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UC San Francisco Previously Published Works

Volumetric hyperthermia delivery using the ExAblate Body MR-guided focused ultrasound system

(2024)

Objectives

To investigate image-guided volumetric hyperthermia strategies using the ExAblate Body MR-guided focused ultrasound ablation system, involving mechanical transducer movement and sector-vortex beamforming.

Materials and methods

Acoustic and thermal simulations were performed to investigate volumetric hyperthermia using mechanical transducer movement combined with sector-vortex beamforming, specifically for the ExAblate Body transducer. The system control in the ExAblate Body system was modified to achieve fast transducer movement and MR thermometry-based hyperthermia control, mechanical transducer movements and electronic sector-vortex beamforming were combined to optimize hyperthermia delivery. The experimental validation was performed using a tissue-mimicking phantom.

Results

The developed simulation framework allowed for a parametric study with varying numbers of heating spots, sonication durations, and transducer movement times to evaluate the hyperthermia characteristics for mechanical transducer movement and sector-vortex beamforming. Hyperthermic patterns involving 2-4 sequential focal spots were analyzed. To demonstrate the feasibility of volumetric hyperthermia in the system, a tissue-mimicking phantom was sonicated with two distinct spots through mechanical transducer movement and sector-vortex beamforming. During hyperthermia, the average values of Tmax, T10, Tavg, T90, and Tmin over 200 s were measured within a circular ROI with a diameter of 10 pixels. These values were found to be 8.6, 7.9, 6.6, 5.2, and 4.5 °C, respectively, compared to the baseline temperature.

Conclusions

This study demonstrated the volumetric hyperthermia capabilities of the ExAblate Body system. The simulation framework developed in this study allowed for the evaluation of hyperthermia characteristics that could be implemented with the ExAblate MRgFUS system.

Cover page of Feasibility and acceptability of chaplain decision coaching on Periviable resuscitation decision quality: A pilot study.

Feasibility and acceptability of chaplain decision coaching on Periviable resuscitation decision quality: A pilot study.

(2024)

OBJECTIVE: To pilot test and assess the feasibility and acceptability of chaplain-led decision coaching alongside the GOALS (Getting Optimal Alignment around Life Support) decision support tool to enhance decision-making in threatened periviable delivery. METHODS: Pregnant people admitted for threatened periviable delivery and their important other (IO) were enrolled. Decisional conflict, acceptability, and knowledge were measured before and after the intervention. Chaplains journaled their impressions of training and coaching encounters. Descriptive analysis and conventional content analysis were completed. RESULTS: Eight pregnant people and two IOs participated. Decisional conflict decreased by a mean of 6.7 (SD = 9.4) and knowledge increased by a mean of 1.4 (SD = 1.8). All rated their experience as good or excellent, and the amount of information was just right. Participants found it helpful to have someone to talk to and noted chaplains helped them reach a decision. Chaplains found the intervention a valuable use of their time and skillset. CONCLUSION: This is the first small-scale pilot study to utilize chaplains as decision coaches. Our results suggest that chaplain coaching with a decision support tool is feasible and well-accepted by parents and chaplains. INNOVATIONS: Our findings recognize chaplains as an underutilized, yet practical resource in value-laden clinical decision-making.

Cover page of Mobile-enhanced Family Integrated Care for preterm infants: A qualitative study of parents views.

Mobile-enhanced Family Integrated Care for preterm infants: A qualitative study of parents views.

(2024)

OBJECTIVE: The Family Integrated Care (FICare) model improves outcomes for preterm infants and parents compared with family-centered care (FCC). FICare with mobile technology (mFICare) may improve uptake and impact. Research on FICare in the United States (US) is scarce and little is known about parents experience. METHODS: We conducted qualitative interviews with nine parents, exploring their NICU experiences, participation in and perceptions of the mFICare program. A directed content analysis approach was used, and common themes were derived from the data. RESULTS: Overall, parents had positive NICU experiences and found mFICare helpful in meeting three common parenting priorities: actively caring for their infant, learning how to care for their infant, and learning about the clinical status of their infant. They described alignment and misalignment with mFICare components relative to their personal parenting priorities and offered suggestions for improvement. Nurses were noted to play key roles in providing or facilitating parent support and encouragement to participate in mFICare and parenting activities. CONCLUSION: The mFICare program showed potential for parental acceptance and participation in US NICUs. INNOVATION: The mFICare model is an innovation in neonatal care that can advance the consistent delivery of NICU family-centered care planning and caregiving.Clinical Trial Registration:NCT03418870 01/02/2018.

Cover page of Fecal microbiota is associated with extraintestinal manifestations in inflammatory bowel disease.

Fecal microbiota is associated with extraintestinal manifestations in inflammatory bowel disease.

(2024)

INTRODUCTION: A large proportion of patients with inflammatory bowel disease (IBD) experience IBD-related inflammatory conditions outside of the gastrointestinal tract, termed extraintestinal manifestations (EIMs) which further decreases quality of life and, in extreme cases, can be life threatening. The pathogenesis of EIMs remains unknown, and although gut microbiota alterations are a well-known characteristic of patients with IBD, its relationship with EIMs remains sparsely investigated. This study aimed to compare the gut microbiota of patients with IBD with and without EIMs. METHODS: A total of 131 Danish patients with IBD were included in the study, of whom 86 had a history of EIMs (IBD-EIM) and 45 did not (IBD-C). Stool samples underwent 16S rRNA sequencing. Amplicon sequence variants (ASVs) were mapped to the Silva database. Diversity indices and distance matrices were compared between IBD-EIM and IBD-C. Differentially abundant ASVs were identified using a custom multiple model statistical analysis approach, and modules of co-associated bacteria were identified using sparse correlations for compositional data (SparCC) and related to patient EIM status. RESULTS: Patients with IBD and EIMs exhibited increased disease activity, body mass index, increased fecal calprotectin levels and circulating monocytes and neutrophils. Microbiologically, IBD-EIM exhibited lower fecal microbial diversity than IBD-C (Mann-Whitneys test, p = .01) and distinct fecal microbiota composition (permutational multivariate analysis of variance; weighted UniFrac, R2 = 0.018, p = .01). A total of 26 ASVs exhibited differential relative abundances between IBD-EIM and IBD-C, including decreased Agathobacter and Blautia and increased Eggerthella lenta in the IBD-EIM group. SparCC analysis identified 27 bacterial co-association modules, three of which were negatively related to EIM (logistic regression, p < .05) and included important health-associated bacteria, such as Agathobacter and Faecalibacterium. CONCLUSIONS: The fecal microbiota in IBD patients with EIMs is distinct from that in IBD patients without EIM and could be important for EIM pathogenesis.

Cover page of A family-centered approach to social needs awareness in the pediatric emergency department.

A family-centered approach to social needs awareness in the pediatric emergency department.

(2024)

OBJECTIVE: We aimed to understand family preferences around reporting and receiving health-related social needs (HRSN) information by assessment modality during pediatric emergency department (PED) visits. METHODS: Families were randomized into paper (control), cell phone, or tablet modality groups by their childs exam room. Nurses alerted families to complete a single HRSN assessment during routine workflow. We used logistic regression and McNemars test to assess discordance in modality preference. RESULTS: Forty-seven percent of families disclosed at least one HRSN across a total 611 assessments. Disclosure of HRSN was similar by modality. Twenty-three percent of those assigned tablet preferred cell phone (p < 0.001). Two-thirds of families preferred receiving digitally formatted community resources (email or text). There was no difference in preferred timing of HRSN assessment completion. CONCLUSIONS: Assessment modality did not appear to influence family HRSN disclosure. Families were generally satisfied with all HRSN assessment modalities but demonstrated a particular preference in using personal cell phones over tablets. Digitally formatted community referrals also pose numerous advantages over conventional paper handouts. INNOVATION: Use of personal cell phones is a novel, streamlined method of HRSN interventions in the clinical setting, performing similar to more conventional modalities, with a preference among families when compared to tablets.

Cover page of Adaptation of a health literacy screener for computerized, self-administered use by U.S. adults.

Adaptation of a health literacy screener for computerized, self-administered use by U.S. adults.

(2024)

OBJECTIVE: Health literacy is a critical health determinant, for which few computerized, self-administered assessments exist. This study adapted and tested the reliability of the Newest Vital Sign© (NVS) as a computerized, self-administered health literacy screener. METHODS: Phase one involved 33 participants to create response options for a computerized, self-administered NVS (C-NVS). Phase two was a randomized crossover trial to test the consistency of C-NVS and original, interviewer-administered NVS (I-NVS) scores in 89 participants. RESULTS: Linear mixed-effects regression model results showed a significant carryover effect (p < .001). Crossover trial data from time 1 showed that participants who initially received the C-NVS had significantly higher average scores (M = 5.7, SD = 0.6) than participants who received the I-NVS (M = 4.5, SD = 1.5; t(87) = 5.25, p < .001). Exploratory analysis results showed that when the washout period was longer than 33 days (75th percentile) the carryover effect was not statistically significant (p = .077). CONCLUSION AND INNOVATION: Findings suggest learning can occur when health literacy screeners are administered more than once in less than a months time and computerized, self-administered health literacy screeners may produce ceiling effects. A universal precautions approach to health literacy therefore remains germane.

Cover page of Cannabis use trajectories over time in relation to minority stress and gender among sexual and gender minority people

Cannabis use trajectories over time in relation to minority stress and gender among sexual and gender minority people

(2024)

Substance use disparities among sexual and gender minority (SGM) people are attributed to minority stress, but few studies have examined minority stress and cannabis use over time or investigated differences in cannabis use trajectories by less-studied gender subgroups. We examined if longitudinal cannabis use trajectories are related to baseline minority stressors and if gender differences persisted after accounting for minority stress. Cannabis use risk was measured annually over four years (2017-2021) within a longitudinal cohort study of SGM adults in the United States (N = 11,813). Discrimination and victimization, internalized stigma, disclosure and concealment, and safety and acceptance comprised minority stress (n = 5,673). Latent class growth curve mixture models identified five cannabis use trajectories: 'low or no risk', 'low moderate risk', 'high moderate risk', 'steep risk increase', and 'highest risk'. Participants who reported past-year discrimination and/or victimization at baseline had greater odds of membership in any cannabis risk category compared to the 'low risk' category (odds ratios [OR] 1.17-1.33). Internalized stigma was related to 'high moderate' and 'highest risk' cannabis use (ORs 1.27-1.38). After accounting for minority stress, compared to cisgender men, gender expansive people and transgender men had higher odds of 'low moderate risk' (ORs 1.61, 1.67) or 'high moderate risk' (ORs 2.09, 1.99), and transgender men had higher odds of 'highest risk' (OR 2.36) cannabis use. This study indicates minority stress is related to prospective cannabis use risk trajectories among SGM people, and transgender men and gender expansive people have greater odds of trajectories reflecting cannabis use risk.

Cover page of β-catenin mRNA encapsulated in SM-102 lipid nanoparticles enhances bone formation in a murine tibia fracture repair model.

β-catenin mRNA encapsulated in SM-102 lipid nanoparticles enhances bone formation in a murine tibia fracture repair model.

(2024)

Fractures continue to be a global economic burden as there are currently no osteoanabolic drugs approved to accelerate fracture healing. In this study, we aimed to develop an osteoanabolic therapy which activates the Wnt/β-catenin pathway, a molecular driver of endochondral ossification. We hypothesize that using an mRNA-based therapeutic encoding β-catenin could promote cartilage to bone transformation formation by activating the canonical Wnt signaling pathway in chondrocytes. To optimize a delivery platform built on recent advancements in liposomal technologies, two FDA-approved ionizable phospholipids, DLin-MC3-DMA (MC3) and SM-102, were used to fabricate unique ionizable lipid nanoparticle (LNP) formulations and then tested for transfection efficacy both in vitro and in a murine tibia fracture model. Using firefly luciferase mRNA as a reporter gene to track and quantify transfection, SM-102 LNPs showed enhanced transfection efficacy in vitro and prolonged transfection, minimal fracture interference and no localized inflammatory response in vivo over MC3 LNPs. The generated β-cateninGOF mRNA encapsulated in SM-102 LNPs (SM-102-β-cateninGOF mRNA) showed bioactivity in vitro through upregulation of downstream canonical Wnt genes, axin2 and runx2. When testing SM-102-β-cateninGOF mRNA therapeutic in a murine tibia fracture model, histomorphometric analysis showed increased bone and decreased cartilage composition with the 45 μg concentration at 2 weeks post-fracture. μCT testing confirmed that SM-102-β-cateninGOF mRNA promoted bone formation in vivo, revealing significantly more bone volume over total volume in the 45 μg group. Thus, we generated a novel mRNA-based therapeutic encoding a β-catenin mRNA and optimized an SM-102-based LNP to maximize transfection efficacy with a localized delivery.

Cover page of Association of body mass index with progression from binge-eating behavior into binge-eating disorder among adolescents in the United States: A prospective analysis of pooled data

Association of body mass index with progression from binge-eating behavior into binge-eating disorder among adolescents in the United States: A prospective analysis of pooled data

(2024)

The association between body mass index (BMI) and binge-eating disorder (BED) is well-established. However, data on the extent to which BMI is associated with progression from binge-eating behavior into BED among adolescents are limited, which was the aim of this investigation. Participants were 9964 U.S. adolescents from the Adolescent Brain Cognitive Development (ABCD) Study, aged 9-13 at the time of study enrollment. A computerized parent-reported assessment was used to establish adolescents' binge-eating behaviors and BED. Cox proportional hazards models adjusting for sociodemographic covariates were used to examine prospective associations between BMI and likelihood of BED onset among a) adolescents with binge-eating behavior, and b) adolescents with no binge-eating behavior. Of 975 adolescents who met the study criteria for binge-eating behavior, 89 (9.1%) subsequently met the study criteria for BED. Of 8989 adolescents with no binge-eating behavior, 82 (0.9%) subsequently met the study criteria for BED. BMI percentile was significantly associated with the likelihood of BED onset in participants with (adjusted HR = 1.03, 95% confidence interval [CI] 1.00, 1.06) and participants without (adjusted HR = 1.05, 95% CI 1.03, 1.07) binge-eating behavior. Results were also significant when examining BMI as a dichotomous predictor (above and below 85th percentile) among those with (adjusted HR = 2.60, 95% CI 1.00, 6.68) and those without (adjusted HR = 6.01, 95% CI 3.90, 11.10) binge-eating behavior. Overall, results indicate that elevated BMI is prospectively associated with a greater risk for BED onset among U.S. adolescents with or without binge-eating behavior. Adolescents with a higher BMI may benefit from screening for binge eating, and prevention/early intervention strategies to mitigate the risk for developing BED.