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464 papers

Audience Interpretation of Risks in Health Promotion Campaigns About Underage Drinking: Qualitative Interviews With Parents of Adolescents.

Nguyen HV. · Jul 1, 2026

Issue addressed Underage alcohol use has been linked to risks of physical, mental, and social harms to young people. Despite the known risks, research shows that parents may choose to supply alcohol to their children on occasions for various reasons. This has prompted several health promotional campaigns aimed at parents to discourage the practice of parental supply of alcohol, but there has been little evidence of how the messages are received by the target audiences, i.e., parents of adolescents. Methods Grounded in the existing literature on alcohol-related harms, social dimensions and communication of risks, the current paper conducted a qualitative analysis of interviews with parents of adolescents to understand their interpretation of risks in a series of Australian health promotion campaigns that addressed underage drinking. Result The study demonstrated how target audiences brought in their own lived experiences and social worldviews to interpret and internalise messaging about risks in ways that are nuanced and situational. Conclusions The findings demonstrated how parents' lived experiences and worldviews influenced their interpretation and alignment with the health promotion messages about parental supply of alcohol. While the ways the parents negotiated with the health promotion messages may not be scientifically-grounded, it was not always due to unawareness of risks but based upon strategies and assessment of risks in situational contexts. SO WHAT?: Understanding of how lived experiences inform interpretation of health promotion campaigns has implications for more effective alcohol-related risk communication aimed at behaviour change to reduce alcohol-related harms among young people.

Medicine

Radiolabeled Angiopep-2 Peptide Vector as a Preclinical Platform for Blood-Brain Barrier Targeting: Synthesis, Radiolabeling, and Preliminary In Vivo Biodistribution in Mice.

Fotou E et al. · Jul 1, 2026

Brain tumor therapy remains limited by the blood-brain barrier (BBB), which restricts drug access. BBB-penetrating peptides offer a promising strategy for delivering therapeutic and diagnostic payloads. Angiopep-2 is a well-established vector, yet novel radioconjugates based on this vector remain of interest. We report the synthesis and evaluation of DOTA-Angiopep-2 for radiolabeling with Lutetium-177 ( 177 Lu) and Terbium-161 ( 161 Tb). Notably, 177 Lu serves as a β- and γ-emitter, whereas 161 Tb is an Auger and β-emitter; both are utilized in therapy and SPECT imaging. Peptides were synthesized via solid-phase peptide synthesis. Cytotoxicity assays in T98 glioblastoma cells showed that Angiopep-2 is well-tolerated, maintaining ~100% viability at 20 μM and a moderate decline up to 100 μM. Radiolabeling achieved yields > 95% with excellent radiochemical stability at room temperature for up to 10 days and moderate stability in the presence of human serum. Biodistribution in healthy CFW mice showed a brain-associated radioactivity of 0.24% ± 0.05% IA/g at 5 min p.i. and a 12-fold increase in the brain-to-blood ratio (0.028-0.339) by 60 min p.i. These results support DOTA-Angiopep-2 as a versatile platform for radionuclide delivery and a potential candidate for future glioma-targeted studies. Further studies in tumor-bearing models are ongoing to evaluate therapeutic efficacy and translational potential.

Materials Science

Healthy Public Policy Must Build Capacity: Analysing the Implementation of 3.2.2A, Australia's New Food Safety Standard.

Barnes J et al. · Jul 1, 2026

Issue addressed The integration of a new standard for food safety in Australia signifies a notable step toward national unity in the adoption of Hazard Analysis and Critical Control Point (HACCP) principles and contemporary food safety management tools for the food service and retail sector. The standard introduces key measures, including certification of food safety supervisors, food safety training requirements for food handlers, and means for substantiating control of food safety hazards throughout key food handling processes. Methods This study explored the experiences and perspectives of local regulators regarding the implementation and feasibility of the new standard. Data were collected via an online survey and semi-structured interviews with Environmental Health Practitioners across two Australian states. Results Findings reveal that implementation of the standard varied between states, largely shaped by the degree of support provided by respective state authorities. Six key barriers to effective implementation emerged from participant accounts. Conclusions In response, five targeted recommendations are proposed, grounded in established health promotion principles. Until these challenges are adequately addressed, the standard risks remaining ineffectual, limiting its capacity to enhance public health outcomes. SO WHAT?: The key to effective implementation and realisation of Standard 3.2.2A as healthy public policy lies within the central tenets of public health theory and practice.

Agricultural and Biological Sciences

Dipolar Order Mapping Based on Spin-Lock Magnetic Resonance Imaging.

Gao Z et al. · Jul 1, 2026

Inhomogeneous magnetization transfer (ihMT) is sensitive to dipolar order associated with motion-restricted macromolecules and can be characterized by the dipolar relaxation time T1D$$ {T}_{1D} $$ . In this study, we propose a spin-lock MRI framework for T1D$$ {T}_{1D} $$ quantification. Specifically, we introduce a T1D$$ {T}_{1D} $$ -sensitive metric, RATIOdosl$$ RATI{O}_{dosl} $$ , derived from the distinct relaxation rate Rdosl$$ {R}_{dosl} $$ , defined as the difference between dual-frequency and single-frequency R1ρ$$ {R}_{1\rho } $$ measurements. To enable dual-frequency spin-lock acquisition, we developed a dedicated rotary-echo spin-lock sequence. Based on this framework, we further estimated T1D$$ {T}_{1D} $$ and the macromolecular proton fraction (MPF) within a unified acquisition. The proposed method was evaluated using numerical simulations, phantom experiments, and in vivo imaging in the healthy human brain. Simulations demonstrated high sensitivity of RATIOdosl$$ RATI{O}_{dosl} $$ to T1D$$ {T}_{1D} $$ and supported the robustness of the proposed approach under the investigated conditions. Phantom experiments showed measurable ihMT contrast and supported the feasibility of T1D$$ {T}_{1D} $$ estimation using RATIOdosl$$ RATI{O}_{dosl} $$ . In vivo experiments demonstrated simultaneous T1D$$ {T}_{1D} $$ and MPF mapping using only three spin-lock-prepared images. Across 10 healthy volunteers, mean white matter T1D$$ {T}_{1D} $$ values ranged from approximately 3.70 to 4.80 ms. By requiring only three contrast-prepared images, the proposed technique provides a rapid framework for simultaneous T1D$$ {T}_{1D} $$ and MPF mapping and may facilitate further investigation of dipolar-order-sensitive microstructural imaging in vivo.

Medicine

Diffusion-weighted Imaging Distortion in Prostate MRI: A Cross-sectional Study Comparing Supine and Prone Positioning.

Lee KL et al. · Jul 1, 2026

Objectives Diffusion weighted imaging (DWI) is a key component of multiparametric (mp) prostate MRI. DWI using echo-planar techniques is susceptible to distortion at the recto-prostatic air-tissue interface. This study was to determine whether prone patient positioning reduces adjacent rectal air and DW image distortion when compared with standard-of-care supine positioning. Materials and methods This prospective study included consecutive patients undergoing mpMRI for suspected PCa between 2023 and 2024. Prostate segmentation was performed on DW and contrast-enhanced images. DWI distortion was measured quantitatively. Qualitative image quality of DWI and T2-weighted imaging (T2WI) was evaluated using PI-QUAL version 2; a separate 5-point clinically based Likert scale was employed to evaluate the volume of rectal air adjacent to the prostate. Results Fifty-two patients were enrolled. In total, 58% of patients expressed a preference for supine imaging versus 20% for prone imaging. Qualitative DWI image quality improved significantly in the prone position [median: 4 (3 to 4)] versus supine [3 (1 to 4)]; P 4 cm 3 of supine rectal air (n = 19), distortion was significantly reduced by prone imaging [3.49 mm (2.84 to 4.03)] compared with supine [4.60 mm (3.17 to 5.95)]; P = 0.02. The mean additional scanning time for the necessary prone imaging was 8 minutes 18 seconds. Conclusions Prone positioning significantly reduces DWI distortion artefact when rectal air is present, but consistently results in degraded T2WI quality.

Medicine

Early Identification of DLD in Paediatric Practice: A Pilot Validation of the CLAP Screening Tool in Italian Outpatient Settings.

Ricotti A et al. · Jul 1, 2026

Background Language development in early childhood varies considerably, making early detection of Developmental Language Disorders (DLDs) challenging despite their high prevalence and long-term effects on learning and mental health. In Italy, no culturally adapted, easy-to-use screening tools are currently available in primary care. To address this gap, a screening tool was developed to support the early identification of children aged 24-72 months at risk of DLD and other clinically relevant language difficulties. Aims To evaluate the psychometric properties and accuracy of the Comunicazione e Linguaggio in Ambulatorio Pediatrico (CLAP), a brief age-specific screening tool designed for use in Italian paediatric outpatient settings. Methods and procedures In this pilot validation study, children were recruited by primary care paediatricians during routine well-child visits and stratified into four age groups: 24-30, 36-42, 48-54, and 60-72 months. After administration of the CLAP screening tool, each child underwent a blinded speech-language pathologist (SLP) assessment. Psychometric evaluation included internal consistency, item-total correlations, confirmatory factor analysis, and item response theory indices (discrimination and difficulty). Diagnostic accuracy was assessed using ROC curves, area under the curve (AUC), sensitivity, specificity, and optimal cut-offs. Analyses were conducted separately for each age group. Outcomes and results Fifty children were enrolled in each age group; overall, 24% of the sample fell into the pathological subgroup after the blinded SLP assessment. Internal consistency was acceptable in the 24-30-month (KR-20 = 0.695) and 36-42-month (KR-20 = 0.777) groups, but lower in older children. Factor analyses supported a mainly unidimensional structure in the younger groups. Item response theory showed good discrimination and informativeness for several items. ROC analyses indicated excellent diagnostic accuracy in the 24-30-month group (AUC = 0.93; sensitivity = 92%; specificity = 87%), fair accuracy in the 36-42- and 48-54-month groups (AUC = 0.75 and 0.74), and poor performance in the 60-72-month group (AUC = 0.46). Conclusion and implications The CLAP demonstrates promising psychometric properties and good-to-fair accuracy as a brief screening tool for identifying children aged 24-54 months at risk of clinically relevant language difficulties, including those who may need further assessment for DLD. Its age-specific design, quick administration, and non-invasive nature support its potential integration into routine primary care. For older children, an age-specific revision or an alternative tool might be required. A larger validation study is currently in progress. What this paper adds What is already known on this subject Developmental Language Disorder (DLD) is common in early childhood; however, early identification remains difficult due to variable developmental pathways and the absence of validated screening tools in primary care. Currently, no brief, culturally adapted instrument is available for routine use in Italian paediatric settings. What does this study add to existing knowledge This study demonstrates that the CLAP tool has promising psychometric properties, with good accuracy in the youngest age group and fair accuracy up to 54 months for identifying children at risk of clinically relevant language difficulties, including those who may later meet criteria for DLD. It provides the first evidence supporting an age-specific, feasible screening option that can be integrated into Italian primary care, while also identifying areas requiring revision for older pre-schoolers. What are the potential or actual clinical implications of this work? CLAP can assist paediatricians in the early detection of clinically relevant language difficulties in children during routine well-child visits. Its adoption could help standardize early language screening in Italy, leading to earlier referral for further diagnostic assessment and appropriate speech-language evaluation.

Psychology

Combined electrospun fibre-microneedle patches for enhanced transmucosal delivery of benzodiazepines and proteins.

Berry C et al. · Jul 1, 2026

The oral mucosa is highly vascularised, which permits rapid drug uptake into the systemic circulation, avoiding first-pass metabolism for chemicals that penetrate the epithelial permeability barrier. Electrospun mucoadhesive patches have been developed for controlled drug delivery and although contact times and drug distribution are improved, transmucosal drug permeation is still limited to small lipophilic molecules. Incorporation of solid microneedles with an electrospun patch to physically disrupt the epithelial barrier whilst simultaneously delivering a payload, can overcome these issues whilst addressing the drug-loading limitations often experienced with microneedles. Here, we developed a mucoadhesive patch and microneedle composite for delivery of the benzodiazepine, midazolam hydrochloride, required for rapid, systemic delivery to treat status epilepticus and antigen-binding fragments (f(ab)), proteins too large to cross the epithelial permeability barrier. Solid polylactic acid microneedles were manufactured through reverse micromoulding, optimised for buccal permeation and imaged using optical coherence tomography. Electrospun mucoadhesive patches, loaded with midazolam hydrochloride or f(ab), were combined with the microneedles and permeation through tissue-engineered buccal mucosa quantified by high-performance liquid chromatography or immunoassay and imaged by fluorescence confocal microscopy. Microneedle-mediated patch delivery enhanced patch retention time, drug delivery rates and overall permeation when compared to patch-only controls, facilitating rapid delivery of time-sensitive midazolam within minutes, and a 15-fold increase in f(ab) permeation over 2 h, importantly delivering it through the epithelium into the underlying lamina propria. This study demonstrates that microneedle-mediated mucoadhesive patches can enhance transmucosal drug delivery for poorly-permeable drugs and holds significant potential when rapid, systemic drug delivery is required.

Pharmacology, Toxicology and Pharmaceutics

2-Pyrazoline-5-One Derivative Suppresses Cell Proliferation and Induces Apoptosis With Upregulation of Bax in Breast Cancer Cells.

Sevinc SK et al. · Jul 1, 2026

The most common cancer in women worldwide is still breast cancer. Among its subtypes, luminal A and triple-negative breast cancers present significant therapeutic challenges due to intrinsic drug resistance and absence of effective targeted treatments. The pharmacological potential of heterocyclic compounds has garnered more attention in recent years, and structures like pyrazolines, hydrazones, and triazoles are important in the development of new drugs. Compounds incorporating these scaffolds have been shown in numerous studies to have strong anticancer action. In this regard, pyrazoline derivatives have become a viable field of study for focused treatment approaches. This study focused on evaluating the cytotoxic potential of the 2-pyrazoline-5-one derivative compound against luminal-A (MCF-7) and triple-negative (MDA-MB-231) breast cancer cell lines. The CCK-8 test was used to assess the impact on cell viability. Additionally, Annexin V/PI staining was used to identify the apoptotic effects, and fluorescence microscopy was used for analysis. The wound healing experiment was used to measure the capacity of cells to migrate, and migration process was monitored following scratch formation. The colony formation assay was used to assess the potential for cell proliferation, and clonal growth capacities were compared. Bax protein levels in compound-treated cancer cells were quantified by ELISA to investigate the apoptotic mechanism. IC50 values in MCF-7 and MDA-MB-231 cell lines were used to evaluate the cytotoxic effects of the 2-pyrazoline-5-one derivative. The compound exhibited strong cytotoxic activity and reduced cell viability in both cell lines in a concentration-dependent manner, with IC 50 values of 13 µM in MCF-7 cells and 16 µM in MDA-MB-231 cell. Furthermore, the compound effectively induced apoptosis and significantly suppressed colony formation and cell migration in both cell lines. Additionally, it showed a concentration-dependent rise in Bax protein levels, suggesting a pro-apoptotic action. These results confirm that the 2-pyrazoline-5-one derivative has strong antiproliferative and pro-apoptotic activity through Bax activation, providing a possible pathway for the creation of targeted treatments for breast cancer.

Chemistry

Efficacy of Metformin in Prevention of Glucocorticoid-Induced Hyperglycemia in Patients Without Diabetes: A Meta-Analysis.

Murtaza S et al. · Jul 1, 2026

Purpose The glucocorticoids are increasingly being used in the management of different autoimmune conditions and cancers. Our meta-analysis aims to leverage metformin's potential to reverse the metabolic complications of glucocorticoids by activating AMP-activated protein kinase (AMPK), while sparing their anti-inflammatory benefits. Methods PubMed, Cochrane Library, trial registries and Google Scholar were searched from inception to June 2025 for Randomized Controlled Trials (RCTs) and observational studies comparing metformin and placebo to prevent metabolic side effects of glucocorticoid therapy in non-diabetic patients. After screening by two independent reviewers according to PRISMA guidelines, four studies involving 187 patients were analysed using the random-effects model in RevMan 5.4.1, and mean differences (MD) were calculated. Results Preventive metformin administration during glucocorticoid treatment is superior to placebo with respect to glycaemic control as shown by statistically significant reduction in fasting blood glucose [MD = -0.60 (95% CI: -0.86 to -0.34)], HOMA index of insulin resistance [MD = -0.53 (95% CI: -0.97 to -0.08)], LDL levels [MD = -0.20 (95% CI: -0.40 to -0.00)] and total cholesterol [MD = -0.27 (95% CI: -0.54 to -0.01)]. However, our study failed to show significant improvement in area under the curve glucose (mmol/L × min) after challenge [MD = -176.66 (95% CI: -415.42, 62.11)], basal metabolic rate (BMR) [MD = 51.99 (95% CI: -53.08, 157.07)], HDL [MD = -0.04 (95% CI: -0.13, 0.05)], insulin levels [MD = -2.26 (95% CI: -5.90, 1.38)], triglycerides [MD = -0.15 (95% CI: -0.42, 0.13)] and body weight [MD = -0.93 (95% CI: -2.29 to 0.44)]. Conclusion While glucocorticoids remain essential in various clinical contexts, their detrimental effects on glucose metabolism are well documented. This study supports metformin as a promising preventive treatment in non-diabetic patients receiving systemic glucocorticoid therapy. Improvement in insulin sensitivity and resulting fasting glucose levels may offset glucocorticoid-exacerbated inflammation. Further studies are needed to address long-term outcomes, including adiposity, bone metabolism, appetite, liver function and muscle wasting, as well as to identify possible predictors of therapeutic response. Trial registration International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD420251104082.

Biochemistry, Genetics and Molecular Biology

Mex-3 RNA-binding family member A limits macrophage ferroptosis-associated injury linked to the SLC7A11/GPX4 pathway in diabetic atherosclerosis.

Ma Y et al. · Jul 1, 2026

Background Diabetes accelerates atherosclerotic plaque expansion and loss of stability, but the plaque-resident mechanisms through which the diabetic milieu promotes macrophage lipid-oxidative injury are not fully understood. Methods We used apolipoprotein E-deficient (ApoE -/- ) mice with Mex-3 RNA-binding family member A (MEX3A) deficiency and primary bone marrow-derived macrophage (BMDM) experiments under diabetic conditions to investigate the role of MEX3A in diabetic atherosclerosis and macrophage lipid-peroxidation injury. Results MEX3A loss worsened diabetic atherosclerosis while leaving body weight, glycaemia and lipid measurements largely unchanged relative to diabetes alone. MEX3A deficiency enlarged aortic lesions, enhanced lipid deposition, increased macrophage content, expanded necrotic cores and thinned fibrous caps, while reducing collagen content. In lesional macrophages, loss of MEX3A coincided with increased lipid reactive oxygen species, malondialdehyde, increased labile iron, 4-hydroxynonenal, a disturbed glutathione redox state, mitochondrial abnormalities compatible with ferroptotic stress, lower GPX4/SLC7A11 and higher ACSL4. CRISPR/Cas9-mediated Mex3a knockout in BMDMs recapitulated this phenotype, whereas restoring MEX3A blunted it. RNA immunoprecipitation-qPCR together with actinomycin D decay analyses demonstrated preferential recovery of Slc7a11 and Gpx4 transcripts with MEX3A and decreased stability of Slc7a11 and Gpx4 mRNAs after Mex3a knockout. GPX4 or SLC7A11 overexpression reduced lipid-peroxidation injury in Mex3a-knockout macrophages, whereas Gpx4 or Slc7a11 knockdown weakened the protection conferred by MEX3A re-expression. Ferrostatin-1 partially attenuated macrophage lipid peroxidation and plaque injury. Conclusions Together, these results place MEX3A among the protective regulators of diabetic plaque stability and support a MEX3ASLC7A11/GPX4-linked ferroptosis-associated mechanism in plaque macrophages. Key points MEX3A deficiency worsens diabetic atherosclerosis without further aggravating systemic metabolic indices. Loss of MEX3A promotes plaque lipid deposition, macrophage accumulation, necrotic core expansion and fibrous cap thinning. MEX3A limits macrophage lipid-peroxidation injury linked to the SLC7A11/GPX4 pathway. Ferrostatin-1 partially attenuates macrophage lipid peroxidation and plaque injury associated with MEX3A deficiency.

Medicine