Assessing the Effect of Cervical Transcutaneous Spinal Stimulation with an Upper Limb Robotic Exoskeleton and Surface Electromyography.

Transcutaneous Spinal Stimulation (TSS) is a promising rehabilitative intervention to restore motor function and coordination for individuals with spinal cord injury (SCI). The effects of TSS are most commonly assessed by evaluating muscle response to stimulation using surface electromyography (sEMG). Given the increasing use of robotic devices to deliver therapy and the emerging potential of hybrid rehabilitation interventions that combine neuromodulation with robotic devices, there is an opportunity to leverage the on-board sensors of the robots to measure kinematic and torque changes of joints in the presence of stimulation. This paper explores the potential for robotic assessment of the effects of TSS delivered to the cervical spinal cord. We used a four degree-of-freedom exoskeleton to measure the torque response of upper limb joints during stimulation, while simultaneously recording sEMG. We analyzed joint torque and electromyography data generated during TSS delivered over individual sites of the cervical spinal cord in neurologically intact participants. We show that site-specific effects of TSS are manifested not only by modulation of the amplitude of spinally evoked motor potentials in upper limb (UL) muscles, but also by changes in torque generated by individual UL joints. We observed preferential resultant action of proximal muscles and joints with stimulation at the rostral site, and of proximal joints with rostral-lateral stimulation. Robotic assessment can be used to measure the effects of TSS, and could be integrated into complex control algorithms that govern the behavior of hybrid neuromodulation-robotic systems.

May Measurement Month 2021: an analysis of blood pressure screening results from a suburban community in the Democratic Republic of the Congo.

Hypertension remains the most powerful contributor to the global morbidity and mortality. May Measurement Month (MMM), a worldwide screening campaign initiated by the International Society of Hypertension (ISH), is organized annually to increase awareness of high blood pressure (BP). We screened 20 913 adult (≥18 years) residents of suburb hamlets of Mbujimayi (mean age 35.1 ± 15.1 years; Black ethnicity: 98.8%; women: 29.6%; diabetes: 1.6%; alcohol drinkers: 16.8% and smokers: 6.7%, previous myocardial infarction: 1.4%; stroke: 0.8%; taking aspirin: 3.2%; taking statins: 1.9%). Three sitting BP readings were taken, and hypertension was defined as a systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg or being on antihypertensive medication. Half of the participants had never had their BP checked, whilst 4.2% of respondents had participated in the MMM19 campaign. 0.9% and 1.7% reported COVID-19 vaccination and positive test, respectively. After multiple imputation of missing BP readings, 14.0% of respondents had hypertension of which 35.8% were aware, 28.0% were on antihypertensive medication and 14.1% had controlled BP. Of those on antihypertensive medication, 40.4% were on monotherapy, 37.2% adhered to taking their medication regularly, and 50.4% had controlled BP (<140/90 mmHg). In regression analyses adjusted for age, sex, and antihypertensive treatment, smoking was associated with lower systolic BP, having more years of education was associated with higher systolic and diastolic BP, and physical activity was associated with lower systolic and diastolic BP. This campaign contributes somewhat to reducing the 'black hole' on the prevalence of hypertension in DRC pending systematic countrywide BP screening.

Childhood Sexual Abuse and Compulsive Sexual Behavior Among Men Who Have Sex with Men Newly Diagnosed with HIV.

Childhood sexual abuse (CSA) continues to be a public health challenge. The prevalence of experiencing CSA is higher among men who have sex with men (MSM) than the general population. CSA has been linked to compulsive sexual behavior (CSB) among varying populations but has not been examined among MSM who were newly diagnosed with HIV. Therefore, the aims of this study were to assess the direct association between CSA and CSB among newly diagnosed MSM living with HIV, and to identify the potential mediating roles of depressive symptoms and emotion regulation in the association between CSA and CSB. The study was a secondary data analysis using data obtained from 2012 to 2017 from two community HIV clinics in New York City (n = 202). CSA was operationalized with questions asking about sexual abuse during childhood/adolescence. CSB was measured using the 13-item Compulsive Sexual Behavior Inventory (CSBI). Depressive symptoms were measured using the 20-item Centers for Epidemiologic Studies Depression (CES-D) scale and emotion regulation was measured using a 36-item Difficulties in Emotion Regulation Scale (DERS). Path analysis was conducted to determine the mediating role of depressive symptoms and emotion regulation in the association between CSA and CSB. There was a statistically significant association between CSA and CSB (ß = 0.160; p = 0.019). There were statistically significant indirect associations between CSA, depressive symptoms, emotion regulation, and CSB (depressive symptoms ß = 0.0.071; p = 0.010; DERS: ß = 0.080; p = 0.006). Depressive symptoms were also correlated with emotion regulation (r = 0.596; p < 0.001). The relationship between CSA and CSB was significantly mediated by depressive symptoms and emotion regulation. Trauma-informed interventions addressing depressive symptoms and difficulties in emotion regulation may help to reduce CSB among MSM living with HIV.

Cannabinoid residuals in tissues of lambs fed spent hemp biomass and consumer's exposure assessment.

Spent hemp biomass (SHB) contains trace amounts of cannabinoids, including Δ9-tetrahydrocannabinol (Δ9-THC), that may accumulate in the tissues of animals consuming SHB. We measured cannabinoid residues in the liver, adipose tissue, and muscle of finishing lambs fed either 10% or 20% SHB for 8 weeks, or 4 weeks followed by 4 weeks SHB withdrawal. We detected multiple cannabinoids in the liver at a similar proportion to the SHB. However, CBD and Δ9-THC were enriched >20-fold in the adipose and muscle, compared to their proportion in SHB. The highest concentration of Δ9-THC was detected in adipose tissue and was 7.4-times higher than in muscle. Most cannabinoids were undetectable in tissues after 4 weeks of clearance. The consumers' exposure assessment on Δ9-THC revealed tissue levels of total THC (THCA+Δ9-THC) that exceed the acute reference dose of 1 µg/kg BW across population groups. When consuming meat from the lambs fed 10% and 20% SHB, the maximum total THC exposure was 2.03 and 7.32 µg/kg BW, respectively, equal to or below the Lowest Observed Adverse Effect Level of 36 µg/kg BW, the No Observed Adverse Effect Level of 12 µg/kg BW or a tolerable dose intake of 7 µg/kg BW.

Chronic paronychia associated with fluconazole use in two pediatric patients with coccidioidomycosis.

Azoles are frequently used to treat systemic mycoses but have been associated with a number of adverse effects of the skin and skin appendages. Herein we describe two cases of chronic paronychia in pediatric patients receiving fluconazole for coccidioidomycosis. Their clinical characteristics are described, and the literature reviewed.

Targeting both GD2 and B7-H3 using bispecific antibody improves tumor selectivity for GD2-positive tumors.

Objectives: Disialoganglioside 2 (GD2), overexpressed by cancers such as melanoma and neuroblastoma, is a tumor antigen for targeted therapy. The delivery of conventional IgG antibody technologies targeting GD2 is limited clinically by its co-expression on nerves that contributes to toxicity presenting as severe neuropathic pain. To improve the tumor selectivity of current GD2-targeting approaches, a next-generation bispecific antibody targeting GD2 and B7-H3 (CD276) was generated. Methods: Differential expression of human B7-H3 (hB7-H3) was transduced into GD2+ B78 murine melanoma cells and confirmed by flow cytometry. We assessed the avidity and selectivity of our GD2-B7-H3 targeting bispecific antibodies (INV34-6, INV33-2, and INV36-6) towards GD2+/hB7-H3- B78 cells relative to GD2+/hB7-H3+ B78 cells using flow cytometry and competition binding assays, comparing results an anti-GD2 antibody (dinutuximab, DINU). The bispecific antibodies, DINU, and a non-targeted bispecific control (bsAb CTRL) were conjugated with deferoxamine for radiolabeling with Zr-89 (t1/2 = 78.4 h). Using positron emission tomography (PET) studies, we evaluated the in vivo avidity and selectivity of the GD2-B7-H3 targeting bispecific compared to bsAb CTRL and DINU using GD2+/hB7-H3+ and GD2+/hB7-H3- B78 tumor models. Results: Flow cytometry and competition binding assays showed that INV34-6 bound with high avidity to GD2+/hB7-H3+ B78 cells with high avidity but not GD2+/hB7-H3+ B78 cells. In comparison, no selectivity between cell types was observed for DINU. PET in mice bearing the GD2+/hB7-H3- and GD2+/hB7-H3+ B78 murine tumor showed similar biodistribution in normal tissues for [89Zr]Zr-Df-INV34-6, [89Zr]Zr-Df-bsAb CTRL, and [89Zr]Zr-Df-DINU. Importantly, [89Zr]Zr-Df-INV34-6 tumor uptake was selective to GD2+/hB7-H3+ B78 over GD2+/hB7-H3- B78 tumors, and substantially higher to GD2+/hB7-H3+ B78 than the non-targeted [89Zr]Zr-Df-bsAb CTRL control. [89Zr]Zr-Df-DINU displayed similar uptake in both GD2+ tumor models, with uptake comparable to [89Zr]Zr-Df-INV34-6 in the GD2+/hB7-H3+ B78 model. Conclusion: The GD2-B7-H3 targeting bispecific antibodies successfully improved selectivity to cells expressing both antigens. This approach should address the severe toxicities associated with GD2-targeting therapies by reducing off-tumor GD2 binding in nerves. Continued improvements in bispecific antibody technologies will continue to transform the therapeutic biologics landscape.

"It's another gay disease": an intersectional qualitative approach contextualizing the lived experiences of young gay, bisexual, and other sexual minoritized men in the United States during the mpox outbreak.

BACKGROUND: The U.S. mpox outbreak in 2022 introduced new and exacerbated existing challenges that disproportionately stigmatize gay, bisexual, and other sexual minoritized men (GBSMM). This study contextualizes the perceptions, susceptibility, and lived experiences of the mpox outbreak among GBSMM in the U.S. using an intersectional framework. METHODS: Between September 2022 to February 2023, we conducted 33 semi-structured qualitative interviews with purposively sampled GBSMM in the Northeast and the South region of the United States on various aspects related to their experience during the mpox outbreak. RESULTS: We identified four themes: (1) understanding and conceptualizations of mpox, (2) mpox vaccine availability and accessibility, (3) mpox vaccine hesitancy and mistrust, and (4) call to action and recommendations. GBSMM collectively discussed the elevated mpox stigmatization and homophobic discourse from mainstream social media and news outlets. GBSMM also discussed the lack of availability of mpox vaccines, unclear procedures to receive the vaccine, and continued mistrust in government, non-government, and other institutions of health that were complicit in anti-LGBTQ + narratives related to mpox. However, they expressed that these challenges may be addressed through more LGTBQ + representation and leveraging ways to empower these communities. CONCLUSION: GBSMM have mpox experiences that are distinct and multifaceted. Effectively addressing mpox and mitigating public health emergencies for GBSMM requires prioritizing destigmatizing communication channels and vaccine distribution strategies by centering their stories and lived experiences to advance health equity.

Monitoring post-spawning movement, habitat use, and survival of adult anadromous rainbow smelt using acoustic telemetry in a New Hampshire estuary.

Anadromous rainbow smelt (Osmerus mordax, [Mitchill 1814]) are found along the northeast Atlantic coastline of North America, with their range now limited to north of Cape Cod, Massachusetts, USA. Although their anadromous life cycles are described broadly, gaps remain regarding how adult rainbow smelt use estuaries post-spawning, including movement behaviors, habitats used, and specific timing of emigration to coastal waters. In spring 2021, we used acoustic telemetry to characterize movements during and after the spawning season of rainbow smelt captured in tributaries to Great Bay, New Hampshire, USA, a large estuarine system near the southern edge of their range. Forty-four adult rainbow smelt (n = 35 male, n = 9 female) were tagged with Innovasea V5 180-kHz transmitters and an array of 22,180 kHz VR2W receivers were deployed throughout Great Bay to detect movements of tagged fish from March to October 2021. Rainbow smelt were detected 14,186 times on acoustic telemetry receivers, with 41 (93%) of the tagged individuals being detected at least once post-tagging. Individuals were detected moving between tributaries, revealing that rainbow smelt can use multiple rivers during the spawning season (March-April). Mark-recapture Cormack-Jolly-Seber models estimated 83% (95% confidence interval 66%-92%) of rainbow smelt survived to the mainstem Piscataqua River, and a minimum of 50% (22 of 44) reached the seaward-most receivers and were presumed to have survived emigration. Most individuals that survived remained in the estuary for multiple weeks (average = 19.47 ± 1.99 standard error days), displaying extended use of estuarine environments. Downstream movements occurred more frequently during ebb tides and upstream movements with flood tides, possibly a mechanism to reduce energy expenditures. Fish emigrated from the estuary by mid-May to the coastal Gulf of Maine. Our results underscore that rainbow smelt need access to a variety of habitats, including multiple tributaries and high-quality estuarine habitat, to complete their life cycle.

Impact of drone-specific dispatch instructions on the safety and efficacy of drone-delivered emergency medical treatments: A randomized simulation pilot study.

Introduction: Medical drones have potential for improving the response times to out-of-hospital emergencies. However, widespread adoption is hindered by unanswered questions surrounding medical dispatch and bystander safety. This study evaluated the impact of novel drone-specific dispatch instructions (DSDI) on bystanders' ability to interact effectively with a medical drone and provide prompt, safe, and high-quality treatment in a simulated emergency scenario. We hypothesized DSDI would improve bystanders' performance and facilitate safer bystander-drone interactions. Methods: Twenty-four volunteers were randomized to receive either DSDI and standard Medical Priority Dispatch (MPD) instructions or MPD alone in a simulated out-of-hospital cardiac arrest (OHCA) or pediatric anaphylaxis.,3 Participants in the DSDI group received detailed instructions on locating and interacting with the drone and its enclosed medical kit. The simulations were video recorded. Participants completed a semi-structured interview and survey. Results: The addition of DSDI did not lead to statistically significant changes to the overall time to provide care in either the anaphylaxis or OHCA simulations. However, DSDI did have an impact on bystander safety. In the MPD only group, 50% (6/12) of participants ignored the audio and visual safety cues from the drone instead of waiting for it to be declared safe compared to no DSDI participants ignoring these safety cues. Conclusions: All participants successfully provided patient care. However, this study indicates that DSDI may be useful to ensure bystander safety and should be incorporated in the continued development of emergency medical drones.

A HIV-1 Gp41 Peptide-Liposome Vaccine Elicits Neutralizing Epitope-Targeted Antibody Responses in Healthy Individuals.

Background: HIV-1 vaccine development is a global health priority. Broadly neutralizing antibodies (bnAbs) which target the HIV-1 gp41 membrane-proximal external region (MPER) have some of the highest neutralization breadth. An MPER peptide-liposome vaccine has been found to expand bnAb precursors in monkeys. Methods: The HVTN133 phase 1 clinical trial (NCT03934541) studied the MPER-peptide liposome immunogen in 24 HIV-1 seronegative individuals. Participants were recruited between 15 July 2019 and 18 October 2019 and were randomized in a dose-escalation design to either 500 mcg or 2000 mcg of the MPER-peptide liposome or placebo. Four intramuscular injections were planned at months 0, 2, 6, and 12. Results: The trial was stopped prematurely due to an anaphylaxis reaction in one participant ultimately attributed to vaccine-associated polyethylene glycol. The immunogen induced robust immune responses, including MPER+ serum and blood CD4+ T-cell responses in 95% and 100% of vaccinees, respectively, and 35% (7/20) of vaccine recipients had blood IgG memory B cells with MPER-bnAb binding phenotype. Affinity purification of plasma MPER+ IgG demonstrated tier 2 HIV-1 neutralizing activity in two of five participants after 3 immunizations. Conclusions: MPER-peptide liposomes induced gp41 serum neutralizing epitope-targeted antibodies and memory B-cell responses in humans despite the early termination of the study. These results suggest that the MPER region is a promising target for a candidate HIV vaccine.

Distinct CD16a features on human NK cells observed by flow cytometry correlate with increased ADCC.

Natural killer (NK) cells destroy tissue that have been opsonized with antibodies. Strategies to generate or identify cells with increased potency are expected to enhance NK cell-based immunotherapies. We previously generated NK cells with increased antibody-dependent cell mediated cytotoxicity (ADCC) following treatment with kifunensine, an inhibitor targeting mannosidases early in the N-glycan processing pathway. Kifunensine treatment also increased the antibody-binding affinity of Fc γ receptor IIIa/CD16a. Here we demonstrate that inhibiting NK cell N-glycan processing increased ADCC. We reduced N-glycan processing with the CRIPSR-CAS9 knockdown of MGAT1, another early-stage N-glycan processing enzyme, and showed that these cells likewise increased antibody binding affinity and ADCC. These experiments led to the observation that NK cells with diminished N-glycan processing capability also revealed a clear phenotype in flow cytometry experiments using the B73.1 and 3G8 antibodies binding two distinct CD16a epitopes. We evaluated this "affinity profiling" approach using primary NK cells and identified a distinct shift and differentiated populations by flow cytometry that correlated with increased ADCC.

Bystander interaction with a novel multipurpose medical drone: A simulation trial.

Intro: Medical drones are an emerging technology which may facilitate rapid treatment in time-sensitive emergencies. However, drones rely on lay rescuers, whose interactions with multipurpose medical drones have not been studied, and the optimal drone design remains unclear. Methods: We conducted 24 simulations of adult out-of-hospital cardiac arrest (OHCA) and pediatric anaphylaxis with a prototype drone equipped with spoken and visual cues and a multipurpose medical kit. 24 layperson volunteers encountered one of the two scenarios and were supported through administering treatment by a simulated 911 dispatcher. Bystander-drone interactions were evaluated via a convergent parallel mixed methods approach using surveys, video event review, and semi-structured interviews. Results: 83% (20/24) of participants voiced comfort interacting with the drone. 96% (23/24) were interested in future interaction. Participants appreciated the drone's spoken instructions but found visual cues confusing. Participants retrieved the medical kit from the drone in a mean of 5 seconds (range 2-14) of drone contact; 79% (19/24) found this step easy or very easy. The medical kit's layered design caused difficulty in retrieving appropriate equipment. Participants expressed a wide range of reactions to the unique drone design. Conclusions: Laypeople can effectively and comfortably interact with a medical drone with a novel design. Feedback on design elements will result in further refinements and valuable insights for other drone designers. A multipurpose medical kit created more challenges and indicates the need for further refinement to facilitate use of the equipment.

Short-Term (6 Months or Less) Pain in Cemented versus Cementless Total Knee Arthroplasty: A Systematic Review and Meta-Analysis.

BACKGROUND: Cementless total knee arthroplasty (TKA) has increased in popularity to potentially improve survivorship. Radiostereometric studies demonstrate increased component migration during the first 3 to 6 months in cementless constructs, generating concern for increased postoperative pain during early osseointegration. The purpose of this study was to evaluate short-term (≤ 6 months) pain and function in cemented versus cementless TKA. We hypothesized that cementless TKA patients report increased pain during the short-term (≤ 6 months) postoperative period. METHODS: The MEDLINE, EMBASE, CINAHL, and Cochrane Libraries were searched for studies evaluating short-term (≤ 6 months) outcomes of cemented versus cementless primary TKA. Studies involving hybrid fixation were excluded. A meta-analysis was performed using standardized mean difference for primary outcomes (early postoperative pain) and weighted mean difference (WMD) for secondary outcomes (early postoperative function). RESULTS: There were eleven studies included. There was no significant difference in acute postoperative pain between cemented and cementless TKA within 6 months of index TKA (standardized mean difference 0.08 in favor of cemented TKA; P = .10). Early postoperative forgotten joint scores (WMD 0.81; P = .81) and knee injury and osteoarthritis outcome scores for joint replacement (WMD 0.80 in favor of cemented TKA; P = .14) were also similar between groups. CONCLUSIONS: There is no difference in short-term (≤ 6 months) pain or early function between patients receiving cemented and cementless TKA. This suggests that surgeons may utilize cementless TKA without fear of increased pain due to micromotion within 6 months of index arthroplasty. However, additional studies with uniform assessment methods are needed to further inform differences in short-term pain and early functional outcomes between cemented and cementless TKA.

Analysis of seizure-cluster circadian periodicity from a long-term, open-label safety study of diazepam nasal spray.

OBJECTIVE: Seizure clusters require prompt medical treatment to minimize possible progression to status epilepticus, increased health care use, and disruptions to daily life. Isolated seizures may exhibit cyclical patterns, including circadian and longer rhythms. However, little is known about the cyclical patterns in seizure clusters. This post hoc analysis of data from a long-term, phase 3, open-label, repeat-dose safety study of diazepam nasal spray modeled the periodicity of treated seizure clusters. METHODS: Mixed-effects cosinor analysis evaluated circadian rhythmicity, and single component cosinors using 12 and 24 h were used to calculate cosinor parameters (e.g., midline statistic of rhythm, wave ampitude, and acrophase [peak]). Analysis was completed for the full cohort and a consistent cohort of participants with two or more seizure clusters in each of four, 3-month periods. The influence of epilepsy type on cosinor parameters was also analyzed. RESULTS: Seizure-cluster events plotted across 24 h showed a bimodal distribution with acrophases (peaks) at ~06:30 and ~18:30. A 12-h plot showed a single peak at ~06:30. Cosinor analyses of the full and consistent cohort aligned, with acrophases for both models predicting peak seizure activity at ~23:30 on a 24-h scale and ~07:30 on a 12-h scale. The consistent cohort was associated with increases in baseline and peak seizure-cluster activity. Analysis by epilepsy type identified distinct trends. Seizure clusters in the focal epilepsy group peaked in the evening (acrophase 19:19), whereas events in the generalized epilepsy group peaked in the morning (acrophase 04:46). Together they compose the bimodal clustering observed over 24 h. SIGNIFICANCE: This analysis of seizure clusters treated with diazepam nasal spray demonstrated that seizure clusters occur cyclically in 12- and 24-h time frames similar to that reported with isolated seizures. Further elucidation of these patterns may provide important information for patient care, ranging from improved patient-centered outcomes to seizure-cluster prediction.

Understanding the Effects of Trauma Exposure, Life Stress, Intimate Partner Violence, and Depression on Sexually Transmitted Infection Risk in Post-Conflict Liberia.

In sub-Saharan Africa, sexually transmitted infections (STIs) are a public health concern. The impact of STIs are exacerbated in post-conflict low- and middle-income countries, such as Liberia, where exposure to traumatic events is prevalent and access to mental health services are limited. Following a syndemics framework, this study used regression analyses to explore the independent, additive, and multiplicative effects of four psychosocial conditions (exposure to war-related traumatic events, intimate partner violence [IPV], stressful life events, and depressive symptoms) on self-reported STIs. Data were collected from 379 youth aged 18-30 years (n = 170 women; n = 179 men) in Montserrado County, Liberia. Results revealed that psychosocial variables correlated with each other and STI risk. In multivariable analysis, stressful life events, depressive symptoms, and IPV were statistically significant predictors of STI risk. We found support for an additive effect between the number of psychosocial conditions reported and STI risk, as well as a multiplicative effect (interaction) between IPV and depressive symptoms on STI risk. Our results suggest a synergy between experiencing psychosocial conditions and STI risk and point to the potential benefit of multi-level sexual health approaches that simultaneously address mental health and IPV among youth in Liberia.

Efficient and Targeted siRNA Delivery to M2 Macrophages by Smart Polymer Blends for M1 Macrophage Repolarization as a Promising Strategy for Future Cancer Treatment.

Cancer remains an issue on a global scale. It is estimated that nearly 10 million people succumbed to cancer worldwide in 2020. New treatment options are urgently needed. A promising approach is a conversion of tumor-promoting M2 tumor-associated macrophages (TAMs) as part of the tumor microenvironment to tumor-suppressive M1 TAMs by small interfering RNA (siRNA). In this work, we present a well-characterized polymeric nanocarrier system capable of targeting M2 TAMs by a ligand-receptor interaction. Therefore, we developed a blended PEI-based polymeric nanoparticle system conjugated with mannose, which is internalized after interaction with macrophage mannose receptors (MMRs), showing low cytotoxicity and negligible IL-6 activation. The PEI-PCL-PEI (5 kDa-5 kDa-5 kDa) and Man-PEG-PCL (2 kDa-2 kDa) blended siRNA delivery system was optimized for maximum targeting capability and efficient endosomal escape by evaluation of different polymer and N/P ratios. The nanoparticles were formulated by surface acoustic wave-assisted microfluidics, achieving a size of ∼80 nm and a zeta potential of approximately +10 mV. Special attention was given to the endosomal escape as the so-called bottleneck of RNA drug delivery. To estimate the endosomal escape capability of the nanocarrier system, we developed a prediction method by evaluating the particle stability via the inflection temperature. Our predictions were then verified in an in vitro setting by applying confocal microscopy. For cellular experiments, however, human THP-1 cells were polarized to M2 macrophages by cytokine treatment and validated through MMR expression. To show the efficiency of the nanoparticle system, GAPDH and IκBα knockdown was performed in the presence or absence of an MMR blocking excess of mannan. Cellular uptake, GAPDH knockdown, and NF-κB western blot confirmed efficient mannose targeting. Herein, we presented a well-characterized nanoparticle delivery system and a promising approach for targeting M2 macrophages by a mannose-MMR interaction.

Epilepsy monitoring unit practices and safety among NAEC epilepsy centers: A census survey.

OBJECTIVE: An epilepsy monitoring unit (EMU) is a specialized unit designed for capturing and characterizing seizures and other paroxysmal events with continuous video electroencephalography (vEEG). Nearly 260 epilepsy centers in the United States are accredited by the National Association of Epilepsy Centers (NAEC) based on adherence to specific clinical standards to improve epilepsy care, safety, and quality. This study examines EMU staffing, safety practices, and reported outcomes. METHOD: We analyzed NAEC annual report data and results from a supplemental survey specific to EMU practices reported in 2019 from 341 pediatric or adult center directors. Data on staffing, resources, safety practices and complications were collated with epilepsy center characteristics. We summarized using frequency (percentage) for categorical variables and median (inter-quartile range) for continuous variables. We used chi-square or Fisher's exact tests to compare staff responsibilities. RESULTS: The supplemental survey response rate was 100%. Spell classification (39%) and phase 1 testing (28%) were the most common goals of the 91,069 reported admissions. The goal ratio of EEG technologist to beds of 1:4 was the most common during the day (68%) and off-hours (43%). Compared to residents and fellows, advanced practice providers served more roles in the EMU at level 3 or pediatric-only centers. Status epilepticus (SE) was the most common reported complication (1.6% of admissions), while cardiac arrest occurred in 0.1% of admissions. SIGNIFICANCE: EMU staffing and safety practices vary across US epilepsy centers. Reported complications in EMUs are rare but could be further reduced, such as with more effective treatment or prevention of SE. These findings have potential implications for improving EMU safety and quality care.

Childhood sexual abuse and antiretroviral therapy adherence among older adults living with HIV: a mixed methods study.

Findings on the association between childhood sexual abuse (CSA) and antiretroviral therapy (ART) adherence have been varied, with some studies showing a relationship, or a lack thereof. However, to our knowledge, no study has examined this association among older adults living with HIV (OALH). Therefore, the purpose of this study was to examine the association between CSA and ART adherence among OALH using a mixed methods approach. This study, which involved a concurrent design, had two phases. The first phase comprised in-depth, semi-structured interviews of 24 adults aged 50 and older living with HIV in South Carolina. The second phase included data from 91 OALH. Thematic analysis and multivariable regression models, adjusting for age, gender, race, and income, were used to determine the association between CSA and ART adherence. The main theme emerging from the qualitative data was that CSA was not linked with ART adherence. However, contrastingly, quantitative analyses revealed a negative statistically significant association between CSA and ART adherence (adjusted ß: -3.35; 95% CI: -5.37, -1.34). This difference in findings could be due to the hidden impact of trauma and/or the use of different study populations. Future research should assess mediating pathways between CSA and ART adherence.

Integrating Youth Readiness Intervention and Entrepreneurship in Sierra Leone: A Hybrid Type II Cluster Randomized Trial.

OBJECTIVE: Conflict-affected youth are at risk for poor psychological and social outcomes, yet few receive mental health services. Strategies to expand access and sustain evidence-based interventions (EBIs) across novel delivery platforms must be tested. The present study was a hybrid type II implementation-effectiveness trial using a cluster randomized design. The primary goal was to evaluate feasibility and impact of using the collaborative team approach to deliver the Youth Readiness Intervention (YRI), an EBI, integrated into a youth entrepreneurship program (ENTR) with quality control in post-conflict Sierra Leone. METHOD: Youth were screened and randomly assigned to control, ENTR, or combined YRI and ENTR (YRI+ENTR). Implementation outcomes were dissemination and implementation indicators, competence, and fidelity. Effectiveness outcomes were emotion regulation, psychological distress, and interpersonal functioning. Secondary outcomes were third-party reporter assessments of youth functioning and behavior. RESULTS: Data were collected and analyzed from 1,151 youth participants and 528 third-party reporters. Scores on implementation constructs, competence, and fidelity demonstrated acceptable intervention response and quality. YRI+ENTR participants showed overall improvements in depression (ß = -.081, 95% CI -0.124 to -0.038, d = -0.154) and anxiety (ß = -.043, 95% CI -0.091 to -0.005, d = 0.082) symptoms compared with control participants. Community leaders indicated that YRI+ENTR participants demonstrated improvements in overall work or training performance compared with control participants (ß = -.114, 95% CI 0.004 to 0.232, d = 0.374). CONCLUSION: Integration of EBIs such as the YRI into youth employment programs has the potential to address limited reach of EBIs in conflict and post-conflict settings. A collaborative team implementation approach can facilitate integration and fidelity. PLAIN LANGUAGE SUMMARY: In a Hybrid Type-II Implementation-Effectiveness trial conducted in Sierra Leone, researchers tested a Collaborative Team Approach (CTA) for delivering an evidence-based mental health intervention, the Youth Readiness Intervention (YRI), within a youth entrepreneurship program. A total of 1,151 youth participated in the study, with outcomes measured on youth mental health indicators of emotional regulation, psychological distress, and interpersonal functioning, as well as implementation indicators, competence, and fidelity. Results demonstrated that the integrated YRI and entrepreneurship program led to significant improvements in depression and anxiety symptoms compared to the control group. Community leaders also noted enhanced overall performance in YRI participants, suggesting that integrating evidence-based interventions into youth employment programs can effectively address mental health challenges in low-resource regions. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. One or more of the authors of this paper received support from a program designed to increase minority representation in science. CLINICAL TRIAL REGISTRATION INFORMATION: Youth FORWARD Phase 2 YRI and EPP Study; https://clinicaltrials.gov/; NCT03542500. STUDY PREREGISTRATION INFORMATION: Youth Functioning and Organizational Success for West African Regional Development (Youth FORWARD): Study Protocol; https://doi.org/10.1176/appi.ps.202000009.