Efficacy of life goals collaborative care for bipolar disorder: A systematic review.

BACKGROUND: Bipolar disorder remains a disabling mental health condition despite the availability of effective treatments. Collaborative chronic care models (CCMs) represent an evidence-based way to structure care for conditions like bipolar disorder. Life Goals Collaborative Care (LGCC) was designed specifically for bipolar disorder, featuring psychoeducation alongside collaborative components (e.g. nurse care management or expert psychiatric consultation). Despite the use of Life Goals across health systems, a systematic review summarizing its effectiveness has never been conducted. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) of LGCC through December 2023 to help guide the field in treating bipolar disorder (PROSPERO: #404581). We evaluated study quality and outcomes in several symptom and quality of life domains. RESULTS: Ten articles describing eight studies met inclusion criteria. All studies featured group-based LGCC; most were compared to treatment as usual (TAU). Three of eight studies found LGCC to be associated with statistically significant effects for the prevention of manic episodes. Most studies finding positive effects featured additional collaborative care components beyond psychoeducation and were conducted in capitated healthcare systems. LIMITATIONS: Limitations include: several types of potential bias in included studies; exclusion of observational studies of LGCC; lack of generalizability to pediatric populations; insufficient studies to conduct subgroup analyses; and low confidence in the quality of the evidence. CONCLUSIONS: In this systematic review, group-based LGCC demonstrated some positive effects for reducing mania recurrence; results for other outcome domains were equivocal. Future studies should investigate one-on-one LGCC, both in person and virtually, to enhance well-being for people with bipolar disorder.

Generation of human alveolar epithelial type I cells from pluripotent stem cells.

Alveolar epithelial type I cells (AT1s) line the gas exchange barrier of the distal lung and have been historically challenging to isolate or maintain in cell culture. Here, we engineer a human in vitro AT1 model system via directed differentiation of induced pluripotent stem cells (iPSCs). We use primary adult AT1 global transcriptomes to suggest benchmarks and pathways, such as Hippo-LATS-YAP/TAZ signaling, enriched in these cells. Next, we generate iPSC-derived alveolar epithelial type II cells (AT2s) and find that nuclear YAP signaling is sufficient to promote a broad transcriptomic shift from AT2 to AT1 gene programs. The resulting cells express a molecular, morphologic, and functional phenotype reminiscent of human AT1 cells, including the capacity to form a flat epithelial barrier producing characteristic extracellular matrix molecules and secreted ligands. Our results provide an in vitro model of human alveolar epithelial differentiation and a potential source of human AT1s.

Generation of human alveolar epithelial type I cells from pluripotent stem cells.

In the distal lung, alveolar epithelial type I cells (AT1s) comprise the vast majority of alveolar surface area and are uniquely flattened to allow the diffusion of oxygen into the capillaries. This structure along with a quiescent, terminally differentiated phenotype has made AT1s particularly challenging to isolate or maintain in cell culture. As a result, there is a lack of established models for the study of human AT1 biology, and in contrast to alveolar epithelial type II cells (AT2s), little is known about the mechanisms regulating their differentiation. Here we engineer a human in vitro AT1 model system through the directed differentiation of induced pluripotent stem cells (iPSC). We first define the global transcriptomes of primary adult human AT1s, suggesting gene-set benchmarks and pathways, such as Hippo-LATS-YAP/TAZ signaling, that are enriched in these cells. Next, we generate iPSC-derived AT2s (iAT2s) and find that activating nuclear YAP signaling is sufficient to promote a broad transcriptomic shift from AT2 to AT1 gene programs. The resulting cells express a molecular, morphologic, and functional phenotype reminiscent of human AT1 cells, including the capacity to form a flat epithelial barrier which produces characteristic extracellular matrix molecules and secreted ligands. Our results indicate a role for Hippo-LATS-YAP signaling in the differentiation of human AT1s and demonstrate the generation of viable AT1-like cells from iAT2s, providing an in vitro model of human alveolar epithelial differentiation and a potential source of human AT1s that until now have been challenging to viably obtain from patients.

Culture impact on the transcriptomic programs of primary and iPSC-derived human alveolar type 2 cells.

Dysfunction of alveolar epithelial type 2 cells (AEC2s), the facultative progenitors of lung alveoli, is implicated in pulmonary disease pathogenesis, highlighting the importance of human in vitro models. However, AEC2-like cells in culture have yet to be directly compared to their in vivo counterparts at single-cell resolution. Here, we performed head-to-head comparisons among the transcriptomes of primary (1°) adult human AEC2s, their cultured progeny, and human induced pluripotent stem cell-derived AEC2s (iAEC2s). We found each population occupied a distinct transcriptomic space with cultured AEC2s (1° and iAEC2s) exhibiting similarities to and differences from freshly purified 1° cells. Across each cell type, we found an inverse relationship between proliferative and maturation states, with preculture 1° AEC2s being most quiescent/mature and iAEC2s being most proliferative/least mature. Cultures of either type of human AEC2s did not generate detectable alveolar type 1 cells in these defined conditions; however, a subset of iAEC2s cocultured with fibroblasts acquired a transitional cell state described in mice and humans to arise during fibrosis or following injury. Hence, we provide direct comparisons of the transcriptomic programs of 1° and engineered AEC2s, 2 in vitro models that can be harnessed to study human lung health and disease.

Generating 3D Spheres and 2D Air-Liquid Interface Cultures of Human Induced Pluripotent Stem Cell-Derived Type 2 Alveolar Epithelial Cells.

In the lung, the alveolar epithelium is a physical barrier from environmental stimuli and plays an essential role in homeostasis and disease. Type 2 alveolar epithelial cells (AT2s) are the facultative progenitors of the distal lung epithelium. Dysfunction and injury of AT2s can result from and contribute to various lung diseases. Improved understanding of AT2 biology is, thus, critical for understanding lung biology and disease; however, primary human AT2s are generally difficult to isolate and limited in supply. To overcome these limitations, human induced pluripotent stem cell (iPSC)-derived type 2 alveolar epithelial cells (iAT2s) can be generated through a directed differentiation protocol that recapitulates in vivo lung development. iAT2s grow in feeder-free conditions, share a transcriptomic program with human adult primary AT2s, and execute key functions of AT2s such as production, packaging, and secretion of surfactant. This protocol details the methods for maintaining self-renewing iAT2s through serial passaging in three-dimensional (3D) culture or adapting iAT2s to air-liquid interface (ALI) culture. A single-cell suspension of iAT2s is generated before plating in 3D solubilized basement membrane matrix (hereafter referred to as "matrix"), where they self-assemble into monolayered epithelial spheres. iAT2s in 3D culture can be serially dissociated into single-cell suspensions to be passaged or plated in 2D ALI culture. In ALI culture, iAT2s form a polarized monolayer with the apical surface exposed to air, making this platform readily amenable to environmental exposures. Hence, this protocol generates an inexhaustible supply of iAT2s, producing upwards of 1 x 1030 cells per input cell over 15 passages while maintaining the AT2 program indicated by SFTPCtdTomato expression. The resulting cells represent a reproducible and relevant platform that can be applied to study genetic mutations, model environmental exposures, or screen drugs.

Age and Year of HIV Diagnosis are Associated with Perceptions of Discrimination and Internalized Stigma Among Sexual Minority Men Who Use Substances.

Discrimination and internalized stigma are barriers to engagement in HIV self-care among men who have sex with men (MSM) living with HIV. However, differences in perceptions of discrimination and internalized stigmas by age, year of HIV-diagnosis, and race are poorly understood. We assessed differences in reported discrimination related to HIV, race, sexual orientation, and substance use and internalized stigmas among 202 MSM living with HIV who use substances. Younger participants reported higher levels of all types of discrimination and internalized stigmas (p-values < 0.001-0.030). Those diagnosed after the advent of antiretrovirals reported higher levels of discrimination related to HIV, sexual orientation, and substance use, as well as internalized stigma related to HIV and substance use (p-values 0.001-0.049). We explored perceived community HIV stigma, which accounted for associations involving age and year of diagnosis. Age, year of diagnosis, and race should be considered when assessing and intervening with stigma.

RESUMEN: La discriminación y el estigma internalizado son barreras para el autocuidado del VIH en hombres que tienen sexo con hombres (HSH) que viven con VIH. Sin embargo, se conoce poco acerca de las diferencia que existe en la percepción de discriminación y estigma internalizado por edad, año de diagnóstico del VIH y raza. Evaluamos diferencias en torno a discriminación relacionada con el VIH reportada, raza, orientación sexual y uso de sustancias además del estigmas internalizado en 202 HSH que viven con VIH y usan sustancias. Los participantes más jóvenes reportaron los niveles más altos de cualquier forma de discriminación y estigma internalizado (valores de p <.001 - .030). Los diagnosticados después de 1996 reportaron niveles más altos de discriminación relacionada con el VIH, la orientación sexual y el uso de sustancias, así como el estigma internalizado relacionado con el VIH y uso de sustancias (valores de p .001 - 049). Para comprender mejor estas diferencias, exploramos el impacto del estigma de VIH comunitario percibido que representó la mayoría de las asociaciones relacionadas con la edad y el año del diagnóstico. Cuando se evalúan las perceptiones de discriminación y estigma internalizado, la edad, el año del diagnóstico y la raza deben ser tomados en cuenta.

Manipulation of Molecular Vibrations on Condensing Er3+ State Densities for 1.5 µm Application.

Vibrational modes of chemical bonds in organic erbium (Er3+) materials play an important role in determining the efficiency of the 1.5 µm Er3+ emission. This work studies the energy coupling of the Er3+ intra-4f transitions and vibrational modes. The results demonstrate that the coupling introduces enormous nonradiative internal relaxation, which condenses the excited erbium population on to the 4I13/2 state. This suggests that vibrational modes can be advantageous for optimizing the branching ratio for the 1.5 µm transition in organic erbium materials. Through control of the quenching effect on to the 4I13/2 state and a reliable determination of intrinsic radiative rates, it is found that the pump power for population inversion can be reduced by an order of magnitude at high erbium concentrations compared to conventional inorganic erbium materials.

Liver-Dependent Lung Remodeling during Systemic Inflammation Shapes Responses to Secondary Infection.

Systemic duress, such as that elicited by sepsis, burns, or trauma, predisposes patients to secondary pneumonia, demanding better understanding of host pathways influencing this deleterious connection. These pre-existing circumstances are capable of triggering the hepatic acute-phase response (APR), which we previously demonstrated is essential for limiting susceptibility to secondary lung infections. To identify potential mechanisms underlying protection afforded by the lung-liver axis, our studies aimed to evaluate liver-dependent lung reprogramming when a systemic inflammatory challenge precedes pneumonia. Wild-type mice and APR-deficient littermate mice with hepatocyte-specific deletion of STAT3 (hepSTAT3-/-), a transcription factor necessary for full APR initiation, were challenged i.p. with LPS to induce endotoxemia. After 18 h, pneumonia was induced by intratracheal Escherichia coli instillation. Endotoxemia elicited significant transcriptional alterations in the lungs of wild-type and hepSTAT3-/- mice, with nearly 2000 differentially expressed genes between genotypes. The gene signatures revealed exaggerated immune activity in the lungs of hepSTAT3-/- mice, which were compromised in their capacity to launch additional cytokine responses to secondary infection. Proteomics revealed substantial liver-dependent modifications in the airspaces of pneumonic mice, implicating a network of dispatched liver-derived mediators influencing lung homeostasis. These results indicate that after systemic inflammation, liver acute-phase changes dramatically remodel the lungs, resulting in a modified landscape for any stimuli encountered thereafter. Based on the established vulnerability of hepSTAT3-/- mice to secondary lung infections, we believe that intact liver function is critical for maintaining the immunological responsiveness of the lungs.

Sexual and Gender Minority Health Care Disparities: Barriers to Care and Strategies to Bridge the Gap.

Gender and sexual minority individuals face considerable physical and mental health disparities, health risk factors, and barriers to care. These disparities are rooted in systemic and interpersonal prejudice, discrimination, and violence toward lesbian, gay, bisexual, transgender, queer, and other (LGBTQ+) individuals and communities that place LGBTQ+ individuals at increased risk for negative social determinants of health. While also advocating for systemic change, individual providers and clinics have an ethical duty to promote an openly affirming, culturally competent health care environment that can help to address these disparities on an individual patient level.

Patterns of Bullying Behavior by Sexual Orientation.

Bullying has a long-lasting effect on both victims and their perpetrators; however, there is little literature dedicated to understanding the roles of sexual minority adolescents beyond being a victim or the specific types of bullying behaviors (verbal, relational, physical) in which sexual minority adolescents engage. Even less is known about the experiences of mostly heterosexual youth, as distinct from their lesbian, gay, and bisexual (LGB) peers. This exploratory study sought to identify sexual orientation differences in bullying behavior participation using a random cluster sample obtained from a county school district in the Southeastern United States. The sample included 3,463 middle and high school students from 66 schools. Four latent classes of bullies and victims emerged, with similar patterns of behaviors for heterosexual, mostly heterosexual, and LGB groups.

Evolving Sex and Gender in Electronic Health Records.

Development, training, and documentation for the implementation of a self-identified gender identity field in the electronic health record system may improve patient-centered care for transgender and gender nonconforming patients.

Post-polymerisation functionalisation of conjugated polymer backbones and its application in multi-functional emissive nanoparticles.

Backbone functionalisation of conjugated polymers is crucial to their performance in many applications, from electronic displays to nanoparticle biosensors, yet there are limited approaches to introduce functionality. To address this challenge we have developed a method for the direct modification of the aromatic backbone of a conjugated polymer, post-polymerisation. This is achieved via a quantitative nucleophilic aromatic substitution (SNAr) reaction on a range of fluorinated electron-deficient comonomers. The method allows for facile tuning of the physical and optoelectronic properties within a batch of consistent molecular weight and dispersity. It also enables the introduction of multiple different functional groups onto the polymer backbone in a controlled manner. To demonstrate the versatility of this reaction, we designed and synthesised a range of emissive poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT)-based polymers for the creation of mono and multifunctional semiconducting polymer nanoparticles (SPNs) capable of two orthogonal bioconjugation reactions on the same surface.

High-Efficiency Fullerene Solar Cells Enabled by a Spontaneously Formed Mesostructured CuSCN-Nanowire Heterointerface.

Fullerenes and their derivatives are widely used as electron acceptors in bulk-heterojunction organic solar cells as they combine high electron mobility with good solubility and miscibility with relevant semiconducting polymers. However, studies on the use of fullerenes as the sole photogeneration and charge-carrier material are scarce. Here, a new type of solution-processed small-molecule solar cell based on the two most commonly used methanofullerenes, namely [6,6]-phenyl-C61-butyric acid methyl ester (PC60BM) and [6,6]-phenyl-C71-butyric acid methyl ester (PC70BM), as the light absorbing materials, is reported. First, it is shown that both fullerene derivatives exhibit excellent ambipolar charge transport with balanced hole and electron mobilities. When the two derivatives are spin-coated over the wide bandgap p-type semiconductor copper (I) thiocyanate (CuSCN), cells with power conversion efficiency (PCE) of ≈1%, are obtained. Blending the CuSCN with PC70BM is shown to increase the performance further yielding cells with an open-circuit voltage of ≈0.93 V and a PCE of 5.4%. Microstructural analysis reveals that the key to this success is the spontaneous formation of a unique mesostructured p-n-like heterointerface between CuSCN and PC70BM. The findings pave the way to an exciting new class of single photoactive material based solar cells.

Sexual orientation, minority stress, social norms, and substance use among racially diverse adolescents.

BACKGROUND: Sexual minority adolescents are more likely than their heterosexual peers to use substances. This study tested factors that contribute to sexual orientation disparities in substance use among racially and ethnically diverse adolescents. Specifically, we examined how both minority stress (i.e., homophobic bullying) and social norms (i.e., descriptive and injunctive norms) may account for sexual orientation disparities in recent and lifetime use of four substances: tobacco, alcohol, marijuana, and prescription drugs. PROCEDURES: A probability sample of middle and high school students (N=3012; aged 11-18 years old; 71.2% racial and ethnic minorities) using random cluster methods was obtained in a mid-size school district in the Southeastern United States. RESULTS: Sexual minority adolescents were more likely than heterosexual adolescents to use substances, experience homophobic bullying, and report higher descriptive norms for close friends and more permissive injunctive norms for friends and parents. While accounting for sociodemographic characteristics, multiple mediation models concurrently testing all mediators indicated that higher descriptive and more permissive injunctive norms were significant mediators of the associations between sexual orientation and recent and lifetime use of the four substances, whereas homophobic bullying was not a significant mediator of the associations between sexual orientation and recent and lifetime use of any of the substances. CONCLUSIONS: Descriptive and injunctive norms, in conjunction with minority stress, are important to consider in explaining sexual orientation disparities in substance use among racially diverse adolescents. These results have implications for substance use interventions among sexual minority adolescents.

Global dynamics of a colorectal cancer treatment model with cancer stem cells.

We present and analyze a mathematical model of the treatment of colorectal cancer using a system of nonlinear ordinary differential equations. The model describes the effectiveness of immunotherapy and chemotherapy for treatment of tumor cells and cancer stem cells (CSCs). The effects of CD8+T cells, natural killer cells, and interleukin proteins on tumor cells and CSCs under the influence of treatment are also illustrated. Using the method of localization of compact invariant sets, we present conditions on treatment parameters to guarantee a globally attracting tumor clearance state. Numerical simulations using estimated parameters from the literature are included to showcase various global dynamics of the model.

Sexual Orientation Disparities in the Use of Emerging Drugs.

BACKGROUND: Prescription drug, e-cigarette, smokeless tobacco, and synthetic marijuana use has risen dramatically in the United States over the past decade. OBJECTIVES: This paper investigates the use of risky substances among adolescents, and examines disparities between sexual minority (i.e., mostly heterosexual and lesbian, gay, bisexual; LGB) and heterosexual adolescents in use of novel and emerging substances. Given the public health risk and the imminence of these substances in the media, emerging drug use was examined in a county wide sample of adolescents in a Southern state. METHODS: A probability sample of middle and high school students (N = 3012; ages 11-18) using random cluster methods was obtained in a mid-sized school district in the Southeastern United States. RESULTS: LGB adolescents reported higher past-30 day and lifetime use of cigarettes (AORs =2.77, 2.90, respectively), smokeless tobacco (lifetime only: AOR = 1.88), e-cigarettes (lifetime only; AOR = 1.92), alcohol (AORs = 1.7, 2.20), marijuana (AORs = 3.02, 3.06), synesthetic marijuana (AORs = 3.77, 2.48), and prescription drugs (AORs = 3.82, 2.55). Adolescents who self-identified as "mostly heterosexual" reported higher lifetime cigarette use, and past 30-day use of e-cigarettes and prescription drugs as compared with heterosexual adolescents. CONCLUSIONS: Our results are notable given the dearth of data documenting use of increasingly emerging or "trendy" substances such as prescription drugs. More research is needed to understand the underlying cause of these disparities, and efforts should be targeted toward this population to reduce negative outcomes from misuse.

Radio Frequency Coplanar ZnO Schottky Nanodiodes Processed from Solution on Plastic Substrates.

Coplanar radio frequency Schottky diodes based on solution-processed C60 and ZnO semiconductors are fabricated via adhesion-lithography. The development of a unique asymmetric nanogap electrode architecture results in devices with a high current rectification ratio (10(3) -10(6) ), low operating voltage (<3 V), and cut-off frequencies of >400 MHz. Device fabrication is scalable and can be performed at low temperatures even on plastic substrates with very high yield.