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1.
bioRxiv ; 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38948734

ABSTRACT

Comprehensive molecular and cellular phenotyping of human islets can enable deep mechanistic insights for diabetes research. We established the Human Islet Data Analysis and Sharing (HI-DAS) consortium to advance goals in accessibility, usability, and integration of data from human islets isolated from donors with and without diabetes at the Alberta Diabetes Institute (ADI) IsletCore. Here we introduce HumanIslets.com, an open resource for the research community. This platform, which presently includes data on 547 human islet donors, allows users to access linked datasets describing molecular profiles, islet function and donor phenotypes, and to perform various statistical and functional analyses at the donor, islet and single-cell levels. As an example of the analytic capacity of this resource we show a dissociation between cell culture effects on transcript and protein expression, and an approach to correct for exocrine contamination found in hand-picked islets. Finally, we provide an example workflow and visualization that highlights links between type 2 diabetes status, SERCA3b Ca2+-ATPase levels at the transcript and protein level, insulin secretion and islet cell phenotypes. HumanIslets.com provides a growing and adaptable set of resources and tools to support the metabolism and diabetes research community.

2.
Appl Environ Microbiol ; 90(6): e0029924, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38786360

ABSTRACT

Bacteria, fungi, and mammals contain lactonases that can degrade the Gram-negative bacterial quorum sensing (QS) molecules N-acyl homoserine lactones (AHLs). AHLs are critical for bacteria to coordinate gene expression and pathogenicity with population density. However, AHL-degrading lactonases present variable substrate ranges, including degradation of the Pencillium expansum lactone mycotoxin patulin. We selected Erwinia spp. as our model bacteria to further investigate this interaction. We find both native apple microbiome Erwinia spp. and the fruit tree pathogen Erwinia amylovora to be inhibited by patulin. At patulin concentrations that inhibited E. amylovora growth, expression of E. amylovora lactonase encoded by EaaiiA was increased. EaAiiA demonstrated the ability to degrade patulin in vitro, as well, as in vivo where it reduced apple disease and patulin production by P. expansum. Fungal-bacterial co-cultures revealed that the E. amylovora Δeaaiia strain failed to protect apples from P. expansum infections, which contained significant amounts of patulin. Our results suggest that bacterial lactonase production can modulate the pathogenicity of P. expansum in response to the secretion of toxic patulin. IMPORTANCE: Chemical signaling in the microbial world facilitates the regulation of gene expression as a function of cell population density. This is especially true for the Gram-negative bacterial signal N-acyl homoserine lactone (AHL). Lactonases that deactivate AHLs have attracted a lot of attention because of their antibacterial potential. However, the involvement of these enzymes in inhibiting fungal pathogens and the potential role of these enzymes in bacterial-fungal interactions are unknown. Here, we find that a bacterial enzyme involved in the degradation of AHLs is also induced by and degrades the fungal lactone mycotoxin, patulin. This work supports the potential use of bacterial enzymes and/or the producing bacteria in controlling the post-harvest fruit disease caused by the patulin-producing fungus Penicillium expansum.


Subject(s)
Carboxylic Ester Hydrolases , Erwinia amylovora , Malus , Patulin , Patulin/metabolism , Carboxylic Ester Hydrolases/metabolism , Carboxylic Ester Hydrolases/genetics , Malus/microbiology , Erwinia amylovora/genetics , Erwinia amylovora/drug effects , Erwinia amylovora/enzymology , Erwinia amylovora/metabolism , Plant Diseases/microbiology , Penicillium/genetics , Penicillium/enzymology , Penicillium/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Microbial Interactions , Quorum Sensing , Lactones/metabolism , Lactones/pharmacology
3.
J Prim Care Community Health ; 15: 21501319241258948, 2024.
Article in English | MEDLINE | ID: mdl-38818953

ABSTRACT

OBJECTIVES: Healthcare screening identifies factors that impact patient health and well-being. Hunger as a Vital Sign (HVS) is widely applied as a screening tool to assess food security. However, there are no common practice screening questions to identify patients who are nutrition insecure or acquire free food from community-based organizations. This study used self-reported survey data from a non-Medicaid insured adult population approximately one year after the start of the COVID-19 pandemic (2021). The survey examined the extent to which the HVS measure might have under-estimated population-level food insecurity and/or nutrition insecurity, as well as under-identified food and nutrition insecurity among patients being screened for social risks in the healthcare setting. METHODS: Data from a 2021 English-only mailed/online survey were analyzed for 2791 Kaiser Permanente Northern California (KPNC) non-Medicaid insured members ages 35-85 years. Sociodemographics, financial strain, food insecurity, acquiring free food from community-based organizations, and nutrition insecurity were assessed. Data from respondents' electronic health records were abstracted to identify adults with diet-related chronic health conditions. Data were weighted to the age × sex × racial/ethnic composition of the 2019 KPNC adult membership. Differences between groups were evaluated for statistical significance using adjusted prevalence ratios (aPRs) derived from modified log Poisson regression models. RESULTS: Overall, 8.5% of participants reported moderate or high food insecurity, 7.7% had acquired free food from community-based organizations, and 13% had nutrition insecurity. Black and Latino adults were significantly more likely than White adults to have food insecurity (17.4% and 13.1% vs 5.6%, aPRs = 2.97 and 2.19), acquired free food from community-based organizations (15.1% and 15.3% vs 4.1%, aPRs = 3.74 and 3.93), nutrition insecurity (22.1% and 23.9% vs 7.9%, aPRs = 2.65 and 2.64), and food and nutrition insecurity (32.4% and 32.5% vs 12.3%, aPRs = 2.54 and 2.44). Almost 20% of adults who had been diagnosed with diabetes, prediabetes, ischemic CAD, or heart failure were food insecure and 14% were nutrition insecure. CONCLUSIONS: Expanding food-related healthcare screening to identify and assess food insecurity, nutrition insecurity, and use of community-based emergency food resources together is essential for supporting referrals that will help patients achieve optimal health.


Subject(s)
COVID-19 , Delivery of Health Care, Integrated , Food Insecurity , Humans , Female , Male , Adult , Cross-Sectional Studies , Middle Aged , Aged , COVID-19/epidemiology , Delivery of Health Care, Integrated/statistics & numerical data , Aged, 80 and over , California , Mass Screening/statistics & numerical data
4.
J Subst Use Addict Treat ; 164: 209410, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38802048

ABSTRACT

BACKGROUND: Individuals in early recovery face significant biopsychosocial stressors causing a preponderance of negative affect. Novel interventions are needed to improve mood and well-being to support recovery. Positive Recovery Journaling (PRJ) combines elements of positive psychology, behavioral activation, and journaling to emphasize what is going right and to encourage small, positive steps that align with an individual's values to make life in recovery more rewarding and therefore more reinforcing. Our objective was to determine PRJ's feasibility, acceptability, and impact on a set of strengths-based, multidimensional aspects of recovery, including satisfaction with life, happiness with recovery, and commitment to sobriety. METHODS: The study randomized adults in substance-use disorder treatment (N = 81) to PRJ or control. Those in PRJ were asked to practice PRJ daily and complete online surveys for four weeks; those in the control group completed online surveys for four weeks. We used multi-level modelling to determine intercept and slope for feasibility and acceptability outcomes as well as to compare differences in recovery indicators between treatment and control at baseline and Weeks 2, 4, and 8. We conducted intention-to-treat and per-protocol analyses for each recovery indicator. RESULTS: Participants were 53 % female, and 26 % Black, Indigenous, People of Color (BIPOC) and mean age of 39 years. PRJ participants attended 71 % of groups and completed 56 % of the daily PRJ entries. Treatment and control groups rated their study tasks (PRJ for the treatment group, surveys for the control group) as equally easy; however, the PRJ group rated PRJ as significantly more satisfying, helpful, and pleasant. Treatment and control were not significantly different on any recovery indicator. In post hoc analyses, we found that for those with <90 days sobriety at baseline (51 %), PRJ had a statistically significant beneficial effect for satisfaction with life, happiness with recovery, and numerous secondary recovery indicators. DISCUSSION: Results suggest a positive impact of PRJ on numerous recovery indices for those in earliest recovery. Integrating PRJ into support services among those with <90 days sobriety could reinforce what is going well in recovery to encourage its continued maintenance and thereby improve treatment outcomes.

5.
Nat Commun ; 15(1): 3770, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38704366

ABSTRACT

Aspergillus fumigatus is the leading causative agent of life-threatening invasive aspergillosis in immunocompromised individuals. One antifungal class used to treat Aspergillus infections is the fungistatic echinocandins, semisynthetic drugs derived from naturally occurring fungal lipopeptides. By inhibiting beta-1,3-glucan synthesis, echinocandins cause both fungistatic stunting of hyphal growth and repeated fungicidal lysis of apical tip compartments. Here, we uncover an endogenous mechanism of echinocandin tolerance in A. fumigatus whereby the inducible oxylipin signal 5,8-diHODE confers protection against tip lysis via the transcription factor ZfpA. Treatment of A. fumigatus with echinocandins induces 5,8-diHODE synthesis by the fungal oxygenase PpoA in a ZfpA dependent manner resulting in a positive feedback loop. This protective 5,8-diHODE/ZfpA signaling relay is conserved among diverse isolates of A. fumigatus and in two other Aspergillus pathogens. Our findings reveal an oxylipin-directed growth program-possibly arisen through natural encounters with native echinocandin producing fungi-that enables echinocandin tolerance in pathogenic aspergilli.


Subject(s)
Antifungal Agents , Aspergillosis , Aspergillus fumigatus , Echinocandins , Fungal Proteins , Oxylipins , Antifungal Agents/pharmacology , Echinocandins/pharmacology , Aspergillus fumigatus/drug effects , Aspergillus fumigatus/metabolism , Fungal Proteins/metabolism , Fungal Proteins/genetics , Fungal Proteins/antagonists & inhibitors , Oxylipins/metabolism , Oxylipins/pharmacology , Aspergillosis/drug therapy , Aspergillosis/microbiology , Signal Transduction/drug effects , Gene Expression Regulation, Fungal/drug effects , Hyphae/drug effects , Hyphae/growth & development , Hyphae/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics
6.
Int J Part Ther ; 11: 100006, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38757081

ABSTRACT

Purpose: In breast cancer, improved treatment approaches that reduce injury to lung tissue and early diagnosis and intervention for lung toxicity are increasingly important in survivorship. The aims of this study are to (1) compare lung tissue radiographic changes in women treated with conventional photon radiation therapy and those treated with proton therapy (PT), (2) assess the volume of lung irradiated to 5 Gy (V5) and 20 Gy (V20) by treatment modality, and (3) quantify the effects of V5, V20, time, and smoking history on the severity of tissue radiographic changes. Patients and Methods: A prospective observational study of female breast cancer patients was conducted to monitor postradiation subclinical lung tissue radiographic changes. Repeated follow-up x-ray computed tomography scans were acquired through 2 years after treatment. In-house software was used to quantify an internally normalized measure of pulmonary tissue density change over time from the computed tomography scans, emphasizing the 6- and 12-month time points. Results: Compared with photon therapy, PT was associated with significantly lower lung V5 and V20. Lung V20 (but not V5) correlated significantly with increased subclinical lung tissue radiographic changes 6 months after treatment, and neither correlated with lung effects at 12 months. Significant lung tissue density changes were present in photon therapy patients at 6 and 12 months but not in PT patients. Significant lung tissue density change persisted at 12 months in ever-smokers but not in never-smokers. Conclusion: Patients treated with PT had significantly lower radiation exposure to the lungs and less statistically significant tissue density change, suggesting decreased injury and/or improved recovery compared to photon therapy. These findings motivate additional studies in larger, randomized, and more diverse cohorts to further investigate the contributions of treatment modality and smoking regarding the short- and long-term radiographic effects of radiation on lung tissue.

8.
JMIR Res Protoc ; 13: e53684, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38564243

ABSTRACT

BACKGROUND: Both alcohol consumption and HIV infection are associated with worse brain, cognitive, and clinical outcomes in older adults. However, the extent to which brain and cognitive dysfunction is reversible with reduction or cessation of drinking is unknown. OBJECTIVE: The 30-Day Challenge study was designed to determine whether reduction or cessation of drinking would be associated with improvements in cognition, reduction of systemic and brain inflammation, and improvement in HIV-related outcomes in adults with heavy drinking. METHODS: The study design was a mechanistic experimental trial, in which all participants received an alcohol reduction intervention followed by repeated assessments of behavioral and clinical outcomes. Persons were eligible if they were 45 years of age or older, had weekly alcohol consumption of 21 or more drinks (men) or 14 or more drinks (women), and were not at high risk of alcohol withdrawal. After a baseline assessment, participants received an intervention consisting of contingency management (money for nondrinking days) for at least 30 days followed by a brief motivational interview. After this, participants could either resume drinking or not. Study questionnaires, neurocognitive assessments, neuroimaging, and blood, urine, and stool samples were collected at baseline, 30 days, 90 days, and 1 year after enrollment. RESULTS: We enrolled 57 persons with heavy drinking who initiated the contingency management protocol (mean age 56 years, SD 4.6 years; 63%, n=36 male, 77%, n=44 Black, and 58%, n=33 people with HIV) of whom 50 completed 30-day follow-up and 43 the 90-day follow-up. The planned study procedures were interrupted and modified due to the COVID-19 pandemic of 2020-2021. CONCLUSIONS: This was the first study seeking to assess changes in brain (neuroimaging) and cognition after alcohol intervention in nontreatment-seeking people with HIV together with people without HIV as controls. Study design strengths, limitations, and lessons for future study design considerations are discussed. Planned analyses are in progress, after which deidentified study data will be available for sharing. TRIAL REGISTRATION: ClinicalTrials.gov NCT03353701; https://clinicaltrials.gov/study/NCT03353701. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53684.

9.
AJPM Focus ; 3(3): 100211, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38633726

ABSTRACT

Introduction: The prevalence of hypertension increases with age and differs by race and ethnicity. Among U.S. Asian adults, prevalence is higher for Filipino adults than for other major Asian subgroups, but whether this disparity exists across the adult lifespan is unknown. This study examined hypertension prevalence by age decade, comparing Filipino adults with South Asian, Chinese, Black, Hispanic, and White adults. Methods: This cross-sectional study used 2015-2016 electronic health record data from a Northern California integrated healthcare delivery system for 1,839,603 adults aged 30-79 years, including 128,124 Filipino adults. Hypertension was defined by diagnosis codes. Sex-specific prevalence was calculated by race and ethnicity overall and by 10-year age decade from ages 30-39 years to 70-79 years. The prevalence of hypertension among 5 racial and ethnic groups was compared within each decade (with Filipino as the reference), adjusting for age, English language, diabetes, smoking, and weight category. Results: Decade-specific prevalence of hypertension among Filipino men and women, respectively, was 9.7% and 8.5% for ages 30-39 years, 26.0% and 23.9% for ages 40-49 years, 45.9% and 44.4% for ages 50-59 years, 65.4% and 63.9% for ages 60-69 years, and 82.1% and 82.9% for ages 70-79 years. Across all age decades, hypertension prevalence among Filipino adults largely tracked with Black adults and was much higher than among South Asian, Chinese, White, and Hispanic adults. This pattern remained after adjusting for covariates, with the largest differences observed for adults aged <60 years. Conclusions: Similar to Black adults, Filipino adults have persistently higher hypertension prevalence than South Asian, Chinese, Hispanic, and White adults across the adult lifespan. These findings underscore the importance of surveillance and prevention efforts for this high-risk Asian group beginning in early adulthood.

10.
JMIR Res Protoc ; 13: e50241, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38578672

ABSTRACT

BACKGROUND: While ecological momentary assessment (EMA) is commonly used to study social contexts and social influence in the real world, EMA almost exclusively relies on participant self-report of present circumstances, including the proximity to influential peers. There is the potential for developing a proximity sensing approach that uses small Bluetooth beacons and smartphone-based detection and data collection to collect information about interactions between individuals passively in real time. OBJECTIVE: This paper aims to describe the methods for evaluating the functionality and validity of a Bluetooth-based beacon and a smartphone app to identify when ≥2 individuals are physically proximal. METHODS: We will recruit 20 participants aged 18 to 29 years with Android smartphones to complete a 3-week study during which beacon detection and self-report data will be collected using a smartphone app (MEI Research). Using an interviewer-administered social network interview, participants will identify up to 3 peers of the same age who are influential on health behavior (alcohol use in this study). These peers will be asked to carry a Bluetooth beacon (Kontakt asset tag) for the duration of the study; each beacon has a unique ID that, when detected, will be recorded by the app on the participant's phone. Participants will be prompted to respond to EMA surveys (signal-contingent reports) when a peer beacon encounter meets our criteria and randomly 3 times daily (random reports) and every morning (morning reports) to collect information about the presence of peers. In all reports, the individualized list of peers will be presented to participants, followed by questions about peer and participant behavior, including alcohol use. Data from multiple app data sets, including beacon encounter specifications, notification, and app logs, participant EMA self-reports and postparticipation interviews, and peer surveys, will be used to evaluate project goals. We will examine the functionality of the technology, including the stability of the app (eg, app crashes and issues opening the app), beacon-to-app detection (ie, does the app detect proximal beacons?), and beacon encounter notification when encounter criteria are met. The validity of the technology will be defined as the concordance between passive detection of peers via beacon-to-app communication and the participant's EMA report of peer presence. Disagreement between the beacon and self-report data (ie, false negatives and false positives) will be investigated in multiple ways (ie, to determine if the reason was technology-related or participant compliance-related) using encounter data and information collected from participants and peers. RESULTS: Participant recruitment began in February 2023, and enrollment was completed in December 2023. Results will be reported in 2025. CONCLUSIONS: This Bluetooth-based technology has important applications and clinical implications for various health behaviors, including the potential for just-in-time adaptive interventions that target high-risk behavior in real time. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50241.

11.
J Fungi (Basel) ; 10(4)2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38667937

ABSTRACT

In 1999, the first biosynthetic gene cluster (BGC), synthesizing the virulence factor DHN melanin, was characterized in Aspergillus fumigatus. Since then, 19 additional BGCs have been linked to specific secondary metabolites (SMs) in this species. Here, we provide a comprehensive timeline of A. fumigatus BGC discovery and find that initial advances centered around the commonly expressed SMs where chemical structure informed rationale identification of the producing BGC (e.g., gliotoxin, fumigaclavine, fumitremorgin, pseurotin A, helvolic acid, fumiquinazoline). Further advances followed the transcriptional profiling of a ΔlaeA mutant, which aided in the identification of endocrocin, fumagillin, hexadehydroastechrome, trypacidin, and fumisoquin BGCs. These SMs and their precursors are the commonly produced metabolites in most A. fumigatus studies. Characterization of other BGC/SM pairs required additional efforts, such as induction treatments, including co-culture with bacteria (fumicycline/neosartoricin, fumigermin) or growth under copper starvation (fumivaline, fumicicolin). Finally, four BGC/SM pairs were discovered via overexpression technologies, including the use of heterologous hosts (fumicycline/neosartoricin, fumihopaside, sphingofungin, and sartorypyrone). Initial analysis of the two most studied A. fumigatus isolates, Af293 and A1160, suggested that both harbored ca. 34-36 BGCs. However, an examination of 264 available genomes of A. fumigatus shows up to 20 additional BGCs, with some strains showing considerable variations in BGC number and composition. These new BGCs present a new frontier in the future of secondary metabolism characterization in this important species.

12.
J Hazard Mater ; 471: 134385, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38678711

ABSTRACT

Nitric oxide (NO) is a signaling molecule with diverse roles in various organisms. However, its role in the opportunistic pathogen Aspergillus flavus remains unclear. This study investigates the potential of NO, mediated by metabolites from A. oryzae (AO), as an antifungal strategy against A. flavus. We demonstrated that AO metabolites effectively suppressed A. flavus asexual development, a critical stage in its lifecycle. Transcriptomic analysis revealed that AO metabolites induced NO synthesis genes, leading to increased intracellular NO levels. Reducing intracellular NO content rescued A. flavus spores from germination inhibition caused by AO metabolites. Furthermore, exogenous NO treatment and dysfunction of flavohemoglobin Fhb1, a key NO detoxification enzyme, significantly impaired A. flavus asexual development. RNA-sequencing and metabolomic analyses revealed significant metabolic disruptions within tricarboxylic acid (TCA) cycle upon AO treatment. NO treatment significantly reduced mitochondrial membrane potential (Δψm) and ATP generation. Additionally, aberrant metabolic flux within the TCA cycle was observed upon NO treatment. Further analysis revealed that NO induced S-nitrosylation of five key TCA cycle enzymes. Genetic analysis demonstrated that the S-nitrosylated Aconitase Acon and one subunit of succinate dehydrogenase Sdh2 played crucial roles in A. flavus development by regulating ATP production. This study highlights the potential of NO as a novel antifungal strategy to control A. flavus by compromising its mitochondrial function and energy metabolism.


Subject(s)
Aspergillus flavus , Citric Acid Cycle , Mitochondria , Nitric Oxide , Citric Acid Cycle/drug effects , Aspergillus flavus/metabolism , Aspergillus flavus/growth & development , Aspergillus flavus/drug effects , Nitric Oxide/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , Antifungal Agents/pharmacology , Membrane Potential, Mitochondrial/drug effects , Spores, Fungal/drug effects , Spores, Fungal/growth & development , Fungal Proteins/metabolism , Fungal Proteins/genetics
14.
J Leukoc Biol ; 116(1): 118-131, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38417030

ABSTRACT

Neutrophils are rapidly recruited to sites of infection and are critical for pathogen clearance. Therapeutic use of primary neutrophils has been limited, as they have a short lifespan and are not amenable to genetic manipulation. Human induced pluripotent stem cells (iPSCs) can provide a robust source of neutrophils for infusion and are genetically tractable. However, current work has indicated that dampened intracellular signaling limits iPSC-derived neutrophil (iNeutrophil) cellular activation and antimicrobial response. Here, we show that protein tyrosine phosphatase 1B (PTP1B) inhibits intracellular signaling and dampens iNeutrophil effector function. Deletion of the PTP1B phosphatase increased PI3K and ERK signaling and was associated with increased F-actin polymerization, cell migration, and phagocytosis. In contrast, other effector functions like NETosis and reactive oxygen species production were reduced. PTP1B-deficient neutrophils were more responsive to Aspergillus fumigatus and displayed rapid recruitment and control of hyphal growth. Accordingly, depletion of PTP1B increased production of inflammatory factors including the neutrophil chemokine interleukin-8. Taken together, these findings suggest that PTP1B limits iNeutrophil motility and antimicrobial function.


Subject(s)
Cell Movement , Induced Pluripotent Stem Cells , Neutrophils , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 1/genetics , Neutrophils/metabolism , Neutrophils/immunology , Humans , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , Aspergillus fumigatus , Phagocytosis , Phosphatidylinositol 3-Kinases/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction , Extracellular Traps/metabolism , Extracellular Traps/immunology , Actins/metabolism
15.
Addict Behav ; 152: 107956, 2024 05.
Article in English | MEDLINE | ID: mdl-38301589

ABSTRACT

Peer alcohol use, commonly assessed via perceptions of how many drinks peers consume, is a robust predictor of college drinking. These perceptions are formed by in-person exposure to peer drinking but also may be affected by seeing alcohol-related content (ARC) shared on peer social media accounts. Most research assesses exposure by asking about the frequency of ARC sharing by a whole friend group, potentially missing influences from specific friends. Social network methods collect information about specific friends and their behavior but few studies have used these methods to examine the effects of ARC on drinking, nor have they examined potential moderators of this relationship. The purpose of this study was to examine whether perceived frequency of exposure to ARC shared by social network members on social media is associated with participant alcohol use after controlling for network members' self-reported alcohol use, and if participant gender and relationship qualities with network members moderate this association. Participants were 994 college students (Mage = 21.17, SD = 0.47; 61.8 % female; 55.4 % White; 12.3 % Hispanic) who completed a web-based survey. Due to the social network design, network autocorrelation analyses were conducted, which revealed that greater perceived frequency of exposure to network member ARC was significantly associated with higher alcohol quantity above and beyond network members' alcohol use. Peer ARC had a unique association with drinking behavior independent of in-person peer alcohol use, although the cross-sectional design precludes making causal inferences. Clinicians delivering alcohol interventions to college students may wish to discuss exposure to ARC as another important source of peer influence and how media literacy may help reduce the effects.


Subject(s)
Interpersonal Relations , Peer Group , Humans , Female , Male , Cross-Sectional Studies , Students , Social Networking
16.
Sci Adv ; 10(8): eadk7416, 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38381828

ABSTRACT

Filamentous fungi produce numerous uncharacterized natural products (NPs) that are often challenging to characterize because of cryptic expression in laboratory conditions. Previously, we have successfully isolated novel NPs by expressing fungal artificial chromosomes (FACs) from a variety of fungal species into Aspergillus nidulans. Here, we demonstrate a twist to FAC utility wherein heterologous expression of a Pseudogymnoascus destructans FAC in A. nidulans altered endogenous terpene biosynthetic pathways. In contrast to wild type, the FAC transformant produced increased levels of squalene and aspernidine type compounds, including three new nidulenes (1- 2, and 5), and lost nearly all ability to synthesize the major A. nidulans characteristic terpene, austinol. Deletion of a squalene synthase gene in the FAC restored wild-type chemical profiles. The altered squalene to farnesyl pyrophosphate ratio leading to synthesis of nidulenes and aspernidines at the expense of farnesyl pyrophosphate-derived austinols provides unexpected insight into routes of terpene synthesis in fungi.


Subject(s)
Aspergillus nidulans , Polyisoprenyl Phosphates , Sesquiterpenes , Aspergillus nidulans/genetics , Aspergillus nidulans/metabolism , Farnesyl-Diphosphate Farnesyltransferase/genetics , Farnesyl-Diphosphate Farnesyltransferase/metabolism , Squalene , Terpenes/metabolism
17.
Cancers (Basel) ; 16(4)2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38398171

ABSTRACT

PURPOSE: To demonstrate the feasibility of improving prostate cancer patient outcomes with PBS proton LETd optimization. METHODS: SFO, IPT-SIB, and LET-optimized plans were created for 12 patients, and generalized-tissue and disease-specific LET-dependent RBE models were applied. The mean LETd in several structures was determined and used to calculate mean RBEs. LETd- and dose-volume histograms (LVHs/DVHs) are shown. TODRs were defined based on clinical dose goals and compared between plans. The impact of robust perturbations on LETd, TODRs, and DVH spread was evaluated. RESULTS: LETd optimization achieved statistically significant increased target volume LETd of ~4 keV/µm compared to SFO and IPT-SIB LETd of ~2 keV/µm while mitigating OAR LETd increases. A disease-specific RBE model predicted target volume RBEs > 1.5 for LET-optimized plans, up to 18% higher than for SFO plans. LET-optimized target LVHs/DVHs showed a large increase not present in OARs. All RBE models showed a statistically significant increase in TODRs from SFO to IPT-SIB to LET-optimized plans. RBE = 1.1 does not accurately represent TODRs when using LETd optimization. Robust evaluations demonstrated a trade-off between increased mean target LETd and decreased DVH spread. CONCLUSION: The demonstration of improved TODRs provided via LETd optimization shows potential for improved patient outcomes.

18.
Perm J ; 28(1): 68-75, 2024 03 15.
Article in English | MEDLINE | ID: mdl-38317596

ABSTRACT

INTRODUCTION: Patients are being encouraged to complete forms electronically using patient portals rather than on paper, but willingness of older adults to make this transition is uncertain. METHODS: The authors analyzed data for 4105 Kaiser Permanente Northern California 2020 Member Health Survey respondents aged 65-85 years who answered a question about willingness to complete online forms and questionnaires using a patient portal. Data weighted to the Kaiser Permanente Northern California membership were used to estimate percentages of older adults willing to complete patient portal forms and questionnaires. Chi-square tests and log-Poisson regression models that included sociodemographic, internet use, and patient portal variables were used to identify factors predictive of willingness. RESULTS: Overall, 59.6% of older adults were willing to complete patient portal forms, 17.6% were not willing, and 22.8% were not sure. Adults aged 75-85 (49.5%) vs 65-74 years (64.8%) and Black (51.9%) and Latino (46.5%) vs White (62.8%) adults were less likely to indicate willingness. In addition to racial and ethnic differences and younger age, higher educational attainment, use of the internet alone (vs internet use with help or not at all), having an internet-enabled computer or tablet, and having sent at least 1 message through the patient portal increased likelihood of being willing. CONCLUSIONS: Health care teams should assess older adults' capabilities and comfort related to completion of patient portal-based forms and support those willing to make the digital transition. Paper forms and oral collection of information should remain available for those unable or unwilling to make this digital transition.


Subject(s)
Patient Portals , Surveys and Questionnaires , Aged , Humans , Health Surveys , Racial Groups , Aged, 80 and over
19.
J Autism Dev Disord ; 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38231382

ABSTRACT

PURPOSE: To understand the ways in which autistic Latinx children experience disparities in diagnosis, healthcare, and receipt of specialty services. METHODS: 417 individuals who identified as Latinx caregivers of autistic children who were members of the same integrated healthcare system in Northern California were surveyed. Responses were analyzed using the child's insurance coverage (Government or Commercial) and caregiver's primary language (Spanish or English). RESULTS: Compared to the commercially-insured, government-insured participants accessed several services at a higher rate and were less likely to cite the high cost of co-pays as a barrier. CONCLUSION: There were no significant differences in service access by language status, but Spanish speakers were more likely to cite health literacy as a barrier to receiving care.

20.
Alcohol Clin Exp Res (Hoboken) ; 48(2): 375-388, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38240663

ABSTRACT

BACKGROUND: Heavy-drinking college students tend to have close social networks, and there is theoretical and empirical support for the idea that behavior change can spread through those networks via close ties. The objective of this research was to determine whether intervention-induced behavior change in a subset of heavy drinkers in a sociometric (whole) college class-year social network is transmitted to other heavy drinkers in the network, resulting in reduced behavioral risk and change in network ties. METHODS: We conducted a controlled trial in which most of a first-year college class (N = 1236; 56.9% female) was enrolled, with alcohol use and social network ties measured early in each of three semesters. Following a baseline assessment, the network was divided into two groups, brief motivational intervention (BMI) and natural history control (NHC) according to dormitory residence location. A subset of heavy drinkers in each group was selected, and those in the BMI group received an in-person intervention. RESULTS: Using stochastic actor-oriented modeling, we found a significant tendency for participants in the BMI group to shed ties with individuals with similar drinking behaviors between the first and second semesters, relative to the NHC group. Furthermore, heavy drinkers with reciprocal ties to intervention recipients in the BMI group showed a significant reduction in drinks per week. CONCLUSIONS: Individual alcohol interventions appear to have effects both on behavior and network connections among individuals who did not receive the intervention. Continued research is needed to identify the optimal conditions for the diffusion of behavior change.

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