how various cultural stressors impact participants' daily interactions and mental health outcomes. A total of 319 adult Hurricane Maria survivors residing on the U.S. mainland participated in the study. A mixed method sequential explanatory design was used. First, we used latent profile analysis (LPA) and multinomial logistic regression to identify the varied cultural stress experiences that participants had. Then we used data from semistructured interviews to better understand the experiences of participants classified into the different LPA profiles. Four profiles were identified: "moderate cultural stress" (35%), "overall low" (29%), "high cultural stress" (26%), and "low language stress" (10%). Multinomial regression indicated that members of the moderate cultural stress, high cultural stress, and low language stress profiles all reported significantly higher depressive and anxiety symptoms compared to members of the overall low profile. Qualitative data exemplified the daily experiences of participants placed into each profile, demonstrating that participants have rich and varied experiences that can contribute to their mental health symptoms. The present study documents the contributions of hurricane trauma and cultural stress vis-à-vis current mental health symptoms. Clinicians working with Hurricane Maria survivors should be cognizant of and inquire about migration-related cultural stressors including discrimination, feelings of being unwelcomed, and difficulty communicating in the destination community's dominant language. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A construct validation of the perceived Negative Context of Reception Scale with Indian American youth.

OBJECTIVES: Crucial to the resettlement experiences of immigrants is the degree to which the receiving country accepts them and affords them social support and opportunities. Through the factor structure and incremental validity of scores generated by the Negative Context of Reception (NCR) Scale, in the present study, we examine Indian American youths' perception of their context of reception using a sample of youth residing in the United States. METHOD: Data came from a sample of 223 Indian American youth (aged 12-17) as part of a larger convergent mixed-methods project. Using confirmatory factor analysis, we examined the scale's validity and the relationship between perceived NCR and criterion-related factors such as perceived discrimination and depressive and anxiety symptoms. Interpretive Phenomenological Analysis was then used to analyze qualitative data from 11 of these Indian American youth. Qualitative data provided additional insights about NCR in this population. RESULTS: NCR scores evidenced strong psychometric properties among Indian American youth. Confirmatory factor models demonstrated good model fit. NCR yielded significant associations with perceived discrimination (r = .33, p < .001) and depressive symptoms (r = .25, p < .002). Two major themes (parental/family sacrifices and being treated differently from White peers) emerged from the qualitative data. CONCLUSIONS: Results validate NCR as a construct relevant to Indian American youth and associated with negative mental health symptoms such as anxiety and depression. Furthermore, these results underscore the importance of a welcoming and supportive environment for Indian American youths' well-being. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Interplay of premigration crisis exposure and postmigration cultural stress on depressive symptoms among Venezuelan crisis migrants in Colombia.

OBJECTIVES: A growing body of research points to a relationship between exposure to migration-related cultural stress and mental health problems. However, such research is often conducted with the tacit assumption that postmigration experiences are the primary-if not singular-driver of psychological distress. In the present study, we aim to extend the cultural-stress paradigm by examining the influences of both premigration crisis exposure and postmigration cultural stress on depression in a sample of Venezuelan crisis migrants in Colombia. METHOD: Survey data for the present study were collected from Venezuelan youth (N = 429, ages 12-17, Mage = 14.0 years, 49% female) and adults (N = 566, ages 18+, Mage = 35.1 years, 82% female) in Bogota and Medellin, Colombia between April and June 2023. RESULTS: Both crisis exposure and discrimination were independently related to depressive symptoms. However, when examined in a multivariate model along with discrimination, crisis exposure was not a significant predictor of depressive symptoms among youth, and its influence weakened considerably among adults. Among both youth and adults, a Crisis Exposure × Discrimination interaction term significantly predicted depressive symptoms, indicating that discrimination was a more robust predictor of depressive symptoms among those endorsing lower levels of crisis exposure than among those reporting high levels of crisis exposure. CONCLUSION: Our research provides new insights into the experiences of Venezuelan migrant youth and adults in Colombia. It provides further support for the importance of drawing from a crisis-informed cultural-stress framework when working with crisis migrant populations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Precommitment low-level Neurog3 expression defines a long-lived mitotic endocrine-biased progenitor pool that drives production of endocrine-committed cells.

The current model for endocrine cell specification in the pancreas invokes high-level production of the transcription factor Neurogenin 3 (Neurog3) in Sox9(+) bipotent epithelial cells as the trigger for endocrine commitment, cell cycle exit, and rapid delamination toward proto-islet clusters. This model posits a transient Neurog3 expression state and short epithelial residence period. We show, however, that a Neurog3(TA.LO) cell population, defined as Neurog3 transcriptionally active and Sox9(+) and often containing nonimmunodetectable Neurog3 protein, has a relatively high mitotic index and prolonged epithelial residency. We propose that this endocrine-biased mitotic progenitor state is functionally separated from a pro-ductal pool and endows them with long-term capacity to make endocrine fate-directed progeny. A novel BAC transgenic Neurog3 reporter detected two types of mitotic behavior in Sox9(+) Neurog3(TA.LO) progenitors, associated with progenitor pool maintenance or derivation of endocrine-committed Neurog3(HI) cells, respectively. Moreover, limiting Neurog3 expression dramatically increased the proportional representation of Sox9(+) Neurog3(TA.LO) progenitors, with a doubling of its mitotic index relative to normal Neurog3 expression, suggesting that low Neurog3 expression is a defining feature of this cycling endocrine-biased state. We propose that Sox9(+) Neurog3(TA.LO) endocrine-biased progenitors feed production of Neurog3(HI) endocrine-committed cells during pancreas organogenesis.

PDX1 dynamically regulates pancreatic ductal adenocarcinoma initiation and maintenance.

Aberrant activation of embryonic signaling pathways is frequent in pancreatic ductal adenocarcinoma (PDA), making developmental regulators therapeutically attractive. Here we demonstrate diverse functions for pancreatic and duodenal homeobox 1 (PDX1), a transcription factor indispensable for pancreas development, in the progression from normal exocrine cells to metastatic PDA. We identify a critical role for PDX1 in maintaining acinar cell identity, thus resisting the formation of pancreatic intraepithelial neoplasia (PanIN)-derived PDA. Upon neoplastic transformation, the role of PDX1 changes from tumor-suppressive to oncogenic. Interestingly, subsets of malignant cells lose PDX1 expression while undergoing epithelial-to-mesenchymal transition (EMT), and PDX1 loss is associated with poor outcome. This stage-specific functionality arises from profound shifts in PDX1 chromatin occupancy from acinar cells to PDA. In summary, we report distinct roles of PDX1 at different stages of PDA, suggesting that therapeutic approaches against this potential target need to account for its changing functions at different stages of carcinogenesis. These findings provide insight into the complexity of PDA pathogenesis and advocate a rigorous investigation of therapeutically tractable targets at distinct phases of PDA development and progression.

The impact of cultural stress on family functioning among Puerto Rican displaced families and the effect on mental health.

Hurricane María caused significant devastation on the island of Puerto Rico, impacting thousands of lives. Puerto Rican crisis migrant families faced stress related to displacement and relocation (cultural stress), often exhibited mental health symptoms, and experienced distress at the family level. Although cultural stress has been examined as an individual experience, little work has focused on the experience as a family. To address this gap, we conducted a mixed-methods study designed to examine the predictive effects of cultural stress on family conflict and its mental health implications among Puerto Rican Hurricane María parent and child dyads living on the U.S. mainland. In the quantitative phase of the study, 110 parent-child dyads completed an online survey assessing cultural stress, family dynamics, and mental health. As part of our primary analysis, we estimated a structural equation path model. Findings from the quantitative phase showed a significant positive relationship between family cultural stress and family conflict, as well as individual parent and child mental health symptoms. In the qualitative phase of the study, 35 parent-child dyads participated in individual interviews. Findings from the interviews revealed variations in difficulties related to language, discrimination, and financial burdens, with some participants adapting more quickly and experiencing fewer stressors. Findings also highlight the impact on mental health for both parents and youth, emphasizing the family-level nature of cultural stress, while noting a potential discrepancy between qualitative and quantitative findings in the discussion of family conflict.

Muscle in the caterpillar Manduca sexta responds to an immune challenge, but at a cost, suggesting a physiological trade-off.

Although skeletal muscle is a specialized tissue that provides the motor for movement, it also participates in other functions, including the immune response. However, little is known about the effects of this multitasking on muscle. We show that muscle loses some of its capacity while it is participating in the immune response. Caterpillars (Manduca sexta) were exposed to an immune challenge, predator stress or a combination of immune challenge and predator stress. The expression of immune genes (toll-1, domeless, cactus, tube and attacin) increased in body wall muscle after exposure to an immune challenge. Muscle also showed a reduction in the amount of the energy storage molecule glycogen. During an immune challenge, the force of the defensive strike, an important anti-predator behaviour in M. sexta, was reduced. Caterpillars were also less able to defend themselves against a common enemy, the wasp Cotesia congregata, suggesting that the effect on muscle is biologically significant. Our results support the concept of an integrated defence system in which life-threatening events activate organism-wide responses. We suggest that increased mortality from predation is a non-immunological cost of infection in M. sexta. Our study also suggests that one reason non-immunological costs of infection exist is because of the participation of diverse organs, such as muscle, in immunity.

Toward a typology of driving under the influence of alcohol and drugs.

PURPOSE: Most research on driving under the influence (DUI) has relied upon variable-centered methods that examine predictors/correlates of DUI. In the present study, we utilize a person-level approach-latent class analysis (LCA)-to model a typology of individuals reporting DUI. This allows us to understand the degree to which individuals drive under the influence of a particular substance or do so across multiple substance types. METHODS: We use public-use data collected between 2016 and 2019 from the National Survey on Drug Use and Health. The analytic sample was 189,472 participants with a focus on those reporting DUI of psychoactive substances in the past-year (n = 24,619). LCA was conducted using self-reported DUI of past-year alcohol, cannabis, cocaine, heroin, hallucinogens, and methamphetamine as indicator variables. RESULTS: More than 1 in 10 Americans reported a DUI within the past-year. One in five people who reported DUI of one substance also reported DUI of at least one additional substance. Using LCA to model heterogeneity among individuals reporting DUI, four classes emerged: "Alcohol Only" (55%), "Cannabis and Alcohol" (36%), "Polydrug" (5%), and "Methamphetamine" (3%). Rates of risk propensity, drug involvement, illicit drug use disorders, and criminal justice system involvement were highest among members of the "Polydrug" and "Methamphetamine" classes. CONCLUSION: Drug treatment centers should take care to include discussions of the dangers and decision-making processes related to DUI of the full spectrum of illicit substances. Greater investment in drug treatment across the service continuum, including the justice system, could prevent/reduce future DUI episodes.

Alcohol Use Severity among Hispanic Emerging Adults: Examining Intragroup Marginalization, Bicultural Self-Efficacy, and the Role of Gender within a Stress and Coping Framework.

Most research on cultural stressors and alcohol has focused on intercultural stressors. Continuing to exclude intracultural stressors (e.g., intragroup marginalization) from alcohol research will yield a biased understanding of the experiences of Hispanics living in a bicultural society. As we amass more studies on intracultural stressors, research will be needed to identify mutable sociocultural factors that may mitigate the association between intracultural stressors and alcohol. To address these limitations, we examined the association between intragroup marginalization and alcohol use severity and the extent to which gender and bicultural self-efficacy may moderate this association. A convenience sample of 200 Hispanic emerging adults ages 18-25 (men = 101, women = 99) from Arizona (n = 99) and Florida (n = 101) completed a cross-sectional survey. Data were analyzed using hierarchical multiple regression and moderation analyses. Higher intragroup marginalization was associated with higher alcohol use severity. Gender functioned as a moderator whereby intragroup marginalization was associated with higher alcohol use severity among men, but not women. Also, higher social groundedness functioned as a moderator that weakened the association between intragroup marginalization and alcohol use severity. Role repertoire did not function as a moderator. Our findings are significant because they enhance the reliability of the association between intragroup marginalization and alcohol use severity, and the moderating effect of gender in this respective association. This emerging line of research suggests that alcohol interventions targeting Hispanics may have a significant limitation by not accounting for intracultural stressors.

The impact of hurricane trauma and cultural stress on posttraumatic stress among hurricane Maria survivors relocated to the U.S. mainland.

OBJECTIVES: Following Hurricane Maria, scores of Puerto Rican "Maria migrants" fled the island with thousands permanently resettling on the United States (U.S.) mainland. Emerging evidence suggests that many Maria migrants are exposed to migration-related cultural stressors, including discrimination, negative context of reception, and language stress. The present study examines the associations of premigration hurricane trauma and postmigration cultural stress with posttraumatic stress disorder (PTSD) symptom severity and positive PTSD screens. METHOD: Participants were 319 adult (age 18+, 71% female) Puerto Rican Hurricane Maria survivors on the U.S. mainland. Data were collected virtually between August 2020 and October 2021. Participants completed Spanish-language measures of hurricane-related trauma, postmigration cultural stress exposure, PTSD symptoms, and positive screens. RESULTS: One in five (20.5%) Maria migrants reported PTSD scores in the range indicating a likely PTSD diagnosis (i.e., positive screen of 50+). Both hurricane trauma and migration-related cultural stressors independently predicted posttraumatic stress and positive PTSD screens. Additionally, controlling for the effect of hurricane trauma, discrimination and language stress were strongly linked with PTSD. Further, hurricane trauma and cultural stressors interact such that cultural stress predicts PTSD-positive screens at low-to-moderate levels of hurricane trauma exposure but not at high-to-very-high levels. CONCLUSION: Findings underscore the importance of providing mental health and other psychosocial supports to hurricane survivors and evacuees beyond the immediate aftermath of the disaster, and the need to consider both premigration trauma and postmigration experiences in terms of the mental health of crisis migrant populations. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Feedback control of growth, differentiation, and morphogenesis of pancreatic endocrine progenitors in an epithelial plexus niche.

In the mammalian pancreas, endocrine cells undergo lineage allocation upon emergence from a bipotent duct/endocrine progenitor pool, which resides in the "trunk epithelium." Major questions remain regarding how niche environments are organized within this epithelium to coordinate endocrine differentiation with programs of epithelial growth, maturation, and morphogenesis. We used EdU pulse-chase and tissue-reconstruction approaches to analyze how endocrine progenitors and their differentiating progeny are assembled within the trunk as it undergoes remodeling from an irregular plexus of tubules to form the eventual mature, branched ductal arbor. The bulk of endocrine progenitors is maintained in an epithelial "plexus state," which is a transient intermediate during epithelial maturation within which endocrine cell differentiation is continually robust and surprisingly long-lived. Within the plexus, local feedback effects derived from the differentiating and delaminating endocrine cells nonautonomously regulate the flux of endocrine cell birth as well as proliferative growth of the bipotent cell population using Notch-dependent and Notch-independent influences, respectively. These feedback effects in turn maintain the plexus state to ensure prolonged allocation of endocrine cells late into gestation. These findings begin to define a niche-like environment guiding the genesis of the endocrine pancreas and advance current models for how differentiation is coordinated with the growth and morphogenesis of the developing pancreatic epithelium.

The importance of acculturation orientation in understanding the impact of pre- and post-migration stressors on behavioral health: Evidence from a crisis migrant sample.

OBJECTIVE: We examine the interplay of acculturation orientation, cultural stress, and hurricane trauma exposure with behavioral health among Puerto Rican crisis migrants who relocated to the US mainland after Hurricane Maria. METHOD: Participants were 319 adult (Mage = 39 years; 71% female; 90% arriving in 2017-2018) Hurricane Maria survivors surveyed on the US mainland. Latent profile analysis was used to model acculturation subtypes. In turn, ordinary least squares regression was executed to examine the associations of cultural stress and hurricane trauma exposure with behavioral health while stratifying by acculturation subtype. RESULTS: Five acculturation orientation subtypes were modeled, three of which-Separated (24%), Marginalized (13%), and Full Bicultural (14%)-align closely with prior theorizing. We also identified Partially Bicultural (21%) and Moderate (28%) subtypes. Stratifying by acculturation subtype, with behavioral health (depression/anxiety symptoms) specified as the dependent variable, hurricane trauma and cultural stress accounted for only 4% of explained variance in the Moderate class, a somewhat greater percentage in the Partial Bicultural (12%) and Separated (15%) classes, and substantially greater amounts of variance in the Marginalized (25%) and Full Bicultural (56%) classes. CONCLUSION: Findings underscore the importance of accounting for acculturation in understanding the relationship between stress and behavioral health among climate migrants.

Perceptions of and barriers to cancer screening by the sexual and gender minority community: a glimpse into the health care disparity.

PURPOSE: A disparity exists in cancer screening rates for the Sexual and Gender Minority (SGM) community. We sought to understand the perceptions and baseline knowledge of cancer screening among SGM community members. METHODS: Survey administered via social media from June 2018 to October 2018. We asked 31 questions focused on cancer screening, human papillomavirus, emotional distress, and experience with the health care system. Those included were 18 years or older. Cancer screening attitudes and knowledge, as well as perceptions of the health care system were investigated. RESULTS: There were 422 respondents analyzed: 24.6% identified as female, 25.5% as male, 40.1% transgender, and 9.6% as other. 65.4% of the SGM community is not certain what cancer screening to do for themselves. Only 27.3% and 55.7% knew that HPV was a risk factor associated with head and neck cancer and anal cancer, respectively. Half stated their emotional distress prevents them from getting cancer screening. It was identified that process changes in making appointments, comforts during the visit, and formal training for physicians and nurses could increase cancer screening compliance for this community. The transgender population had a trend in more gaps in knowledge of appropriate cancer screening and significant excess emotional distress. CONCLUSION: Gaps in cancer screening knowledge and emotional and financial distress may be responsible for the disparity of lower cancer screening rates for the SGM population and the transgender population may be most at risk. Appreciating the cancer screening concerns of the SGM population can help shape future clinical and institutional approaches to improve health care delivery.

Stage I-II nodular lymphocyte-predominant Hodgkin lymphoma: a multi-institutional study of adult patients by ILROG.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon histologic variant, and the optimal treatment of stage I-II NLPHL is undefined. We conducted a multicenter retrospective study including patients ≥16 years of age with stage I-II NLPHL diagnosed from 1995 through 2018 who underwent all forms of management, including radiotherapy (RT), combined modality therapy (CMT; RT+chemotherapy [CT]), CT, observation after excision, rituximab and RT, and single-agent rituximab. End points were progression-free survival (PFS), freedom from transformation, and overall survival (OS) without statistical comparison between management groups. We identified 559 patients with median age of 39 years: 72.3% were men, and 54.9% had stage I disease. Median follow-up was 5.5 years (interquartile range, 3.1-10.1). Five-year PFS and OS in the entire cohort were 87.1% and 98.3%, respectively. Primary management was RT alone (n = 257; 46.0%), CMT (n = 184; 32.9%), CT alone (n = 47; 8.4%), observation (n = 37; 6.6%), rituximab and RT (n = 19; 3.4%), and rituximab alone (n = 15; 2.7%). The 5-year PFS rates were 91.1% after RT, 90.5% after CMT, 77.8% after CT, 73.5% after observation, 80.8% after rituximab and RT, and 38.5% after rituximab alone. In the RT cohort, but not the CMT cohort, variant immunoarchitectural pattern and number of sites >2 were associated with worse PFS (P < .05). Overall, 21 patients (3.8%) developed large-cell transformation, with a significantly higher transformation rate in those with variant immunoarchitectural pattern (P = .049) and number of involved sites >2 (P = .0006). OS for patients with stage I-II NLPHL was excellent after all treatments.

Trends and distinct profiles of persons who inject drugs in the United States, 2015-2019.

Drug injection represents a major health problem in the US, with severe health consequences including the transmission of blood-borne infections. An examination of the most recent trends in drug injection is warranted by the fast-evolving drug epidemic and recent policy changes such as the federal funding ban on needle exchange programs. This research examines current drug injection trends, patterns, and socioeconomic and behavioral profiles of people who inject drugs (PWID). Data were derived from the 2002 to 2019 National Survey on Drug Use and Health (NSDUH). After examining the annual prevalence of drug injection since 2002, a latent class analysis was conducted to identify drug injection and other substance misuse patterns among PWID using the latest (2015-2019) NSDUH datasets. Associations between class membership and behavioral health comorbidities and treatment receipt were also assessed. The drug injection prevalence among US adults aged 18-64 increased from 0.21% in 2002/2004 to 0.36% in 2017/2019. Three distinctive groups were identified: the heroin injection group (45.2%), the methamphetamine injection group (28.0%), and the multi-drug injection group (26.8%). The methamphetamine injection group reported greater risks of experiencing serious psychological distress, suicidality, and limited substance use treatment. Special attention is needed for those who primarily injected methamphetamine. Programs to promote harm reduction and increase access to addiction treatment need to be expanded in at-risk communities while accounting for their distinct socioeconomic and drug use/misuse profiles.