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IntroductionPrevious research has tended to focus on early-life education for dementia risk reduction, yet there are great gains for building cognitive reserve in mid- to later-life through educational interventions. ISLAND (Island Study Linking Ageing and Neurodegenerative Disease) Campus offered free university study to all ISLAND participants, with flexible in-person/online learning models to remove educational, socioeconomic and geographical barriers. Here the core hypothesis of ISLAND Campus was investigated: that engagement in later life education leads to improvements in modifiable risk factors for dementia, cognition and blood-based biomarkers.MethodsISLAND Campus participants were matched on age and gender to non-Campus participants via propensity score method, with optimal matching based on logistic regression. Participants completed online surveys on health, demographics, modifiable dementia risk factors via a customized Dementia Risk Profile (DRP) tool and provided blood samples for APOE genotyping and plasma phosphorylated-tau (p-tau). Cognition was measured online via the validated Cambridge Neuropsychological Test Automated Battery Paired Associates Learning (PAL) and Spatial Working Memory (SWM) tasks. Impact of the opt-in formal educational intervention was tested in R via ANCOVA.ResultsTotal participants were 986 (intervention = 492, control = 492), mean age of 61.2 years, 73.2% female, 11.7 mean years of education and 25.0% APOE e4+. Over 4 years of follow-up, intervention participants significantly improved working memory (SWM) and their risk factor profiles as measured via the DRP (p

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Background Cytoreductive surgery is critical for optimal tumor clearance in advanced epithelial ovarian cancer (EOC). Despite best efforts, some patients may experience R2 (>1 cm) resection, while others may not undergo surgery at all. We aimed to compare outcomes between advanced EOC patients undergoing R2 resection and those who had no surgery. Methods Retrospective data from 51 patients with R2 resection were compared to 122 patients with no surgery between January 2015 and December 2019 at a UK tertiary referral centre. Progression-free survival (PFS) and overall survival (OS) were the study endpoints. Principal Component Analysis and Term Frequency – Inverse Document Frequency scores were utilized for data discrimination and prediction of R>2 cm from computed tomography pre-operative reports, respectively. Results No statistical significance was observed, except for age (73 vs 67 years in the no- surgery vs R2 group, P : .001). Principal Components explained 34% of data variances. Reasons for no surgery included age, co-morbidities, patient preference, refractory disease, patient deterioration or disease progression, and absence of measurable intra- abdominal disease). The median PFS and OS were 12 and 14 months for no-surgery, vs 14 and 26 months for R2 ( P : .138 and P : .001, respectively). Serous histology and performance status independently predicted PFS in both no-surgery and R2 cohorts. In the no-surgery cohort, serous histology independently predicted OS, while in the R2 cohorts, both serous histology and adjuvant chemotherapy were independent prognostic features for OS. The bi-grams “abdominopelvic ascites” and “solid omental” were amongst those best discriminating between R>2 cm and R1-2 cm. Conclusions R2 resection and no-surgery cohorts displayed unfavourable prognosis with a notable degree of uniformity. When cytoreduction results in suboptimal results, the survival benefit may still be higher compared to those who underwent no surgery.

Background and Objectives: Recent studies have focused on the association between the risk of diabetic retinopathy (DR) and the rs1501299 and rs2241766 polymorphisms of the ADIPOQ gene; however, their results remain inconclusive. Thus, a systematic review and meta-analysis were carried out to clarify the role of these polymorphisms in the development of DR. Materials and Methods: A systematic search of electronic databases (PubMed, Scopus, and Cochrane Library) was conducted until 25 June 2024, and a reference list of relevant articles was collected, which explored the association between the rs1501299 and rs2241766 polymorphisms of the ADIPOQ gene and the risk of DR. The pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated via random-effects model, and the meta-analysis was implemented by using Review Manager 5.4. Results: In total, 6 out of 182 studies, with 1888 cases (DR) and 2285 controls (without DR), were included in the meta-analysis. A statistically significant association between the rs1501299 polymorphism and the DR risk was recorded in G vs. T in the overall analysis (OR = 0.84, 95% CI = 0.72–0.99, p = 2 = 23%, n = 5 studies). Additionally, the summary results in the subgroup analysis according to the control type were as follows: the DR versus diabetes mellitus (DM) control type revealed a statistically significant association in G vs. T: OR = 0.81, 95% CI = 0.67–0.97, p = 2 = 27%, n = 4 studies; GG vs. GT: OR = 0.72, 95% CI = 0.53–0.98, p = 2 = 49%, n = 4 studies; GG vs. (GT + TT): OR = 0.73, 95% CI = 0.55–0.96, p = 2 = 44%, n = 4 studies. No significant association was observed between the rs2241766 polymorphism and the DR risk. Conclusions: The current meta-analysis supports the association between the rs1501299 polymorphism of the ADIPOQ gene and the DR risk in patients with DM.

Abstract Background Unmanaged cardiometabolic health, low physical and cognitive activity, poor diet, obesity, smoking and excessive alcohol consumption are modifiable health risk factors for dementia and public health approaches to dementia prevention have been called for. The Island Study Linking Ageing and Neurodegenerative Disease (ISLAND) is a dementia prevention public health study examining whether improving knowledge about modifiable dementia risk factors supports behaviour changes that reduce future dementia risk. Methods Residents of Tasmania, Australia, aged 50 + years who joined the 10-year ISLAND study were asked to complete annual online surveys about their knowledge, motivations and behaviours related to modifiable dementia risk. ISLAND included two knowledge-based interventions: a personalised Dementia Risk Profile (DRP) report based on survey responses, and the option to do a 4-week Preventing Dementia Massive Open Online Course (PDMOOC). Longitudinal regression models assessed changes in the number and type of risk factors, with effects moderated by exposures to the DRP report and engagement with the PDMOOC. Knowledge and motivational factors related to dementia risk were examined as mediators of risk behaviour change. Results Data collected between October 2019 and October 2022 (n = 3038, av. 63.7 years, 71.6% female) showed the mean number of modifiable dementia risk factors per participant (range 0 to 9) reduced from 2.17 (SD 1.24) to 1.66 (SD 1.11). This change was associated with the number of exposures to the DRP report (p = .042) and was stronger for PDMOOC participants (p = .001). The interaction between DRP and PDMOOC exposures yielded a significant improvement in risk scores (p = .004). The effect of PDMOOC engagement on behaviour change was partly mediated by increased knowledge (12%, p = .013). Self-efficacy enhanced the effect of knowledge on behaviour change, while perceived susceptibility to dementia mitigated this relationship. Conclusions The ISLAND framework and interventions, a personalised DRP report and the four-week PDMOOC, work independently and synergistically to increase dementia risk knowledge and stimulate health behaviour change for dementia risk reduction. ISLAND offers a feasible and scalable public health approach for redressing the rising prevalence of dementia.

Abstract Objective The increasing global prevalence of obesity, coupled with its association with chronic health conditions and rising healthcare costs, highlights the need for effective interventions; however, despite the availability of treatment options, the ongoing success of primary interventions in maintaining long‐term weight loss remains limited. This study examined the prescription medication dispensing changes following sleeve gastrectomy in Australians aged 45 years and over. Methods In a retrospective analysis of 847 bariatric surgery patients from the New South Wales 45 and Up Study, the assessment of medication patterns categorizing into three groups: gastrointestinal, metabolic, cardiorespiratory, musculoskeletal, and nervous systems was conducted. Each drug class was analyzed, focusing on patients with dispensing records within the 12 months before surgery. This study employed interrupted time‐series analysis to compare pre‐ and post‐surgery medication usage. Results With a predominantly female population (76.9%) and an average age of 57.2 (standard deviation 5.71), there were statistically significant reductions in both unique medications (12.5% decrease, p = 0.004) and total medications dispensed (15.9% decrease, p = 0.003) from 12 months before surgery to 13–24 months after bariatric surgery. All medication categories, except opioids, showed reductions. Notably, the most significant reductions were observed in diabetes (38.6%), agents acting on the renin‐angiotensin system (40.4%), lipid modifying agents (26.5%), anti‐inflammatory products (46.3%), and obstructive airway diseases (53.3%) medications during this time frame. Conclusion These findings suggest that sleeve gastrectomy provides an effective therapeutic intervention for patients with comorbidities requiring multiple medications, especially for obesity‐related diseases such as diabetes, cardiovascular, respiratory and musculoskeletal disorders.

Multidrug resistance (MDR) mechanisms in cancer cells are greatly influenced by glutathione transferase P1-1 (hGSTP1-1). The use of synthetic or natural compounds as hGSTP1-1 inhibitors is considered an effective approach to overcome MDR. Nine compounds consisting of coumarin-6-sulfonamide linked to chalcone derivatives were synthesized and evaluated for their ability to inhibit hGSTP1-1. Among the synthetic derivatives, compounds 5g, 5f, and 5a displayed the most potent inhibitory effect, with IC50 values of 12.2 ± 0.5 μΜ, 12.7 ± 0.7 and 16.3 ± 0.6, respectively. Kinetic inhibition analysis of the most potent molecule, 5g, showed that it behaves as a mixed-type inhibitor of the target enzyme. An in vitro cytotoxicity assessment of 5a, 5f, and 5g against the human prostate cancer cell lines DU-145 and PC3, as well as the breast cancer cell line MCF-7, demonstrated that compound 5g exhibited the most pronounced cytotoxic effect on all tested cell lines. Molecular docking studies were performed to predict the structural and molecular determinants of 5g, 5f, and 5a binding to hGSTP1-1. In agreement with the experimental data, the results revealed that 5g exhibited the lowest docking score among the three studied inhibitors as a consequence of shape complementarity, governed by van der Waals, hydrogen bonds and a π-π stacking interaction. These findings suggest that coumarin-chalcone hybrids offer new perspectives for the development of safe and efficient natural product-based sensitizers that can target hGSTP1-1 for anticancer purposes.

Introduction: Breast pseudoaneurysm is a rare complication following breast interventional procedures such as core biopsies and vacuum-assisted biopsies. The occurrence of pseudoaneurysm increases with the conditions of increased breast vascularity like cancer, pregnancy and lactation. Case Report: We present two cases of pseudoaneurysm formation secondary to core biopsies of the breasts. The first patient was an 82-year-old female patient who presented with breast swelling and bruising after multiple clinical core biopsies of the left breast. Our second patient was a 47-year-old lady who presented with a palpable lump following ultrasound-guided core biopsies of the left breast. Ultrasound showed hypoechoic pulsating area with evidence of internal colour flow in connection with a vessel in both cases. Imaging appearances were in keeping with a pseudoaneurysm of the breast. Discussion: Most pseudoaneurysms are secondary to interventional procedures in the breast. Common clinical presentation is a pulsatile, palpable mass at the biopsy site soon after the biopsy or later. On B mode imaging, it presents as a well-circumscribed mass of mixed echogenicity. Typical waveform in spectral Doppler and 'yin-yang' sign in colour Doppler is demonstrated with a turbulent internal flow. There are different treatment options to manage pseudoaneurysms of the breast. Conclusion: Pseudoaneurysm of the breast should be considered if a patient presents with a breast mass/lump close to a recent biopsy site. On clinical examination, pulsatility of the mass should raise the suspicion and definite diagnosis can be made with spectral and colour Doppler US scan. [ABSTRACT FROM AUTHOR]

This paper explores the processes behind legitimacy building and its role in new path creation and the path transformation or the 'de-locking' of an established industry. We use a mixed-methods approach and focus on the emergence of 'New Space' or Space 2.0 in the UK, a new-to-the-world industry, with radically different products and/or conventions. Legitimation of new product categories is essential to enable future adoption by regulators and consumers. Our findings suggest that this is not a linear process but involves interlayering, or complex feedback loops, between three distinct types of legitimacy building: regulatory, normative, and cognitive. Failure in some of these feedback loops, for example, problems with altering regulatory legitimacy, would prevent the formation of new industrial pathways with significant implications for the development of new-to-the-world and new-to-region industries. [ABSTRACT FROM AUTHOR]

Aims: To estimate the direct costs during the prenatal, delivery and postpartum periods in mothers with diabetes in pregnancy, compared to those without. Methods: This study used a population‐based dataset from 2004 to 2017, including 57,090 people with diabetes and 114,179 people without diabetes in Tasmania, Australia. Based on diagnostic codes, delivery episodes with gestational diabetes mellitus (GDM) were identified and matched with delivery episodes without diabetes in pregnancy. A group of delivery episodes with pre‐existing diabetes was identified for comparison. Hospitalisation, emergency department and pathology costs of these groups were calculated and adjusted to 2020–2021 Australian dollars. Results: There were 2774 delivery episodes with GDM, 2774 delivery episodes without diabetes and 237 delivery episodes with pre‐existing diabetes identified. Across the 24‐month period, the pre‐existing diabetes group required the highest costs, totalling $23,536/person. This was followed by the GDM ($13,210/person), and the no diabetes group ($11,167/person). The incremental costs of GDM over the no diabetes group were $890 (95% CI 635; 1160) in the year preceding delivery; $812 (616; 1031) within the delivery period and $341 (110; 582) in the year following delivery (p < 0.05). Within the year preceding delivery, the incremental costs in the prenatal period were $803 (579; 1058) (p < 0.05). Within the year following delivery, the incremental costs in the postpartum period were $137 (55; 238) (p < 0.05). Conclusions: Our results emphasised the importance of proper management of diabetes in pregnancy in the prenatal and postpartum periods and highlighted the significance of screening and preventative strategies for diabetes in pregnancy. [ABSTRACT FROM AUTHOR]