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BackgroundMen live shorter lives and suffer more often from preventable diseases than women. This health pattern is associated with masculine norms that incentivize health-risk behavior. Masculinity threats represent a potential mechanism by which masculinity norms causally impact men's health behavior. In this scoping review, we map experimental evidence for health effects and moderators of masculinity threat.MethodsFollowing PRISMA-ScR guidance, we conducted a scoping review of experimentally manipulated masculinity threat and men's health across PsycNet, CINAHL, SCOPUS, MEDLINE, Embase, and Web of Science. Searches were supplemented using Consensus AI, Google Scholar and web searches. We included experimental studies with male participants manipulating masculinity threat and measuring health-related outcomes.ResultsA total of k = 38 experiments across 25 papers were included, covering food and beverage intake (k = 16), emotional well-being and physiological stress (k = 9), body image and fitness (k = 6), risk-taking behaviors (k = 5), and interpersonal relationships (k = 2). Masculinity threat was consistently associated with a preference for stereotypically masculine foods, particularly meat. Effects in other domains were mixed or limited. We found that endorsement of masculinity-related traits, and beliefs about the precarious nature of manhood, most consistently shaped when, and for whom, masculinity threats motivated compensatory reactions or disengagement.ConclusionFindings may inform public health messaging by showing that challenges to men's masculine status can lead to health risk behavior. This review aims to guide future research to clarify existing patterns and explore new health domains and moderators related to masculinity threat.
Life stress accumulation across the life course disproportionately negatively impacts wellbeing, cognition, and health in ageing women, yet there is a paucity of research exploring the perceptions of ageing women in work. This study draws upon unique data to provide an understanding through illuminating the intersectional wellbeing of gendered ageing in ageing women in the workplace in UK focusing on lower-paid roles in the Northwest of England. Semi-structured interviews were used to explore the perceptions of older women's wellbeing in an opportunity sample of (n = 19) of women aged 60 and over with a focus on those in lower-paid and part time roles (although n = 4 were in senior roles). Reflexive thematic analysis was used to analyze the data. There were two central themes: Barriers to Wellbeing and Facilitators to Wellbeing. Barriers to wellbeing encompassed the following subthemes: (1) the Taboo of Womanhood: the limiting nature of being an ageing woman as a barrier to wellbeing; (2) Feeling of Invisibility: intergenerational barriers to wellbeing; (3) The workplace environment: prolonged standing, and physical and emotional strain nature of role as a barrier to wellbeing; (4) Negative self-perceptions of growing old: health deteriorations, mortality perceptions, and lack of energy; (5) Financial factors as a barrier to ageing women's workplace wellbeing. Whereas facilitators to wellbeing were encompassed in the following subthemes: (1) The value of older women in work as a facilitator to wellbeing; (2) Support from line manager as a facilitator to wellbeing; (3) Rejecting the label/stereotype as 'older' as a facilitator to wellbeing. Workplace policies and practices should actively challenge the taboo surrounding women's wellbeing, value older women in work, and provide flexible, supportive environments and management that enable open conversations and respond to women's changing needs across the life course.
Stable oral delivery of macromolecules, which easily lose conformation and activity, is far more carrier-demanding than small molecules and a long-standing food science challenge. This study developed a cellulose-based IUSRHP to address this issue. Tests under separate independent conditions showed IUSRHP stayed stable in simulated gastric fluid (pH 3.0) for over 3 h, and achieved unidirectional load release in simulated intestinal fluid (pH 7.2). Its loading capacity (96, 125, 200 mg/piece at 10%, 30%, 50% sodium carboxymethylcellulose (NaCMC)) and thermal stability (glass transition temperature (Tg) from 219 °C to 302 °C) rose with NaCMC content. In the gastrointestinal tract, water permeated the pH-responsive layer, swelling the patch into a 3D hydrogel for unidirectional release of proteins (isoelectric point < 7.2) (release rate tunable via protein negative charge). IUSRHP enhances local effective loads concentration, stability and bioavailability, key for stable oral delivery of food nutrient macromolecules or pharmaceutical active proteins. The online version contains supplementary material available at 10.1007/s10068-026-02194-w.
Parkinson's disease is characterized by dopaminergic neuron loss and accumulation of α-synuclein aggregates in the brain. G51D α-synuclein knock-in mice provide a genetically and clinically relevant model of disease, exhibiting early olfactory deficits, age-dependent motor impairment, and progressive phospho-α-synuclein accumulation. In multiple Parkinson's disease models, striatal cholinergic and parvalbumin interneurons, as well as astrocytes, lose primary cilia and the neurotrophic signaling needed to sustain dopaminergic neurons. We show here that G51D α-synuclein mice share these phenotypes. Phospho-Ser129 α-synuclein accumulation correlates with cilia loss in cholinergic interneurons but not in spiny projection neurons that accumulate higher phospho-α-synuclein levels. In the piriform cortex, parvalbumin neurons lose primary cilia and downregulate Neurturin, potentially contributing to olfactory dysfunction. Within the peripheral olfactory epithelium, horizontal basal cells lose cilia, whereas multiciliated olfactory sensory neuron cilia remain intact. These findings reveal convergent cellular vulnerabilities across Parkinson's disease models and highlight a pathogenic role for impaired ciliary signaling.
Our aim was to develop and evaluate the electronic frailty index+, a prognostic tool, including four integrated prognostic-decision models, to stratify older people into subgroups for targeting key interventions. Prognostic model development, internal validation and external validation using large data sets and longitudinal cohort study data, with decision curve and health economic analysis. Patients aged 65+ years. The 12-month outcomes for prognostic models: new home care package care home admission emergency department attendance/hospitalisation with fall/fracture all-cause mortality. We developed and internally validated models for our key outcomes in one large data set. We used internal-external cross-validation for the home care model and full external validation for the remaining three models in a second large data set. We used CARE75+ to investigate additional predictive value of clinical measures practical for primary care. We translated the prognostic models into a framework to support clinical decision-making. We integrated the falls prediction models with effect size estimates from network meta-analysis to examine potential cost savings. We used data from 660,417 patients in SAIL, 88,947 in Connected Bradford and 252 CARE75+ participants. Model performance was promising in internal-external cross-validation, with average calibration slope 1.00 (95% confidence interval 0.99 to 1.01), average calibration-in-the-large -0.01 (95% confidence interval -0.02 to 0.01), average observed/expected ratio 0.99 (95% confidence interval 0.98 to 1.01) and average C-statistic 0.81 (95% confidence interval 0.81 to 0.81). Model performance was promising on internal and external validation, although with some evidence for overprediction of falls risk, with calibration slope 1.25 (95% confidence interval 1.24 to 1.27), calibration-in-the-large -0.931 (95% confidence interval -0.938 to -0.920), observed/expected ratio 0.43 (95% confidence interval 0.42 to 0.44), C-statistic 0.83 (0.82 to 0.83). Model performance was promising on internal validation, but it showed some miscalibration on external validation, with calibration slope 0.75 (95% CI 0.74 to 0.76), calibration-in-the-large -1.60 (-1.62 to -1.58) and observed/expected ratio 0.25 (95% CI 0.24 to 0.25), C-statistic of 0.86 (95% CI 0.86 to 0.86). The model showed excellent performance across the full range of predicted risks on external validation, with average calibration slope 1.00 (0.98 to 1.01), average calibration-in-the-large -0.23 (-0.27 to -0.19), average observed/expected ratio 0.77 (0.75 to 0.79) and average C-statistic 0.83 (0.82 to 0.83). Modelling indicated that provision of multifactorial assessment and treatment for people with an annual falls risk of ≥ 40% has the largest cost reduction per targeted person (£1025). All four prediction models have promising predictive performance, although some had evidence of overprediction of risk (miscalibration). Decision curve analysis indicates potential clinical utility, and economic modelling provides novel information for policy-makers and commissioners. Future research should include model impact studies to evaluate use of the models in routine care. We were unable to complete external validation of the home care prediction model. This study is registered as ClinicalTrials.gov ID NCT04113174. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 127905) and is published in full in Health Technology Assessment; Vol. 30, No. 61. See the NIHR Funding and Awards website for further award information. Some text in this summary is reproduced from Clegg A. Development and Evaluation of the Electronic Frailty Index+ (eFI+) Tool: Integrated Prognostic-decision Modelling to Target Interventions for Older People With Moderate or Severe Frailty. University of Leeds; 2020. URL: https://lida.leeds.ac.uk/development-and-evaluation-of-the-electronic-frailty-index-efi-tool-integrated-prognostic-decision-modelling-to-target-interventions-for-older-people-with-moderate-or-severe-frailty/. Frailty is common in older age. It develops because, as we get older, our bodies change, and can lose their inbuilt reserves, for example we lose muscle strength. These changes mean that older people with frailty can experience sudden, dramatic changes in their health as a result of seemingly small problems, such as infection or new medication. This means that they can be at risk of losing their independence, falling, being admitted to a nursing home or dying. In this study, we used anonymised information from two very large databases to develop four ‘risk prediction tools’ that predict, in the next 12 months, which older people are at risk of: needing new or increased home care services hospital admission with a fall or fracture (serious falls) nursing home admission dying. We then used a separate database to see if simple tests, like measuring walking speed or grip strength, can help us identify people with frailty at risk of serious falls. The final step was to test whether offering treatments to prevent serious falls is likely to offer value for money – important information for the NHS and social care. All four risk prediction tools have promising performance and thus can help identify people likely to experience the four outcomes over the next 12 months. However, there were some limitations, particularly relating to the tool to identify people at risk of nursing home admission. Also, the addition of walking speed and grip strength measures did not make a notable improvement to the falls prediction tool. We found that the greatest cost saving for individuals was if falls’ prevention interventions were provided to people at higher risk of serious falls (over 40% risk of falling in next 12 months). Through our work, we expect to have a positive impact on the health and well-being of older people living with frailty, their families and carers along with major benefits to the NHS and social care.
Shared decision-making (SDM) is recommended in obesity treatment. Yet, little is known about how it occurs in real-world practice, particularly given recent advances in treatment options. This prospective mixed-methods study aimed to understand patient preferences and decision-making processes for obesity treatment. Adults with obesity (N = 103) seeking specialty weight management treatment completed a survey, and a subset (n = 17) participated in qualitative interviews. Both assessed weight loss history, knowledge and expectations of obesity treatment options, decision-making factors, and perceptions of SDM. Participants reported an average of 10.1 (SD = 13.5) prior weight loss attempts and were primarily motivated by physical well-being (86.4%). Key factors influencing decision-making included desired weight loss (84.5%), provider recommendations (76.7%), and cost (62.1%). Anti-obesity medications were viewed most favorably, followed by behavioral and surgical approaches. Qualitative analysis generated four themes: (i) a chronic cycle of weight loss and regain; (ii) guided by stories, not science alone; (iii) navigating trade-offs in choosing weight-loss strategies; and (iv) feeling heard, but still seeking direction. Patients demonstrate strong awareness of obesity treatments and value SDM and personalized recommendations when making decisions. Findings highlight the need for interventions that strengthen SDM and deliver tailored, high-quality health communication. People with obesity are often encouraged to use shared decision-making, a process in which patients work with their healthcare provider to choose the best treatment approach. However, little is known about how this actually works in everyday clinical care, especially as new treatment options become available. In this study, 103 adults seeking specialized weight management care completed surveys and some also participated in interviews to share their experiences with weight loss and shared decision-making. Most participants had tried to lose weight many times before and were mainly motivated by improving their physical health. When deciding on treatment options, people considered how much weight they hoped to lose, what their provider recommended, and how much treatment would cost. Weight loss medications were viewed most positively followed by lifestyle programs and bariatric surgery. Interviews showed participants relied on personal stories as well as medical information and carefully weighed pros and cons of different treatments. Many wanted more guidance even when they felt listened to by providers. Overall, patients valued shared decision-making and personalized recommendations. These findings highlight the need for better tools and communication strategies to support clear, personalized obesity care.
Amorphous metal alloys (AMAs) are metastable materials that are characterized by good mechanical properties and corrosion properties. It is known that with certain thermal modifications, these properties improve or lose their value. The purpose of this research work is to investigate the optimal conditions of thermal modification that improve the mechanical properties of this alloy. The DSC method established the temperatures of phase transitions in the temperature range of 624-643 K, which correspond to the following processes: crystal nucleation (T1 = 624 ± 1 K), growth (T2 = 633 ± 1 K), and stable crystallization (T3 = 643 ± 1 K). The XRD and TEM/HREM methods revealed structural changes in the amorphous matrix as a result of thermal modification. As a result of isothermal annealing for 2 min. at temperatures T1, T2, T3, a solid solution based on aluminum and a thermally stable compound Al19Ni5(Y,Gd)3 were formed. The equation for the transformation of an amorphous matrix AMA Al87Y4Gd1Ni8 in the temperature range (624-643) ± 1 K during isothermal 2 min annealing is given by: Am → Am'resid+ solid solution Al(X) → Am'(enriched REE) + solid solution Al(X) + nano-Al19Ni5(Y,Gd)3 → Am'(enriched REE) + solid solution Al(X) + nano-Al19Ni5(Y,Gd)3. The Oliver-Pharr method established that AMAs annealed at temperatures T1 and T2 have microhardness indicators 5-9 times higher than amorphous samples; however, the material loses its elasticity under such thermal deformation conditions.
Regulatory T (Treg) cells are essential for controlling inflammation and maintaining tissue homeostasis. Transcriptional intermediary factor 1-γ (TIF1γ) has been implicated in noncanonical TGFβ-Smad signaling in hematopoietic stem cells, but its role in Treg cell function has not been explored. Here we show that TIF1γ-deficient Treg cells lose Foxp3 expression and acquire effector phenotypes in a cell-intrinsic manner upon inflammatory challenge. In vivo, TIF1γ-deficient Treg cells adopt type 1 helper T cell-like or pro-inflammatory ex-Treg cell states in autoimmune settings and display type 2 helper T cell-like features during helminth infection. These cells exhibit transcriptional programs associated with proliferation, T cell activation and T helper differentiation, along with increased chromatin accessibility at regulatory regions enriched for key transcription factors controlling T cell activation and lineage specification. Mechanistically, Treg cell instability in the absence of TIF1γ is largely independent of transforming growth factor beta signaling and instead is driven by activation of the β-catenin pathway. TIF1γ-deficient Treg cells accumulate β-catenin and display enhanced TCF7 activity. Genetic or pharmacological targeting of β-catenin restores Treg cell stability and function. We identify TIF1γ as a critical regulator of Treg cell stability that restrains β-catenin-TCF7 signaling, thereby preserving Foxp3 expression and preventing inflammatory reprogramming.
The aim of this study was to provide robust evidence on the long-term use of non-nutritive sweetened (NNS) beverages on weight management, by comparing NNS beverages and water during 1 year of assisted weight management followed by a voluntary, unassisted 1-year extension. In this parallel-group, open-label, controlled equivalence trial, 493 adults with body mass index 27-35 kg/m2 who regularly consumed cold beverages were randomised 1:1 to water (n 246) or NNS beverages (n 247). Participants joined a group behavioural weight-management programme comprising assisted meetings weekly (12-week weight-loss phase) then monthly (40-week weight-maintenance phase), followed by unassisted monitoring for 52 weeks with a final meeting at week 104. The final 52 week unassisted phase was completed by 220 participants (water: n 117; NNS beverages: n 103), 27·7% of whom were NNS beverage-naïve (naïve was defined as NNS beverages comprising ≤ 25% of beverages in the 5 years before screening). In the unassisted monitoring phase, the primary endpoint was weight change from baseline at week 104 (equivalence: two-sided P > 0·05). Participants consuming water maintained a weight loss of 3·7 kg over 104 weeks, compared with 4·8 kg with NNS beverages; the between-group difference was not significant. After the final 52-week unassisted phase of the 104-week behavioural weight-management programme, water and NNS beverages showed equivalence regarding weight change from baseline. Our findings suggest people can lose weight, and maintain it for two years, when drinking either NNS beverages or water and taking part in weight-management programmes.
Patients with autoimmune rheumatic diseases, particularly rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), experience excess cardiovascular risk that is not fully captured by conventional lipid measurements. In active RA, lower cholesterol may coexist with higher vascular risk, a pattern known as the lipid paradox. We propose that systemic inflammation can uncouple lipid concentration from lipoprotein function and organize the evidence along five mechanistic axes. Inflammatory cytokines, mainly interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), IL-1β, IL-17/IL-23 and type I interferons, remodel lipoprotein metabolism. High-density lipoproteins (HDL) lose protective functions and may become pro-inflammatory. Apolipoprotein-B particles are oxidized or otherwise modified, linking lipid metabolism to autoimmunity. Macrophage cholesterol imbalance and cholesterol crystals activate inflammasome pathways in experimental atherosclerosis, while immune-cell metabolic rewiring may amplify cytokine output; these mechanisms are treated as extrapolated when direct rheumatic-disease evidence is limited. The pathways converge on endothelial dysfunction and thrombo-inflammation. RA and SLE are the mechanistic anchors, whereas psoriatic disease, axial spondyloarthritis, systemic sclerosis, vasculitides and antiphospholipid syndrome are weighted by evidence category. Standard lipid panels may therefore underestimate risk in selected contexts, especially during active inflammatory disease.
Patients with vitiligo reportedly have an increased risk of sensorineural hearing loss (SNHL), driven by the loss of extracutaneous melanocytes in the inner ear. In a phase 2 dose-ranging study, the oral, selective Janus kinase 1 inhibitor povorcitinib demonstrated substantial repigmentation in patients with extensive nonsegmental vitiligo through 52 weeks of treatment. This exploratory post hoc analysis of the phase 2 study evaluated the prevalence of hearing loss among enrolled patients and examined their associated demographic and clinical characteristics, as well as their audiometric response to povorcitinib. SNHL was defined as a bone-conduction threshold of ≥ 25 dB in either ear and was assessed using all-frequencies average (AFA: 250, 500, 1000, 2000, 3000, 4000, 6000, 8000 Hz), pure-tone average (PTA: 500, 1000, 2000, 4000 Hz), and high-frequencies average (HFA: 2000, 3000, 4000, 6000, 8000 Hz). Of 162 patients assessed for hearing loss, SNHL prevalence at baseline was 10.5% (AFA), 11.7% (PTA), and 14.2% (HFA). Patients with versus without SNHL were significantly older and had significantly greater facial involvement. Following up to 52 weeks of povorcitinib treatment, bone-conduction hearing thresholds improved across all frequency ranges, although no definitive conclusions can be drawn. At week 52, mean percentage change from baseline in the left and right ears was as follows: AFA, - 18.7% (P = 0.08) and - 16.1% (P = 0.10); PTA, - 13.9% (P = 0.18) and - 7.2% (P = 0.25); and HFA, - 11.0% (P = 0.21) and - 12.6% (P = 0.18), respectively. SNHL was common in this patient population, suggesting that audiologic evaluation may be appropriate for some patients with vitiligo to support early detection and management of hearing loss. Changes in hearing with povorcitinib treatment require confirmation in larger patient populations. Graphical abstract available for this article. ClinicalTrials.gov identifier, NCT04818346. Vitiligo is a disease that causes patches of skin to lose color. The same cells that give skin its color, called melanocytes, are also found in the inner ear and help with hearing. When these cells are lost, it may lead to a type of hearing loss called sensorineural hearing loss. This means patients with vitiligo may be at higher risk for hearing loss. In a recent study, patients with widespread vitiligo took an oral medicine called povorcitinib and saw a significant return of their skin color, which means that their melanocytes were being restored. The analysis described here looked at data from that same study to see how many patients had hearing loss at the beginning of the study and whether their hearing changed after treatment. It also looked at any patient traits that might be linked to hearing loss, such as age or how much of their skin had lost color from vitiligo. At the start of the study, just over one in ten patients had at least some sensorineural hearing loss. The patients with hearing loss were generally older and had more color loss of the skin on their faces than patients who did not have hearing loss. After up to a year of treatment with povorcitinib, patients showed some improvement in hearing, but this needs to be confirmed in larger studies. These findings suggest that hearing loss is relatively common in patients with vitiligo, so regular hearing checkups could be helpful for them.
Neotropical seasonally dry biomes are amongst the world's most threatened ecosystems and are predicted to lose more biodiversity with climate change. The capacity of natural populations to respond to these changes depends on their genetic variation, but is poorly understood in most Neotropical seasonally dry forest species. Here, we used genome-wide single nucleotide polymorphism (SNP) data for 109 individuals across 12 Colombian populations of Enterolobium cyclocarpum, a widespread deciduous legume tree found in seasonally dry tropical forests, human-disturbed and open landscapes from Central and Northern South America, to (1) explore population structure across the landscape, (2) determine local adaptation to heat and drought stress, and (3) assess genomic offset and adaptive potential under future climate change. Our results suggest clear genomic differentiation among regions and populations, as well as an uneven spatial distribution of adaptive alleles associated with drought and heat stress, together suggesting different degrees of local adaptation to climate across the landscape. Furthermore, all regions investigated (i.e., Caribbean, inter-Andean valleys, and Orinoquía) showed limited adaptive potential under future climate change scenarios. For some regions, gene flow may help buffer the effects of environmental change by bringing in adaptive alleles, however, this will likely be insufficient to counteract predicted mal-adaptation in certain regions, such as in the Orinoquía. Our results suggest that both barriers to gene flow (e.g., orography) and varying heat and drought stress conditions have shaped the genomic composition and adaptive potential of the species. Enterolobium cyclocarpum populations have adapted locally to current climate, but this adaptation may not be sufficient to cope with future climate change, particularly where population connectivity is low. Our findings have relevance for the conservation of species in highly threatened Neotropical biomes, such as seasonally dry tropical forests, which are expected to experience rising temperatures and greater drought under future climate change.
Drug repositioning accelerates clinical translation by identifying new therapeutic indications for approved drugs. However, therapeutic associations in biomolecular networks often exist indirectly, through transitive chains and long-range mechanisms, rather than as directly observed links. Shallow methods are confined to direct similarity and miss such indirect associations, whereas deep graph neural networks suffer from over-smoothing and lose discriminative power in highly connected networks. We propose a spatial-spectral collaborative framework. In the spatial domain, a wave-evolution process propagates similarity from local to global, capturing multi-hop transitive associations while preserving discriminative representations. In the spectral domain, network-specific spectral transforms model global connectivity for long-range dependencies over homogeneous similarity and heterogeneous drug-protein-disease networks, with the two views aligned by contrastive learning. On three benchmarks the method outperforms state-of-the-art baselines on most evaluation metrics; case studies on Alzheimer's and Parkinson's disease and molecular docking confirm its ability to recover non-explicit therapeutic associations. The source code and data are available at https://github.com/Juniper-cola/BIO_SSF.
Peanut oral immunotherapy (OIT) is an effective way to treat peanut allergy. Patients undergoing OIT show high rates of desensitization to the triggering food items after a completed therapy. Long-term tolerance is often achieved, but the mechanism of tolerance after OIT is not well understood. In this study, we aimed to characterize the changes in allergen-specific B cell gene expression caused by peanut OIT and the effects of extended allergen avoidance after OIT. We analyzed the gene expression of Ara h 2-specific B cells from 34 peanut allergic children from the peanut OIT IMPACT trial. We labeled PBMCs using biotinylated allergen to sort and pool allergen-specific B cells for sequencing. We compared the OIT and placebo arm after 30 months of active treatment and additionally after an avoidance phase of 6 months with no allergen exposure. After OIT, there was significantly altered gene expression in allergen-specific B cells. In tolerant participants, they exhibited gene expression related to regulatory B cells, suppressed B cell activation, immune regulation, increased cell-cell communication, and antigen presentation. These tolerance-induced changes in gene expression are different from remission as the 6-month avoidance period caused some participants to lose clinical tolerance. The difference between tolerance and desensitization appeared in increased antiviral response in desensitized individuals, whereas IL-10 and TGFβ-related signaling increased in the tolerant group. Allergen-specific B cells from OIT participants display a transcriptional profile associated with clinical remission, characterized by the expression of genes previously linked to regulatory B cell function.
A total of 86 sows (Line 241, DNA Genetics, Columbus, NE) were used to determine the effects of a cheese co-product added to lactation diets on sow and litter performance. Sows in three separate farrowing groups (approximately 31 ± 1 sows per group) were moved into the farrowing house and blocked by parity on day 112 ± 1 of gestation. Sows then were assigned to one of two dietary treatments which consisted of a standard corn-soybean-based lactation diet (control) or the control diet with 4% cheese co-product (Pro88; Keys Manufacturing, Paris, IL, USA) added at the expense of soybean meal on a digestible Lys-basis. The addition of the cheese co-product in lactation diets did not affect sow or litter performance. Offspring from the third farrowing group (395 pigs; DNA Line 241 × 600; initially 5.8 kg) were followed into the nursery and used in a 2 × 2 factorial to evaluate the effects of previous sow lactation feed treatment and addition of the cheese co-product in nursery diets in a 35-d growth trial. Nursery treatments included either a control diet or the control diet with 4% added cheese co-product fed in phases 1 (days 0 to 9) and 2 (days 9 to 21) followed by a common diet fed to all pigs in phase 3 (days 21 to 35). The cheese co-product was added at the expense of enzyme treated soybean meal in the nursery diets on a digestible Lys-basis. No sow × nursery interactions were observed. Offspring from the third group of sows fed the cheese co-product were heavier (P < 0.001) at weaning than those not fed cheese co-product, and this body weight advantage was maintained throughout the experiment. There was a tendency (P = 0.058) for fewer pigs fed the cheese co-product in the nursery to lose body weight from days 0 to 3 after weaning, regardless of previous sow treatment. During the nursery experimental period (days 0 to 21 post-weaning) and overall (days 0 to 35), pigs weaned from sows fed the cheese co-product tended to have increased (P < 0.10) gain-to-feed ratio (G: F). There were no effects on average daily gain or feed intake due to previous sow treatment. In addition, during the experimental period and overall, feeding the cheese co-product in the nursery diet increased (P < 0.05) G: F compared with pigs fed the control diet. In conclusion, feeding a cheese co-product either in lactation or early nursery diets at the expense of soybean meal or a specialty soy protein, respectively, increased G: F of pigs throughout the nursery period.
Aquaporin 4 (AQP4) water channels are polarized to astrocytic endfeet at blood vessel interfaces, and lose polarity in vascular diseases, including stroke, chronic traumatic encephalopathy, and Alzheimer's disease. AQP4 modulates water influx and efflux in the interstitial fluid, yet how AQP4 localization impacts cerebral amyloid angiopathy (CAA) remains poorly understood. Here we show that astrocytic end feet and AQP4 are displaced from amyloid-bearing vessels in a prion-CAA mouse model that expresses GPI-anchorless PrPC. Displacing AQP4 genetically through deleting alpha-syntrophin (Snta1 -/-) led to a marked prolongation in survival, together with reduced microglial inflammation and C1q, in prion-CAA-affected mice. Additionally, synaptic structural proteins were better maintained. Finally, the level and distribution of prion aggregates were similar among the mice, indicating that prion conversion and spread was not affected. These results suggest that reducing AQP4 water channel function slows the decline in a vascular amyloid disease by reducing neuroinflammation.
Delayed cancer diagnosis leads to poorer outcomes. Unintended weight loss (UWL) is a nonspecific symptom associated with cancer and other serious conditions, which can make it complex to identify the underlying cause. Clinical decision support systems (CDSSs) can provide evidence-based recommendations to facilitate timely investigation and diagnosis. This study aimed to pilot the implementation of a CDSS for improving early cancer detection in primary care patients with UWL. Five practices reviewed patients identified by the UWL CDSS. Staff were interviewed on the acceptability and feasibility of the CDSS. Interviews were analyzed thematically using 2 relevant frameworks: the acceptability of health care interventions and the sociotechnical model for evaluation of digital interventions framework. Clinical audits assessed the correct identification of UWL, follow-up rates, and patient characteristics. Of 60 patients identified by the CDSS as potentially having UWL, 36 (60%) had true UWL. Among the misclassified cases, most patients (16/55, 30%) were intentionally trying to lose weight; this intention was documented as free text in the clinical notes for 98% (58/60) of patients and in a structured field for only 20% of patients. Of the 36 patients, 5 (14%) were actively recalled by their practices for further follow-up; the others (31/36, 86%) were not recalled, as most were deemed already under appropriate follow-up. By 6 months, 94% (34/36) of the cohort had received follow-up care regardless of whether they had been formally recalled. One-third (12/36, 33%) of patients had no additional symptoms, while 36% (13/36) had recorded additional abdominal symptoms. Mental health conditions accounted for 19% of diagnoses linked to UWL consultation. Practice staff were generally receptive to the UWL CDSS concept. It was particularly appreciated by practices with strong quality improvement processes and prior CDSS experience. A high proportion of misclassified patients, poor workflow integration, and conflicting patients' agendas were cited as implementation barriers. Our study revealed challenges and potential benefits of implementing a CDSS for identifying patients with UWL at risk of cancer in primary care. While integration issues and misclassification of patients were noted, high rates of follow-up care were observed regardless of the CDSS. These high follow-up rates prompt consideration of whether they reflect Australian primary care and whether a CDSS with these characteristics is the most appropriate approach to support early cancer detection. Future research should focus on improving CDSS integration with existing workflows, enhancing correct identification through access to clinical notes and the use of more sophisticated digital methods (eg, AI). These findings highlight the potential of CDSS in improving patient care and the complexities involved in their successful implementation.
Sublethal pesticide risk to biological control agents is often judged by survival alone, although predators that survive exposure may still lose predatory performance. Here, we quantified the functional response of F1 and F2 Orius similis (third- to fifth-instar nymphs and male and female adults) to second-instar Frankliniella occidentalis after exposure to imidacloprid at the lethal concentrations causing 10% or 20% mortality (LC10 and LC20, respectively) through residual contact or prey-mediated ingestion. All stages retained a Holling type II response, but the magnitude and expression of impairment were strongly stage-, route-, concentration-, and generation-dependent. Fifth-instar nymphs and adults contributed most to prey suppression, whereas younger nymphs were most sensitive to performance loss. Residual contact tended to increase handling time, especially in younger nymphs, whereas prey-mediated ingestion more consistently reduced attack rate; both routes affected multiple functional-response parameters. Some control-standardized deficits were evident in the F2 generation, particularly in younger nymphs. Sublethal imidacloprid eroded the predatory performance of O. similis in a route-specific and generation-dependent manner during continuous multigenerational exposure, indicating that compatibility with this predator should be judged using functional endpoints in addition to survival in integrated pest management programs. © 2026 Society of Chemical Industry.
Testicular tissue cryopreservation is a key strategy for preserving fertility in adult males, yet optimal cryoprotective protocols have yet to be established. This study evaluated the effects of varying concentrations of chitosan oligosaccharide (COS, 0-25%) and chitosan (CS, 0-25%) on rabbit testicular tissues. Right testes from 35 male New Zealand rabbits were assigned to COS groups and left testes to CS groups. Each group was further divided into seven subgroups: fresh control, 0% control, and 5%, 10%, 15%, 20%, and 25% treatment groups. After one month of slow freezing, tissues were assessed by histomorphological scoring (cell swelling, cell loss, basement membrane integrity, and seminiferous tubule architecture) and seminiferous tubule diameter measurement. The 20% COS group achieved the highest histomorphological score, significantly exceeding the 0% control and comparable to the fresh control. Among CS treatments, the 15% group yielded the best score, also significantly higher than the 0% control. All frozen groups exhibited significantly reduced seminiferous tubule diameters compared with the fresh control, and these diameter changes did not correlate with the morphological scores. Concentrations exceeding the optimal level led to lose tubular structure and severe exfoliation of epithelial cells, suggesting that excessive osmotic stress may have contributed to the observed structural damage. COS demonstrated superior cryoprotection compared with CS under the present experimental conditions, which may be attributed to its lower molecular weight and improved diffusibility. These findings indicate that COS may represent a promising candidate for optimizing polysaccharide-based cryoprotectants in testicular tissue banking, although further functional validation is required.