Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 117
Filter
3.
Am J Prev Med ; 67(2): 291-295, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38555031

ABSTRACT

INTRODUCTION: Health-related social problems may be conceptualized as the presence of either a social risk (i.e., food insecurity as defined by a screening tool) or a social need (i.e., desire for referral to a food program). Identification of social risks may not correlate with patients' desire to receive help. This study aimed to identify and compare patients and families with social risks versus social needs in a pediatric emergency department. METHODS: This was a planned secondary analysis conducted in 2023 of a previously published prospective intervention study, which screened and referred caregivers and adult patients for health-related social problems in an urban tertiary pediatric emergency department between May 2019 and October 2020. Participants completed a screening tool for social risks and self-identified social needs by selecting desired assistance from a list of social service categories. Participants' social risk screening results were compared with their selection of resources for social needs across demographic and socioeconomic characteristics and the number of positive social risks using chi-squared or Fisher's exact tests. RESULTS: Of 258 participants, 42.2% (109) screened positive for any social risk, and 38.0% (98) self-selected a social need. Of those, only 59.2% (77/130) both screened positive and self-selected a need. Among those who screened positive for a social risk, several demographic and socioeconomic factors including race, ethnicity, and income were significantly different between those interested versus not interested in assistance. CONCLUSIONS: Both social risks and self-identified social needs should be considered within social care interventions in the pediatric healthcare setting.


Subject(s)
Emergency Service, Hospital , Food Insecurity , Humans , Emergency Service, Hospital/statistics & numerical data , Female , Male , Child , Prospective Studies , Adolescent , Adult , Child, Preschool , Needs Assessment , Socioeconomic Factors
4.
iScience ; 27(2): 108836, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38303687

ABSTRACT

Systemic administration of interleukin (IL)-12 induces potent anti-tumor immune responses in preclinical cancer models through the systemic activation of effector immune cells and release of proinflammatory cytokines. IL-12-loaded PLGA nanospheres (IL12ns) are hypothesized to improve therapeutic efficacy and thwart unwanted side effects observed in previous human clinical trials. Through the investigation of peripheral blood and local tissue immune responses in healthy BALB/c mice, the immune-protective pharmacodynamics of IL12ns were suggested. Nanospheres increased pro-inflammatory plasma cytokines/chemokines (IFN-γ, IL-6, TNF-α, and CXCL10) without inducing maladaptive transcriptomic signatures in circulating peripheral immune cells. Gene expression profiling revealed activation of pro-inflammatory signaling pathways in systemic tissues, the likely source of these effector cytokines. These data support that nanosphere pharmacodynamics, including shielding IL-12 from circulating immune cells, depositing peripherally in systemic immune tissues, and then slowly eluting bioactive cytokine, thereafter, are essential to safe immunostimulatory therapy.

5.
J Telemed Telecare ; : 1357633X231224491, 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38254285

ABSTRACT

INTRODUCTION: The goal of this systematic review was to examine the efficacy of behavioral health care treatments for posttraumatic stress disorder (PTSD), depression, and anxiety delivered via telehealth. METHODS: We searched a combination of keywords related to telehealth, relevant mental health disorders, and evidence-based psychotherapies in three databases (PubMed, PsycInfo, and Embase) from database inception to April 2022. We included randomized controlled trials published in English wherein at least one arm received an evidence-based psychotherapy via telehealth. To be included, studies also had to enroll an adult population with symptoms or diagnosis of PTSD, depressive disorder, or anxiety disorder. RESULTS: Moderate quality of evidence was consistent with only small differences, if any, in efficacy between video teleconferencing (VTC) and in-person delivery for patients with PTSD (d = 0.06, 95% CI -0.17, 0.28). However, for those with depression, in-person delivery was associated with better outcomes compared to VTC (d = 0.28, 95% CI 0.03, 0.54; low quality of evidence). We also found that evidence-based treatments delivered over telephone were more efficacious for depression compared to treatment as usual (d = -0.47, 95% CI -0.66, -0.28; very low quality of evidence). Very low quality of evidence supported the use of telehealth versus waitlist for anxiety (d = -0.48, 95% CI -0.89, -0.09). CONCLUSIONS: A synthesis across 29 studies indicates that the efficacy of telehealth for delivery of evidence-based behavioral health interventions varies by target diagnosis and telehealth modality. More research is needed on the efficacy of telehealth treatments for depression and anxiety.

6.
Mil Med ; 188(Suppl 6): 621-628, 2023 11 08.
Article in English | MEDLINE | ID: mdl-37948289

ABSTRACT

INTRODUCTION: To assist in addressing medical readiness challenges, the DOD has established various Centers of Excellence to focus efforts to protect, treat, train, and educate service members concerning risks and potential injuries. Using the hearing health domain as a pilot, this effort used DOD methods to evaluate all facets of successful health behavior change (HBC) practices within a military environment and developed a framework and pathway for HBC. METHODS: The DOD uses the Joint Capabilities Integration and Development System (JCIDS) to ensure new DOD capabilities are identified and fielded in a manner that is interoperable, resilient, and supportables. The study sponsor for the Health Behavioral Change Framework study is the Defense Health Agency Deputy Assistant Director for Research and Engineering (R&E). The main objective of this group was to ensure that final products would both meet the requirements as defined by the JCIDS process, as well as be used by the operational force in addressing HBCs that improve readiness of the joint force. RESULTS: The Health Behavior Change Guidebook applies to all organizations across the DOD and military health system that may participate in or support specific tasks related to the design, conduct, and assessment of the HBC campaign. The advantage of the process is the ability to define gaps and solutions at an enterprise level. The HBC framework can be applied to a variety of health domains to include behavioral health. CONCLUSIONS: Use of the "Guidebook for Design, Conduct and Assessment of Health Behavior Change Campaign Within the DOD" and DOTMLPF-P analysis will move Defense Health Agency toward more disciplined use of the JCIDS. The HBC framework allowed the Hearing Center of Excellence to lead the hearing health community to create a capability-based assessment for hearing HBC.


Subject(s)
Health Behavior , Military Personnel , Humans , United States , Hearing , Health Promotion , United States Department of Defense
7.
Acad Pediatr ; 2023 Nov 08.
Article in English | MEDLINE | ID: mdl-37949169

ABSTRACT

OBJECTIVE: To explore barriers, facilitators, and benefits of collaboration between academic pediatricians and institutional offices of government relations (OGR) to enhance policy advocacy efforts. METHODS: The Academic Pediatric Associations' Health Policy Scholars met with the government relations team in their affiliated institutions as part of their experiential learning curriculum. Afterward, they submitted written reflections, which were coded and analyzed using inductive qualitative content analysis to identify key themes. RESULTS: Reflections were completed by 21 of 23 (91.3%) participants. Most participants (76.2%) were faculty at free-standing children's hospitals and had been at their institutions <5 years (52.3%) or 5 to 10 years (33.3%). Institutional OGR structure varied widely and not all institutions had well-defined priorities. Key themes of the reflections included that OGRs often had dynamic priorities and fiscal considerations frequently took precedence. Barriers to physician involvement with OGR are often related to difficulty identifying the correct staff contact and not having the time and support for advocacy work. Facilitators included leveraging existing relationships and collaborations, including those of peer or mentor connections to the OGR staff. Anticipated benefits to both OGR and physicians included improved knowledge of advocacy opportunities, enhanced advocacy efforts leveraging physicians' expertise and patient stories, and message alignment and amplification of physician and institutional advocacy work. CONCLUSIONS: Collaboration between physician-advocates and institutional OGR is feasible and, with orientation and mentorship, may facilitate improved physician and institutional policy advocacy efforts. Supporting this type of collaboration may enhance physician and institutional advocacy on behalf of their shared patients and communities.

9.
Pediatrics ; 152(2)2023 08 01.
Article in English | MEDLINE | ID: mdl-37465910

ABSTRACT

Research suggests that increased voting among adults is associated with improved child health. Despite the benefits of voting, the United States has low voter turnout compared with peer nations. Turnout is especially low among marginalized people in the United States. Voter registration is essential for increasing voter turnout, and registration efforts have been successfully carried out in clinical settings. Working with a nonprofit called Vot-ER, we advocated for nonpartisan voter registration efforts in pediatric settings nationwide preceding the November 2020 US elections. We describe lessons learned from these efforts. Using data obtained from Vot-ER, we also provide the first estimates of participation in a national voter registration campaign in pediatric settings. There was widespread engagement in voter registration efforts among pediatricians in 2020. Many lessons were learned from these efforts, including the benefits of advanced planning because registration deadlines can be up to 1 month in advance of Election Day. Obtaining buy-in from numerous stakeholders (e.g., health center leadership, public relations teams) supports widespread staff participation. Also important is to consider the tradeoffs between active voter registration (in which staff can broach the topic of voting with patients and families) and passive efforts (in which voting is discussed only if patients or families inquire about it). These and other lessons can inform future voter registration efforts in diverse pediatric settings across the country.


Subject(s)
Politics , Adult , Humans , United States
10.
JAMA Pediatr ; 177(6): 637-640, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37036731

ABSTRACT

This cross-sectional study uses statewide data to evaluate the association of homelessness with emergency department use patterns of children in New York.


Subject(s)
Ill-Housed Persons , Humans , Child , New York/epidemiology , Social Problems , Emergency Service, Hospital
11.
JAMA Netw Open ; 6(4): e239646, 2023 04 03.
Article in English | MEDLINE | ID: mdl-37093600

ABSTRACT

Importance: Infant mortality in the United States is highest among peer nations; it is also inequitable, with the highest rates among Black infants. The association between tax policy and infant mortality is not well understood. Objective: To examine the association between state-level tax policy and state-level infant mortality in the US. Design, Setting, and Participants: This state-level, population-based cross-sectional study investigated the association between tax policy and infant mortality in the US from 1996 through 2019. All US infant births and deaths were included, with data obtained from the National Center for Health Statistics. Data were analyzed from November 28, 2021, to July 9, 2022. Exposures: State-level tax policy was operationalized as tax revenue per capita and tax progressivity. The Suits index was used to measure tax progressivity, with higher progressivity indicating increased tax rates for wealthier individuals. Main Outcomes and Measures: The association between tax policy and infant mortality rates was analyzed using a multivariable, negative binomial, generalized estimating equations model. Since 6 years of tax progressivity data were available (1995, 2002, 2009, 2012, 2014, and 2018), 300 state-years were included. Adjusted incidence rate ratios (aIRRs) were calculated controlling for year, state-level demographic variables, federal transfer revenue, and other revenue. Secondary analyses were conducted for racial and ethnic subgroups. Results: There were 148 336 infant deaths in the US from 1996 through 2019, including 27 861 Hispanic infants, 1882 non-Hispanic American Indian or Alaska Native infants, 5792 non-Hispanic Asian or Pacific Islander infants, 41 560 non-Hispanic Black infants, and 68 666 non-Hispanic White infants. The overall infant mortality rate was 6.29 deaths per 1000 live births. Each $1000 increase in tax revenue per capita was associated with a 2.6% decrease in the infant mortality rate (aIRR, 0.97; 95% CI, 0.95-0.99). An increase of 0.10 in the Suits index (ie, increased tax progressivity) was associated with a 4.6% decrease in the infant mortality rate (aIRR, 0.95; 95% CI, 0.91-0.99). Increased tax progressivity was associated with decreased non-Hispanic White infant mortality (aIRR, 0.95; 95% CI, 0.91-0.99), and increased tax revenue was associated with increased non-Hispanic Black infant mortality (aIRR, 1.04; 95% CI, 1.01-1.08). Conclusions and Relevance: In this cross-sectional study, an increase in tax revenue and the Suits index of tax progressivity were both associated with decreased infant mortality. These associations varied by race and ethnicity. Tax policy is an important, modifiable social determinant of health that may influence state-level infant mortality.


Subject(s)
Ethnicity , Infant Mortality , Taxes , Humans , Infant , Cross-Sectional Studies , Hispanic or Latino , Policy , United States , American Indian or Alaska Native , White , Black or African American
12.
J Food Sci ; 88(4): 1700-1717, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36855311

ABSTRACT

Although alcoholic or "hard" cider is a beverage of growing popularity throughout the Northeastern and Mid-Atlantic United States (US), the industry lacks a consistent language for describing the sensory quality of its products. The main objective of this research was to explore the sensory attributes that can be used to describe a large representative sample (N = 42 samples) of ciders from Virginia, Vermont, and New York, using classical descriptive analysis (DA). The secondary objective of the research was to determine if cider samples' sensory attributes differ based on extrinsic factors, such as style, packaging, and apple varieties. The study was conducted using a standard DA: 8 panelists were trained for 13 h to develop a lexicon of aroma, taste, and mouthfeel descriptors for 42 cider samples (15 single varietal ciders, 27 blended ciders). Then, subjects evaluated each cider in duplicate for all descriptive attributes in standard sensory-evaluation conditions. Results were analyzed to determine overall differences among the individual cider samples, geographic origins, cider styles, and packaging formats, as well as significant differences across individual attributes. Herein, we report on 29 attributes that can be used to discriminate cider samples, as well as a subset of attributes which differentiate ciders based on extrinsic product variables. These results provide a framework for describing ciders from the Northeast and Mid-Atlantic regions of the US, which may be further generalizable to other North American ciders. As well, these results highlight the potential for more descriptive, sensory-based style guidelines may inspire future research related to cider production practices and terroir.


Subject(s)
Alcoholic Beverages , Malus , Humans , United States , Alcoholic Beverages/analysis , Beverages/analysis , Taste Perception , Odorants/analysis
13.
Nature ; 617(7961): 555-563, 2023 May.
Article in English | MEDLINE | ID: mdl-36996873

ABSTRACT

An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland1 in April 2022 and has now been identified in 35 countries2. Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10-12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a 'helper virus' to support AAV2 replication) and disease susceptibility related to HLA class II status.


Subject(s)
Adenovirus Infections, Human , Dependovirus , Hepatitis , Child , Humans , Acute Disease/epidemiology , Adenovirus Infections, Human/epidemiology , Adenovirus Infections, Human/genetics , Adenovirus Infections, Human/virology , Alleles , Case-Control Studies , CD4-Positive T-Lymphocytes/immunology , Coinfection/epidemiology , Coinfection/virology , Dependovirus/isolation & purification , Genetic Predisposition to Disease , Helper Viruses/isolation & purification , Hepatitis/epidemiology , Hepatitis/genetics , Hepatitis/virology , Hepatocytes/virology , HLA-DRB1 Chains/genetics , HLA-DRB1 Chains/immunology , Liver/virology
14.
Am J Prev Med ; 64(6): 918-926, 2023 06.
Article in English | MEDLINE | ID: mdl-36610922

ABSTRACT

INTRODUCTION: The objective of this study was to determine the rates and trends in the reporting of preferred language, socioeconomic factors, sexual orientation, and gender identity in published pediatric clinical trials. METHODS: A cross-sectional study of pediatric clinical trials conducted in the U.S. published from January 1, 2011 through December 31, 2020 in 5 general pediatric and 5 general medical journals with the highest impact factor in their respective fields was performed. Outcomes were reporting of preferred language, socioeconomic factors, sexual orientation, and gender identity. In late 2021, descriptive statistics and logistic regression to understand how reporting of preferred language and socioeconomic factors changed over time were performed. RESULTS: Of 612 trials, 29.6% (n=181) reported preferred language. Among these, 64.6% (n=117 of 181) exclusively enrolled participants whose preferred language was English. From 2011 to 2020, there was a relative increase in the reporting of preferred language (8.6% per year, 95% CI=1.8, 16.0). Socioeconomic factors were reported in 47.9% (n=293) of trials. There was no significant change in the reporting of socioeconomic factors (8.2% per year, 95% CI= -1.9, 15.1). Only 5.1% (9 of 179) of published trial results among adolescent participants reported any measure of sexual orientation, and 1.1% (2 of 179) reported gender identity. CONCLUSIONS: Preferred language, socioeconomic factors, sexual orientation, and gender identity were infrequently reported in pediatric clinical trial results despite these characteristics being increasingly recognized as social determinants of health. To achieve more inclusiveness and to reduce unmeasured disparities, these characteristics should be incorporated into routine trial registration, design, funding decisions, and reporting.


Subject(s)
Gender Identity , Social Determinants of Health , Adolescent , Humans , Male , Female , Child , Cross-Sectional Studies , Sexual Behavior , Socioeconomic Factors
15.
Prev Med ; 167: 107423, 2023 02.
Article in English | MEDLINE | ID: mdl-36641128

ABSTRACT

The legal and medical rights of lesbian, gay, bisexual, transgender, queer (LGBTQ+) and other gender and sexual minority (GSM) youth are under attack in the United States. Approximately 160 anti-LGBTQ+ bills were proposed across the United States during the 2021 legislative session, with 70% of states considering at least one anti-LGBTQ+ bill. Over one hundred of the proposed bills specifically target transgender youth and have already resulted in the prohibition of nearly 85,000 13-17-year-old trans youth from participating in sports as their affirmed gender. Such legislation directly impacts the health of youth including in Arkansas and Tennessee which passed bills that limit youth access to evidenced-based, gender-affirming care; in February 2022, the governor of Texas directed state agencies to investigate gender-affirming care for trans youths as 'child abuse'. Despite these anti-LGBTQ+ proposed and passed laws, 22 states have full non-discrimination protections for LQBTQ+ individuals, and 24 states have laws that protect LGBTQ+ students from bullying on the basis of their sexual orientation and/or gender identity. Civil rights policies have the power to grant protections to LGBTQ+ youth under the law. Conversely, the rollback of those liberties may lead to irreparable harm and preventable deaths. The consequences of anti-LGBTQ+ legislation can additionally deleteriously affect local and state economies as companies and organizations move to supportive communities. Clinicians can, and should, play an important role to engage stakeholders and advocate for LGBTQ+ inclusive policies at the institutional, local, state, and national policy level.


Subject(s)
Homosexuality, Female , Sexual and Gender Minorities , Transgender Persons , Adolescent , Female , Humans , Male , Gender Identity , Policy , Sexual Behavior , United States
16.
Pediatrics ; 151(2)2023 02 01.
Article in English | MEDLINE | ID: mdl-36655372

ABSTRACT

ABSTRACT: A 2012 Massachusetts shelter eligibility regulation required many families to spend a night in a location "not meant for human habitation" before qualifying for the state-run shelter system, and many families experiencing homelessness stayed in pediatric emergency departments (EDs) overnight to meet this requirement. ED clinicians initially recognized an increase in ED visits for homelessness after this regulation and began compiling and sharing stories with key institutional and community partners and stakeholders. To bolster advocacy efforts, the authors collected data on the magnitude of the problem and its associated health care costs. Guided by the policy knowledge of community partners, the authors leveraged the expertise and advocacy power of clinicians to share these data and stories with legislators via written and oral testimony, community events, and the media. Academic publication lent additional credibility and exposure to their research. In 2019, the Massachusetts Legislature passed budget language to overturn the 2012 shelter eligibility regulation. However, despite this policy victory, some families continue to present to EDs for homelessness. Therefore, current advocacy efforts have shifted focus toward implementation and enforcement of the new policy, monitoring issues, and developing new programmatic responses. In this advocacy case study, we illustrate how clinicians have unique abilities to serve as effective advocates for social policy change using a framework of strategies including storytelling, coalition building, tailored communication, and data sharing. Partnering with existing advocacy networks within their institution and community enhances the advocacy efforts of all stakeholders to influence social and health outcomes for children and families.


Subject(s)
Ill-Housed Persons , Child , Humans , Social Problems , Housing , Health Care Costs , Government Agencies
17.
Psychol Serv ; 20(1): 74-83, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35420858

ABSTRACT

Caring Contacts (CC), a low-cost intervention originally designed and tested by Jerome Motto in 1976, remains one of the few strategies to demonstrate efficacy in the prevention of suicide deaths. Interest in CC has increased steadily over the last several years in tandem with rising U.S. suicide rates and the acceleration of suicide prevention initiatives. There have been several efforts to design interventions modeled after Motto's strategy, and the recent publication of additional large-scale randomized controlled trials (RCTs) in alignment with the intent of Motto's original model afford an opportunity to systematically review efficacy findings. The current systematic review provides an updated and focused analysis of the evidence supporting the efficacy of CC. A systematic literature search of MEDLINE, EMBASE, PsycINFO, Cochrane Library, and ClinicalTrials.gov was conducted, and PRISMA, Cochrane, and GRADE guidelines were followed. Of 2,746 abstracts reviewed, 13 publications, comprising six randomized controlled trials (RCTs) met inclusion criteria. The studies encompassed 6,218 participants across four countries and military, veteran, and civilian health care systems. The primary outcome was suicide mortality; secondary outcomes were suicide attempts and emergency department (ED) presentations/hospitalizations. The DerSimonian-Laird random-effects univariate meta-analysis was used to estimate summary effect sizes and evaluate statistical heterogeneity. Summary risk ratio estimates ranged from 0.57 to 1.29 across outcomes and time points; most estimates indicated a protective effect. For suicide deaths and ED presentations/hospitalization, interval estimates at 1-year postrandomization were consistent with either an increase or a decrease in risk. A protective effect was observed for suicide attempts at 1-year postrandomization. Implications and methodological recommendations for future work in this area reviewed and discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Subject(s)
Military Personnel , Veterans , Humans , Suicide, Attempted/prevention & control , Suicide Prevention
18.
Mil Med ; 188(5-6): 907-913, 2023 05 16.
Article in English | MEDLINE | ID: mdl-35446423

ABSTRACT

INTRODUCTION: This study evaluated the use of an online learning platform [Joint Knowledge Online (JKO)] for dissemination of the Veterans Affairs and Department of Defense Clinical Practice Guidelines for Management of Posttraumatic Stress Disorder (PTSD) and Acute Stress Disorder (ASD). User satisfaction with the training program was assessed, users were asked to estimate their knowledge base about PTSD and ASD, and users provided comments about how they might use the course material in their clinical practice. MATERIALS AND METHODS: A total of 4,442 users took at least one of three courses offered via JKO related to the PTSD Clinical Practice Guidelines (CPG) between July 1, 2019 and June 25, 2020. A total of 1,663 users took the post-test after the JKO courses and 235 applied to a second website (J7) which granted Continuing Education (CE) credits. Data were gathered from the JKO post-course survey, as well as the J7 course survey, which also asked for respondents' written comments. RESULTS: User satisfaction was analyzed using the JKO survey Likert scale data for each course, and results found most users rated the courses as "good" or "great." Users were also asked to evaluate their knowledge about PTSD management before and after the course. Results from all three courses showed a statistically significant change in pre-post knowledge with a medium effect size. Thematic analysis was performed on the write-in comments from each course. Comments indicated participants found the assessment tools provided in the courses to be of particular value. CONCLUSIONS: The VA/DoD's online learning platform (JKO) was a user-friendly, effective tool for training users on PTSD and ASD clinical practice guidelines. Users were satisfied with their experience of the trainings on JKO and improved their knowledge base about the CPG. This study did not evaluate patient data for CPG compliance, but the future study may benefit from these outcomes to demonstrate provider adherence to the guidelines.


Subject(s)
Stress Disorders, Post-Traumatic , Stress Disorders, Traumatic, Acute , Veterans , United States , Humans , Stress Disorders, Post-Traumatic/therapy , United States Department of Veterans Affairs , United States Government Agencies
19.
J Orthop Res ; 41(7): 1565-1581, 2023 07.
Article in English | MEDLINE | ID: mdl-36453532

ABSTRACT

Clinical trials exploring bolus intravenous delivery of interleukin-12 (IL-12) for treatment of solid tumors ultimately failed due to lack of clinical response and severe dose-limiting toxicities. The present study was conducted to evaluate whether recombinant murine IL-12 (rmIL-12) could be successfully encapsulated within Poly (D, l-lactide-co-glycolide) (PLGA) nanospheres (rmIL-12ns) for safe and effective systemic delivery at pharmacologic scale. Optimal fabrication of rmIL-12ns occurs with dichloromethane as the organic solvent and emulsion formation via ultrasonication at 50% power (250 W sonicator) for 10 s (50W10s). We then determined whether utilization of synthesis modifiers including fetal bovine serum (FBS), magnesium hydroxide [Mg(OH)2 ], trehalose, or the surfactants polysorbate 80 and Span 60 alone or in combination could increase the encapsulation efficiency (EE) and/or modify the burst elution profile characteristic of the 50W10s rmIL-12ns formulation. The greatest EEs compared to the unmodified formulation were measured with modifications containing the surfactants polysorbate 80 and Span 60 (surfactant: 28.3 ± 6.10%, p = 0.29 and Surf/FBS: 85.4 ± 2.19%, p = 0.039). The Surf/FBS formulation was further modified for in vivo murine injection by substituting FBS with mouse serum albumin (MSA). The resulting Surf/MSA rmIL-12ns were then characterized before delivery at three doses (0.1, 1, and 10 mg rmIL-12ns) in our established murine model of metastatic osteosarcoma to assess efficacy. Preliminary results suggested no evidence of disease with delivery of the 0.1 mg dose in 75% of mice (3 of 4) versus a nontreated historical control (2 of 34).


Subject(s)
Nanospheres , Osteosarcoma , Mice , Animals , Interleukin-12 , Polysorbates , Surface-Active Agents , Osteosarcoma/drug therapy
20.
Bioact Mater ; 23: 353-367, 2023 May.
Article in English | MEDLINE | ID: mdl-36474659

ABSTRACT

Articular cartilage has a limited capacity to self-heal once damaged. Tissue-specific stem cells are a solution for cartilage regeneration; however, ex vivo expansion resulting in cell senescence remains a challenge as a large quantity of high-quality tissue-specific stem cells are needed for cartilage regeneration. Our previous report demonstrated that decellularized extracellular matrix (dECM) deposited by human synovium-derived stem cells (SDSCs), adipose-derived stem cells (ADSCs), urine-derived stem cells (UDSCs), or dermal fibroblasts (DFs) provided an ex vivo solution to rejuvenate human SDSCs in proliferation and chondrogenic potential, particularly for dECM deposited by UDSCs. To make the cell-derived dECM (C-dECM) approach applicable clinically, in this study, we evaluated ex vivo rejuvenation of rabbit infrapatellar fat pad-derived stem cells (IPFSCs), an easily accessible alternative for SDSCs, by the abovementioned C-dECMs, in vivo application for functional cartilage repair in a rabbit osteochondral defect model, and potential cellular and molecular mechanisms underlying this rejuvenation. We found that C-dECM rejuvenation promoted rabbit IPFSCs' cartilage engineering and functional regeneration in both ex vivo and in vivo models, particularly for the dECM deposited by UDSCs, which was further confirmed by proteomics data. RNA-Seq analysis indicated that both mesenchymal-epithelial transition (MET) and inflammation-mediated macrophage activation and polarization are potentially involved in the C-dECM-mediated promotion of IPFSCs' chondrogenic capacity, which needs further investigation.

SELECTION OF CITATIONS
SEARCH DETAIL
...