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1.
Am J Med Genet A ; : e63819, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39016627

ABSTRACT

Turner syndrome (TS) is defined by partial or complete absence of a sex chromosome. Little is known about the phenotype of individuals with TS mosaic with trisomy X (45,X/47,XXX or 45,X/46,XX/47,XXX) (~3% of TS). We compared the diagnostic, perinatal, medical, and neurodevelopmental comorbidities of mosaic 45,X/47,XXX (n = 35, 9.4%) with nonmosaic 45,X (n = 142) and mosaic 45,X/46,XX (n = 66). Females with 45,X/47,XXX had fewer neonatal concerns and lower prevalence of several TS-related diagnoses compared with 45,X; however the prevalence of neurodevelopmental and psychiatric diagnoses were not different. Compared to females with 45,X/46,XX, the 45,X/47,XXX group was significantly more likely to have structural renal anomalies (18% vs. 3%; p = 0.03). They were twice as likely to have congenital heart disease (32% vs. 15%, p = 0.08) and less likely to experience spontaneous menarche (46% vs. 75% of those over age 10, p = 0.06), although not statistically significant. Congenital anomalies, hypertension, and hearing loss were primarily attributable to a higher proportion of 45,X cells, while preserved ovarian function was most associated with a higher proportion of 46,XX cells. In this large TS cohort, 45,X/47,XXX was more common than previously reported, individuals were phenotypically less affected than those with 45,X, but did have trends for several more TS-related diagnoses than individuals with 45,X/46,XX.

2.
Palliat Care Soc Pract ; 18: 26323524241263108, 2024.
Article in English | MEDLINE | ID: mdl-39045292

ABSTRACT

Advance care planning (ACP) supports individuals in aligning their medical care with personal values and preferences in the face of serious illness. The variety of ACP tools available reflects diverse strategies intended to facilitate these critical conversations, yet evaluations of their effectiveness often show mixed results. Following the Arskey and O'Malley framework, this scoping review aims to synthesize the range of ACP tools targeted at patients and families, highlighting their characteristics and delivery methods to better understand their impact and development over time. Studies included focused on patient-facing ACP tools across all settings and mediums. Exclusions were applied to studies solely targeting healthcare providers or those only aiming at completion of advance directives without broader ACP discussions. Searches were conducted across PubMed, Embase, CINAHL, The Cochrane Library, and Web of Science. Data were extracted using a predesigned spreadsheet, capturing study population, setting, intervention modality, and intervention theme. Tools were categorized by delivery method and further analyzed through a year-wise distribution to track trends and developments. We identified 99 unique patient-facing tools, with those focusing on counseling (31) and video technologies (21) being the most prevalent while others incorporated online platforms, print materials, games, or some combination of different delivery methods. Over half the tools were designed for specific patient groups, especially for various diseases and racial or ethnic communities. Recent years showed a surge in tool variety and innovation, including integrated patient portals and psychological techniques. The review demonstrates a broad array of innovative ACP tools that facilitate personalized and effective ACP. Our findings contribute to an enhanced understanding of their utilization and potential impacts, offering valuable insights for future tool development and policy making in ACP.


Scanning the landscape of tools to assist patients with advance care planning This review investigates the variety of tools, programs, and interventions designed to help patients plan their healthcare in advance, a process known as advance care planning (ACP). ACP is crucial because it ensures individuals receive medical care aligned with their wishes, especially during serious illness or near the end of life. Our study gathered information from various sources, focusing on tools aimed directly at patients and their families. We found 99 unique tools that assist in ACP, including individual counseling sessions, video-based tools, and digital platforms. Some tools are designed specifically for certain patient groups, such as those with particular diseases or belonging to diverse racial and ethnic communities. Our review highlights the recent surge in the variety and innovation of these tools, such as integrated patient portals and methods incorporating psychological techniques, suggesting a growing effort to make ACP more accessible and tailored to individual needs. However, despite this variety, more research is needed to understand how these tools impact healthcare outcomes and how they can be effectively implemented in different care settings. Our findings aim to guide future development of ACP tools, improve their integration into healthcare practices, and ensure they meet the diverse needs of patients and families.

4.
J Clin Invest ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38916965

ABSTRACT

Leukemia relapse is a major cause of death after allogeneic hematopoietic cell transplantation (allo-HCT). We tested the potential of targeting TIM-3 for improving graft-versus-leukemia (GVL) effects. We observed differential expression of TIM-3 ligands when hematopoietic stem cells overexpressed certain oncogenic-driver mutations. Anti-TIM-3 Ab-treatment improved survival of mice bearing leukemia with oncogene-induced TIM-3 ligand expression. Conversely, leukemia cells with low ligand expression were anti-TIM-3 treatment-resistant. In vitro, TIM-3 blockade or genetic deletion in CD8+ T cells (Tc) enhanced Tc activation, proliferation and IFN-γ production while enhancing GVL effects, preventing Tc exhaustion and improving Tc cytotoxicity and glycolysis in vivo. Conversely, TIM-3 deletion in myeloid cells did not affect allogeneic Tc proliferation and activation in vitro, suggesting that anti-TIM-3-treatment-mediated GVL effects are Tc-induced. In contrast to anti-PD-1 and anti-CTLA-4-treatment, anti-TIM-3-treatment did not enhance acute graft-versus-host-disease (aGVHD). TIM-3 and its ligands were frequently expressed in acute myeloid leukemia (AML) cells of patients with post-allo-HCT relapse. We deciphered the connection between oncogenic mutations found in AML and TIM-3 ligands expression and identify anti-TIM-3-treatment as a strategy to enhance GVL effects via metabolic and transcriptional Tc-reprogramming, without exacerbation of aGVHD. Our findings support clinical testing of anti-TIM-3 Abs in patients with AML relapse post-allo-HCT.

5.
Eur J Endocrinol ; 190(6): G53-G151, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38748847

ABSTRACT

Turner syndrome (TS) affects 50 per 100 000 females. TS affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and United States culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: (1) diagnosis and genetics, (2) growth, (3) puberty and estrogen treatment, (4) cardiovascular health, (5) transition, (6) fertility assessment, monitoring, and counselling, (7) health surveillance for comorbidities throughout the lifespan, and (8) neurocognition and its implications for mental health and well-being. Each group produced proposals for the present guidelines, which were meticulously discussed by the entire group. Four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with systematic review of the literature. The guidelines project was initiated by the European Society for Endocrinology and the Pediatric Endocrine Society, in collaboration with members from the European Society for Pediatric Endocrinology, the European Society of Human Reproduction and Embryology, the European Reference Network on Rare Endocrine Conditions, the Society for Endocrinology, and the European Society of Cardiology, Japanese Society for Pediatric Endocrinology, Australia and New Zealand Society for Pediatric Endocrinology and Diabetes, Latin American Society for Pediatric Endocrinology, Arab Society for Pediatric Endocrinology and Diabetes, and the Asia Pacific Pediatric Endocrine Society. Advocacy groups appointed representatives for pre-meeting discussions and the consensus meeting.


Subject(s)
Turner Syndrome , Humans , Turner Syndrome/therapy , Turner Syndrome/diagnosis , Female , Child , Adolescent , Puberty/physiology , Adult , Europe , Practice Guidelines as Topic/standards
6.
Horm Res Paediatr ; : 1-10, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38684152

ABSTRACT

INTRODUCTION: Phase 3 trial of 6-month subcutaneous leuprolide acetate (SC-LA) in children with central precocious puberty (CPP) demonstrated efficacy and safety. The aims of this secondary analysis were to evaluate unstimulated luteinizing hormone (LH) as efficacy measure, assess clinical suppression metrics, and present biochemical and clinical data for subgroups not achieving hormone suppression. METHODS: Sixty-two children with treatment-naïve CPP received 2 doses of 45 mg SC-LA at 24-week intervals. Unstimulated and GnRH-stimulated LH, E2, and T concentrations were measured. Clinical measures included bone age (BA) and predicted adult height (PAH). RESULTS: Eighty-four percentage and 86% of children achieved unstimulated LH <1 IU/L at weeks 24 and 48, respectively. Of 8 children not achieving unstimulated LH <1 IU/L at week 24 that completed the study, all showed a lack of pubertal stage progression and stable/decreased BA to chronological age ratio (BA/CA). Received operating characteristic (ROC) analyses suggested unstimulated LH is a good diagnostic predictor of GnRH-stimulated LH <4 IU/L at weeks 24 and 48 (AUC = 0.88). Across all children, mean BA/CA improved from 1.4 (screening) to 1.3 (week 48) and mean PAH increased by 3 cm. Of 7 girls not achieving stimulated LH <4 IU/L at week 24, all achieved E2 <10 pg/mL, showed a lack of pubertal stage progression, and had stable or decreased BA/CA by week 48. Additionally, 6/7 had increased PAH by week 48 and 4 had unstimulated LH <1 IU/L. CONCLUSION: Unstimulated LH has value as an efficacy measure and concentrations <1 IU/L may be an adequate surrogate of treatment response in children with CPP. All children who completed the study had evidence of pubertal suppression.

7.
Cancer Discov ; 14(4): 669-673, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38571430

ABSTRACT

SUMMARY: The field of cancer neuroscience has begun to define the contributions of nerves to cancer initiation and progression; here, we highlight the future directions of basic and translational cancer neuroscience for malignancies arising outside of the central nervous system.


Subject(s)
Neoplasms , Neurosciences , Humans , Central Nervous System , Forecasting , Proteomics
8.
J Pediatr Endocrinol Metab ; 37(5): 451-461, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38618862

ABSTRACT

OBJECTIVES: To understand possible predictors of the onset of menses after gonadotropin-releasing hormone agonist treatment cessation in girls with central precocious puberty (CPP). METHODS: This exploratory post hoc analysis of a phase 3 and 4 trial of girls with CPP treated with once-monthly intramuscular leuprolide acetate examined onset of menses after treatment completion using a time-to-event analysis. Pretreatment and end-of-treatment chronologic age (CA), bone age (BA)/CA ratio, and Tanner breast stage; pretreatment menses status; and end-of-treatment BA and body mass index (BMI) were studied as potential factors influencing the onset of menses. RESULTS: Median time to first menses after stopping treatment was 18.3 months among 35 girls (mean age at onset of treatment, 6.8 years) examined. Of 26 girls experiencing menses, 11 (42 %) menstruated at 16-21 months after stopping treatment. Most girls with pretreatment BA/CA≥1.4 started menstruating very close to 18 months after stopping treatment; those with less advanced BA/CA experienced menses at 9-18 months. End-of-treatment BA/CA≥1.2 was associated with a quicker onset of menses (14.5 vs. 18.5 months for BA/CA<1.2, p=0.006). End-of-treatment BA≥12 years predicted longer time to menses. No relationship with time to menses was observed for pretreatment menarche status, pretreatment or end-of-treatment Tanner breast stage (<3/≥3) or CA (<6/≥6 or ≤11/>11), or end-of-treatment BMI percentiles (<85.6/≥85.6 and <92.6/≥92.6). CONCLUSIONS: Pretreatment menarche status or CA do not appear to predict onset of menses, but pre- and end-of-treatment BA/CA may be helpful in anticipating time to first menses after stopping treatment.


Subject(s)
Gonadotropin-Releasing Hormone , Leuprolide , Menstruation , Puberty, Precocious , Child , Female , Humans , Age Determination by Skeleton , Body Mass Index , Follow-Up Studies , Gonadotropin-Releasing Hormone/agonists , Leuprolide/therapeutic use , Leuprolide/administration & dosage , Menarche/drug effects , Menstruation/drug effects , Prognosis , Puberty, Precocious/drug therapy , Time Factors
9.
Endocrinol Metab Clin North Am ; 53(2): 229-238, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38677866

ABSTRACT

The age of thelarche has declined in the past few decades but not the age of menarche. This is important when assessing girls who present with breast development between 6 and 8 years because not all of them will need treatment. The decision for treatment depends on age, bone age (BA), rate of pubertal progression, height velocity, psychosocial factors, and predicted adult height (PAH), with the caveat that height predictions are not precise and BA interpretation is variable.


Subject(s)
Puberty, Precocious , Humans , Puberty, Precocious/therapy , Female , Child , Body Height/physiology
10.
Front Pediatr ; 12: 1352295, 2024.
Article in English | MEDLINE | ID: mdl-38545431

ABSTRACT

Background and aim of the study: We previously published the increased frequency of new CPP cases during the Covid-19 pandemic in our pediatric endocrinology clinic at Rady Children's Hospital in San Diego, CA, US. We conducted this follow-up study to examine the incidence of new CPP cases requiring treatment with GnRH agonist (GnRHa) in our clinic during 2 years post-pandemic. Methods: We performed a retrospective comparison of the number of visits of children newly diagnosed with CPP treated with GnRHa during the 2 years following the first year of Covid-19 pandemic (5/2021-7/2023). We evaluated clinical and bone maturation data as well as differences in timing from diagnosis to onset of treatment. Results: We previously reported in the pre-Covid year, 28 children (1 boy, 27 girls) treated with GnRHa for CPP out of 2,340 new endocrinology visits (1.2% of patients seen). During Covid-19 year, 64 children (7 boys, 57 girls) were treated out of 2,261 new visits (2.8%). The incidence of new CPP cases requiring GnRHa during the pandemic more than doubled compared to pre-pandemic. In the first year post-year 1 of the pandemic (5/2021-4/2022), 46 children (3 boys, 40 girls) started treatment with GnRHa for CPP out of 2,595 new endocrinology visits (1.6% of patients seen). During the second follow-up year (5/2022-4/2023), 22 children (4 boys, 18 girls) started treatment with GnRHa for CPP out of 2,676 new endocrinology visits (0.8% of patients seen). Age at onset of treatment, degree of bone age (BA) advancement, time from diagnosis to onset of treatment, and changes in BMI during the pandemic were not different from pre-pandemic or post-pandemic. Conclusions: CPP cases requiring GnRHa treatment significantly increased during the first year of the Covid-19 pandemic and then decreased each year post-pandemic. This was not related to BMI, age at diagnosis, degree of bone age advancement, or time from diagnosis to onset of treatment as all these factors have been similar during pre-pandemic, pandemic, and post-pandemic years. It is reasonable that the postulated hypotheses published regarding the increase during the pandemic would resolve post-pandemic.

11.
Sci Immunol ; 9(93): eadf2223, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38457514

ABSTRACT

T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) is an important immune checkpoint molecule initially identified as a marker of IFN-γ-producing CD4+ and CD8+ T cells. Since then, our understanding of its role in immune responses has significantly expanded. Here, we review emerging evidence demonstrating unexpected roles for TIM-3 as a key regulator of myeloid cell function, in addition to recent work establishing TIM-3 as a delineator of terminal T cell exhaustion, thereby positioning TIM-3 at the interface between fatigued immune responses and reinvigoration. We share our perspective on the antagonism between TIM-3 and T cell stemness, discussing both cell-intrinsic and cell-extrinsic mechanisms underlying this relationship. Looking forward, we discuss approaches to decipher the underlying mechanisms by which TIM-3 regulates stemness, which has remarkable potential for the treatment of cancer, autoimmunity, and autoinflammation.


Subject(s)
Hepatitis A Virus Cellular Receptor 2 , Neoplasms , Humans , CD8-Positive T-Lymphocytes , Myeloid Cells , T-Cell Exhaustion
12.
Psychol Addict Behav ; 38(1): 124-133, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37141036

ABSTRACT

OBJECTIVE: Racial and ethnic disparities in smoking cessation persist. This randomized controlled trial compared the efficacy of group cognitive behavioral therapy (CBT) for cessation among African American/Black, Latino/Hispanic, and White adults. METHOD: African American/Black (39%), Latino/Hispanic (29%), and White (32%) adults (N = 347) were randomly assigned to eight group sessions of CBT or general health education (GHE), both including nicotine patch therapy. Biochemically confirmed 7-day point prevalence abstinence (7-day ppa) was measured at the end-of-therapy, and at 3-, 6-, and 12-month follow-ups. Generalized linear mixed models and logistic regressions tested abstinence rates by condition, stratified by race and ethnicity, and interaction effects. RESULTS: CBT led to greater abstinence than GHE across 12-months of follow-up (AOR = 1.84, 95% CI [1.59, 2.13]) overall [12-month follow-up: CBT = 54% vs. GHE = 38%] and within racial and ethnic groups [12-months: African American/Black (CBT = 52%, GHE = 29%), Latino/Hispanic (CBT = 57%, GHE = 47%), and White (CBT = 54%, GHE = 41%)]. African American participants were less likely than White participants to quit irrespective of condition, as were persons with lower education and income. Socioeconomic status indicators positively predicted abstinence among racial and ethnic minority participants, but not White participants. CONCLUSIONS: Group CBT was efficacious compared with GHE. However, cessation patterns suggested that intensive group interventions were less beneficial over the longer term among lower socioeconomic African American and Latino individuals, compared with White participants. Tobacco interventions should target racial and ethnic and socioeconomic differences, via culturally specific approaches and other means. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Cognitive Behavioral Therapy , Smoking Cessation , Adult , Humans , Smoking Cessation/psychology , Ethnicity/psychology , Minority Groups , Health Education
13.
Am J Med Genet A ; 194(2): 311-319, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37827984

ABSTRACT

Inspiring New Science to Guide Healthcare in Turner Syndrome (InsighTS) Registry is a national, multicenter registry for individuals with Turner syndrome (TS) designed to collect and store validated longitudinal clinical data from a diverse cohort of patients with TS. Herein, we describe the rationale, design, and approach used to develop the InsighTS registry, as well as the demographics of the initial participants to illustrate the registry's diversity and future utility. Multiple stakeholder groups have been involved from project conceptualization through dissemination, ensuring the registry serves the priorities of the TS community. Key features of InsighTS include recruitment strategies to facilitate enrollment of participants that appropriately reflect the population of individuals with TS receiving care in the US, clarity of data ownership and sharing, and sustainability of this resource. The registry gathers clinical data on diagnosis, treatment, comorbidities, health care utilization, clinical practices, and quality of life with the goal of improving health outcomes for this population. Future directions include multiple patient-centered clinical-translational research projects that will use the InsighTS platform. This thorough and thoughtful planning will ensure InsighTS is a valuable and sustainable resource for the TS community for decades to come.


Subject(s)
Turner Syndrome , Humans , Turner Syndrome/diagnosis , Turner Syndrome/epidemiology , Turner Syndrome/therapy , Quality of Life , Delivery of Health Care , Registries , Patient Acceptance of Health Care
14.
Nurs Res ; 72(5): 404-408, 2023.
Article in English | MEDLINE | ID: mdl-37625184

ABSTRACT

BACKGROUND: At-home self-collection of specimens has become more commonplace because of measures taken in response to the coronavirus pandemic. Self-collection of hair cortisol is important because chronic stress is present in many populations, such as older adults living with Alzheimer's disease and their family caregivers. For the evaluation of chronic stress, scalp hair can be used as a predictive biomarker because it examines the cumulative, retrospective stress from previous months. OBJECTIVES: The aim of the paper is to provide a study procedure for at-home, scalp hair self-collection for cortisol concentration analysis from dyads consisting of a person living with Alzheimer's disease and their family caregiver. METHODS: After informed electronic consent is obtained, a package containing the necessary tools for self-collection of hair samples from the dyad is mailed to the participant's home. Participants are provided detailed print and video multimedia guides outlining how to obtain the hair samples. Ideally, the hair samples are obtained during the virtual data collection meeting with research personnel. Participants mail back the hair sample in a prepaid package to the biomedical laboratory for analysis. DISCUSSION: At-home, self-collection of hair provides potential advantages such as reduced participant burden, especially for vulnerable populations where transportation and different environments are challenging. At-home sample collection options may increase research participation and can be applied to multiple research foci. Research considerations for dyads, such as people living with Alzheimer's disease and their caregivers, are discussed.


Subject(s)
Alzheimer Disease , Hydrocortisone , Humans , Aged , Hydrocortisone/analysis , Retrospective Studies , Caregivers , Hair/chemistry
15.
J Endocr Soc ; 7(7): bvad071, 2023 Jun 05.
Article in English | MEDLINE | ID: mdl-37334213

ABSTRACT

Context: Treatment options for central precocious puberty (CPP) are important for individualization of therapy. Objective: We evaluated the efficacy and safety of 6-month 45-mg leuprolide acetate (LA) depot with intramuscular administration. Methods: LA depot was administered at weeks 0 and 24 to treatment-naïve (n = 27) or previously treated (n = 18) children with CPP in a phase 3, multicenter, single-arm, open-label study (NCT03695237). Week 24 peak-stimulated luteinizing hormone (LH) suppression (<4 mIU/mL) was the primary outcome. Secondary/other outcomes included basal sex hormone suppression (girls, estradiol <20 pg/mL; boys, testosterone <30 ng/dL), suppression of physical signs, height velocity, bone age, patient/parent-reported outcomes, and adverse events. Results: All patients (age, 7.8 ± 1.27 years) received both scheduled study doses. At 24 weeks, 39/45 patients (86.7%) had LH suppressed. Six were counted as unsuppressed; 2 because of missing data, 3 with LH of 4.35-5.30 mIU/mL and 1 with LH of 21.07 mIU/mL. Through 48 weeks, LH, estradiol, and testosterone suppression was achieved in ≥86.7%, ≥97.4%, and 100%, respectively (as early as week 4 for LH and estradiol and week 12 for testosterone). Physical signs were suppressed at week 48 (girls, 90.2%; boys, 75.0%). Mean height velocity ranged 5.0 to 5.3 cm/year post-baseline in previously treated patients and declined from 10.1 to 6.5 cm/year at week 20 in treatment-naïve patients. Mean bone age advanced slower than chronological age. Patient/parent-reported outcomes remained stable. No new safety signals were identified. No adverse event led to treatment discontinuation. Conclusion: Six-month intramuscular LA depot demonstrated 48-week efficacy with a safety profile consistent with other GnRH agonist formulations.

16.
J Immunother Cancer ; 11(5)2023 05.
Article in English | MEDLINE | ID: mdl-37208130

ABSTRACT

BACKGROUND: Although immune checkpoint inhibitors have been a breakthrough in clinical oncology, these therapies fail to produce durable responses in a significant fraction of patients. This lack of long-term efficacy may be due to a poor pre-existing network linking innate and adaptive immunity. Here, we present an antisense oligonucleotide (ASO)-based strategy that dually targets toll-like receptor 9 (TLR9) and programmed cell death ligand 1 (PD-L1), aiming to overcome resistance to anti-PD-L1 monoclonal therapy. METHODS: We designed a high-affinity immunomodulatory IM-TLR9:PD-L1-ASO antisense oligonucleotide (hereafter, IM-T9P1-ASO) targeting mouse PD-L1 messenger RNA and activating TLR9. Then, we performed in vitro and in vivo studies to validate the IM-T9P1-ASO activity, efficacy, and biological effects in tumors and draining lymph nodes. We also performed intravital imaging to study IM-T9P1-ASO pharmacokinetics in the tumor. RESULTS: IM-T9P1-ASO therapy, unlike PD-L1 antibody therapy, results in durable antitumor responses in multiple mouse cancer models. Mechanistically, IM-T9P1-ASO activates a state of tumor-associated dendritic cells (DCs), referred to here as DC3s, which have potent antitumor potential but express the PD-L1 checkpoint. IM-T9P1-ASO has two roles: it triggers the expansion of DC3s by engaging with TLR9 and downregulates PD-L1, thereby unleashing the antitumor functions of DC3s. This dual action leads to tumor rejection by T cells. The antitumor efficacy of IM-T9P1-ASO depends on the antitumor cytokine interleukin-12 (IL-12), produced by DC3s, and Batf3, a transcription factor required for DC development. CONCLUSIONS: By simultaneously targeting TLR9 and PD-L1, IM-T9P1-ASO amplifies antitumor responses via DC activation, leading to sustained therapeutic efficacy in mice. By highlighting differences and similarities between mouse and human DCs, this study could serve to develop similar therapeutic strategies for patients with cancer.


Subject(s)
Neoplasms , Toll-Like Receptor 9 , Humans , Mice , Animals , Toll-Like Receptor 9/metabolism , Immunotherapy/methods , Neoplasms/drug therapy , Oligonucleotides, Antisense , Dendritic Cells
17.
medRxiv ; 2023 Mar 14.
Article in English | MEDLINE | ID: mdl-36993695

ABSTRACT

Objectives: Xylazine is an alpha-2 agonist increasingly prevalent in the illicit drug supply. Our objectives were to curate information about xylazine through social media from People Who Use Drugs (PWUDs). Specifically, we sought to answer the following: 1) what are the demographics of Reddit subscribers reporting exposure to xylazine? 2) is xylazine a desired additive? and 3) what adverse effects of xylazine are PWUDs experiencing? Methods: Natural Language Processing (NLP) was used to identify mentions of "xylazine" from posts by Reddit subscribers who also posted on drug-related subreddits. Posts were qualitatively evaluated for xylazine-related themes. A survey was developed to gather additional information about the Reddit subscribers. This survey was posted on subreddits that were identified by NLP to contain xylazine-related discussions from March 2022 to October 2022. Results: 76 posts mentioning xylazine were extracted via NLP from 765,616 posts by 16,131 Reddit subscribers (January 2018 to August 2021). People on Reddit described xylazine as an unwanted adulterant in their opioid supply. 61 participants completed the survey. Of those that disclosed their location, 25/50 (50%) participants reported locations in the Northeastern United States. The most common eoute of xylazine use was intranasal use (57%). 31/59 (53%) reported experiencing xylazine withdrawal. Frequent adverse events reported were prolonged sedation (81%) and increased skin wounds (43%). Conclusions: Among respondents on these Reddit forums, xylazine appears to be an unwanted adulterant. PWUDs may be experiencing adverse effects such as prolonged sedation and xylazine withdrawal. This appeared to be more common in the Northeast.

18.
Drug Alcohol Depend ; 244: 109768, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36645978

ABSTRACT

BACKGROUND: The combined use of cigarettes and alcohol is associated with a synergistic increase in the risk of morbidity and mortality. Continued alcohol use during a smoking quit attempt is a considerable risk factor for smoking relapse. As such, there is a need for interventions that address both behaviors concurrently. Mindfulness-based interventions hold much promise for simultaneously addressing tobacco and alcohol use. METHOD: This pilot study evaluated the feasibility and acceptability of a mindfulness-based intervention using a two-arm randomized controlled trial of Mindfulness-Based Relapse Prevention for Smoking and Alcohol (MBRP-SA) vs Cognitive Behavioral Therapy (CBT). Interventions were delivered via telehealth in a group setting; all participants received a 6-week supply of the nicotine patch. Participants (N = 69) were adults who smoked cigarettes who reported binge drinking and were motivated to both quit smoking and change their alcohol use. Primary outcomes were feasibility and acceptability of MBRP-SA compared to CBT. Changes in tobacco and alcohol use are also presented. RESULTS: Participants in MBRP-SA and CBT indicated that the treatments were highly acceptable, meeting a priori benchmarks. Feasibility was mixed with some outcomes meeting benchmarks (e.g., recruitment) and others falling below (e.g., retention). Participants in both conditions demonstrated significant reductions in tobacco and alcohol use at the end of treatment. CONCLUSIONS: In sum, MBRP-SA had comparable outcomes to CBT on all metrics measured. Future research should evaluate the efficacy of MBRP-SA on smoking abstinence and drinking reductions in a large-scale, fully powered trial. This study was registered on clinicaltrials.gov (NCT03734666).


Subject(s)
Cognitive Behavioral Therapy , Mindfulness , Adult , Humans , Pilot Projects , Secondary Prevention , Smoking , Nicotiana
19.
Behav Med ; 49(4): 392-401, 2023.
Article in English | MEDLINE | ID: mdl-35614523

ABSTRACT

Prior research indicates bisexual individuals have higher smoking and vaping rates and heightened vulnerability to negative health outcomes. Thus, we compared adult bisexual (n = 294) and heterosexual (n = 2412) participants enrolled in a smoking cessation trial on baseline smoking and vaping use behaviors, motivations, and expectancies/beliefs as well as follow-up smoking and vaping status. This is a secondary analysis of a large randomized controlled trial testing a smoking cessation intervention for dual users of combustible and electronic cigarettes (e-cigarettes) in the United States. Self-reported 7-day point prevalence smoking and vaping abstinence were collected at 3-, 12-, and 24-month assessments. Bisexual and heterosexual participants did not differ in sociodemographic variables or baseline smoking and vaping history and behavior. We found significant differences among bisexual and heterosexual individuals in smoking and vaping beliefs/expectancies. Specifically, bisexual participants expressed overall greater positive expectancies regarding smoking and vaping, such as smoking and vaping to reduce negative affect and stress. There were no differences in smoking at any follow-up assessment. Only at 3 months were bisexual individuals more likely to be abstinent from vaping and less likely to be dual users than heterosexual individuals. Despite similar smoking and vaping status over time, bisexual individuals reported greater positive expectancies regarding smoking and vaping. Our findings revealed few targets for tailoring cessation interventions to bisexual individuals; thus, it is possible that there may be greater utility in targeting the disparities in prevalence (i.e., via prevention efforts).

20.
Am J Hosp Palliat Care ; 40(4): 431-439, 2023 Apr.
Article in English | MEDLINE | ID: mdl-35666474

ABSTRACT

Background: Relative to curative and traditional care delivery, hospice care has been associated with superior end of life (EOL) outcomes for both patient and caregiver. Still, comprehensive orientation and caregiver preparation for the transition to hospice is variable and often inadequate. From the perspective of the caregiver, it is unclear what information would better prepare them to support the transition of their loved one to hospice. Objectives: Our two sequential objectives were: 1) Explore caregivers' experiences and perceptions on the transition of their loved one to hospice; and 2) Develop a preliminary checklist of considerations for a successful transition. Design: We conducted semi-structured interviews and used a descriptive inductive/deductive thematic analysis to identify themes. Subjects: 19 adult caregivers of patients across the United States who had enrolled in hospice and died in the year prior (January - December 2019). Measurements: An interview guide was iteratively developed based on prior literature and expanded through collaborative coding and group discussion. Results: Four key themes for inclusion in our framework emerged: hospice intake, preparedness, burden of care and hospice resources. Conclusions: Focusing on elements of our preliminary checklist, such as educating families on goals of hospice or offering opportunities for respite care, into the orientation procedures may be opportunities to improve satisfaction with the transition and the entirety of the hospice experience. Future directions include testing the effectiveness of the checklist and adapting for expanded poputlations.


Subject(s)
Hospice Care , Hospices , Adult , Humans , Caregivers , Checklist , Communication
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