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1.
Sci Total Environ ; : 173706, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38866169

ABSTRACT

BACKGROUND: Air pollution is a modifiable risk factor for dementia. Yet, studies on specific sources of air pollution (i.e., toxic chemical emissions from industrial facilities) and dementia risk are scarce. We examined associations between toxicity-weighted concentrations of industrial pollution and dementia outcomes among a large, multi-site cohort of older adults. METHODS: Participants (n = 2770) were ≥ 65 years old (Mean = 75.3, SD = 5.1 years) from the Cardiovascular Health Cognition Study (1992-1999). Toxicity-weighted concentrations were estimated using the Risk Screening Environmental Indicator (RSEI) model which incorporates total reported chemical emissions with toxicity, fate, and transport models. Estimates were aggregated to participants' baseline census tract, averaged across 1988-1992, and log2-transformed. Dementia status was clinically adjudicated in 1998-1999 and categorized by subtype (Alzheimer's, vascular, mixed). We assessed whether RSEI-estimated toxicity-weighted concentrations were associated with 1) odds of prevalent dementia and 2) incident dementia risk by subtype. RESULTS: After adjusting for individual and census-tract level covariates, a doubling in toxicity-weighted concentrations was associated with 9 % higher odds of prevalent dementia (OR = 1.09, 95 % CI: 1.00, 1.19). In discrete-time survival models, each doubling in toxicity-weighted concentrations was associated with a 16 % greater hazard of vascular dementia (HR = 1.16, 95 % CI: 1.01, 1.34) but was not significantly associated with all-cause, Alzheimer's disease, or mixed dementia (p's > 0.05). DISCUSSION: Living in regions with higher toxicity-weighted concentrations was associated with higher odds of prevalent dementia and a higher risk of incident vascular dementia in this large, community-based cohort of older adults. These findings support the need for additional studies to examine whether toxic chemical emissions from industrial and federal facilities may be a modifiable target for dementia prevention.

2.
BMC Med Res Methodol ; 24(1): 132, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849718

ABSTRACT

Accelerometers, devices that measure body movements, have become valuable tools for studying the fragmentation of rest-activity patterns, a core circadian rhythm dimension, using metrics such as inter-daily stability (IS), intradaily variability (IV), transition probability (TP), and self-similarity parameter (named α ). However, their use remains mainly empirical. Therefore, we investigated the mathematical properties and interpretability of rest-activity fragmentation metrics by providing mathematical proofs for the ranges of IS and IV, proposing maximum likelihood and Bayesian estimators for TP, introducing the activity balance index (ABI) metric, a transformation of α , and describing distributions of these metrics in real-life setting. Analysis of accelerometer data from 2,859 individuals (age=60-83 years, 21.1% women) from the Whitehall II cohort (UK) shows modest correlations between the metrics, except for ABI and α . Sociodemographic (age, sex, education, employment status) and clinical (body mass index (BMI), and number of morbidities) factors were associated with these metrics, with differences observed according to metrics. For example, a difference of 5 units in BMI was associated with all metrics (differences ranging between -0.261 (95% CI -0.302, -0.220) to 0.228 (0.18, 0.268) for standardised TP rest to activity during the awake period and TP activity to rest during the awake period, respectively). These results reinforce the value of these rest-activity fragmentation metrics in epidemiological and clinical studies to examine their role for health. This paper expands on a set of methods that have previously demonstrated empirical value, improves the theoretical foundation for these methods, and evaluates their empirical use in a large dataset.


Subject(s)
Accelerometry , Rest , Humans , Female , Aged , Male , Accelerometry/methods , Accelerometry/statistics & numerical data , Middle Aged , Rest/physiology , Aged, 80 and over , Bayes Theorem , Body Mass Index , Circadian Rhythm/physiology , Likelihood Functions , Motor Activity/physiology
3.
Cancer Res Commun ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38856749

ABSTRACT

PURPOSE: Sipuleucel-T is an autologous cellular immunotherapy that targets prostatic acid phosphatase (PAP) and is available for treatment of men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). In this single-arm, two-cohort, multicenter clinical study, potential racial differences in immune responses to sipuleucel-T in men with mCRPC were explored. PATIENTS AND METHODS: Patients' blood samples were obtained to assess serum cytokines, humoral responses, and cellular immunity markers pre- and post-treatment. Baseline cumulative product parameters (total nucleated and CD54+ cell counts, and CD54 upregulation) were evaluated. IgM titers against the immunogen PA2024, the target antigen PAP, prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA) were quantified by ELISA. Cytotoxic T lymphocyte activity was determined by ELISpots, and cytokine and chemokine concentrations by Luminex. RESULTS: Twenty-nine African Americans (AA) and 28 non-African Americans (non-AA) with mCRPC received sipuleucel-T. Baseline total nucleated cell count, CD54+ cell count, CD54 expression, and cumulative product parameters were higher in non-AA. Although PSA baseline levels were higher in AA, there were no racial differences in IgM antibody and IFN- ELISpots responses against PA2024, PAP, PSA and PSMA pre- and post-treatment. Expression of co-stimulatory receptor ICOS on CD4+ and CD8+ T cells, and the levels of Th1 cytokine granulocyte-macrophage colony-stimulating factor and chemokines CCL4 and CCL5, were significantly higher in AA pre- and/or post-treatment. Despite no difference in the overall survival, PSA changes from baseline were significantly different between the two races. CONCLUSIONS: The data suggest that immune correlates in blood differ in AA and non-AA with mCRPC pre- and post-sipuleucel-T.

4.
bioRxiv ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38853988

ABSTRACT

Drosophila models for tumorigenesis and metastasis have revealed conserved mechanisms of signaling that are also involved in mammalian cancer. Many of these models use the proliferating tissues of the larval stages of Drosophila development, when tissues are highly mitotically active, or stem cells are abundant. Fewer Drosophila tumorigenesis models use adult animals to initiate tumor formation when many tissues are largely terminally differentiated and postmitotic. The Drosophila accessory glands are prostate-like tissues and a model for some aspects of prostate tumorigenesis using this tissue has been explored. In this model, oncogenic signaling was induced during the proliferative stage of accessory gland development, raising the question of how oncogenic activity would impact the terminally differentiated and postmitotic adult tissue. Here, we show that oncogenic signaling in the adult Drosophila accessory gland leads to activation of a conserved pro-tumorigenic program, similar to that observed in mitotic larval tissues, but in the absence of proliferation. Oncogenic signaling in the adult postmitotic gland leads to tissue hyperplasia with nuclear anaplasia and aneuploidy through endoreduplication, which increases polyploidy and occasionally results in non-mitotic neoplastic-like extrusions. We compare gene expression changes in our Drosophila model with that of endocycling prostate cancer cells induced by chemotherapy, which potentially mediate tumor recurrence after treatment. Similar signaling pathways are activated in the Drosophila gland and endocycling cancer cells, suggesting the adult accessory glands provide a useful model for aspects of prostate cancer progression that do not involve cellular proliferation.

5.
bioRxiv ; 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38853939

ABSTRACT

A major barrier that hampers our understanding of the precise anatomic distribution of pain sensing nerves in and around the joint is the limited view obtained from traditional two dimensional (D) histological approaches. Therefore, our objective was to develop a workflow that allows examination of the innervation of the intact mouse knee joint in 3D by employing clearing-enabled light sheet microscopy. We first surveyed existing clearing protocols (SUMIC, PEGASOS, and DISCO) to determine their ability to clear the whole mouse knee joint, and discovered that a DISCO protocol provided the most optimal transparency for light sheet microscopy imaging. We then modified the DISCO protocol to enhance binding and penetration of antibodies used for labeling nerves. Using the pan-neuronal PGP9.5 antibody, our protocol allowed 3D visualization of innervation in and around the mouse knee joint. We then implemented the workflow in mice intra-articularly injected with nerve growth factor (NGF) to determine whether changes in the nerve density can be observed. Both 3D and 2D analytical approaches of the light sheet microscopy images demonstrated quantifiable changes in midjoint nerve density following 4 weeks of NGF injection in the medial but not in the lateral joint compartment. We provide, for the first time, a comprehensive workflow that allows detailed and quantifiable examination of mouse knee joint innervation in 3D.

6.
J Clin Child Adolesc Psychol ; : 1-10, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38805627

ABSTRACT

OBJECTIVE: Although the significance of the general factor of psychopathology (p) is being increasingly recognized, it remains unclear how to best operationalize and measure p. To test variations in the operationalizations of p and make practical recommendations for its assessment, we compared p-factor scores derived from four models. METHODS: We compared p scores derived from principal axis (Model 1), hierarchical factor (Model 2), and bifactor (Model 3) analyses, plus a Total Problem score (sum of unit-weighted ratings of all problem items; Model 4) for parent- and self-rated youth psychopathology from 24 societies. Separately for each sample, we fitted the models to parent-ratings on the Child Behavior Checklist for Ages 6-18 (CBCL/6-18) and self-ratings on the Youth Self-Report (YSR) for 25,643 11-18-year-olds. Separately for each sample, we computed correlations between p-scores obtained for each pair of models, cross-informant correlations between p-scores for each model, and Q-correlations between mean item x p-score correlations for each pair of models. RESULTS: Results were similar for all models, as indicated by correlations of .973-.994 between p-scores for Models 1-4, plus similar cross-informant correlations between CBCL/6-18 and YSR Model 1-4 p-scores. Item x p correlations had similar rank orders between Models 1-4, as indicated by Q correlations of .957-.993. CONCLUSIONS: The similar results obtained for Models 1-4 argue for using the simplest model - the unit-weighted Total Problem score - to measure p for clinical and research assessment of youth psychopathology. Practical methods for measuring p may advance the field toward transdiagnostic patterns of problems.

8.
Am Psychol ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38815064

ABSTRACT

Aggression and violence against educators and school personnel have raised public health concerns that require attention from researchers, policymakers, and training providers in U.S. schools. School aggression and violence have negative effects on school personnel health and retention and on student achievement and development. In partnership with several national organizations, the American Psychological Association (APA) Task Force on Violence Against Educators and School Personnel administered two national, multi-informant, cross-sectional surveys. Time 1 data were collected in 2020-2021 from 14,966 respondents; participants reflected on their experiences of violence and aggression before COVID-19 and during COVID-19 restrictions in this survey. One year later, in 2022, 11,814 respondents completed the Time 2 survey after COVID-19 restrictions ended. Participants included teachers, school psychologists, social workers, counselors, staff members, and administrators from all 50 states and Puerto Rico. Rates of violence and aggression directed against educators by students, parents, colleagues, and administrators were substantial before COVID-19, were lower during COVID-19 restrictions, and returned to prepandemic levels or higher after COVID-19 restrictions. After COVID-19 restrictions, 22%-80% of respondents reported verbal or threatening aggression, and 2%-56% of respondents reported physical violence at least once during the year, varying by stakeholder role and aggressor. Rates of intentions to quit the profession ranged from 21% to 43% during COVID-19 restrictions (2020-2021) and from 23% to 57% after COVID-19 restrictions (2021-2022), varying by stakeholder role. Participants across roles reported substantial rates of anxiety and stress, especially during and after COVID-19 restrictions, and identified specific training needs. Implications for theory, research, training, and policy are presented. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

9.
Int Endod J ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38813933

ABSTRACT

AIM: Post-operative pain may occur after non-surgical root canal treatment (NSRCT). The root filling technique and choice of sealer may be contributing factors. This randomized controlled clinical trial compared post-operative pain and analgesics intake after NSRCT using a sealer-based obturation technique (SBO) with single-cone gutta-percha and calcium silicate sealer (CSS) versus a warm-vertical compaction (WVC) technique with gutta-percha and a resin-based sealer (RBS). METHODOLOGY: This study was designed as a parallel-two arm, double-blind, randomized superiority clinical trial registered at www. CLINICALTRIALS: gov (NCT04753138). Patients referred for NSRCT fulfilling the inclusion criteria participated in this study. Pre-operative periapical radiographs and CBCT scans were taken and numerical rating scale (NRS) pain scores were recorded. Upon completion of canal instrumentation, participants were randomly allocated to either Group SBO: SBO with CSS or Group WVC: Warm-vertical compaction with RBS. Post-operative pain and analgesics intake were recorded at 1, 3 and 7 days after endodontic treatment completion. Non-parametric Mann-Whitney U and Friedman tests and a generalized estimating equation were used to assess differences in pain scores between the groups, within each treatment group at different time points and for correlations, respectively. RESULTS: The study included 195 participants (212 teeth). One participant declined to submit the NRS form. Therefore, 194 participants (211 teeth) were included in the final analysis (99.5% response rate). No statistically significant differences in post-operative pain or analgesic intake existed between the two groups at any time point (p > .05). Age, pre-operative pain, apical diagnosis and post-operative analgesic intake were significantly related to post-operative pain (p < .05). CONCLUSIONS: Sealer-based obturation technique with CSS was associated with similar post-operative pain levels and analgesics intake as WVC with RBS. Regarding post-operative pain, SBO with CSSs may be a suitable clinical alternative.

10.
JAMA Netw Open ; 7(5): e247535, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38771577

ABSTRACT

Importance: While ß-blockers are associated with decreased mortality in cardiovascular disease (CVD), exacerbation-prone patients with chronic obstructive pulmonary disease (COPD) who received metoprolol in the Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease (BLOCK-COPD) trial experienced increased risk of exacerbations requiring hospitalization. However, the study excluded individuals with established indications for the drug, raising questions about the overall risk and benefit in patients with COPD following acute myocardial infarction (AMI). Objective: To investigate whether ß-blocker prescription at hospital discharge is associated with increased risk of mortality or adverse cardiopulmonary outcomes in patients with COPD and AMI. Design, Setting, and Participants: This prospective, longitudinal cohort study with 6 months of follow-up enrolled patients aged 35 years or older with COPD who underwent cardiac catheterization for AMI at 18 BLOCK-COPD network hospitals in the US from June 2020 through May 2022. Exposure: Prescription for any ß-blocker at hospital discharge. Main Outcomes and Measures: The primary outcome was time to the composite outcome of death or all-cause hospitalization or revascularization. Secondary outcomes included death, hospitalization, or revascularization for CVD events, death or hospitalization for COPD or respiratory events, and treatment for COPD exacerbations. Results: Among 3531 patients who underwent cardiac catheterization for AMI, prevalence of COPD was 17.1% (95% CI, 15.8%-18.4%). Of 579 total patients with COPD and AMI, 502 (86.7%) were prescribed a ß-blocker at discharge. Among the 562 patients with COPD included in the final analysis, median age was 70.0 years (range, 38.0-94.0 years) and 329 (58.5%) were male; 553 of the 579 patients (95.5%) had follow-up information. Among those discharged with ß-blockers, there was no increased risk of the primary end point of all-cause mortality, revascularization, or hospitalization (hazard ratio [HR], 1.01; 95% CI, 0.66-1.54; P = .96) or of cardiovascular events (HR, 1.11; 95% CI, 0.65-1.92; P = .69), COPD-related or respiratory events (HR, 0.75; 95% CI, 0.34-1.66; P = .48), or treatment for COPD exacerbations (rate ratio, 1.01; 95% CI, 0.53-1.91; P = .98). Conclusions and Relevance: In this cohort study, ß-blocker prescription at hospital discharge was not associated with increased risk of adverse outcomes in patients with COPD and AMI. These findings support use of ß-blockers in patients with COPD and recent AMI.


Subject(s)
Adrenergic beta-Antagonists , Myocardial Infarction , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/complications , Adrenergic beta-Antagonists/therapeutic use , Male , Female , Myocardial Infarction/complications , Myocardial Infarction/drug therapy , Myocardial Infarction/mortality , Aged , Middle Aged , Prospective Studies , Longitudinal Studies , Hospitalization/statistics & numerical data
11.
J Chem Theory Comput ; 20(11): 4790-4803, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38768310

ABSTRACT

The impact of exciton-vibrational (EV) coupling involving low-energy ("slow") intermolecular vibrations and higher-energy ("fast") intramolecular vibrations on the absorption and emission spectra of H- and J-dimers is studied theoretically for a pair of chromophores with excitonic coupling dominated by transition dipole-dipole coupling, JC. Exact quantum-mechanical solutions based on a Frenkel-Holstein-Peierls Hamiltonian reveal a fascinating interplay between the two coupling sources in determining the spectral line widths, Stoke shifts and radiative decay rates. It is shown that the ratio rules derived from the vibronic progression of the fast mode in molecular dimers remain valid under the influence of slow-mode EV coupling under most conditions. However, a highly unusual aggregate behavior occurs when the product of local and nonlocal couplings, |gLgNL|, exceeds 2ℏωs|JC|, where ℏωs is the energy of the slow mode. In this regime and when gL and gNL are in-phase, an H-dimer (JC > 0) becomes strongly emissive and can even be super-radiant, while a J-dimer (JC < 0) with out-of-phase gL and gNL values becomes subradiant. Such behaviors are in marked contrast to the predictions of Kasha theory and demonstrate the richness of the photophysical behavior resulting from EV coupling involving inter- and intramolecular vibrations.

12.
JAMA Netw Open ; 7(5): e249474, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38696166

ABSTRACT

Importance: The National Cancer Institute comprehensive cancer centers (CCCs) lack spatial and temporal evaluation of their self-designated catchment areas. Objective: To identify disparities in cancer stage at diagnosis within and outside a CCC's catchment area across a 10-year period using spatial and statistical analyses. Design, Setting, and Participants: This cross-sectional, population-based study conducted between 2010 and 2019 utilized cancer registry data for the Johns Hopkins Sidney Kimmel CCC (SKCCC). Eligible participants included patients with cancer in the contiguous US who received treatment for cancer, a diagnosis of cancer, or both at SKCCC. Patients were geocoded to zip code tabulation areas (ZCTAs). Individual-level variables included sociodemographic characteristics, smoking and alcohol use, treatment type, cancer site, and insurance type. Data analysis was performed between March and July 2023. Exposures: Distance between SKCCC and ZCTAs were computed to generate a catchment area of the closest 75% of patients and outer zones in 5% increments for comparison. Main Outcomes and Measures: The primary outcome was cancer stage at diagnosis, defined as early-stage, late-stage, or unknown stage. Multinomial logistic regression was used to determine associations of catchment area with stage at diagnosis. Results: This study had a total of 94 007 participants (46 009 male [48.94%] and 47 998 female [51.06%]; 30 195 aged 22-45 years [32.12%]; 4209 Asian [4.48%]; 2408 Hispanic [2.56%]; 16 004 non-Hispanic Black [17.02%]; 69 052 non-Hispanic White [73.45%]; and 2334 with other or unknown race or ethnicity [2.48%]), including 47 245 patients (50.26%) who received a diagnosis of early-stage cancer, 19 491 (20.73%) who received a diagnosis of late-stage cancer , and 27 271 (29.01%) with unknown stage. Living outside the main catchment area was associated with higher odds of late-stage cancers for those who received only a diagnosis (odds ratio [OR], 1.50; 95% CI, 1.10-2.05) or only treatment (OR, 1.44; 95% CI, 1.28-1.61) at SKCCC. Non-Hispanic Black patients (OR, 1.16; 95% CI, 1.10-1.23) and those with Medicaid (OR, 1.65; 95% CI, 1.46-1.86) and no insurance at time of treatment (OR, 2.12; 95% CI, 1.79-2.51) also had higher odds of receiving a late-stage cancer diagnosis. Conclusions and Relevance: In this cross-sectional study of CCC data from 2010 to 2019, patients residing outside the main catchment area, non-Hispanic Black patients, and patients with Medicaid or no insurance had higher odds of late-stage diagnoses. These findings suggest that disadvantaged populations and those living outside of the main catchment area of a CCC may face barriers to screening and treatment. Care-sharing agreements among CCCs could address these issues.


Subject(s)
Cancer Care Facilities , Catchment Area, Health , Neoplasm Staging , Neoplasms , Humans , Female , Male , Middle Aged , Cross-Sectional Studies , Neoplasms/epidemiology , Cancer Care Facilities/statistics & numerical data , Catchment Area, Health/statistics & numerical data , Adult , Aged , Healthcare Disparities/statistics & numerical data , United States , Registries
13.
Ther Adv Respir Dis ; 18: 17534666241232264, 2024.
Article in English | MEDLINE | ID: mdl-38698565

ABSTRACT

What is this summary about?This summary describes the results of a clinical study called MANDALA that was published in the New England Journal of Medicine in 2022. In the MANDALA study, researchers looked at a new asthma rescue inhaler that contains both albuterol and budesonide in a single inhaler (known as albuterol-budesonide, AIRSUPRA™). This summary describes the results for people aged 18 yearsand older who took part in the study.


Subject(s)
Albuterol , Asthma , Bronchodilator Agents , Budesonide , Drug Combinations , Nebulizers and Vaporizers , Humans , Asthma/drug therapy , Albuterol/administration & dosage , Administration, Inhalation , Bronchodilator Agents/administration & dosage , Budesonide/administration & dosage , Adult , Middle Aged , Male , Female , Treatment Outcome , Adolescent , Young Adult , Aged , Anti-Asthmatic Agents/administration & dosage
14.
Nat Microbiol ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649409

ABSTRACT

The ability to sense prey-derived cues is essential for predatory lifestyles. Under low-nutrient conditions, Arthrobotrys oligospora and other nematode-trapping fungi develop dedicated structures for nematode capture when exposed to nematode-derived cues, including a conserved family of pheromones, the ascarosides. A. oligospora senses ascarosides via conserved MAPK and cAMP-PKA pathways; however, the upstream receptors remain unknown. Here, using genomic, transcriptomic and functional analyses, we identified two families of G protein-coupled receptors (GPCRs) involved in sensing distinct nematode-derived cues. GPCRs homologous to yeast glucose receptors are required for ascaroside sensing, whereas Pth11-like GPCRs contribute to ascaroside-independent nematode sensing. Both GPCR classes activate conserved cAMP-PKA signalling to trigger trap development. This work demonstrates that predatory fungi use multiple GPCRs to sense several distinct nematode-derived cues for prey recognition and to enable a switch to a predatory lifestyle. Identification of these receptors reveals the molecular mechanisms of cross-kingdom communication via conserved pheromones also sensed by plants and animals.

15.
Cell Rep ; 43(4): 114042, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38573858

ABSTRACT

Pathogenic infection elicits behaviors that promote recovery and survival of the host. After exposure to the pathogenic bacterium Pseudomonas aeruginosa PA14, the nematode Caenorhabditis elegans modifies its sensory preferences to avoid the pathogen. Here, we identify antagonistic neuromodulators that shape this acquired avoidance behavior. Using an unbiased cell-directed neuropeptide screen, we show that AVK neurons upregulate and release RF/RYamide FLP-1 neuropeptides during infection to drive pathogen avoidance. Manipulations that increase or decrease AVK activity accelerate or delay pathogen avoidance, respectively, implicating AVK in the dynamics of avoidance behavior. FLP-1 neuropeptides drive pathogen avoidance through the G protein-coupled receptor DMSR-7, as well as other receptors. DMSR-7 in turn acts in multiple neurons, including tyraminergic/octopaminergic neurons that receive convergent avoidance signals from the cytokine DAF-7/transforming growth factor ß. Neuromodulators shape pathogen avoidance through multiple mechanisms and targets, in agreement with the distributed neuromodulatory connectome of C. elegans.


Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Neuropeptides , Pseudomonas aeruginosa , Animals , Caenorhabditis elegans/metabolism , Caenorhabditis elegans/microbiology , Neuropeptides/metabolism , Pseudomonas aeruginosa/metabolism , Caenorhabditis elegans Proteins/metabolism , Biogenic Monoamines/metabolism , Neurons/metabolism , Avoidance Learning/physiology , Receptors, G-Protein-Coupled/metabolism , Signal Transduction
17.
J Clin Med ; 13(7)2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38610657

ABSTRACT

Background: Systemic microvascular regression and dysfunction are considered important underlying mechanisms in heart failure with preserved ejection fraction (HFpEF), but retinal changes are unknown. Methods: This prospective study aimed to investigate whether retinal microvascular and structural parameters assessed using optical coherence tomography angiography (OCT-A) differ between patients with HFpEF and control individuals (i.e., capillary vessel density, thickness of retina layers). We also aimed to assess the associations of retinal parameters with clinical and echocardiographic parameters in HFpEF. HFpEF patients, but not controls, underwent echocardiography. Macula-centered 6 × 6 mm volume scans were computed of both eyes. Results: Twenty-two HFpEF patients and 24 controls without known HFpEF were evaluated, with an age of 74 [68-80] vs. 68 [58-77] years (p = 0.027), and 73% vs. 42% females (p = 0.034), respectively. HFpEF patients showed vascular degeneration compared to controls, depicted by lower macular vessel density (p < 0.001) and macular ganglion cell-inner plexiform layer thickness (p = 0.025), and a trend towards lower total retinal volume (p = 0.050) on OCT-A. In HFpEF, a lower total retinal volume was associated with markers of diastolic dysfunction (septal e', septal and average E/e': R2 = 0.38, 0.36, 0.25, respectively; all p < 0.05), even after adjustment for age, sex, diabetes mellitus, or atrial fibrillation. Conclusions: Patients with HFpEF showed clear levels of retinal vascular changes compared to control individuals, and retinal alterations appeared to be associated with markers of more severe diastolic dysfunction in HFpEF. OCT-A may therefore be a promising technique for monitoring systemic microvascular regression and cardiac diastolic dysfunction.

18.
Am Psychol ; 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38602786

ABSTRACT

Memorializes Thomas Max Achenbach (1940-2023). He is known for groundbreaking contributions to developmental psychopathology, a field that was shaped in part by his 1974 book with that title, and for creating the Achenbach System of Empirically Based Assessment (ASEBA), arguably the world's most widely used suite of procedures for assessing child, youth, adult, and older adult strengths and emotional and behavioral problems. His research revealed robust broadband syndromes of psychopathology, giving rise to the terms "internalizing" and "externalizing." The Child Behavior Checklist, the first measure of the ASEBA suite, has been translated into more than 110 languages and is used in science and clinical service settings around the world. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

19.
Neurourol Urodyn ; 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38623999

ABSTRACT

Surgical approaches for pelvic organ prolapse have evolved over the last 30 years and is a popular topic for debate, particularly when discussing apical prolapse. Transvaginal native tissue repairs remain the mainstay of POP surgeries, however, transabdominal approaches continue to evolve. Use of interposition material, such as synthetic polypropylene mesh, is the standard when performing an abdominal sacrocolpopexy, however, use of autologous fascia can be considered. This debate article provides an overview of this subject and highlights the value of different approaches to apical prolapse. The authors were asked to support their approach in various scenarios including:extremes of age, prior hysterectomy and intact uterus, desire to avoid mesh, sexual activity, and presence of comorbidities. In discussing common patient scenarios, ultimate decision making on specific POP surgeries is determined by patient preference and goals.

20.
Attach Hum Dev ; : 1-22, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38629407

ABSTRACT

This paper explores John Bowlby's foundational contributions to attachment theory, particularly his fascination with 'separation' and its impact on child development. Tracing the origins of Bowlby's interest to his personal experiences and his exposure to ideas of mental hygiene and child guidance in the 1930s, it underscores the alignment of his ideas with key figures in the English school of psychoanalysis. The central narrative of this paper unfolds during Bowlby's 1950 WHO research trip, investigating orphaned and separated children in Europe and the USA. Utilizing archival materials from the Wellcome Library in London, the authors offer unique insights into Bowlby's journey, highlighting his evolving views on mother-child separation through interactions with his American colleagues. This comprehensive exploration sheds light on Bowlby's pioneering work, emphasizing the American influence on his ideas, and the evolving theoretical framework that continues to shape our understanding of child development and attachment today.

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