Baclofen-induced excessive perspiration: A case report and review of literature.

This report highlights an unexpected baclofen side effect, a medication known for its safety profile. The rarity of excessive perspiration as a side effect distinguishes this case from typical baclofen adverse reactions. Documenting uncommon reactions is vital for physicians to broaden their awareness of baclofen's side effects and improve care.

Preventing Cognitive Decline in Older Latino Adults With HIV Through a Culturally Tailored Health Promotion Intervention: Protocol for a Single-Arm Pilot Trial.

BACKGROUND: Older Latino adults with HIV are at increased risk for mild cognitive impairment and earlier onset of aging-related cognitive decline. Improvements in cognitive functioning and cognitive outcomes are possible among people with HIV who adopt health promotion behaviors. However, health promotion interventions for older Latino adults with HIV have not been extensively used or widely recognized as viable treatment options. Happy Older Latinos are Active (HOLA) is a multicomponent, health promotion intervention that is uniquely tailored for older Latino adults with HIV. OBJECTIVE: This study aims to (1) determine the feasibility and acceptability of an adapted version of HOLA aimed at improving cognitive functioning among older Latino adults with HIV; (2) explore whether HOLA will produce changes in cognitive functioning; (3) explore whether HOLA will produce changes in activity, psychosocial functioning, or biomarkers of cognition; and (4) explore whether changes in activity, psychosocial functioning or cognitive biomarkers correlate with changes in cognition, while accounting for genetic risk for dementia. METHODS: A single-arm pilot trial with 30 Latino (aged 50 years and older) men and women with HIV was conducted to assess feasibility, acceptability, and preliminary effects on cognition. Participants were assessed at 2 time points (baseline and postintervention) on measures of neurocognitive and psychosocial functioning. In addition, blood samples were collected to determine biomarkers of cognition at baseline and postintervention. Successful recruitment was defined as meeting 100% of the targeted sample (N=30), with 20% (n=6) or less of eligible participants refusing to participate. Adequate retention was defined as 85% (n=25) or more of participants completing the postintervention assessment and acceptability was defined as 80% (n=38) or more of sessions attended by participants. RESULTS: Participant recruitment began on February 22, 2022, and was completed on August 15, 2022. The last study visit took place on February 20, 2023. Data analysis is currently ongoing. CONCLUSIONS: Encouraging findings from this exploratory study may provide a blueprint for scaling up the HOLA intervention to a larger cohort of older Latino adults with HIV who may be currently experiencing or are at risk for HIV-related cognitive challenges. TRIAL REGISTRATION: ClinicalTrials.gov NCT04791709; https://clinicaltrials.gov/study/NCT04791709. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55507.

Structural Determinants of Health and Markers of Immune Activation and Systemic Inflammation in Sexual Minority Men With and Without HIV.

Among sexual minority men (SMM), HIV and use of stimulants such as methamphetamine are linked with immune activation and systemic inflammation. Throughout the COVID-19 pandemic, SMM encountered financial challenges and structural obstacles that might have uniquely contributed to immune dysregulation and systemic inflammation, beyond the impacts of HIV and stimulant use. Between August 2020 and February 2022, 72 SMM with and without HIV residing in South Florida enrolled in a COVID-19 prospective cohort study. Multiple linear regression analyses examined unemployment, homelessness, and history of arrest as structural correlates of soluble markers of immune activation (i.e., sCD14 and sCD163) and inflammation (i.e., sTNF-α receptors I and II) at baseline after adjusting for HIV status, stimulant use, and recent SARS-CoV-2 infection. Enrolled participants were predominantly Latino (59%), gay-identified (85%), and with a mean age of 38 (SD, 12) years with approximately one-third (38%) of participants living with HIV. After adjusting for HIV status, SARS-CoV-2 infection, and recent stimulant use, unemployment independently predicted higher levels of sCD163 (ß = 0.24, p = 0.04) and sTNF-α receptor I (ß = 0.26, p = 0.02). Homelessness (ß = 0.25, p = 0.02) and history of arrest (ß = 0.24, p = 0.04) independently predicted higher levels of sCD14 after adjusting for HIV status, SARS-CoV-2 infection, and recent stimulant use. Independent associations exist between structural barriers and immune activation and systemic inflammation in SMM with and without HIV. Future longitudinal research should further elucidate complex bio-behavioral mechanisms linking structural factors with immune activation and inflammation.

Multifaceted manifestations: A case report of MRSA pneumonia with sepsis, pyelonephritis, and ileus muscle abscess.

Methicillin-resistant staph aureus (MRSA) infections are challenging to treat, and with the emergence of community-associated MRSA (CA-MRSA) strains, early consideration of this pathogen in populations without typical risk factors is critical. Here we present a case of CA-MRSA pneumonia that resulted in Community-acquired pneumonia (CAP) with septic shock, pyelonephritis, and muscle abscess.

Loneliness, Methamphetamine Use, and Cardiovascular Risk Factors Among Sexual Minority Men in the COVID-19 Era.

BACKGROUND: Important gaps exist in our understanding of loneliness and biobehavioral outcomes among sexual minority men (SMM), such as faster HIV disease progression. At the same time, SMM who use methamphetamine are approximately one-third more likely than non-users to develop cardiovascular disease. This study examined associations of loneliness, stimulant use, and cardiovascular risk in SMM with and without HIV. METHOD: Participants were enrolled from August 2020 to February 2022 in a 6-month prospective cohort study. The study leveraged self-report baseline data from 103 SMM, with a subset of 56 SMM that provided a blood sample to measure markers of cardiovascular risk. RESULTS: Loneliness showed negative bivariate associations with total cholesterol and LDL cholesterol in the cardiometabolic subsample (n = 56). SMM with methamphetamine use (t(101) = 2.03, p < .05; d = .42) and those that screened positive for a stimulant use disorder (t(101) = 2.07, p < .05; d = .46) had significantly higher mean loneliness scores. In linear regression analyses, negative associations of loneliness with LDL and total cholesterol were observed only among SMM who used methamphetamine. CONCLUSION: We observed lower cholesterol in SMM reporting loneliness and methamphetamine use. Thus, in addition to the observed associations of loneliness with cholesterol, there are important medical consequences of methamphetamine use including cardiovascular risk, higher HIV acquisition risk and progression, as well as stimulant overdose death. This cross-sectional study underscores the need for clinical research to develop and test interventions targeting loneliness among SMM with stimulant use disorders.

The impact of different co-morbidities on clinical outcomes and resource utilization in critically ill burn and surgical patients: A population-based analysis of social determinants of health.

BACKGROUND: This study aims to establish the significance of social determinants of health and prevalent co-morbidities on multiple indicators for quality of care in patients admitted to the Burn and Surgical Intensive Care Unit (ICU). METHODS: We performed a retrospective analysis of population group data for patients admitted at the Burn and Surgical ICU from January 1, 2016, to November 18, 2019. The primary outcomes were length of hospital stay (LOS), mortality, 30-day readmission, and hospital charges. Pearson's chi-square test for categorical variables and t-test for continuous variables were used to compare population health groups. RESULTS: We analyzed a total of 487 burn and 510 surgical patients. When comparing ICU patients, we observed significantly higher mean hospital charges and length of stay (LOS) in BICU v. SICU patients with a history of mental health ($93,259.40 v. $50,503.36, p = 0.013 and 16.28 v. 9.16 days, p = 0.0085), end-stage-renal-disease (ESRD) ($653,871.05 v. $75,746.35, p = 0.0047 and 96.15 v. 17.53 days, p = 0.0104), sepsis ($267,979.60 v. $99,154.41, p = <0.001 and 39.1 v. 18.42 days, p = 0.0043), and venous thromboembolism (VTE) ($757,740.50 v. $117,816.40, p = <0.001 and 93.11 v. 20.21 days, p = 0.002). Also, higher mortality was observed in burn patients with ESRD, ST-Elevation Myocardial Infarction (STEMI), sepsis, VTE, and diabetes mellitus. 30-day-readmissions were greater among burn patients with a history of mental health, drug dependence, heart failure, and diabetes mellitus. CONCLUSIONS: Our study provides new insights into the variability of outcomes between burn patients treated in different critical care settings, underlining the influence of comorbidities on these outcomes. By comparing burn patients in the BICU with those in the SICU, we aim to highlight how differences in patient backgrounds, including the quality of care received, contribute to these outcomes. This comparison underscores the need for tailored healthcare strategies that consider the unique challenges faced by each patient group, aiming to mitigate disparities in health outcomes and healthcare spending. Further research to develop relevant and timely interventions that can improve these outcomes.

Translatability of In Vitro Stress for Predicting Deamidation and Oxidation Biotransformation on Biotherapeutics.

Biotransformation leading to single residue modifications (e.g., deamidation, oxidation) can contribute to decreased efficacy/potency, poor pharmacokinetics, and/or toxicity/immunogenicity for protein therapeutics. Identifying and characterizing such liabilities in vivo are emerging needs for biologics drug discovery. In vitro stress assays involving PBS for deamidation or AAPH for oxidation are commonly used for predicting liabilities in manufacturing and storage and are sometimes considered a predictive tool for in vivo liabilities. However, reports discussing their in vivo translatability are limited. Herein, we introduce a mass spectrometry workflow that characterizes in vivo oxidation and deamidation in pharmacokinetically relevant compartments for diverse protein therapeutic modalities. The workflow has low bias of <10% in quantitating degradation in the relevant pharmacokinetic concentration range for monkey and rabbit serum/plasma (1-100 µg/mL) and allows for high sequence coverage (∼85%) for discovery/monitoring of amino acid modifications. For oxidation and deamidation, the assay was precise, with percent coefficient of variation of <8% at 1-100 µg/mL and ≤6% method-induced artifacts. A high degree of in vitro and in vivo correlation was observed for deamidation on the six diverse protein therapeutics (seven liability sites) tested. In vivo translatability for oxidation liabilities were not observed for the 11 molecules tested using in vitro AAPH stress. One of the molecules dosed in eyes resulted in a false positive and a false negative prediction for in vivo oxidation following AAPH stress. Finally, peroxide stress was also tested but resulted in limited success (1 out of 4 molecules) in predicting oxidation liabilities.

Overamped: Stimulant Use and HIV Pathogenesis.

PURPOSE OF REVIEW: In the era of HIV treatment as prevention (TasP), more clarity is needed regarding whether people with HIV who use stimulants (i.e., methamphetamine, powder cocaine, and crack cocaine) display elevated HIV viral load and greater immune dysregulation. RECENT FINDINGS: Although rates of viral suppression have improved in the TasP era, stimulant use was independently associated with elevated viral load in 23 of 28 studies included in our review. In the 12 studies examining other HIV disease markers, there was preliminary evidence for stimulant-associated alterations in gut-immune dysfunction and cellular immunity despite effective HIV treatment. Studies generally focused on documenting the direct associations of stimulant use with biomarkers of HIV pathogenesis without placing these in the context of social determinants of health. Stimulant use is a key barrier to optimizing the effectiveness of TasP. Elucidating the microbiome-gut-brain axis pathways whereby stimulants alter neuroimmune functioning could identify viable targets for pharmacotherapies for stimulant use disorders. Examining interpersonal, neighborhood, and structural determinants that could modify the associations of stimulant use with biomarkers of HIV pathogenesis is critical to guiding the development of comprehensive, multi-level interventions.

Unsettling the treatment imperative? Chemotherapy decision-making in the wake of genomic techniques.

Social scientists have argued that a treatment imperative shapes experiences of biomedicine. This is evident within oncology, where discourses of hope are tempered by persistent fears surrounding cancer. It is within this context that genomic decision-making tools are entering routine care. These may indicate that a treatment is not appropriate for a particular disease profile. We draw on qualitative interviews and observations centred on gene expression profiling to consider the implications of this technique for the treatment imperative in early breast cancer. Influenced by sociological perspectives on medical technologies, we discuss how fallibilities of established tools have forged a space for the introduction of genomic testing into chemotherapy decision-making. We demonstrate how high expectations shaped patients' interpretations of this tool as facilitating the 'right' treatment choice. We then unpick these accounts, highlighting the complex relationship between gene expression profiling and treatment decision-making. We argue that anticipations for genomic testing to provide certainty in treatment choice must account for the sociocultural and organisational contexts in which it is used, including the powerful entwinement of chemotherapy and cancer. Our research has implications for sociological perspectives on treatment decision-making and clinical expectations for genomic medicine to resolve the 'problem' of overtreatment.

Social needs of dual-enrolled Medicare-Medicaid patients with medication nonadherence in a telehealth medication therapy management program.

BACKGROUND: Telehealth services that identify and address the social needs of patients can improve access to health care and social services. The social needs of medication therapy management (MTM)-eligible Medicare-Medicaid dual-enrolled patients are unknown. OBJECTIVE: To describe the social needs of Medicare-Medicaid dual-enrolled patients participating in a telephonic MTM program. METHODS: This study evaluated the findings of a social needs survey implemented within a telehealth MTM program. Surveys were offered telephonically to eligible Medicare-Medicaid patients of one insurance plan who were identified with medication nonadherence between July 13, 2020, and December 31, 2020. This study described patients who completed the survey during provision of a comprehensive medication review (CMR). Questions screened for social needs in the following social determinant of health domains: community and social context, economic stability, and neighborhood and physical environment. Descriptive statistics were used to describe results. RESULTS: Among 461 patients who completed CMRs, 358 completed the social needs survey. The most prevalent needs and concerns identified included lacking support to perform daily activities (165 [47%]), lacking companionship (81 [23%]), feeling left out (71 [20%]), feeling isolated (81 [23%]), not having enough money to pay bills (177 [49%]), worrying about running out of food (77 [22%]), or having run out of food within the last 12 months (81 [23%]). In this sample, 54 (15%) patients reported avoiding a provider visit because of transportation barriers. Certain individuals were without a steady place to live or were worried about losing their home (40 [11%]) and 35 (10%) reported struggling to keep a job. CONCLUSIONS: The identification of social needs among patient populations is necessary to reduce barriers to medication adherence and optimize health care utilization. This study described important social needs identified during the provision of a telehealth CMR among MTM-eligible Medicare-Medicaid dual-enrolled patients. DISCLOSURES: Dr Nahata was supported in part by the Avatar Foundation. Dr Silva Almodóvar works as a research pharmacist within a medication management program, which provides medication therapy management services.

Toxoplasma effector-induced ICAM-1 expression by infected dendritic cells potentiates transmigration across polarised endothelium.

The obligate intracellular parasite Toxoplasma gondii makes use of infected leukocytes for systemic dissemination. Yet, how infection impacts the processes of leukocyte diapedesis has remained unresolved. Here, we addressed the effects of T. gondii infection on the trans-endothelial migration (TEM) of dendritic cells (DCs) across polarised brain endothelial monolayers. We report that upregulated expression of leukocyte ICAM-1 is a feature of the enhanced TEM of parasitised DCs. The secreted parasite effector GRA15 induced an elevated expression of ICAM-1 in infected DCs that was associated with enhanced cell adhesion and TEM. Consequently, gene silencing of Icam-1 in primary DCs or deletion of parasite GRA15 reduced TEM. Further, the parasite effector TgWIP, which impacts the regulation of host actin dynamics, facilitated TEM across polarised endothelium. The data highlight that the concerted action of the secreted effectors GRA15 and TgWIP modulate the leukocyte-endothelial interactions of TEM in a parasite genotype-related fashion to promote dissemination. In addition to the canonical roles of endothelial ICAM-1, this study identifies a previously unappreciated role for leukocyte ICAM-1 in infection-related TEM.

A Scoping Review of Empirical Asexuality Research in Social Science Literature.

Research on asexuality as a part of the experience of human sexuality has increased over the last two decades. However, there has not yet been a systematic review of the extant literature on asexuality. This paper aims to provide a systematic scoping review of literature on asexuality with articles published in 2004 through August 2021. After a systematic search procedure, 48 studies were included. A codebook was developed to extract broad information about the literature on asexuality, including sampling techniques, research participant sociodemographics, and conceptualization of asexuality. Results of the review indicate that the research is currently split between qualitative and quantitative methods. The literature primarily relied on convenience sampling within asexual online communities. The primary online community was Asexual Visibility and Education Network (AVEN), which may have contributed to the majority of participants being White, presumptively cisgender, women between the ages of 20-30. Analysis of the overall literature scope demonstrates no support for asexuality as a medical condition (i.e., a disorder requiring treatment) and instead supports the need to recognize asexuality as a complex identity and sexual orientation. Implications for research are discussed, such as the need for additional research on the topic of human sexuality that includes asexuality as a sexual orientation as well as the need for more intersectional research within the literature.

Cross-lagged analyses between gastrointestinal symptoms, psychological distress, and disability in emerging adults.

The gut-brain connection refers to communication between the brain and gastrointestinal (GI) system. Disorders of gut-brain interaction (DGBI) are characterized by GI symptoms that accompany distress and disability. Epidemiological research has suggested DGBI rates in emerging adults are increasing. This study investigated the relationship between GI health, distress, and disability in emerging adults across time. Emerging adults were recruited. A repeated-measure design with a 1-month time lag was used to collect data via an online survey (N = 861) across five academic semesters (Spring 2019 to Summer 2020). Measurement equivalence across time was established and a cross-lagged panel model (CLPM) was specified. Distress at Time 1 predicted GI symptoms at Time 2 (ß = .206, SE = .084, p < .05). GI symptoms at Time 1 predicted disability at Time 2 (ß = .117, SE = .039, p < .01). Higher disability at Time 1 predicted distress at Time 2 (ß = .092, SE = .027, p < .01). The cross-lagged design offers stronger causal inferences than cross-sectional studies used to study the effects of GI symptoms. Findings provide initial evidence of a directional pathway between brain and gut rather than a bidirectional network. Findings highlight the importance of psychogastroenterology.

Early passage of Toxoplasma gondii across the blood-brain barrier.

The blood-brain barrier (BBB) efficiently protects the central nervous system (CNS) from infectious insults. Yet, the apicomplexan parasite Toxoplasma gondii has a remarkable capability to establish latent cerebral infection in humans and other vertebrates. In addition to the proposed mechanisms for access to the brain parenchyma, recent findings highlight a paramount role played by the BBB in restricting parasite passage and minimizing parasite loads in the brain. Consistent with clinically asymptomatic primary infections in humans, mounting evidence indicates that the original colonization of the brain by T. gondii encompasses previously unappreciated, nondisruptive translocation processes that precede the onset of parasite-limiting immune responses.

Blood-brain barrier-restricted translocation of Toxoplasma gondii from cortical capillaries.

The cellular barriers of the central nervous system proficiently protect the brain parenchyma from infectious insults. Yet, the single-celled parasite Toxoplasma gondii commonly causes latent cerebral infection in humans and other vertebrates. Here, we addressed the role of the cerebral vasculature in the passage of T. gondii to the brain parenchyma. Shortly after inoculation in mice, parasites mainly localized to cortical capillaries, in preference over post-capillary venules, cortical arterioles or meningeal and choroidal vessels. Early invasion to the parenchyma (days 1-5) occurred in absence of a measurable increase in blood-brain barrier (BBB) permeability, perivascular leukocyte cuffs or hemorrhage. However, sparse focalized permeability elevations were detected adjacently to replicative parasite foci. Further, T. gondii triggered inflammatory responses in cortical microvessels and endothelium. Pro- and anti-inflammatory treatments of mice with LPS and hydrocortisone, respectively, impacted BBB permeability and parasite loads in the brain parenchyma. Finally, pharmacological inhibition or Cre/loxP conditional knockout of endothelial focal adhesion kinase (FAK), a BBB intercellular junction regulator, facilitated parasite translocation to the brain parenchyma. The data reveal that the initial passage of T. gondii to the central nervous system occurs principally across cortical capillaries. The integrity of the microvascular BBB restricts parasite transit, which conversely is exacerbated by the inflammatory response.

Accessing targeted therapies for cancer: self and collective advocacy alongside and beyond mainstream cancer charities.

As precision oncology has evolved, patients and their families have become more involved in efforts to access these treatments via fundraising and campaigning that take place outside of the larger cancer charities. In this paper, we explore the solidarities, networks, and emotional work of the UK-based access advocates, drawing on the stories of nine advocates, which included interviews and content analyses of their social media posts and coverage of their case in news, commentary, and fundraising websites. We consider the emotional and knowledge work of building networks that spanned consumerist and activist agendas, forged individual and collective goals, and orientations toward the public, private, and third sectors as part of securing support and access. Through these various practices, the actors we have studied cultivated personal advantage and solidarities with other patients and advocates, and in so doing engaged in self and collective advocacy alongside and beyond mainstream cancer charities.

Three dimensional modeling of biologically relevant fluid shear stress in human renal tubule cells mimics in vivo transcriptional profiles.

The kidney proximal tubule is the primary site for solute reabsorption, secretion and where kidney diseases can originate, including drug-induced toxicity. Two-dimensional cell culture systems of the human proximal tubule cells (hPTCs) are often used to study these processes. However, these systems fail to model the interplay between filtrate flow, fluid shear stress (FSS), and functionality essential for understanding renal diseases and drug toxicity. The impact of FSS exposure on gene expression and effects of FSS at differing rates on gene expression in hPTCs has not been thoroughly investigated. Here, we performed RNA-sequencing of human RPTEC/TERT1 cells in a microfluidic chip-based 3D model to determine transcriptomic changes. We measured transcriptional changes following treatment of cells in this device at three different fluidic shear stress. We observed that FSS changes the expression of PTC-specific genes and impacted genes previously associated with renal diseases in genome-wide association studies (GWAS). At a physiological FSS level, we observed cell morphology, enhanced polarization, presence of cilia, and transport functions using albumin reabsorption via endocytosis and efflux transport. Here, we present a dynamic view of hPTCs response to FSS with increasing fluidic shear stress conditions and provide insight into hPTCs cellular function under biologically relevant conditions.

Reducing emergency department visits in patients with deep vein thrombosis: introducing a standardised outpatient treatment pathway.

Deep vein thrombosis (DVT) is an acute medical condition that requires urgent diagnosis and treatment to prevent significant morbidity and mortality. Patients with DVT frequently present to the emergency department (ED) because the necessary diagnostic investigations and medical treatment for successful outpatient management are not readily accessible in the outpatient clinics. A collaborative quality improvement project was undertaken to implement and evaluate a standardised outpatient treatment pathway designed to direct patients with a newly diagnosed DVT from the ultrasound department to the thrombosis clinic, where guideline-based management for DVT can be accomplished without ED visits. During the baseline period (1 February 2017 to 31 January 2019), the number of ED visits for DVT was 383 with an average of 16 visits per month. During the intervention period (1 February 2019 to 31 January 2020), the number of ED visits for DVT was 106 with an average of 8.8 visits per month. This represents almost a 50% reduction in the average ED visits during the intervention period. A standardised outpatient treatment pathway can significantly reduce the number of ED visits in patients with DVT, potentially improving patient care and reducing ED overcrowding.

The Use of SMS Text Messaging to Improve the Hospital-to-Community Transition in Patients With Acute Coronary Syndrome (Txt2Prevent): Results From a Pilot Randomized Controlled Trial.

BACKGROUND: Acute coronary syndrome (ACS) is a leading cause of hospital admission in North America. Many patients with ACS experience challenges after discharge that impact their clinical outcomes and psychosocial well-being. SMS text messaging has the potential to provide support to patients during this postdischarge period. OBJECTIVE: This study pilot tested a 60-day SMS text messaging intervention (Txt2Prevent) for patients with ACS. The primary objective was to compare self-management domains between usual care and usual care plus Txt2Prevent. The secondary objectives were to compare medication adherence, health-related quality of life, self-efficacy, and health care resource use between groups. The third objective was to assess the feasibility of the study protocol and the acceptability of the intervention. METHODS: This was a randomized controlled trial with blinding of outcome assessors. We recruited 76 patients with ACS from St. Paul's Hospital in Vancouver, Canada, and randomized them to 1 of 2 groups within 7 days of discharge. The Txt2Prevent program included automated 1-way SMS text messages about follow-up care, self-management, and healthy living. Data were collected during the index admission and at 60 days after randomization. The primary outcome was measured with the Health Education Impact Questionnaire (heiQ). Other outcomes included the EQ-5D-5L, EQ-5D-5L Visual Analog Scale, a modified Sullivan Cardiac Self-Efficacy Scale, and Morisky Medication Adherence Scale scores, and self-reported health care resource use. Analyses of covariance were used to test the effect of group assignment on follow-up scores (controlling for baseline) and were considered exploratory in nature. Feasibility was assessed with descriptive characteristics of the study protocol. Acceptability was assessed with 2 survey questions and semistructured interviews. RESULTS: There were no statistically significant differences between the groups for the heiQ domains (adjusted mean difference [Txt2Prevent minus usual care] for each domain-Health-directed activity: -0.13, 95% CI -0.39 to 0.13, P=.31; Positive and active engagement in life: 0.03, 95% CI -0.19 to 0.25, P=.76; Emotional distress: 0.04, 95% CI -0.22 to 0.29, P=.77; Self-monitoring and insight: -0.14, 95% CI -0.33 to 0.05, P=.15; Constructive attitudes and approaches: -0.10, 95% CI -0.36 to 0.17, P=.47; Skill technique and acquisition: 0.05, 95% CI -0.18 to 0.27, P=.69; Social integration and support: -0.12, 95% CI -0.34 to 0.10, P=.27; and Health services navigation: -0.05, 95% CI -0.29 to 0.19, P=.69). For the secondary outcomes, there were no statistically significant differences in adjusted analyses except in 1 self-efficacy domain (Total plus), where the Txt2Prevent group had lower scores (mean difference -0.36, 95% CI -0.66 to -0.50, P=.03). The study protocol was feasible, but recruitment took longer than expected. Over 90% (29/31 [94%]) of participants reported they were satisfied with the program. CONCLUSIONS: The Txt2Prevent study was feasible to implement; however, although exploratory, there were no differences between the 2 groups in adjusted analyses except for 1 self-efficacy domain. As the intervention appeared acceptable, there is potential in using SMS text messages in this context. The design of the intervention may need to be reconsidered to have more impact on outcome measures. TRIAL REGISTRATION: ClinicalTrials.gov NCT02336919; https://clinicaltrials.gov/ct2/show/NCT02336919. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.6968.

Integrin-dependent migratory switches regulate the translocation of Toxoplasma-infected dendritic cells across brain endothelial monolayers.

Multiple cellular processes, such as immune responses and cancer cell metastasis, crucially depend on interconvertible migration modes. However, knowledge is scarce on how infectious agents impact the processes of cell adhesion and migration at restrictive biological barriers. In extracellular matrix, dendritic cells (DCs) infected by the obligate intracellular protozoan Toxoplasma gondii undergo mesenchymal-to-amoeboid transition (MAT) for rapid integrin-independent migration. Here, in a cellular model of the blood-brain barrier, we report that parasitised DCs adhere to polarised endothelium and shift to integrin-dependent motility, accompanied by elevated transendothelial migration (TEM). Upon contact with endothelium, parasitised DCs dramatically reduced velocities and adhered under both static and shear stress conditions, thereby obliterating the infection-induced amoeboid motility displayed in collagen matrix. The motility of adherent parasitised DCs on endothelial monolayers was restored by blockade of ß1 and ß2 integrins or ICAM-1, which conversely reduced motility on collagen-coated surfaces. Moreover, parasitised DCs exhibited enhanced translocation across highly polarised primary murine brain endothelial cell monolayers. Blockade of ß1, ß2 integrins, ICAM-1 and PECAM-1 reduced TEM frequencies. Finally, gene silencing of the pan-integrin-cytoskeleton linker talin (Tln1) or of ß1 integrin (Itgb1) in primary DCs resulted in increased motility on endothelium and decreased TEM. Adding to the paradigms of leukocyte diapedesis, the findings provide novel insights in how an intracellular pathogen impacts the migratory plasticity of leukocytes in response to the cellular environment, to promote infection-related dissemination.