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The obesogenic maternal environment can lead to cardiac hypertrophy in the offspring. The aim of this study was to investigate whether (-)-epicatechin (Epi) modify the expression of genes related to pathological cardiac hypertrophy (CH), and its physiological pathway, in offspring obese by programing. Four groups of eight male offspring Wistar rats of 110 days were randomly selected to control groups [C and offspring of maternal obesity (MO)] or to Epi groups (C + Epi or MO + Epi). In heart tissue, we evaluated the size of the ventricular walls and cavities, presence of fibrosis, mRNA and protein of Myh6, Myh7, Anp, Bnp, Acta 1, Col1a1, Akt, and Mtor. We observed an increase of the heart weight/body ratio in groups treated with Epi. Only in MO group, heart area and its perimeter were increased, as well as Myh7 and Anp mRNA. We found a significant decrease of fibrosis area in male offspring treatment with Epi. In Epi group Anp mRNA was decreased whilst Anp protein in MO group was increased; further, a decrease in Col1a1 protein was found in MO group. In conclusion, the maternal obesity activates pathological CH markers reactivating fetal cardiac genes involved in histological changes observed in cardiac tissue. Epi treatment decreased the content of collagen area and expression of some fetal cardiac genes participating in this pathway in offspring of maternal obesity.
This work attempts to better understand the significance of morphological diversity among fungal-algal contact zones present in lichens. We used TEM to examine a variety of lichen symbioses involving non-trebouxialean green algae that show intraparietal penetration by the mycobiont. A principal focus was on Endocarpon pusillum, a well-known member of a family (Verrucariaceae; Eurotiomycetes) previously reported to be characterized by unwalled haustoria exposing a naked fungal protoplast. Peg-like haustoria arose from an inner layer(s) of the mycobiont cell wall that broke through outer layers and penetrated a short distance into the wall of the green algal symbiont (Diplosphaera). In both fungal and algal cells at the contact interface, lomasome-like vesicles and tubules occurred as modifications of the plasmalemma intermixed with wall materials at the inner surface of the cell wall. A fungal cell wall was consistently present around the haustorium, which resembled those depicted in earlier TEM studies of Verrucariaceae. Previously published micrographs of Verrucariaceae purporting to show wall-less haustoria surrounded by an empty space are believed to have been misinterpreted. However, in the isidiose Porina and foliicolous Calopadia, Byssoloma and Fellhanera species (Lecanoromycetes), we did observe extreme degrees of reduction in the mycobiont cell wall at symbiont contact interfaces. In those lichens, a broad area of the fungal cell bulged into the adjacent algal symbiont, broadly invaginating the wall of the latter and penetrating it intraparietally without differentiation of a distinct haustorial structure. The mycobiont wall surrounding such protrusions often thinned to near indistinguishability towards its extremity. The protrusion made direct contact with the algal cell wall; no empty space occurred between them. We propose that the short, peg-like intraparietal haustoria bind the symbionts and help maintain cell contacts amid the stresses of tissue expansion and shrinkage, thereby avoiding disruption of the continuous hydrophobic coating that facilitates transfer between them. Broader contact interfaces with extremely thin adjacent walls may facilitate solute flow between symbionts. Reciprocal penetration of algal protrusions into mycobiont cells, noted in Porina as well as other lichens studied previously, is a neglected but potentially significant indication that both symbionts may actively work to maintain functional contact interfaces.
Bipolar depression remains difficult to treat, and people often experience ongoing residual symptoms, decreased functioning and impaired quality of life. Adjunctive therapies targeting novel pathways can provide wider treatment options and improve clinical outcomes. Garcinia mangostana Linn. (mangosteen) pericarp has serotonogenic, antioxidant anti-inflammatory and neurogenic properties of relevance to the mechanisms of bipolar depression.
Aims
The current 28-week randomised, multisite, double-blind, placebo-controlled trial investigated mangosteen pericarp extract as an adjunct to treatment-as-usual for treatment of bipolar depression.
Method
This trial was prospectively registered on the Australia New Zealand Clinical Trials Registry (no. ACTRN12616000028404). Participants aged 18 years and older with a diagnosis of bipolar I or II and with at least moderate depressive symptoms were eligible for the study. A total of 1016 participants were initially approached or volunteered for the study, of whom 712 did not progress to screening, with an additional 152 screened out. Seventy participants were randomly allocated to mangosteen and 82 to a placebo control. Fifty participants in the mangosteen and 64 participants in the placebo condition completed the treatment period and were analysed.
Results
Results indicated limited support for the primary hypothesis of superior depression symptom reduction following 24 weeks of treatment. Although overall changes in depressive symptoms did not substantially differ between conditions over the course of the trial, we observed significantly greater improvements for the mangosteen condition at 24 weeks, compared with baseline, for mood symptoms, clinical impressions of bipolar severity and social functioning compared with controls. These differences were attenuated at week 28 post-discontinuation assessment.
Conclusions
Adjunctive mangosteen pericarp treatment appeared to have limited efficacy in mood and functional symptoms associated with bipolar disorder, but not with manic symptoms or quality of life, suggesting a novel therapeutic approach that should be verified by replication.
Diagnostic accuracy is an unmet need for major depressive disorder (MDD) and major depressive episode (MDE) in bipolar disorder. Very limited research has evaluated bipolar disorder/MDE and MDD using ecological momentary assessment (EMA) time-series data.
Aims
We aimed to examine differentiating phenomenological characteristics in positive affect dynamics, and temporal relationships with pleasure towards current activity and meaning in life (MIL), among MDD, MDE/bipolar disorder and healthy controls using EMA.
Method
Participants (N = 88, mean age 28.7 years, 69% female), including individuals with MDD (n = 29) and MDE/bipolar disorder (n = 29) and healthy controls (n = 30), were assessed for positive affect, pleasure and MIL 5 times daily over a 2-week period. Multilevel modelling analysis was conducted, with estimation of first-order autoregressive model structure and time-lagged relationship between pleasure and positive affect.
Results
From 4632 EMA observations, positive affect dynamics (inertia, variability and instability) did not differ significantly across groups (all P > 0.05). Although all groups demonstrated a bidirectional relationship between positive affect and pleasure, for MDE/bipolar disorder, both pleasuret − 1 (β = −0.11, t[51.09] = −2.31, P = 0.025) and positive affectt − 1 (β = −0.13, t[56.54] = −2.30, P = 0.025) predicted subsequent MIL less significantly than for MDD and healthy controls.
Conclusion
Individuals with MDE/bipolar disorder, but not MDD, had less self-reported MIL from positive affect and pleasure. There is little evidence that emotional experience alone characterises the pathophysiology between MDD and MDE/bipolar disorder; such investigation may be limited by within-group heterogeneity. Our findings provide a new perspective on using a time-series approach beyond bimodal measures in EMA to differentiate bipolar disorder/MDE and MDD.
The rupture of a liquid film, where a thin liquid layer between two other fluids breaks and forms holes, commonly occurs in both natural phenomena and industrial applications. The post-rupture dynamics, from initial hole formation to the complete collapse of the film, are crucial because they govern droplet formation, which plays a significant role in many applications such as disease transmission, aerosol formation, spray drying nanodrugs, oil spill remediation, inkjet printing and spray coating. While single-hole rupture has been extensively studied, the dynamics of multiple-hole ruptures, especially the interactions between neighbouring holes, are less well understood. Here, this study reveals that when two holes ‘meet’ on a curved film, the film evolves into a spinning twisted ribbon before breaking into droplets, distinctly different from what occurs on flat films. We explain the formation and evolution of the spinning twisted ribbon, including its geometry, orbits, corrugations and ligaments, and compare the experimental observations with models. We compare and contrast this phenomena with its counterpart on planar films. While our experiments are based on the multiple-hole ruptures in corona splash, the underlying principles are likely applicable to other systems. This study sheds light on understanding and controlling droplet formation in multiple-hole rupture, improving public health, climate science and various industrial applications.
Our quasi-experimental pilot study between July to September 2024 showed that real-time audit/feedback for antibiotic discharge prescriptions improved appropriateness from 50% to 83%, while decreasing median antibiotic duration compared to preintervention period. Hospital discharges are an important transition point for antimicrobial stewardship interventions at discharge.
Parkinson’s disease (PD) is a severe neurodegenerative disorder characterized by prominent motor and non-motor (e.g., cognitive) abnormalities. Notwithstanding Food and Drug Administration (FDA)-approved treatments (e.g., L-dopa), most persons with PD do not adequately benefit from the FDA-approved treatments and treatment emergent adverse events are often reasons for discontinuation. To date, no current therapy for PD is disease modifying or curative. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are central nervous system (CNS) penetrant and have shown to be neuroprotective against oxidative stress, neuroinflammation, and insulin resistance, as well as promoting neuroplasticity. Preclinical evidence suggests that GLP-1RAs also attenuate the accumulation of α-synuclein. The cellular and molecular effects of GLP-1RAs provide a basis to hypothesize putative therapeutic benefit in individuals with PD. Extant preclinical and clinical trial evidence in PD provide preliminary evidence of clinically meaningful benefit in the cardinal features of PD. Herein, we synthesize extant preclinical and early-phase clinical evidence, suggesting that GLP-1RAs may be beneficial as a treatment and/or illness progression modification therapeutic in PD.
This paper investigates the association between potential serum biomarkers and diabetes status in older Australians by employing traditional and machine learning methods. Data from Sydney Memory and Ageing Study (MAS) were interrogated cross-sectionally in 801 participants aged 70–90 years (n = 801). Twenty-eight serum biomarkers and 6 other factors were investigated as potential indicators that may distinguish diabetes status. Diabetes status was categorised as No-Diabetes, Pre-diabetes, and Type 2 diabetes (T2D). Diabetes is defined as follows when using fasting plasma glucose: no diabetes/ normal: < 5.6 mmol/L; prediabetes: 5.6–6.9 mmol/L; and diabetes: ≥ 7 mmol/L(1). Variable selection was executed using two distinct regression methods (i) multinomial logistic regression with backward selection and (ii) machine learning using elasticNet regression. Multiple imputation was used to address missing data. Age and sex were included as a priori covariates in the multinomial regression model. Using a multinomial logistic regression, Malondialdehyde (MDA), Macrophage inhibiting cytokine 1 (MIC1), and vitamin E were associated with diabetes status. MDA was strongly associated with diabetes with relative risk ratio (RRR) of 4.78 (95% CI = 3.39, 6.75; p < 0.001) when comparing to no diabetes, surpassing usual markers insulin, triglycerides, and waist-to-hip (WHR). Diabetes was associated with lower vitamin E levels, compared to no diabetes, with an RRR of 0.54 (95% CI:0.38, 0.75; p < 0.001). Comparing diabetes to prediabetes, RRR for lower vitamin E levels was 0.71 (95% CI: 0.51, 0.98; p = 0.035). MIC1 distinguished between diabetes and prediabetes status (RRR: 1.84; 95% CI:1.41, 2.41; p < 0.001). Consistent with the traditional methods, machine learning also identified MDA as being associated with T2D, with an odds ratio (OR) of 1.9, followed hierarchically by insulin (OR = 1.23), WHR (OR = 1.22) and triglyceride (OR = 1.13). Higher serum Vitamin E were associated with a lower risk of being in diabetes category (OR = 0.84). MIC1, urate, IL1b, HDL, and carotene were identified by the machine learning model, but showed minimal association. These results suggest that the oxidative stress and inflammation markers distinguish the state of having T2D.
Recent experiments aiming to measure phenomena predicted by strong-field quantum electrodynamics (SFQED) have done so by colliding relativistic electron beams and high-power lasers. In such experiments, measurements of collision parameters are not always feasible. However, precise knowledge of these parameters is required to accurately test SFQED.
Here, we present a novel Bayesian inference procedure that infers collision parameters that could not be measured on-shot. This procedure is applicable to all-optical non-linear Compton scattering experiments investigating radiation reaction. The framework allows multiple diagnostics to be combined self-consistently and facilitates the inclusion of known information pertaining to the collision parameters. Using this Bayesian analysis, the relative validity of the classical, quantum-continuous and quantum-stochastic models of radiation reaction was compared for several test cases, which demonstrates the accuracy and model selection capability of the framework and highlight its robustness if the experimental values of fixed parameters differ from their values in the models.
Diastasis recti abdominis is a weakening or widening of the linea alba of the rectus abdominis muscles. It is more common in the second or third trimesters of pregnancy. The presenting symptoms are usually a “bulge” when the patient performs an abdominal crunch motion and can be associated with lower back pain. Alternatively, it can be incidentally found. The diagnosis is clinical rather than based on imaging, although imaging can help rule out other entities such as primary ventral hernias. If noted in pregnancy, treatment consists of reassurance and use of light abdominal binding, if feasible for the patient. The incidence of ventral hernias in pregnancy are rare, and treatment is usually delayed until the postpartum period.
A conjecture of Jackson from 1981 states that every d-regular oriented graph on n vertices with $n\leq 4d+1$ is Hamiltonian. We prove this conjecture for sufficiently large n. In fact we prove a more general result that for all $\alpha>0$, there exists $n_0=n_0(\alpha )$ such that every d-regular digraph on $n\geq n_0$ vertices with $d \ge \alpha n $ can be covered by at most $n/(d+1)$ vertex-disjoint cycles, and moreover that if G is an oriented graph, then at most $n/(2d+1)$ cycles suffice.
Objectives/Goals: The aim of the study is to identify resistance factors for substance use (i.e., factors that explicitly help to avoid or reduce drug use). Identification of resistance factors could inform strategies that seek to reduce the prevalence of substance use and related disorders. Methods/Study Population: Adult twins aged 30–70 years were recruited from the Mid-Atlantic Twin Registry. A mixed-method approach, group concept mapping, was used to identify factors influencing participants to resist using substances. Approximately 155 participants produced 97 statements reflecting substance use resistance factors. Hierarchical cluster analysis and multidimensional scaling assessed how participants sorted and rated statements for their lifetime and current importance. Factor analysis was used to reduce data dimensionality. Reliability analyses were conducted to identify a subset of statements anticipated to consistently represent each cluster. Results were shared with participants to assess accuracy with their experiences. Results/Anticipated Results: Participants sorted 97 statements into 9 thematic clusters: (1) Controlling Personal, Negative Consequences; (2) Concern About Health and Well-being; (3) Lack of Desire; (4) Outside Influences; (5) Social Norms and My Reputation; (6) Career and Legal Impacts, (7) Avoiding Harm to Family and Relationships; (8) Preserving Family Relationships; and (9) Family and Friends Impact on Me. Participants consistently identified health concerns as an important substance use resistance factor. The statements will be further reduced to represent a smaller subset for future use as a scale to measure exposure to resistance factors. Discussion/Significance of Impact: Health concerns related to substance use were identified as an important resistance factor. This has been supported by research on smoking cessation and implemented in smoking prevention campaigns. Therefore, prioritizing health-related outcomes in prevention may be important to reduce substance use prevalence.
The present study aims to provide an understanding of the influence of an afterbody on the flow-induced vibration (FIV) of cylinders. This is achieved through experimental and numerical investigations into the FIV response of a reverse-D-cross-section cylinder of aspect ratio $AR=5$. By carefully monitoring the point of flow separation to show it always occurs at the sharp top and bottom edges and never further upstream, it is demonstrated that vortex-induced vibration (VIV) can occur without an afterbody. However, for other aspect ratios, an afterbody does play a crucial role in determining the type of fluid forces responsible for sustaining VIV from low to moderate Reynolds numbers in the range $100$–$4700$. For a cylinder without an afterbody, it is found that the viscous force originating from the presence of strong compact vortices forming close to the leeward side of the cylinder is responsible for sustaining strong transverse vibration. In contrast, for a cylinder with an afterbody, the dominant force component depends on the size of the afterbody. In cylinders with a small afterbody, such as a reverse-D semi-circular cylinder, the viscous force dominates, while in cylinders with a larger afterbody such as a circular cylinder, the pressure force dominates.
In major depressive disorder (MDD), only ~35% achieve remission after first-line antidepressant therapy. Using UK Biobank data, we identify sociodemographic, clinical, and genetic predictors of antidepressant response through self-reported outcomes, aiming to inform personalized treatment strategies.
Methods
In UK Biobank Mental Health Questionnaire 2, participants with MDD reported whether specific antidepressants helped them. We tested whether retrospective lifetime response to four selective serotonin reuptake inhibitors (SSRIs) (N = 19,516) – citalopram (N = 8335), fluoxetine (N = 8476), paroxetine (N = 2297) and sertraline (N = 5883) – was associated with sociodemographic (e.g. age, gender) and clinical factors (e.g. episode duration). Genetic analyses evaluated the association between CYP2C19 variation and self-reported response, while polygenic score (PGS) analysis assessed whether genetic predisposition to psychiatric disorders and antidepressant response predicted self-reported SSRI outcomes.
Results
71%–77% of participants reported positive responses to SSRIs. Non-response was significantly associated with alcohol and illicit drug use (OR = 1.59, p = 2.23 × 10−20), male gender (OR = 1.25, p = 8.29 × 10−08), and lower-income (OR = 1.35, p = 4.22 × 10−07). The worst episode lasting over 2 years (OR = 1.93, p = 3.87 × 10−16) and no mood improvement from positive events (OR = 1.35, p = 2.37 × 10−07) were also associated with non-response. CYP2C19 poor metabolizers had nominally higher non-response rates (OR = 1.31, p = 1.77 × 10−02). Higher PGS for depression (OR = 1.08, p = 3.37 × 10−05) predicted negative SSRI outcomes after multiple testing corrections.
Conclusions
Self-reported antidepressant response in the UK Biobank is influenced by sociodemographic, clinical, and genetic factors, mirroring clinical response measures. While positive outcomes are more frequent than remission reported in clinical trials, these self-reports replicate known treatment associations, suggesting they capture meaningful aspects of antidepressant effectiveness from the patient’s perspective.
Antarctic terrestrial ecosystems, covering less than 1% of the continent, are under increasing anthropogenic threats, particularly from climate change and tourism. This study focuses on the impact of human trampling on soil microbial communities in Barrientos Island (South Shetlands archipelago), a frequently visited location. Soil samples were collected within and at the edge of two established paths representing varying levels of human disturbance. Physical and chemical analyses revealed significant differences between the paths, potentially creating anaerobic conditions favorable for specific microbial taxa. Thus, microbial communities also differed between the paths. Aerobic heterotrophic taxa were dominant in the less disturbed path, while anaerobic taxa such as Bacteroidetes vadinHA17 thrived in the more compacted path. Although alpha diversity indices did not differ, beta diversity analyses showed notable distinctions, particularly between the paths rather than trampled and untrampled areas. These findings suggest that microbial communities may recover following the stop of human activity, but also that indigenous microbial communities or other overlooked factors may be influencing the recovery potential. This study thus offers a starting point for similar research, as it highlights the need for further investigation to determine whether human trampling or other environmental factors are primarily responsible for these differences.
In this article, we give a definition of weak stability condition on a triangulated category. The difference between our definition and existing definitions is that we allow objects in the kernel to have non-maximal phases. We then construct four types of weak stability conditions that naturally occur on Weierstraß ellitpic surfaces as limites of Bridgeland stability conditions.