Optically Mediated Hydrogel-Based Ionic Diode.

Ionic diodes with environmentally modulated ion-rectifying characteristics have attracted much attention and show great promise in the construction of smart devices with environmental adaptability. One immediate challenge is to integrate stimuli responsiveness and ion rectification into one single ionic diode, which requires a close cooperation of chemical principles and device technologies. Herein, an ionic diode based on a photoresponsive hydrogel with optically mediated ion-rectifying performances is introduced. Relying on the photoresponsive concentration of proton in the hydrogel, the ionic current rectification can be prominently enhanced upon ultraviolet (UV) irradiation. A maximum ionic current rectification ratio of the optically mediated ionic diode about 4 × 105 is achieved. Furthermore, the hydrogel-based diode can serve as an AND logic gate operated by UV light and voltage bias as two independent inputs. As a proof of concept, to use the optically mediated diode is achieved to modulate the feedback of a robot with logic behaviors. This work provides a novel and valuable strategy for designing functional hydrogel-based devices with the integration of stimuli-responsiveness and logic signal processing through chemical approaches.

Community- and Program-Level Predictors of Funding Streams Used by Coordinated Specialty Care Programs.

OBJECTIVE: Although coordinated specialty care (CSC) is an effective service model to address first-episode psychosis, CSC is not widely accessible in the United States, and funding for this service model often remains challenging. The authors examined whether community- or program-level factors predict the use of public and private funding streams in a national sample of 34 CSC programs in 22 U.S. states and territories. METHODS: As part of a larger mixed-methods study, CSC program leaders completed a brief questionnaire regarding funding sources. Statistical modeling was used to examine program- and community-level predictors of the use of funding sources. RESULTS: Most CSC programs (20 of 34, 59%) reported that Mental Health Block Grant (MHBG) set-aside funds accounted for more than half of their total funding, and 11 of these programs reported that these funds contributed to >75% of their funding. Programs ≤5 years old were more likely to rely on MHBG set-aside funds. Programs in Medicaid expansion states were more likely to rely on Medicaid funding than programs in nonexpansion states. Programs in higher-income service catchment areas used more state funds than did those in lower-income areas, and among programs in lower-income service catchment areas, those that were >4 years old were more likely than those ≤4 years old to rely on state funds other than Medicaid. CONCLUSIONS: CSC programs remain largely dependent on MHBG set-aside funding. Some programs have diversified their funding streams, most notably by including more Medicaid and other state funding. A more comprehensive funding approach is needed to reduce reliance on the MHBG set-aside funds.

State Mental Health Authority Level of Involvement in Coordinated Specialty Care Clinics and Client Outcomes.

OBJECTIVE: State mental health authorities (SMHAs) in all U.S. states and territories administer the Mental Health Block Grant (MHBG) set-aside funding for first-episode psychosis. Funds support implementation of coordinated specialty care (CSC) programs. The authors investigated the relationship between the level of SMHA involvement with CSC programs and clinical outcomes of clients in these programs. METHODS: As part of a mixed-methods study of 34 CSC programs, SMHAs from 21 states and one U.S. territory associated with the 34 CSC programs participated in a 1-hour interview (between November 2018 and May 2019) focused on SMHA involvement in administration of MHBG set-aside funds and the SMHA's ongoing relationship with funded CSC programs. SMHA involvement was rated on a scale of 1 to 5, with 5 indicating the highest involvement. Client outcome data were collected at the 34 study sites over an 18-month period. Multilevel random-effect modeling was used, controlling for response propensity (propensity score), client demographic variables, and program-level covariates (i.e., fidelity score, staff turnover rates, service area urbanicity, and number of clients enrolled). RESULTS: Clients in CSC programs with SMHAs that were the most involved (level 5) had significantly improved symptoms, social functioning, and role functioning, compared with clients in programs with which SMHAs were least involved (level 1). CONCLUSIONS: The findings suggest that increased SMHA involvement in CSC programs is relevant for positive client outcomes. Levels of first-episode psychosis funding doubled in 2021 and 2022, and it is important to identify how SMHAs affect the success of CSC programs and the individuals served.

Client Racial Composition in First-Episode Psychosis Programs Compared With Compositions in Program Service Areas.

OBJECTIVE: The authors examined the extent to which clients served by first-episode psychosis programs reflected the racial composition of the surrounding service area and, to the extent that they did not, explored possible explanatory factors. METHODS: As part of a national study of coordinated specialty care (CSC) sites in the United States, 35 programs documented race for 772 clients. Programs identified a geographic service area for their clients. Using Census data, the authors identified the proportion of clients in this service area who were Black and then examined the extent of disproportionality, calculated as a risk ratio and as a relative difference in racial composition between CSC programs and their service areas. RESULTS: Overall, 71% of CSC programs had a disproportionately greater proportion of Black clients than Black residents within the service area. This disproportionality was still evident after conducting sensitivity analyses that included adjusting for sampling error in the service area population estimates; however, smaller study sites displayed greater fluctuations in disproportionality in the sensitivity analyses. CONCLUSIONS: Using data from diverse CSC programs, the authors illustrate that the odds of Blacks receiving services through a CSC program are much higher than would be expected on the basis of the population living in the area being served by the program. Multiple reasons may explain this finding, but in the absence of clear explanatory factors, this result may be ripe for discussion and further investigation.

Role of microfluidics in accelerating new space missions.

Numerous revolutionary space missions have been initiated and planned for the following decades, including plans for novel spacecraft, exploration of the deep universe, and long duration manned space trips. Compared with space missions conducted over the past 50 years, current missions have features of spacecraft miniaturization, a faster task cycle, farther destinations, braver goals, and higher levels of precision. Tasks are becoming technically more complex and challenging, but also more accessible via commercial space activities. Remarkably, microfluidics has proven impactful in newly conceived space missions. In this review, we focus on recent advances in space microfluidic technologies and their impact on the state-of-the-art space missions. We discuss how micro-sized fluid and microfluidic instruments behave in space conditions, based on hydrodynamic theories. We draw on analyses outlining the reasons why microfluidic components and operations have become crucial in recent missions by categorically investigating a series of successful space missions integrated with microfluidic technologies. We present a comprehensive technical analysis on the recently developed in-space microfluidic applications such as the lab-on-a-CubeSat, healthcare for manned space missions, evaluation and reconstruction of the environment on celestial bodies, in-space manufacturing of microfluidic devices, and development of fluid-based micro-thrusters. The discussions in this review provide insights on microfluidic technologies that hold considerable promise for the upcoming space missions, and also outline how in-space conditions present a new perspective to the microfluidics field.

Escherichia coli and Staphylococcus aureus Differentially Regulate Nrf2 Pathway in Bovine Mammary Epithelial Cells: Relation to Distinct Innate Immune Response.

Escherichia coli and Staphylococcus aureus are major mastitis causing pathogens in dairy cattle but elicit distinct immune and an inflammatory response in the udder. However, the host determinants responsible for this difference remains largely unknown. Our initial studies focused on the global transcriptomic response of primary bovine mammary epithelial cells (pbMECs) to heat-killed E. coli and S. aureus. RNA-sequencing transcriptome analysis demonstrates a significant difference in expression profiles induced by E. coli compared with S. aureus. A major differential response was the activation of innate immune response by E. coli, but not by S. aureus. Interestingly, E. coli stimulation increased transcript abundance of several genes downstream of Nrf2 (nuclear factor erythroid 2-related factor 2) that were enriched in gene sets with a focus on metabolism and immune system. However, none of these genes was dysregulated by S. aureus. Western blot analysis confirms that S. aureus impairs Nrf2 activation as compared to E. coli. Using Nrf2-knockdown cells we demonstrate that Nrf2 is necessary for bpMECs to mount an effective innate defensive response. In support of this notion, nuclear Nrf2 overexpression augmented S. aureus-stimulated inflammatory response. We also show that, unlike E. coli, S. aureus disrupts the non-canonical p62/SQSTM1-Keap1 pathway responsible for Nrf2 activation through inhibiting p62/SQSTM1 phosphorylation at S349. Collectively, our findings provide important insights into the contribution of the Nrf2 pathway to the pathogen-species specific immune response in bovine mammary epithelial cells and raise a possibility that impairment of Nrf2 activation contributes to, at least in part, the weak inflammatory response in S. aureus mastitis.

Annexin A2-Mediated Internalization of Staphylococcus aureus into Bovine Mammary Epithelial Cells Requires Its Interaction with Clumping Factor B.

BACKGROUND: Staphylococcus aureus is a leading cause of contagious mastitis in dairy cattle. Internalization of S. aureus by bovine mammary gland epithelial cells is thought to be responsible for persistent and chronic intramammary infection, but the underlying mechanisms are not fully understood. METHODS: In the present study, we evaluated the role of Annexin A2 (AnxA2), a membrane-binding protein, in S. aureus invasion into bovine mammary epithelial cell line (MAC-T). In vitro binding assays were performed to co-immunoprecipitate the binding proteins of AnxA2 in the lysates of S. aureus. RESULTS: AnxA2 mediated the internalization but not adherence of S. aureus. Engagement of AnxA2 stimulated an integrin-linked protein kinase (ILK)/p38 MAPK cascade to induce S. aureus invasion. One of the AnxA2-precipitated proteins was identified as S. aureus clumping factor B (ClfB) through use of mass spectrometry. Direct binding of ClfB to AnxA2 was further confirmed by using a pull-down assay. Pre-incubation with recombinant ClfB protein enhanced S. aureus internalization, an effect that was specially blocked by anti-AnxA2 antibody. CONCLUSION: Our results demonstrate that binding of ClfB to AnxA2 has a function in promoting S. aureus internalization. Targeting the interaction of ClfB and AnxA2 may confer protection against S. aureus mastitis.

Reducing child restraint misuse: national survey of awareness and use of inspection stations.

OBJECTIVE: Research indicates that hands-on instruction on installation and use of child restraint systems (CRSs) is an effective method to reduce misuse. However, use of these services is low. The objective of the Awareness and Availability of Child Passenger Safety Information Resources (AACPSIR) Survey was to estimate the degree of awareness caregivers have of CRS inspection stations. The survey also evaluated the relationships among caregiver confidence and risk perceptions as well as potential barriers and facilitators to inspection station use. METHODS: The AACPSIR was a web-based cross-sectional survey targeting a nationally representative sample of adults who drove with children aged 0-9 at least twice a month. An address-based sample was selected using a cluster sample design. Caregivers who reported driving frequently with child passengers answered questions on awareness and use of inspection stations, confidence related to CRS use, and barriers and facilitators to inspection station use. RESULTS: Data were collected from 1,565 households. In all, 66.9% of respondents were aware of inspection stations, but only 44.2% reported that they had used these services. Most caregivers indicated that they were confident (91.7%) that the car seat was installed correctly. A quarter of the respondents indicated a reason that might prevent them from using an inspection station was that they "don't think it's necessary". A long wait time (66.5%), distance (65.2%), and schedule conflicts (63.9%) were also frequently indicated as potential barriers. Conversely, among inspection station users, most did not need to make an appointment (73%), and over half indicated that the station was five miles or less from their home and within a 15-minute drive. CONCLUSIONS: The AACPSIR Survey results suggest a segment of caregivers share a positive safety culture, including knowledge of CPS services and use of those services. Of concern are caregivers who did not access an inspection station because they indicated it was not necessary, they already knew how to install the CRS, or pointed to other inconveniences. Future intervention programs that target caregivers unfamiliar with inspection stations or believe that the services are not necessary have the potential to improve child passenger safety.

Patient Navigation for Colonoscopy Completion: Results of an RCT.

INTRODUCTION: Colorectal cancer is a leading cause of cancer-related death in the U.S. Although screening reduces colorectal cancer incidence and mortality, screening rates among U.S. adults remain less than optimal, especially among disadvantaged populations. This study examined the efficacy of patient navigation to increase colonoscopy screening. STUDY DESIGN: RCT. SETTING/PARTICIPANTS: A total of 843 low-income adults, primarily Hispanic and non-Hispanic blacks, aged 50-75 years referred for colonoscopy at Boston Medical Center were randomized into the intervention (n=429) or control (n=427) groups. Participants were enrolled between September 2012 and December 2014, with analysis following through 2015. INTERVENTION: Two bilingual lay navigators provided individualized education and support to reduce patient barriers and facilitate colonoscopy completion. The intervention was delivered largely by telephone. MAIN OUTCOME MEASURE: Colonoscopy completion within 6 months of study enrollment. RESULTS: Colonoscopy completion was significantly higher for navigated patients (61.1%) than control group patients receiving usual care (53.2%, p=0.021). Based on regression analysis, the odds of completing a colonoscopy for navigated patients was one and a half times greater than for controls (95% CI=1.12, 2.03, p=0.007). There were no differences between navigated and control groups in regard to adequacy of bowel preparation (95.3% vs 97.3%, respectively). CONCLUSIONS: Navigation significantly improved colonoscopy screening completion among a racially diverse, low-income population. Results contribute to mounting evidence demonstrating the efficacy of patient navigation in increasing colorectal cancer screening. Screening can be further enhanced when navigation is combined with other evidence-based practices implemented in healthcare systems and the community.

Antiretroviral treatment initiation does not differentially alter neurocognitive functioning over time in youth with behaviorally acquired HIV.

Although youth living with behaviorally acquired HIV (YLWH) are at risk for cognitive impairments, the relationship of impairments to HIV and potential to improve with antiretroviral therapy (ART) are unclear. This prospective observational study was designed to examine the impact of initiation and timing of ART on neurocognitive functioning in YLWH in the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Treatment naïve YLWH age 18-24 completed baseline and four additional assessments of attention/working memory, complex executive, and motor functioning over 3 years. Group 1 co-enrolled in an early ART initiation study and initiated ART at enrollment CD4 >350 (n = 56); group 2 had CD4 >350 and were not initiating ART (n = 66); group 3 initiated ART with CD4 <350 (n = 59) per standard of care treatment guidelines at the time. Treatment was de-intensified to boosted protease inhibitor monotherapy at 48 weeks for those in group 1 with suppressed viral load. Covariates included demographic, behavioral, and medical history variables. Analyses used hierarchical linear modeling. All groups showed improved performance with peak at 96 weeks in all three functional domains. Trajectories of change were not significantly associated with treatment, timing of treatment initiation, or ART de-intensification. Demographic variables and comorbidities were associated with baseline functioning but did not directly interact with change over time. In conclusion, YLWH showed improvement in neurocognitive functioning over time that may be related to practice effects and nonspecific impact of study participation. Neither improvement nor decline in functioning was associated with timing of ART initiation or therapy de-intensification.

Neurocognitive functioning in antiretroviral therapy-naïve youth with behaviorally acquired human immunodeficiency virus.

PURPOSE: Youth living with human immunodeficiency virus (HIV) account for over one third of new HIV infections and are at high risk of adverse psychosocial, everyday living, and health outcomes. Human immunodeficiency virus-associated neurocognitive disorders (HAND) are known to affect health outcomes of HIV-infected adults even in the era of combination antiretroviral therapy. Thus, the current study aimed to characterize the prevalence and clinical correlates of HAND in youth living with HIV. Here, we report baseline neurocognitive data for behaviorally HIV-infected youth enrolled in a prospective study evaluating strategies of antiretroviral treatment initiation and use. METHODS: A total of 220 participants, age 18-24 years, who were naive to treatment (except for prevention of mother-to-child HIV transmission; n = 3), completed a comprehensive neurocognitive, substance use, and behavioral health assessment battery. RESULTS: Sixty-seven percent of youth met criteria for HAND (96.4% were asymptomatic and 3.5% were syndromic); deficits in episodic memory and fine-motor skills emerged as the most commonly affected ability areas. Multivariable models showed that lower CD4 count, longer time since HIV diagnosis, and high-risk alcohol use were uniquely associated with neurocognitive deficits. CONCLUSIONS: Over two thirds of youth with behaviorally acquired HIV evidence neurocognitive deficits, which have modest associations with more advanced HIV disease as well as other factors. Research is needed to determine the impact of such neuropsychiatric morbidity on mental health and HIV disease treatment outcomes (e.g., nonadherence) and transition to independent living responsibilities in HIV-infected youth, as well as its long-term trajectory and possible responsiveness to cognitive rehabilitation and pharmacotherapy.