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1.
Molecules ; 29(18)2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39339444

ABSTRACT

The collaboration between cellular proteases and host cells is pivotal in mounting an effective innate immune defense. Of particular interest is the synergistic interaction between cathepsin G (CatG) and neutrophil elastase (NE), which are proteases secreted by activated neutrophils, and the human alveolar basal epithelial cell line (A549) and the human lung epithelial-like cell line (H1299), because of the potential implications for viral infection. Our study aimed to investigate the binding capacity of CatG and NE on the surface of A549 and H1299 cells through preincubation with purified CatG and NE; thereby, the proteolytic activity could be detected using activity-based probes. Both CatG and NE were capable of binding to the cell surface and exhibited proteolytic activity, leading to increased cell surface levels of MHC I molecules, which is crucial for displaying the endogenous antigenic repertoire. In addition, CatG cleaved the S2' site of the SARS-CoV-2 spike protein at two specific sites (815RS816 and 817FI818) as well as NE (813SK814 and 818IE819), which potentially leads to the destruction of the fusion peptide. Additionally, furin required the presence of Ca2+ ions for the distinct cleavage site necessary to generate the fusion peptide. Overall, the findings suggest that CatG and NE can fortify target cells against viral entry, underscoring the potential significance of cell surface proteases in protecting against viral invasion.


Subject(s)
Cathepsin G , Epithelial Cells , Leukocyte Elastase , Neutrophils , Proteolysis , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Humans , Cathepsin G/metabolism , Leukocyte Elastase/metabolism , Neutrophils/metabolism , Neutrophils/virology , SARS-CoV-2/metabolism , Epithelial Cells/virology , Epithelial Cells/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Spike Glycoprotein, Coronavirus/chemistry , A549 Cells , COVID-19/virology , COVID-19/metabolism , COVID-19/immunology , Lung/virology , Lung/metabolism , Furin/metabolism , Protein Binding , Cell Membrane/metabolism
2.
Blood Adv ; 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39158065

ABSTRACT

Artificial intelligence enabled interpretation of electrocardiogram waveform images (AI-ECG) can identify patterns predictive of future adverse cardiac events. We hypothesized such an approach, which is well described in general medical and surgical patients, would provide prognostic information with respect to the risk of cardiac complications and overall mortality in patients undergoing hematopoietic cell transplantation (HCT) for blood malignancy. We retrospectively subjected ECGs obtained pre-HCT to an externally trained, deep learning model designed to predict risk of atrial fibrillation (AF). Included were 1,377 patients (849 autologous HCT and 528 allogeneic HCT recipients). Median follow-up was 2.9 years. The three-year cumulative incidence of AF was 9% (95% CI: 7-12%) in autologous HCT patients and 13% (10-16%) in allogeneic HCT patients. In the entire cohort, pre-HCT AI-ECG estimate of AF risk correlated highly with development of clinical AF (Hazard Ratio (HR) 7.37, 3.53-15.4, p <0.001), inferior overall survival (HR: 2.4; 1.3-4.5, p = 0.004), and greater risk of non-relapse mortality (HR 3.36, 1.39-8.13, p = 0.007), without increased risk of relapse. Significant associations with mortality were only noted in allo HCT recipients, where the risk of non-relapse mortality was greater. Compared to calcineurin inhibitor-based graft versus host disease prophylaxis, the use of post-transplantation cyclophosphamide resulted in greater 90-day incidence of AF (13% versus 5%, p = 0.01), corresponding to temporal changes in AI-ECG AF prediction post HCT. In summary, AI-ECG can inform risk of post-transplant cardiac outcomes and survival in HCT patients and represents a novel strategy for personalized risk assessment after HCT.

3.
Clin Cancer Res ; 30(17): 3894-3903, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-38949888

ABSTRACT

PURPOSE: Patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) and high tumor mutational burden (TMB-H) prostate cancers are candidates for pembrolizumab. We define the genomic features, clinical course, and response to immune checkpoint blockade (ICB) in patients with MSI-H/dMMR and TMB-H prostate cancers without MSI [TMB-H/microsatellite stable (MSS)]. EXPERIMENTAL DESIGN: We sequenced 3,244 tumors from 2,257 patients with prostate cancer. MSI-H/dMMR prostate cancer was defined as an MSIsensor score ≥10 or MSIsensor score ≥3 and <10 with a deleterious MMR alteration. TMB-H was defined as ≥10 mutations/megabase. PSA50 and RECIST responses were assigned. Overall survival and radiographic progression-free survival (rPFS) were compared using log-rank test. RESULTS: Sixty-three (2.8%) men had MSI-H/dMMR, and 33 (1.5%) had TMB-H/MSS prostate cancers. Patients with MSI-H/dMMR and TMB-H/MSS tumors more commonly presented with grade group 5 and metastatic disease at diagnosis. MSI-H/dMMR tumors had higher TMB, indel, and neoantigen burden compared with TMB-H/MSS. Twenty-seven patients with MSI-H/dMMR and 8 patients with TMB-H/MSS tumors received ICB, none of whom harbored polymerase epsilon (polE) catalytic subunit mutations. About 45% of patients with MSI-H/dMMR had a RECIST response, and 65% had a PSA50 response. No patient with TMB-H/MSS had a RECIST response, and 50% had a PSA50 response. rPFS tended to be longer in patients with MSI-H/dMMR than in patients with TMB-H/MSS who received immunotherapy. Pronounced differences in genomics, TMB, or MSIsensor score were not detected between MSI-H/dMMR responders and nonresponders. CONCLUSIONS: MSI-H/dMMR prostate cancers have greater TMB, indel, and neoantigen burden than TMB-H/MSS prostate cancers, and these differences may contribute to profound and durable responses to ICB.


Subject(s)
Immune Checkpoint Inhibitors , Microsatellite Instability , Mutation , Prostatic Neoplasms , Humans , Male , Immune Checkpoint Inhibitors/therapeutic use , Prostatic Neoplasms/genetics , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/immunology , Prostatic Neoplasms/mortality , Aged , Middle Aged , Biomarkers, Tumor/genetics , Aged, 80 and over , DNA Mismatch Repair , Antibodies, Monoclonal, Humanized/therapeutic use
4.
Ann Surg ; 280(3): 452-462, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38869250

ABSTRACT

OBJECTIVE: To determine the utility of Autologous Skin Cell Suspension (ASCS) in closing full-thickness (FT) defects from injury and infection. BACKGROUND: Although ASCS has documented success in closing partial-thickness burns, far less is known about the efficacy of ASCS in FT defects. METHODS: Fifty consecutive patients with FT defects (burn 17, necrotizing infection 13, crush 7, degloving 5, and other 8) underwent closure with the bilayer technique of 3:1 widely meshed, thin, split-thickness skin graft and 80:1 expanded ASCS. End points were limb salvage rate, donor site reduction, operative and hospital throughput, incidence of complications, and re-epithelialization by 4, 8, and 12 weeks. RESULTS: Definitive wound closure was achieved in 76%, 94%, and 98% of patients, at 4, 8, and 12 weeks, respectively. Limb salvage occurred in 42/43 patients (10 upper and 33 lower extremities). The mean area grafted was 435 cm 2 ; donor site size was 212 cm 2 , representing a potential reduction of 50%. The mean surgical time was 71 minutes; the total operating room time was 124 minutes. The mean length of stay was 26.4 days; the time from grafting to discharge was 11.2 days. Four out of 50 patients (8%) required 6 reoperations for bleeding (1), breakdown (4), and amputation (1). Four out of 50 patients (8%) developed hypertrophic scarring, which responded to silicone sheeting (2) and laser resurfacing (2). The mean follow-up was 92.7 days. CONCLUSIONS: When used for the closure of FT wounds, point-of-care ASCS is effective and safe. Benefits include rapid re-epithelialization, high rate of limb salvage, reduction of donor site size and morbidity, and low incidence of hypertrophic scarring.


Subject(s)
Skin Transplantation , Transplantation, Autologous , Humans , Male , Female , Adult , Middle Aged , Skin Transplantation/methods , Aged , Learning Curve , Trauma Centers , Burns/surgery , Burns/therapy , Wound Healing , Adolescent , Treatment Outcome , Young Adult , Limb Salvage/methods
5.
MMWR Morb Mortal Wkly Rep ; 73(25): 567-574, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38935567

ABSTRACT

In 2022, 81,806 opioid-involved overdose deaths were reported in the United States, more than in any previous year. Medications for opioid use disorder (OUD), particularly buprenorphine and methadone, substantially reduce overdose-related and overall mortality. However, only a small proportion of persons with OUD receive these medications. Data from the 2022 National Survey on Drug Use and Health were applied to a cascade of care framework to estimate and characterize U.S. adult populations who need OUD treatment, receive any OUD treatment, and receive medications for OUD. In 2022, 3.7% of U.S. adults aged ≥18 years needed OUD treatment. Among these, only 25.1% received medications for OUD. Most adults who needed OUD treatment either did not perceive that they needed it (42.7%) or received OUD treatment without medications for OUD (30.0%). Compared with non-Hispanic Black or African American and Hispanic or Latino adults, higher percentages of non-Hispanic White adults received any OUD treatment. Higher percentages of men and adults aged 35-49 years received medications for OUD than did women and younger or older adults. Expanded communication about the effectiveness of medications for OUD is needed. Increased efforts to engage persons with OUD in treatment that includes medications are essential. Clinicians and other treatment providers should offer or arrange evidence-based treatment, including medications, for patients with OUD. Pharmacists and payors can work to make these medications available without delays.


Subject(s)
Opioid-Related Disorders , Humans , United States/epidemiology , Adult , Middle Aged , Male , Female , Opioid-Related Disorders/epidemiology , Opioid-Related Disorders/drug therapy , Young Adult , Adolescent , Buprenorphine/therapeutic use , Aged , Opiate Substitution Treatment/statistics & numerical data , Methadone/therapeutic use
6.
Behav Sleep Med ; 22(5): 697-708, 2024.
Article in English | MEDLINE | ID: mdl-38747569

ABSTRACT

OBJECTIVES: This study examined the associations among maternal sleep quality, executive function, and perceptions of infant sleep in a sample of families recruited from human service and public health systems. METHODS: Seventy-three mothers of infants 5-14 months old were included in the study. Mothers racially and ethnically identified as American Indian/Alaskan Native (4.1%), Asian (4.1%), Black/African American (12.3%), Latina (23.3%), more than one race (12.3%), Pacific Islander (1.4%), and White (42.5%). Mothers completed questionnaires assessing their own sleep (Pittsburgh Sleep Quality Index) and executive function (Behavior Rating Inventory of Executive Function) as well as their perceptions about their infant's sleep (Brief Infant Sleep Questionnaire). RESULTS: Results of the path analysis indicated significant direct effects among maternal sleep quality, executive function, and perceptions of infant sleep. Significant indirect effects were found such that poor maternal sleep quality was linked to poorer perceptions of infant sleep through maternal executive dysfunction, adjusting for infant sleep patterns, infant age, and maternal race and ethnicity. CONCLUSIONS: The current study highlights the potential role of maternal behavioral and cognitive factors in shaping mothers' perceptions about infant sleep. These findings support the need for health professionals and researchers to consider maternal sleep quality and executive function when addressing mothers' concerns about infant sleep.


Subject(s)
Executive Function , Mothers , Sleep Quality , Humans , Female , Adult , Infant , Mothers/psychology , Mothers/statistics & numerical data , Executive Function/physiology , Surveys and Questionnaires , Sleep/physiology , Male , Perception , Mother-Child Relations , Young Adult
7.
Front Behav Neurosci ; 18: 1384578, 2024.
Article in English | MEDLINE | ID: mdl-38660390

ABSTRACT

Introduction: Empathic behaviors are driven by the ability to understand the emotional states of others along with the motivation to improve it. Evidence points towards forms of empathy, like targeted helping, in many species including rats. There are several variables that may modulate targeted helping, including sex, sensory modalities, and activity of multiple neural substrates. Methods: Using a model of social contact-independent targeted helping, we first tested whether sex differences exist in helping behavior. Next, we explored sex differences in sensory and affective signaling, including direct visualization and an analysis of ultrasonic vocalizations made between animal pairs. Finally, we examined the neural activity in males and females of multiple regions of interest across time. Here, we aim to examine any behavioral differences in our lab's social contact independent targeted helping task between males and females. Results and Discussion: These findings are the first to intimate that, like other prosocial behaviors, males and females may exhibit similar social-independent targeted helping behavior, but the underlying sensory communication in males and females may differ. In addition, this is the first set of experiments that explore the neural correlates of social-independent targeted helping in both males and females. These results lay the groundwork for future studies to explore the similarities and differences that drive targeted helping in both sexes.

8.
Nat Chem Biol ; 20(10): 1282-1293, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38664586

ABSTRACT

The natural product hinokitiol mobilizes iron across lipid bilayers at low concentrations and restores hemoglobinization in iron transporter protein-deficient systems. But hinokitiol fails to similarly mobilize iron at higher concentrations, limiting its uses in chemical biology and medicine. Here we show that at higher concentrations, hinokitiol3:Fe(III) complexes form large, higher-order aggregates, leading to loss of transmembrane iron mobilization. Guided by this understanding and systematic structure-function studies enabled by modular synthesis, we identified FeM-1269, which minimally aggregates and dose-dependently mobilizes iron across lipid bilayers even at very high concentrations. In contrast to hinokitiol, FeM-1269 is also well-tolerated in animals at high doses for extended periods of time. In a mouse model of anemia of inflammation, FeM-1269 increases serum iron, transferrin saturation, hemoglobin and hematocrit. This rationally developed iron-mobilizing small molecule has enhanced potential as a molecular prosthetic for understanding and potentially treating iron transporter deficiencies.


Subject(s)
Iron , Animals , Iron/metabolism , Iron/chemistry , Mice , Tropolone/analogs & derivatives , Tropolone/chemistry , Tropolone/pharmacology , Lipid Bilayers/metabolism , Lipid Bilayers/chemistry , Ferric Compounds/chemistry , Ferric Compounds/metabolism , Humans , Mice, Inbred C57BL , Structure-Activity Relationship
9.
J Fam Psychol ; 38(5): 743-750, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38647465

ABSTRACT

Positive and negative aspects of intimate relationships influence mental health and well-being in couples. According to the environmental sensitivity framework, individuals differ in how strongly they are affected by their environment, with some individuals being more or less sensitive to both negative and positive experiences. The present study examined the longitudinal associations between positive and negative relationship dynamics, including marital satisfaction, positive bonding, and negative communication, and psychological distress as well as the extent to which individual differences in genetic and subjective measures of environmental sensitivity moderated the association between relationship dynamics and psychological distress in a sample of couples in the U.S. Army (n = 238 individuals representing 152 unique couples). Sensitivity was measured by self-report and a polygenic score derived from previous genome-wide association study results. Separate three-level multilevel models were conducted for each relationship dynamic and sensitivity variable. Only for subjective (i.e., self-reported) sensitivity did significant cross-level interactions emerge in predicting psychological distress, whereas no such interactions were found for genetic (i.e., polygenic score) sensitivity. Specifically, lower marital satisfaction and positive bonding were associated with higher psychological distress among subjectively highly sensitive individuals, and higher negative communication was associated with higher psychological distress among subjectively highly sensitive individuals. Findings suggest that both low positive and high negative relationship dynamics may have a greater effect on psychological distress among highly sensitive individuals, which may help to inform tailored intervention to meet the unique needs of couples. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Interpersonal Relations , Personal Satisfaction , Psychological Distress , Humans , Male , Female , Adult , Marriage/psychology , Object Attachment , Military Personnel/psychology , Young Adult , United States , Spouses/psychology , Longitudinal Studies , Stress, Psychological/psychology
10.
Blood Adv ; 8(11): 2753-2764, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38429097

ABSTRACT

ABSTRACT: Despite the global unrelated donor (URD) registry size, the degree to which URD availability is a transplant barrier is not established. We evaluated the availability of 3,843 URDs requested for 455 diverse adult patients (predominantly with acute leukemia). URDs for non-Europeans were more likely to be domestic and had markedly lower Donor Readiness scores. Of URDs requested for confirmatory HLA-typing (CT) alone (ie, without simultaneous workup), 1,894 of 3,529 (54%) were available. Availability of domestic URDs was 45%. Donor Readiness score was highly predictive of CT availability. More non-European patients (n = 120) than Europeans (n = 335) had >10 URDs requested and <5 available. Of workup requests (after CT or CT-workup), <70% (604/889 [68%]) were available. More non-Europeans had <2 URDs available. URD availability for CT was markedly worse for non-Europeans, with availabilities for African, non-Black Hispanic, and Asian patients being 150/458 (33%), 120/258 (47%), and 119/270 (44%), respectively, with further decrements in URD workup availability. Our data suggest the functional size of the URD pool is much smaller than appreciated, mandating major operational changes for transplant centers and donor registries. Likelihood of donor availability should have a high priority in donor selection. Considering patient ancestry and URD Donor Readiness scores, centers should pursue, and registries permit, simultaneous pursuit of many URDs and abandon futile searches. Patients should be informed about their likelihood of donor availability and alternative options. Finally, although registries should address high URD attrition and speed procurement, use of all HLA-disparate graft types is needed to facilitate timely transplant for all.


Subject(s)
Hematopoietic Stem Cell Transplantation , Unrelated Donors , Adult , Female , Humans , Male , Middle Aged , African People , Asian People , Black People , Ethnicity , European People , Hispanic or Latino , Racial Groups , Registries , Transplantation, Homologous , Unrelated Donors/supply & distribution , Volunteers
12.
JCO Precis Oncol ; 8: e2300489, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38484212

ABSTRACT

PURPOSE: Observational clinicogenomic data sets, consisting of tumor next-generation sequencing (NGS) data linked to clinical records, are commonly used for cancer research. However, in real-world practice, oncologists frequently request NGS in search of treatment options for progressive cancer. The extent and impact of this dynamic on analysis of clinicogenomic research data are not well understood. METHODS: We analyzed clinicogenomic data for patients with non-small cell lung, colorectal, breast, prostate, pancreatic, or urothelial cancers in the American Association for Cancer Research Biopharmaceutical Consortium cohort. Associations between baseline and time-varying clinical characteristics and time from diagnosis to NGS were measured. To explore the impact of informative cohort entry on biomarker inference, statistical interactions between selected biomarkers and time to NGS with respect to overall survival were calculated. RESULTS: Among 7,182 patients, time from diagnosis to NGS varied significantly by clinical factors, including cancer type, calendar year of sequencing, institution, and age and stage at diagnosis. NGS rates also varied significantly by dynamic clinical status variables; in an adjusted model, compared with patients with stable disease at any given time after diagnosis, patients with progressive disease by imaging or oncologist assessment had higher NGS rates (hazard ratio for NGS, 1.61 [95% CI, 1.45 to 1.78] and 2.32 [95% CI, 2.01 to 2.67], respectively). Statistical interactions between selected biomarkers and time to NGS with respect to survival, potentially indicating biased biomarker inference results, were explored. CONCLUSION: To evaluate the appropriateness of a data set for a particular research question, it is crucial to measure associations between dynamic cancer status and the timing of NGS, as well as to evaluate interactions involving biomarkers of interest and NGS timing with respect to survival outcomes.


Subject(s)
Lung Neoplasms , Urinary Bladder Neoplasms , Humans , Male , Biomarkers, Tumor/genetics , High-Throughput Nucleotide Sequencing/methods , Lung Neoplasms/drug therapy , Female
13.
Cancer Res Commun ; 4(2): 475-486, 2024 02 20.
Article in English | MEDLINE | ID: mdl-38329392

ABSTRACT

Peritoneal metastases (PM) are common in metastatic colorectal cancer (mCRC). We aimed to characterize patients with mCRC and PM from a clinical and molecular perspective using the American Association of Cancer Research Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative (BPC) registry. Patients' tumor samples underwent targeted next-generation sequencing. Clinical characteristics and treatment outcomes were collected retrospectively. Overall survival (OS) from advanced disease and progression-free survival (PFS) from start of cancer-directed drug regimen were estimated and adjusted for the left truncation bias. A total of 1,281 patients were analyzed, 244 (19%) had PM at time of advanced disease. PM were associated with female sex [OR: 1.67; 95% confidence interval (CI): 1.11-2.54; P = 0.014] and higher histologic grade (OR: 1.72; 95% CI: 1.08-2.71; P = 0.022), while rectal primary tumors were less frequent in patients with PM (OR: 0.51; 95% CI: 0.29-0.88; P < 0.001). APC occurred less frequently in patients with PM (N = 151, 64% vs. N = 788, 79%) while MED12 alterations occurred more frequently in patients with PM (N = 20, 10% vs. N = 32, 4%); differences in MED12 were not significant when restricting to oncogenic and likely oncogenic variants according to OncoKB. Patients with PM had worse OS (HR: 1.45; 95% CI: 1.16-1.81) after adjustment for independently significant clinical and genomic predictors. PFS from initiation of first-line treatment did not differ by presence of PM. In conclusion, PM were more frequent in females and right-sided primary tumors. Differences in frequencies of MED12 and APC alterations were identified between patients with and without PM. PM were associated with shorter OS but not with PFS from first-line treatment. SIGNIFICANCE: Utilizing the GENIE BPC registry, this study found that PM in patients with colorectal cancer occur more frequently in females and right-sided primary tumors and are associated with worse OS. In addition, we found a lower frequency of APC alterations and a higher frequency in MED12 alterations in patients with PM.


Subject(s)
Antineoplastic Agents , Colonic Neoplasms , Colorectal Neoplasms , Peritoneal Neoplasms , Rectal Neoplasms , Humans , Female , Colorectal Neoplasms/genetics , Peritoneal Neoplasms/genetics , Retrospective Studies , Antineoplastic Agents/therapeutic use , Colonic Neoplasms/drug therapy , Rectal Neoplasms/drug therapy , Genomics , Registries
14.
bioRxiv ; 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38260368

ABSTRACT

Those with diabetes mellitus are at high-risk of developing psychiatric disorders, yet the link between hyperglycemia and alterations in motivated behavior has not been explored in detail. We characterized value-based decision-making behavior of a streptozocin-induced diabetic mouse model on a naturalistic neuroeconomic foraging paradigm called Restaurant Row. Mice made self-paced choices while on a limited time-budget accepting or rejecting reward offers as a function of cost (delays cued by tone-pitch) and subjective value (flavors), tested daily in a closed-economy system across months. We found streptozocin-treated mice disproportionately undervalued less-preferred flavors and inverted their meal-consumption patterns shifted toward a more costly strategy that overprioritized high-value rewards. We discovered these foraging behaviors were driven by impairments in multiple decision-making systems, including the ability to deliberate when engaged in conflict and cache the value of the passage of time in the form of sunk costs. Surprisingly, diabetes-induced changes in behavior depended not only on the type of choice being made but also the salience of reward-scarcity in the environment. These findings suggest complex relationships between glycemic regulation and dissociable valuation algorithms underlying unique cognitive heuristics and sensitivity to opportunity costs can disrupt fundamentally distinct computational processes and could give rise to psychiatric vulnerabilities.

15.
Transplant Cell Ther ; 30(1): 81-92, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37788792

ABSTRACT

Reduced-intensity conditioning (RIC) and nonmyeloablative (NMA) conditioning are preferred for patients with non-Hodgkin lymphoma (NHL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT). Although prior studies have suggested that higher-intensity regimens in RIC-NMA conditioning are associated with inferior outcomes in patients with NHL, the optimal conditioning regimen remains unknown. We performed a retrospective single-center analysis to determine outcomes of adult patients with B cell and T cell NHL who underwent allo-HCT and received either RIC or NMA conditioning between March 2008 and December 2019. RIC regimens included fludarabine-cyclophosphamide-thiotepa-4 Gy-total body irradiation (Flu-Cy-TT-4Gy-TBI), fludarabine-melphalan (Flu-Mel), fludarabine-cyclophosphamide-4 Gy-total body irradiation (Flu-Cy-4Gy-TBI), and fludarabine-busulfan-4 (Flu-Bu-4). The NMA regimen comprised fludarabine-cyclophosphamide-2 Gy-total body irradiation (Flu-Cy-2Gy-TBI). The primary outcome was overall survival (OS); secondary outcomes included progression-free survival (PFS), nonrelapse mortality (NRM), and the incidence of acute and chronic graft-versus-host-disease (GVHD). Of 279 transplants recipients (median age, 58 years), 110 received RIC (55% Flu-Mel, 38% Flu-Cy-TT-4Gy-TBI, 6% Flu-Bu-4, 1% Flu-Cy-4Gy-TBI) and 169 received NMA conditioning with Flu-Cy-2Gy-TBI. With a median of 64 months of follow-up post-allo-HCT, there was no significant difference in OS between the NMA and RIC groups (median, not reached [NR] versus 103 months; P = .1), and this was maintained on multivariable analysis. Similarly, after adjustment for all independently significant covariates (age, Karnofsky Performance Status [KPS], Hematopoietic Cell Transplantation Comorbidity Index [HCT-CI], and disease histology), the regression analysis showed no significant difference in PFS with RIC compared to NMA conditioning (hazard ratio [HR] 1.38; 95% confidence interval [CI], .92 to 2.09; P = .24). On univariable analysis, there was no significant difference in NRM between the RIC and NMA arms (100-day estimate, 10.0% versus 1.8%; P = .5). After adjustment for age, ethnicity, KPS, HCT-CI, GVHD prophylaxis, and donor source, RIC conditioning was associated with a significantly higher incidence of NRM compared to NMA conditioning (HR, 2.61; 95% CI, 1.04 to 6.52; P = .039). On multivariable analysis, compared with the NMA arm, the RIC arm had higher rates of grade II-IV (HR, 2.25; 95% CI, 1.31 to 3.86; P = .002) and grade III-IV acute GVHD (HR, 5.62; 95% CI, 2.03 to 15.6; P < .001). The findings of this study suggest that NMA conditioning with Flu-Cy-TBI-2Gy may be considered over more intensive RIC regimens for patients with NHL undergoing allo-HCT.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Lymphoma, Non-Hodgkin , Adult , Humans , Middle Aged , Retrospective Studies , Transplantation, Homologous/adverse effects , Survival Analysis , Hematopoietic Stem Cell Transplantation/adverse effects , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/drug therapy , Cyclophosphamide/therapeutic use , Graft vs Host Disease/epidemiology , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Busulfan/therapeutic use , Thiotepa
17.
Addict Behav ; 150: 107929, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38056194

ABSTRACT

BACKGROUND: Substance use and other health-risk risk factors, including mental health, trauma, and sexual-risk behaviors, often co-occur among youth experiencing homelessness (YEH). The present study aimed to identify subgroups of YEH based on polysubstance use and the linkages to sociodemographic and health-risk characteristics. METHODS: From June 2016 to July 2017, 1,426 YEH (aged 18-26 years) were recruited from seven cities (Houston, Los Angeles, Denver, Phoenix, New York City, St. Louis, San Jose). Participants provided information via a self-administered electronic survey on substance use, mental health, trauma, sexual risk behaviors, and sociodemographic characteristics. The majority of YEH identified as Black (37.3%), cisgender (92.8%), and heterosexual (69.2%). On average, YEH were 20.9 years (SD = 2.1). This study employed latent class analysis (LCA) to identify subgroups of YEH according to their substance use. Multinomial logistic regression analyses were conducted to identify sociodemographic and health-risk characteristics associated with class-membership. RESULTS: Four latent classes of YEH substance use were identified: (1) high polysubstance use; (2) moderate stimulant and high marijuana, alcohol, and prescription drug use; (3) high marijuana, alcohol, and prescription drug use; (4) low/moderate marijuana and alcohol use. Multinomial logistic regression models indicated that geographic location, gender, race/ethnicity, mental health, trauma history, and sexual risk behaviors were significant correlates of substance use class membership among YEH. CONCLUSIONS: These findings offer important implications for the prevention and treatment of substance use among YEH. Screening protocols should consider co-occurring risk factors such as traumatic experiences, sexual risk behaviors, and mental health history as indicators of polysubstance use.


Subject(s)
Ill-Housed Persons , Prescription Drugs , Substance-Related Disorders , Adolescent , Humans , United States/epidemiology , Cities , Latent Class Analysis , Substance-Related Disorders/psychology , Los Angeles
18.
Disabil Rehabil ; 46(7): 1391-1399, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37067052

ABSTRACT

PURPOSE: Following stroke, individuals who live in a low-income or are at risk of living in a low-income situation face challenges with timely access to social services and community resources. Understanding the usual care practices of stroke teams, specifically, how they support this access to services and resources, is an important first step in promoting the implementation of practice change. METHOD: A qualitative multiple-case study of acute care, inpatient, and outpatient rehabilitation stroke teams in an urban area of Canada. Semi-structured interviews and questionnaires about the workplace context were conducted with 19 professionals (social workers, occupational therapists, physiotherapists, speech-language pathologists) at four sites. RESULTS: In their usual practice, stroke teams prioritized immediate care needs. The stroke team professionals did not address income or resources unless it directly affected discharge. Usual care was influenced by factors such as time constraints, lack of knowledge about services and resources, and social service system limitations. CONCLUSION: To better support post-stroke access to social services and resource for low-income individuals, a multidisciplinary approach, with actions beginning earlier on and extending throughout the continuum of care, is recommended, in addition to system-level advocacy.


Access to social services and community resources for people with stroke and living in a low-income situation is not consistently addressed in acute care or rehabilitation settings.Supporting access to social services and community resources is influenced by the professionals' availability of time and resources, as well as knowledge about services and resources and the limitations of the social service system.Using a multidisciplinary approach, extending over the continuum of care from acute care to rehabilitation program may be a way forward to better support people with stroke and low income to access services and resources.


Subject(s)
Stroke Rehabilitation , Stroke , Humans , Social Work , Poverty , Surveys and Questionnaires
19.
Article in English | MEDLINE | ID: mdl-38063522

ABSTRACT

Mindfulness-informed interventions (MIIs) are increasingly common but have not been extensively studied among families with elevated levels of risk (e.g., those involved in child protective services and/or receiving financial assistance). These families often experience high rates of stressors that can impact coping strategies, interpersonal dynamics, and relationships. Given that mindfulness has been shown to promote health and wellbeing, this study used a sample from two pilot randomized controlled trials to test the extent to which a mindfulness-informed intervention improved coping strategies and perceptions of children's behavior among 53 families with elevated risk. A principal components analysis with a direct oblimin rotation revealed that cognitive-emotion coping strategies could be characterized by three factors: positive adaptation, negative adaptation, and positive refocusing. Intention-to-treat analysis indicated significant group by time differences, with intervention participants demonstrating improvements in positive refocusing coping, positive adaptation coping, and perceptions of children's behavior problems compared to participants in the waitlist control group. No significant differences were found for negative adaptation coping strategies. Findings provide preliminary support for the benefits of mindfulness training in a sample generally underrepresented in the mindfulness intervention literature.


Subject(s)
Mindfulness , Child , Humans , Health Promotion , Stress, Psychological , Adaptation, Psychological , Randomized Controlled Trials as Topic
20.
PLoS One ; 18(11): e0277150, 2023.
Article in English | MEDLINE | ID: mdl-37992068

ABSTRACT

Risk of birds colliding with wind turbines, especially protected species like bald eagle and golden eagle in the U.S., is a fundamental wildlife challenge the wind industry faces when developing and operating projects. The U.S. Fish and Wildlife Service requires wind energy facilities that obtain eagle take permits document permit compliance through fatality monitoring. If trained Operations and Maintenance (O&M) staff can reliably detect and report carcasses during their normal routines, and their detection probability can be estimated, then their 'incidental detections' could contribute substantially towards demonstrating permit compliance. Our primary objective was to quantify incidental detection of eagle carcasses by O&M staff under a variety of landscape contexts and environmental conditions throughout a single year. We used the incidental detection probabilities, along with raptor carcass persistence data and area adjustments, to calculate overall probability of incidental detection (i.e., incidental g). We used feathered decoys as eagle-carcass surrogates for monthly detection trials at 6 study sites throughout the U.S. We evaluated the primary drivers of incidental detection using logit regression models including season, viewshed complexity, and a derived variable called the "density quartile" as covariates. We used an Evidence of Absence-based approach to estimate the overall probability of incidental detection. The incidental detection probabilities ranged from 0.28 to 0.78 (mean = 0.48). Detection probabilities decreased as viewshed complexity increased and as distance from the turbine increased. The resulting overall probability of incidental detection ranged from 0.07 to 0.47 (mean = 0.31). The primary drivers of variability in incidental g were detection probability and the area adjustment. Results of our research show that O&M staff were effective at detecting trial carcasses incidentally. Incorporating incidental detection in eagle fatality monitoring efforts is a reliable means of improving estimates of a facility's direct impacts on eagles.


Subject(s)
Eagles , Humans , Animals , Conservation of Natural Resources , Animals, Wild , Probability , Seasons
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