Cancer risk following onset of type 2 diabetes in New Zealanders with impaired glucose tolerance over 25 years: a matched prospective cohort study.

BACKGROUND: In people with prediabetes, the link between developing type 2 diabetes (T2D) and cancer risk among those with impaired glucose tolerance (IGT) remains uncertain. We examined this association in IGT individuals from primary care in South and West Auckland, New Zealand, spanning 1994-2019, assessing 5- and 10-year cancer risks. METHODS: Study cohorts were extracted from the Diabetes Care Support Service in Auckland, New Zealand, linking it with national registries for death, cancer, hospital admissions, pharmaceutical claims, and socioeconomic status. We compared cancer risks in individuals with IGT newly diagnosed with or without T2D within a 1-5-year exposure window. Employing tapered matching and landmark analysis to address potential confounding effects, we formed comparative IGT cohorts. Weighted Cox regression models were then employed to assess the association between T2D onset and 5- and 10-year cancer risks. RESULTS: The study included 26,794 patients with IGT, with 629 newly diagnosed with T2D within 5 years and 13,007 without such a diagnosis. Those progressing to T2D had similar 5-year cancer risk but significantly higher 10-year risk (HR 1.35; 95% CI 1.09-1.68). This association was stronger in older individuals, the socioeconomically deprived, current smokers, those with worse metabolic measures, and lower renal function. Patients with IGT of NZ European ethnicity had lower 10-year cancer risk. CONCLUSIONS: T2D diagnosis influences cancer risk in individuals with IGT. Developing risk scores for high-risk IGT individuals and implementing cancer screening and structured diabetes prevention, especially in deprived or minority ethnic populations, is essential.

All-cause, premature, and cardiovascular death attributable to socioeconomic and ethnic disparities among New Zealanders with type 1 diabetes 1994-2019: a multi-linked population-based cohort study.

BACKGROUND: New Zealand (NZ) research into type 1 diabetes mellitus (T1DM) mortality can inform policy and future research. In this study we aimed to quantify the magnitude to which ethnicity and socioeconomic disparities influenced mortality at the population level among people with Type 1 diabetes (T1DM) in Auckland, New Zealand (NZ). METHODS: The cohort data were derived from the primary care diabetes audit program the Diabetes Care Support Service (DCSS), and linked with national primary care, pharmaceutical claims, hospitalisation, and death registration databases. People with T1DM enrolled in DCSS between 1994-2018 were included. All-cause, premature, and cardiovascular mortalities were estimated by Poisson regression models with adjustment for population-level confounders. The mortality rates ratio (MRR) was standardized against the DCSS type 2 diabetes population. Mortality rates were compared by ethnic group (NZ European (NZE) and non-NZE) and socioeconomic deprivation quintile. The population attributable fraction (PAF) was estimated for ethnic and socioeconomic disparities by Cox regression adjusting for demographic, lifestyle, and clinical covariates. The adjusted slope index inequality (SII) and relative index of inequality (RII) were used to measure the socioeconomic disparity in mortalities. RESULTS: Overall, 2395 people with T1DM (median age 34.6 years; 45% female; 69% NZE) were enrolled, among whom the all-cause, premature and CVD mortalities were 6.69 (95% confidence interval: 5.93-7.53), 3.30 (2.77-3.90) and 1.77 (1.39-2.23) per 1,000 person-years over 25 years. The overall MRR was 0.39 (0.34-0.45), 0.65 (0.52-0.80), and 0.31 (0.24-0.41) for all-cause, premature and CVD mortality, respectively. PAF attributable to ethnicity disparity was not significantly different for mortality. The adjusted PAF indicated that 25.74 (0.84-44.39)% of all-cause mortality, 25.88 (0.69-44.69)% of premature mortality, 55.89 (1.20-80.31)% of CVD mortality could be attributed to socioeconomic inequality. The SII was 8.04 (6.30-9.78), 4.81 (3.60-6.02), 2.70 (1.82-3.59) per 1,000 person-years and RII was 2.20 (1.94-2.46), 2.46 (2.09-2.82), and 2.53 (2.03-3.03) for all-cause, premature and CVD mortality, respectively. CONCLUSIONS: Our results suggest that socioeconomic disparities were responsible for a substantial proportion of all-cause, premature and CVD mortality in people with T1DM in Auckland, NZ. Reducing socioeconomic barriers to management and self-management would likely improve clinical outcomes.

Long-term impact of type 2 diabetes onset on dementia incidence rate among New Zealanders with impaired glucose tolerance: A tapered-matched landmark analysis over 25 years.

INTRODUCTION: We aimed to investigate the association between the onset of type 2 diabetes (T2D) and dementia incidence rates (IR) in the population with impaired glucose tolerance (IGT) identified in primary care in New Zealand (NZ) over 25 years. METHODS: Tapered matching and landmark analysis (accounting for immortal bias) were used to control for potential effects of known confounders. The association between T2D onset and 5- and 10-year IR of dementia was estimated by weighted Cox models. RESULTS: The onset of T2D was significantly associated with the 10-year IR of dementia, especially in the socioeconomically deprived, those of non-NZ European ethnicity, those currently smoking, and patients with higher metabolic measures. DISCUSSION: Our findings suggest that the onset of T2D is a significant risk factor for dementia in individuals with IGT. Dementia screening and structured diabetes prevention are vital in the population with IGT, particularly those from deprived or ethnic minority backgrounds. HIGHLIGHTS: Increased dementia incidence rate links with T2D onset in people with IGT. Significant incidence varied by ethnicity, socioeconomic status, and health factors. Results emphasize the diabetes manage and socioeconomic factors on dementia risk. Secondary analysis highlights the key role of vascular health in dementia prevention.

Antitumor Mechanism and Therapeutic Potential of Cordycepin Derivatives.

Cordycepin has good antitumor activity, but its clinical application is limited due to the easy deamination of N6 in structure. In this study, a large lipolysis group was introduced at the cordycepin N6 to improve the problem, cordycepin derivatives (3a-4c) were synthesized, and biological evaluation of compounds was studied. In this study, the vitro antitumor activity of the compounds against MCF7 cells, HepG2 cells and SGC-7901 cells was evaluated by MTT assay. In the results, compound 4a showed the most obvious inhibitory effect on MCF7 cells with an IC50 value of 27.57 ± 0.52 µM, which was much lower than cordycepin. Compound 4a showed high selectivity between MCF7 and normal MCF-10A cells. Further biological evaluation showed that compound 4a promoted apoptosis and blocked the cell cycle in the G0/G1 phase. Then, Western Blot was used to detect related apoptotic proteins. It was found that Compound 4a could down-regulate the expression of Bcl-2 protein and up-regulate the expression of p53, Bax, Caspase-3 and Caspase-9 proteins. The mitochondrial membrane potential decreased continuously and the positive expression rate decreased. It was speculated that compound 4a induced the apoptosis of MCF7 cells through the mitochondrial pathway.

Superior doxorubicin cellular delivery effect established by optically active mesoporous silica nanoparticles.

The impact of optically active biomaterials on drug delivery remains a vital and hot topic. To reveal special advantages of optically active mesoporous silica nanoparticles in delivering drug in cells, optically active mesoporous silica nanoparticles deliver doxorubicin (DOX) with chiral behavior in cancer cells was studied. The present work focused on two types of optically active mesoporous silica nanoparticles named as levorotatory optically active mesoporous silica nanoparticles (LOA-MSNs) and dextrorotatory optically active mesoporous silica nanoparticles (DOA-MSNs) and examined their effects on cellular DOX delivery in cancer cells. The obtained LOA-MSNs and DOA-MSNs were regular spheres with particle diameters ranging from 200 to 250 nm, and their shell layer was filled with interlaced channels. Our results indicated that LOA-MSNs and DOA-MSNs did not exhibit cytotoxicity towards MCF-7 cells and B16 cells. The cytotoxicity of DOX-loaded LOA-MSNs and DOX-loaded DOA-MSNs were stronger than DOX owing to the synergistic retention and accumulation effect of nanoparticles. More importantly, DOX-loaded DOA-MSNs presented stronger cytotoxicity due to the higher synergistic retention and accumulation effect of DOA-MSNs. These findings suggest that DOA-MSNs with superior cellular delivery of DOX have great potential to advance the development of optical anti-tumor delivery system.

Chronic pain-mental health comorbidity and excess prevalence of health risk behaviours: a cross-sectional study.

BACKGROUND: Chronic musculoskeletal pain and anxiety/depression are significant public health problems. We hypothesised that adults with both conditions constitute a group at especially high risk of future cardiovascular health outcomes. AIM: To determine whether having comorbid chronic musculoskeletal pain and anxiety/depression is associated with the excess prevalence of selected known cardiovascular health risk behaviours. METHOD: A cross-sectional survey of adults aged 35+ years randomly sampled from 26 GP practice registers in West Midlands, England. Respondents were classified into four groups based on self-reported presence/absence of chronic musculoskeletal pain (pain present on most days for six months) and anxiety or depression (Hospital Anxiety and Depression Score 11+). Standardised binomial models were used to estimate standardised prevalence ratios and prevalence differences between the four groups in self-reported obesity, tobacco smoking, physical inactivity, and unhealthy alcohol consumption after controlling for age, sex, ethnicity, deprivation, employment status and educational attainment. The excess prevalence of each risk factor in the group with chronic musculoskeletal pain-anxiety/depression comorbidity was estimated. FINDINGS: Totally, 14 519 respondents were included, of whom 1329 (9%) reported comorbid chronic musculoskeletal pain-anxiety/depression, 3612 (25%) chronic musculoskeletal pain only, 964 (7%) anxiety or depression only, and 8614 (59%) neither. Those with comorbid chronic musculoskeletal pain-anxiety/depression had the highest crude prevalence of obesity (41%), smoking (16%) and physical inactivity (83%) but the lowest for unhealthy alcohol consumption (18%). After controlling for covariates, the standardised prevalence ratios and differences for the comorbid group compared with those with neither chronic musculoskeletal pain nor anxiety/depression were as follows: current smoking [1.86 (95% CI 1.58, 2.18); 6.8%], obesity [1.93 (1.76, 2.10); 18.9%], physical inactivity [1.21 (1.17, 1.24); 14.3%] and unhealthy alcohol consumption [0.81 (0.71, 0.92); -5.0%]. The standardised prevalences of smoking and obesity in the comorbid group exceeded those expected from simple additive interaction.

Principle and experimental study of a combined teardrop and heart-shaped channel bluffbody valveless piezoelectric pump.

In this study, we have developed a piezoelectric pump with a combined teardrop- and heart-shaped channel based on the Coanda effect and bionics principle. The bluffbody consists of teardrop- and heart-shaped channels. The vibration and the pump flow rate are evaluated theoretically, and the flow conditions under different bluffbody heights and different main channel widths are simulated. The theoretical and simulation results show that the pump has uneven resistance to flow in forward and reverse directions, and the height of the teardrop bluffbody and the width main channel affect the flow in the channel. Test data show that under the same pressure, when the main channel is 5 mm and the bluffbody height is 8 mm, the pump flow rate is 460.8 ml/min. The pump alleviates the serious backflow problem through the fluid blocking structure and is expected to become an active driver of microfluidic devices.

Recent developments in wearable piezoelectric energy harvesters.

Wearable piezoelectric energy harvesters (WPEHs) have gained popularity and made significant development in recent decades. The harvester is logically built by the movement patterns of various portions of the human body to harvest the movement energy and immediately convert it into usable electrical energy. To directly power different microelectronic devices on the human body, a self-powered device that does not require an additional power supply is being created. This Review provides an in-depth review of WPEHs, explaining the fundamental concepts of piezoelectric technology and the materials employed in numerous widely used piezoelectric components. The harvesters are classed according to the movement characteristics of several portions of a person's body, such as pulses, joints, skin, and shoes (feet). Each technique is introduced, followed by extensive analysis. Some harvesters are compared, and the benefits and drawbacks of each technique are discussed. Finally, this Review presents future goals and objectives for WPEH improvement, and it will aid researchers in understanding WPEH to the point of more efficient wireless energy delivery to wearable electronic components.

Improving the performance of deep learning models in predicting and classifying gamma passing rates with discriminative features and a class balancing technique: a retrospective cohort study.

BACKGROUND: The purpose of this study was to improve the deep learning (DL) model performance in predicting and classifying IMRT gamma passing rate (GPR) by using input features related to machine parameters and a class balancing technique. METHODS: A total of 2348 fields from 204 IMRT plans for patients with nasopharyngeal carcinoma were retrospectively collected to form a dataset. Input feature maps, including fluence, leaf gap, leaf speed of both banks, and corresponding errors, were constructed from the dynamic log files. The SHAP framework was employed to compute the impact of each feature on the model output for recursive feature elimination. A series of UNet++ based models were trained on the obtained eight feature sets with three fine-tuning methods including the standard mean squared error (MSE) loss, a re-sampling technique, and a proposed weighted MSE loss (WMSE). Differences in mean absolute error, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were compared between the different models. RESULTS: The models trained with feature sets including leaf speed and leaf gap features predicted GPR for failed fields more accurately than the other models (F(7, 147) = 5.378, p < 0.001). The WMSE loss had the highest accuracy in predicting GPR for failed fields among the three fine-tuning methods (F(2, 42) = 14.149, p < 0.001), while an opposite trend was observed in predicting GPR for passed fields (F(2, 730) = 9.907, p < 0.001). The WMSE_FS5 model achieved a superior AUC (0.92) and more balanced sensitivity (0.77) and specificity (0.89) compared to the other models. CONCLUSIONS: Machine parameters can provide discriminative input features for GPR prediction in DL. The novel weighted loss function demonstrates the ability to balance the prediction and classification accuracy between the passed and failed fields. The proposed approach is able to improve the DL model performance in predicting and classifying GPR, and can potentially be integrated into the plan optimization process to generate higher deliverability plans. TRIAL REGISTRATION: This clinical trial was registered in the Chinese Clinical Trial Registry on March 26th, 2020 (registration number: ChiCTR2000031276). https://clinicaltrials.gov/ct2/show/ChiCTR2000031276.

Could primary care records be used to identify women at risk of perinatal anxiety? A mixed-methods study.

BACKGROUND: Perinatal anxiety (PNA) occurs throughout the antenatal period or up to 1 year after childbirth, with a prevalence of 21%. AIM: To investigate if primary care records could be used to identify women at 'higher risk' of PNA. METHOD: Mixed-methods approach using quantitative and qualitative methods. Quantitative data analysis used Clinical Practice Research Datalink and IQVIA Medical Research Data to identify risk factors for PNA. Interviews explored the lived experiences of women with PNA about predisposing factors for PNA and acceptability of being informed of risk; and perspectives of primary healthcare professionals and Voluntary, Community, and Social Enterprise practitioners about risk communication. Interviews were conducted online, digitally recorded with consent, transcribed, and anonymised prior to analysis. Data were thematically analysed. Patient and clinical advisory groups informed each stage of the research. RESULTS: Women reflected on both positive and negative impacts of being identified at higher risk of PNA, a lack of understanding of how primary care records are used, and who has access to them. All interview participants suggested predisposing factors that would not be coded in primary care records. Quantitative analysis demonstrated that some predisposing factors for PNA can be identified in a woman's primary care records. Initial analysis suggests associations between PNA and infant health and healthcare use. CONCLUSION: While identification of higher risk of PNA may be acceptable, some factors that may contribute to PNA are not coded in primary care records. Identifying and managing PNA is needed to improve infant health.

Research progress on the chemical components and pharmacological effects of Physalis alkekengi L. var. franchetii (Mast.) Makino.

Physalis Calyx seu Fructus is the dry calyx or the calyx with fruit of the Solanaceae plant Physalis alkekengi L. var. franchetii (Mast.) Makino, with a long history of use in medicine and food. However, despite its many potential therapeutic and culinary applications, P. alkekengi is not being exploited for these applications on a large scale. This study analysed various research related to the different chemical components of P. alkekengi, including steroids, flavonoids, alkaloids, phenylpropanoids, sucrose esters, piperazines, volatile oils, polysaccharides, amino acids, and trace elements. In addition, research related to the pharmacological activities of P. alkekengi, including its anti-inflammatory, anti microbial, antioxidative, hypoglycaemic, analgesic, anti-tumour, and immunomodulatory effects were investigated. Research articles from 1974 to 2023 were obtained from websites such as Google Scholar, Baidu Scholar, and China National Knowledge Infrastructure, and journal databases such as Scopus and PubMed, with the keywords such as Physalis alkekengi, components, effects, and activities. This study aims to provide a comprehensive understanding of the progress of phytochemical and pharmacological research on the phytochemical and pharmacological aspects of P. alkekengi and a reference for the better exploitation of P. alkekengi in the food and pharmaceutical industries.

Opioid use, postoperative complications, and implant survival after unicompartmental versus total knee replacement: a population-based network study.

BACKGROUND: There is uncertainty around whether to use unicompartmental knee replacement (UKR) or total knee replacement (TKR) for individuals with osteoarthritis confined to a single compartment of the knee. We aimed to emulate the design of the Total or Partial Knee Arthroplasty Trial (TOPKAT) using routinely collected data to assess whether the efficacy results reported in the trial translate into effectiveness in routine practice, and to assess comparative safety. METHODS: We did a population-based network study using data from four US and one UK health-care database, part of the Observational Health Data Sciences and Informatics network. The inclusion criteria were the same as those for TOPKAT; briefly, we identified patients aged at least 40 years with osteoarthritis who had undergone UKR or TKR and who had available data for at least one year prior to surgery. Patients were excluded if they had evidence of previous knee arthroplasty, knee fracture, knee surgery (except diagnostic), rheumatoid arthritis, infammatory arthropathies, or septic arthritis. Opioid use from 91-365 days after surgery, as a proxy for persistent pain, was assessed for all participants in all databases. Postoperative complications (ie, venous thromboembolism, infection, readmission, and mortality) were assessed over the 60 days after surgery and implant survival (as measured by revision procedures) was assessed over the 5 years after surgery. Outcomes were assessed in all databases, except for readmission, which was assessed in three of the databases, and mortality, which was assessed in two of the databases. Propensity score matched Cox proportional hazards models were fitted for each outcome. Calibrated hazard ratios (cHRs) were generated for each database to account for observed differences in control outcomes, and cHRs were then combined using meta-analysis. FINDINGS: 33 867 individuals who received UKR and 557 831 individuals who received TKR between Jan 1, 2005, and April 30, 2018, were eligible for matching. 32 379 with UKR and 250 377 with TKR were propensity score matched and informed the analyses. UKR was associated with a reduced risk of postoperative opioid use (cHR from meta-analysis 0·81, 95% CI 0·73-0·90) and a reduced risk of venous thromboembolism (0·62, 0·36-0·95), whereas no difference was seen for infection (0·85, 0·51-1·37) and readmission (0·79, 0·47-1·25). Evidence was insufficient to conclude whether there was a reduction in risk of mortality. UKR was also associated with an increased risk of revision (1·64, 1·40-1·94). INTERPRETATION: UKR was associated with a reduced risk of postoperative opioid use compared with TKR, which might indicate a reduced risk of persistent pain after surgery. UKR was associated with a lower risk of venous thromboembolism but an increased risk of revision compared with TKR. These findings can help to inform shared decision making for individuals eligible for knee replacement surgery. FUNDING: EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative (2) Joint Undertaking (EHDEN).