ObjectiveSingapore is a microcosm of Asia as a whole, and its rapidly ageing, increasingly sedentary population heralds the chronic health problems other Asian countries are starting to face and will likely face in the decades ahead. Forecasting the changing burden of chronic diseases such as type 2 diabetes in Singapore is vital to plan the resources needed and motivate preventive efforts.MethodsThis paper describes an individual-level simulation model that uses evidence synthesis from multiple data streams—national statistics, national health surveys, and four cohort studies, and known risk factors—aging, obesity, ethnicity, and genetics—to forecast the prevalence of type 2 diabetes in Singapore. This comprises submodels for mortality, fertility, migration, body mass index trajectories, genetics, and workforce participation, parameterized using Markov chain Monte Carlo methods, and permits forecasts by ethnicity and employment status.ResultsWe forecast that the obesity prevalence will quadruple from 4.3% in 1990 to 15.9% in 2050, while the prevalence of type 2 diabetes (diagnosed and undiagnosed) among Singapore adults aged 18–69 will double from 7.3% in 1990 to 15% in 2050, that ethnic Indians and Malays will bear a disproportionate burden compared with the Chinese majority, and that the number of patients with diabetes in the workforce will grow markedly.ConclusionsIf the recent rise in obesity prevalence continues, the lifetime risk of type 2 diabetes in Singapore will be one in two by 2050 with concomitant implications for greater healthcare expenditure, productivity losses, and the targeting of health promotion programmes.

Nanomedicine constructed by therapeutics has unique and irreplaceable advantages in biomedical applications, especially in drug delivery for cancer therapy. The strategy, however, used to construct the therapeutics-based nanomedicines with tumor microenvironmental factor responsiveness is still sophisticated. In this study, an easy-operating procedure is used to construct a therapeutics-based nanosystem with active tumor-targeting, enhanced penetration, and stimuli-responsive drug release behavior as well as programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) blockading mediated immunomodulation to enhance tumor immunotherapy. The matrix metalloproteinase-2 responsive peptide with the existence of Lyp-1 sequence contributes to the success of active tumor-targeting and the enhancement of the penetration of the nanoparticles in tumor tissue. The obtained nanosystem strikingly inhibits the primary tumor growth in the first 24 h (more than 97.5% of tumor cells are inhibited), and total inhibition can be achieved with the combination of photothermal therapy. IR820, which is served as the carrier for the therapeutics, is used as a photosensitizer for photothermal therapy. The progress and aggression of distal tumor has further been alleviated by a d-peptide which is an antagonist for PD-1/PD-L1 blockage. Therefore, a therapeutics-constructed multifunctional nanosystem is provided to realize a combinational therapeutic strategy to enhance the therapeutic outcome.

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Photothermal therapy (PTT) is proved to be an efficient manner for superficial tumor therapy in preclinical studying. The tumor suppression of chemotherapy can be enhanced by combining with PTT. In this study, we reported a mesoporous magnetic gold “nanoclusters” (MMGNCs) structure as theranostic carrier for chemo-photothermal co-therapy. MMGNCs were successfully prepared and they exhibited efficient photo-thermal effect for PTT. The mesoporous structure provided MMGNCs with high drug loading capacity. By in vitro cytotoxicity testing, we revealed that the combination of PTT and chemotherapy could cause more damage than chemotherapy or PTT did alone. By topically targeting mediated by the extra-magnetic field (MF), MMGNCs can be targeted to the tumor site efficiently. In vivo chemo-photothermal co-therapy of 4T1 breast cancer, under the combinational treatments of chemo-photothermal co-therapy and extra-MF targeting, the tumor growth has been efficiently inhibited, and the pulmonary and mediastinal metastasis have also been prevented. The survival of the cancer bearing mice was prolonged. The bio-imaging applications of this system and the mechanism of the metastasis prevention are ongoing.

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Aim To compare the efficacy of ultrasonically activated irrigation (UAI), photon‐induced photoacoustic streaming (PIPS) and shock wave enhanced emission photoacoustic streaming (SWEEPS) activation for the removal of accumulated hard‐tissue debris (AHTD) from the root canal system of mandibular molars when assessed using microcomputed tomography (micro‐CT). Methodology A total of 30 mandibular first and second molars with joining mesial root canals containing an isthmus and a single distal canal were subjected to three micro‐CT scans (before and after canal instrumentation and after final irrigation) at a resolution of 15 μm. Mesial canals were prepared up to a ProTaper F3 rotary file, and distal canals were prepared up to a ProTaper F4 rotary file. Teeth were randomly assigned to three groups according to the irrigant activation method (n = 10): the UAI group, the PIPS group and the SWEEPS group. The final irrigation procedures were performed using a total of 15.5 mL of 1% NaOCl for each tooth with an activation time of 3 × 30 s. After three‐dimensional model reconstruction and volumetric measurement of root canals, the percentage reduction (%Rd) of AHTD was calculated. The %Rd of AHTD was analysed statistically using one‐way analysis of variance and nonparametric tests at a significance level of 5%. Results There were no significant differences between the three groups in terms of canal volume before or after instrumentation, or the volume of debris after canal preparation (P > 0.05). In the mesial canals, irrigation with SWEEPS reduced the overall debris by 84.31%, which was significantly more than the reduction associated with PIPS and UAI (58.79% and 50.27%, respectively). In the distal canals, the %Rd of AHTD was significantly different between PIPS and SWEEPS and between UAI and SWEEPS (P < 0.05), but was not significantly different between PIPS and UAI groups (P > 0.05). The SWEEPS was associated with a greater %Rd of AHTD than the PIPS and UAI groups. Conclusions SWEEPS was associated with significantly less debris compared than PIPS and UAI, especially in isthmus‐containing mesial roots. None of the activation techniques completely removed debris from root canal systems.

Discovered in the brains of multiple animal species, piRNAs may contribute to the pathogenesis of neuropsychiatric illnesses. The present study aimed to identify brain piRNAs across transcriptome that are associated with Alzheimer’s disease (AD). Prefrontal cortical tissues of six AD cases and six controls were examined for piRNA expression levels using an Arraystar HG19 piRNA array (containing 23,677 piRNAs) and genotyped for 17 genome-wide significant and replicated risk SNPs. We examined whether piRNAs are expressed differently between AD cases and controls and explored the potential regulatory effects of risk SNPs on piRNA expression levels. We identified a total of 9453 piRNAs in human brains, with 103 nominally (p<0.05) differentially (> 1.5 fold) expressed in AD cases vs. controls and most of the 103 piRNAs nominally correlated with genome-wide significant risk SNPs. We conclude that piRNAs are abundant in human brains and may represent risk biomarkers of AD.

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