General practitioner perspectives on a shared-care model for paediatric patients post-intensive care: A cross-sectional survey.

INTRODUCTION: While paediatric critical illness mortality rates in Australia are declining, the growing cohort of paediatric intensive care unit (PICU) survivors means an increasing number of children facing substantial health challenges after their discharge from intensive care. General practitioners (GPs) play a key role in provision of comprehensive health care to children and families and are ideally positioned to provide developmental surveillance and support the care of both the child and family following critical illness. METHODS: An anonymous, cross-sectional survey of 60 GPs, reached via private invitation (19% response) or via social media weblink, was conducted where the GPs were asked about their current confidence and knowledge in managing children post PICU. This included awareness of short- and long-term problems, of paediatric intensive care syndrome in paediatrics (PICS-p), and of educational materials. Lastly, a parent-completed screening questionnaire and shared-care pathway were proposed to GPs for their feedback on perceived benefit and willingness to participate. Data were analysed using frequency distributions and chi-square statistics. RESULTS: Ninety-three percent of GPs had some level of confidence in caring for a child post PICU admission and low confidence in their knowledge of potential short- and long-term complications. Eighty percent of GPs had not heard of PICS-p, and 93% were unaware of educational materials available on this topic. Ninety-five percent of GPs perceived that the proposed patient-screening tool and shared-care pathways would be beneficial, and 70% predicted that they would definitely use educational materials if accessible through GP central repositories. CONCLUSION: To reduce ongoing health problems for children recovering from critical illness, the family GP plays a pivotal role in providing community-level developmental care, particularly in Australia. Increasing GP confidence and knowledge through education is essential, and using a parent-completed screening questionnaire and shared-care pathway to improve care may be beneficial. GPs must also be involved in the implementation stages of future shared-care models.

Clinical care of children and adolescents with COVID-19: recommendations from the National COVID-19 Clinical Evidence Taskforce.

INTRODUCTION: The epidemiology and clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are different in children and adolescents compared with adults. Although coronavirus disease 2019 (COVID-19) appears to be less common in children, with milder disease overall, severe complications may occur, including paediatric inflammatory multisystem syndrome (PIMS-TS). Recognising the distinct needs of this population, the National COVID-19 Clinical Evidence Taskforce formed a Paediatric and Adolescent Care Panel to provide living guidelines for Australian clinicians to manage children and adolescents with COVID-19 and COVID-19 complications. Living guidelines mean that these evidence-based recommendations are updated in near real time to give reliable, contemporaneous advice to Australian clinicians providing paediatric care. MAIN RECOMMENDATIONS: To date, the Taskforce has made 20 specific recommendations for children and adolescents, including definitions of disease severity, recommendations for therapy, respiratory support, and venous thromboembolism prophylaxis for COVID-19 and for the management of PIMS-TS. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINES: The Taskforce currently recommends corticosteroids as first line treatment for acute COVID-19 in children and adolescents who require oxygen. Tocilizumab could be considered, and remdesivir should not be administered routinely in this population. Non-invasive ventilation or high flow nasal cannulae should be considered in children and adolescents with hypoxaemia or respiratory distress unresponsive to low flow oxygen if appropriate infection control measures can be used. Children and adolescents with PIMS-TS should be managed by a multidisciplinary team. Intravenous immunoglobulin and corticosteroids, with concomitant aspirin and thromboprophylaxis, should be considered for the treatment of PIMS-TS. The latest updates and full recommendations are available at www.covid19evidence.net.au.

Fluvial sediment supply to a mega-delta reduced by shifting tropical-cyclone activity.

The world's rivers deliver 19 billion tonnes of sediment to the coastal zone annually, with a considerable fraction being sequestered in large deltas, home to over 500 million people. Most (more than 70 per cent) large deltas are under threat from a combination of rising sea levels, ground surface subsidence and anthropogenic sediment trapping, and a sustainable supply of fluvial sediment is therefore critical to prevent deltas being 'drowned' by rising relative sea levels. Here we combine suspended sediment load data from the Mekong River with hydrological model simulations to isolate the role of tropical cyclones in transmitting suspended sediment to one of the world's great deltas. We demonstrate that spatial variations in the Mekong's suspended sediment load are correlated (r = 0.765, P < 0.1) with observed variations in tropical-cyclone climatology, and that a substantial portion (32 per cent) of the suspended sediment load reaching the delta is delivered by runoff generated by rainfall associated with tropical cyclones. Furthermore, we estimate that the suspended load to the delta has declined by 52.6 ± 10.2 megatonnes over recent years (1981-2005), of which 33.0 ± 7.1 megatonnes is due to a shift in tropical-cyclone climatology. Consequently, tropical cyclones have a key role in controlling the magnitude of, and variability in, transmission of suspended sediment to the coast. It is likely that anthropogenic sediment trapping in upstream reservoirs is a dominant factor in explaining past, and anticipating future, declines in suspended sediment loads reaching the world's major deltas. However, our study shows that changes in tropical-cyclone climatology affect trends in fluvial suspended sediment loads and thus are also key to fully assessing the risk posed to vulnerable coastal systems.

Baseline Circulating FGF21 Concentrations and Increase after Fenofibrate Treatment Predict More Rapid Glycemic Progression in Type 2 Diabetes: Results from the FIELD Study.

BACKGROUND: It is not known whether circulating fibroblast growth factor 21 (FGF21) concentrations are associated with glycemic progression in patients with established type 2 diabetes. This study reports this relationship in type 2 diabetes patients participating in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. METHODS: Plasma FGF21 was quantified in 9697 study participants. Among patients with lifestyle-only glucose control measures at baseline, glycemic progression was defined as the initiation of oral hypoglycemic agents or insulin therapy. We assessed the relationship of FGF21 concentrations with glycohemoglobin (Hb A1c), the homeostasis model assessment of ß-cell function (HOMA-B) and insulin resistance (HOMA-IR), and glycemic progression. RESULTS: Among 2584 patients with lifestyle-only glycemic therapy at baseline, plasma FGF21 concentrations were positively associated with HOMA-IR (5.1% increase per 100% increase in FGF21 concentrations). Patients with higher baseline plasma FGF21 concentrations had higher risk of glycemic progression over a 5-year period (P = 0.02), but the association was not significant after further adjusting for alanine aminotransferase (ALT) enzyme activity. During the fenofibrate active run-in phase, higher tertiles of fenofibrate-induced increase in FGF21 concentrations were associated with higher risk of glycemic progression (adjusted hazards ratio = 1.09 and 1.18 for tertiles 2 and 3, respectively, P for trend = 0.01), even after adjusting for ALT enzyme activity. This association was statistically significant in the fenofibrate group only (P = 0.01). CONCLUSIONS: Higher baseline and fenofibrate-induced increase in FGF21 concentrations predict more rapid glycemic progression in type 2 diabetes patients. This association may be partly explained by hepatic function.

Microscale Fracture Behavior of Single Crystal Silicon Beams at Elevated Temperatures.

The micromechanical fracture behavior of Si [100] was investigated as a function of temperature in the scanning electron microscope with a nanoindenter. A gradual increase in KC was observed with temperature, in contrast to sharp transitions reported earlier for macro-Si. A transition in cracking mechanism via crack branching occurs at ∼300 °C accompanied by multiple load drops. This reveals that onset of small-scale plasticity plays an important role in the brittle-to-ductile transition of miniaturized Si.

Mothers after Gestational Diabetes in Australia (MAGDA): A Randomised Controlled Trial of a Postnatal Diabetes Prevention Program.

BACKGROUND: Gestational diabetes mellitus (GDM) is an increasingly prevalent risk factor for type 2 diabetes. We evaluated the effectiveness of a group-based lifestyle modification program in mothers with prior GDM within their first postnatal year. METHODS AND FINDINGS: In this study, 573 women were randomised to either the intervention (n = 284) or usual care (n = 289). At baseline, 10% had impaired glucose tolerance and 2% impaired fasting glucose. The diabetes prevention intervention comprised one individual session, five group sessions, and two telephone sessions. Primary outcomes were changes in diabetes risk factors (weight, waist circumference, and fasting blood glucose), and secondary outcomes included achievement of lifestyle modification goals and changes in depression score and cardiovascular disease risk factors. The mean changes (intention-to-treat [ITT] analysis) over 12 mo were as follows: -0.23 kg body weight in intervention group (95% CI -0.89, 0.43) compared with +0.72 kg in usual care group (95% CI 0.09, 1.35) (change difference -0.95 kg, 95% CI -1.87, -0.04; group by treatment interaction p = 0.04); -2.24 cm waist measurement in intervention group (95% CI -3.01, -1.42) compared with -1.74 cm in usual care group (95% CI -2.52, -0.96) (change difference -0.50 cm, 95% CI -1.63, 0.63; group by treatment interaction p = 0.389); and +0.18 mmol/l fasting blood glucose in intervention group (95% CI 0.11, 0.24) compared with +0.22 mmol/l in usual care group (95% CI 0.16, 0.29) (change difference -0.05 mmol/l, 95% CI -0.14, 0.05; group by treatment interaction p = 0.331). Only 10% of women attended all sessions, 53% attended one individual and at least one group session, and 34% attended no sessions. Loss to follow-up was 27% and 21% for the intervention and control groups, respectively, primarily due to subsequent pregnancies. Study limitations include low exposure to the full intervention and glucose metabolism profiles being near normal at baseline. CONCLUSIONS: Although a 1-kg weight difference has the potential to be significant for reducing diabetes risk, the level of engagement during the first postnatal year was low. Further research is needed to improve engagement, including participant involvement in study design; it is potentially more effective to implement annual diabetes screening until women develop prediabetes before offering an intervention. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12610000338066.

Clinical outcomes associated with albuminuria in central Australia: a cohort study.

BACKGROUND: Chronic kidney disease (CKD) and end-stage-kidney disease (ESKD) continue to be under-diagnosed and a major burden for Aboriginal communities in central Australia. The aim of this study was to examine the risk of poor clinical outcomes associated with elevated albumin-to-creatinine ratio (ACR) among Aboriginal people in central Australia. METHODS: Cox proportional hazards models were used to estimate the risk of end stage kidney disease (ESKD), dialysis, CVD (cardiovascular disease) and mortality associated with participants' baseline albuminuria reading from a 10-year cohort study of Aboriginal people (n = 623) from three communities in central Australia. Predictors of progression of albuminuria were also examined in the context of the Kidney Health Australia (KHA) Risk Matrix. RESULTS: A baseline ACR level of ≥3.5 mg/mmol was associated with an almost 10-fold increased risk of ESKD (95%CI 2.07-43.8) and a 15-fold risk of dialysis (95%CI 1.89-121). Albuminuria ≥3.5 mg/mmol was also associated with a borderline 63 % increased risk of CVD (95%CI 0.98-2.71). No significant association was observed with mortality from all-causes or chronic disease. Diabetes and a waist-to-hip ratio ≥0.90 independently predicted a two-fold increased risk of a progression to higher ACR levels. CONCLUSIONS: A single measure of moderately increased albuminuria was a strong predictor of renal failure in this population. A single spot urine ACR analysis in conjunction with the KHA Risk Matrix may be a useful and efficient strategy to screen for risk of CKD and progression to dialysis in remote communities. A focus on individuals with diabetes and/or central obesity for strategies to avoid increases in albuminuria may also prevent future CKD and CVD complications.

Quality of information available via the internet for patients with head and neck cancer: are we improving?

This study aimed to evaluate the type, content, accessibility and quality of information available via the internet for patients with head and neck cancer. The Google search engine was used to generate lists of the first 100 websites for general head and neck cancer and the first ten for head and neck cancers by anatomical location (160 total). Websites were evaluated with the validated DISCERN and LIDA instruments, the SMOG (Simple measure of gobbledygook) readability score and against the JAMA (Journal of the American Medical Association) criteria. 40 of the 160 websites ranked by Google were suitable for analysis. Seven websites (17.5%) partially or fully achieved all four JAMA benchmarks and only one (2.5%) site achieved none. 28 (70%) included reference to quality of life factors. Correlations were identified between Google site rank and all four of our appraisal tools; LIDA (-0.966, p = 0.006), JAMA (-5.93, p = 0.028), DISCERN (-0.568, p = 0.037) and SMOG (4.678, p = 0.04). Google site rank and both government run sites (-35.38, p = 0.034) and sites run by universities or hospitals (-27.32, p = 0.016) also showed an association. Comparing our observations with those of Riordain in 2008, there has been little improvement in the quality of head and neck cancer information available online over this time. Given the variability in quality of information online, patients would benefit from being directed to reliable websites by clinicians.

Favourable effects of fenofibrate on lipids and cardiovascular disease in women with type 2 diabetes: results from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

AIMS/HYPOTHESIS: In the double-blind placebo-controlled Fenofibrate Intervention and Event Lowering in Diabetes trial (n = 9,795), fenofibrate reduced major cardiovascular events in type 2 diabetes. Sex-related differences in fenofibrate response could be clinically relevant and were pre-specified analyses. METHODS: Women (n = 3,657) and men (n = 6,138) with type 2 diabetes not using statins were assigned fenofibrate (200 mg/day) or placebo for 5 years. Effects on lipoproteins and total cardiovascular events were evaluated by sex. RESULTS: Baseline total, LDL-, HDL- and non-HDL cholesterol and apolipoproteins A-I and B differed between sexes, and these and triacylglycerol levels improved with fenofibrate in both sexes (all p < 0.001). Fenofibrate reduced total, LDL- and non-HDL cholesterol and apolipoprotein B more in women (all p < 0.001), independent of menopausal status and statin uptake. Adjusted for covariates, fenofibrate reduced total cardiovascular outcomes (cardiovascular death, fatal and non-fatal stroke and carotid and coronary revascularisation) by 30% in women (95% CI 8%, 46%; p = 0.008) and 13% in men (95% CI -1%, 24%; p = 0.07) with no treatment-by-sex interaction (p > 0.1). In patients with high triacylglycerol levels and low HDL-cholesterol, fenofibrate reduced total cardiovascular outcomes by 30% (95% CI -7%, 54%) in women and 24% (95% CI 2%, 42%) in men, with no treatment-by-sex interaction (p > 0.1). CONCLUSIONS/INTERPRETATION: Fenofibrate improved the lipoprotein profile more in women than men. Cardiovascular event reductions with fenofibrate were consistently similar in women and men, both overall and among those with low HDL-cholesterol and high triacylglycerol levels. These data provide reassurance about fenofibrate efficacy in women and men. Both sexes with type 2 diabetes should be considered for fenofibrate therapy for cardioprotection.

Fundamental studies of hybrid poly(2-(diisopropylamino)ethyl methacrylate)/poly(N-vinylpyrrolidone) films and capsules.

Hybrid and multicompartment carriers are of significant interest for the development of next-generation therapeutic drug carriers. Herein, fundamental investigations on layer-by-layer (LbL) capsules consisting of two different polymers are presented. The hybrid systems were designed to have pH-responsive, charge-shifting poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) inner layers and low-fouling poly(N-vinylpyrrolidone) (PVPON) outer layers. Planar hybrid films with different layer ratios were studied by quartz crystal microgravimetry (QCM) and atomic force microscopy (AFM). The information obtained was translated to particulate templates to prepare hybrid capsules, which were stabilized by click chemistry. The charge-shifting behavior of PDPA improved the cargo encapsulation and initial retention of a model CpG cargo, while outer layers of PVPON improved biofouling properties compared to single-component PDPA capsules. The results demonstrate the need to understand and design multifunctional systems that can successfully embody different functionalities in a single, stable construct for the fabrication of next-generation drug and gene delivery carriers aimed at overcoming the challenges encountered in biological systems.

Stepping up: a nurse-led model of care for insulin initiation for people with type 2 diabetes.

BACKGROUND: Most people with type 2 diabetes (T2D) have glycaemic levels outside of target. Insulin is effective in improving glycaemia and most people with T2D eventually need this. Despite this, transition to insulin therapy is often delayed in primary care. OBJECTIVE: To develop a model of care (Stepping Up) for insulin initiation in routine diabetes care in Australian general practice. To evaluate the model for feasibility of integration within routine general practice care. METHODS: Drawing on qualitative work and normalisation process theory, we developed a model of care that included clarification of roles, in-practice systems and simple clinical tools. The model was introduced in an educational and practice system change intervention for general practitioners (GPs) and practice nurses (PNs). Five practices (seven GPs and five PNs) and 18 patients formed the feasibility study. Evaluation at 3 and 12 months explored experiences of GPs, PNs and patients. RESULTS: Fourteen patients commenced insulin, with average HbA1c falling from 8.4% (68.3 mmol/mol) to 7.5% (58.5 mmol/mol) at 3 months. Qualitative evaluation highlighted how the model of care supported integration of the technical work of insulin initiation within ongoing generalist GP care. Ensuring peer support for patients and issues of clinical accountability and flexibility, managing time and resources were highlighted as important. CONCLUSIONS: The Stepping Up model allowed technical care to be embedded within generalist whole-person care, supported clinicians and practice system to overcome clinical inertia and supported patients to make the timely transition to insulin. Testing of the model's effectiveness is now underway.

An exploratory trial of insulin initiation and titration among patients with type 2 diabetes in the primary care setting with retrospective continuous glucose monitoring as an adjunct: INITIATION study protocol.

BACKGROUND: Insulin initiation and titration in primary care is necessary to respond to the growing epidemic of type 2 diabetes (T2D). The INITIATION study aims to evaluate the impact of implementing a new model of care with Primary Care Physician and Practice Nurse (PN) teams supported by a Credentialed Diabetes Educator-Registered Nurse (CDE-RN) and endocrinologist in initiating and titrating basal and prandial insulin for T2D patients in the Australian healthcare system over 24 weeks. This study also explores the feasibility and efficacy of retrospective continuous glucose monitoring (r-CGM) in comparison with self-monitoring of blood glucose (SMBG) among people with T2D in primary care. METHODS/DESIGN: The study employs a before and after design with a nested exploratory trial of SMBG and r-CGM. A total of 102 insulin naïve T2D patients with a glycated haemoglobin (HbA1c) level of >7.5% in the previous 6 months while treated with maximal oral therapy will be recruited and screened from 22 primary care practices in Melbourne, Australia. All patients will be commenced on a basal insulin regimen following randomization into one of the two blood glucose monitoring arms, with intensification to a "basal plus" regimen if required. The outcomes of the new model of care will be benchmarked with data collected over the same period from a specialist setting in Melbourne, Australia. DISCUSSION: This article describes the study protocol and insulin treatment algorithm employed in the first study to explore r-CGM use among T2D in primary care. Findings from the INITIATION study will inform development of a larger randomized controlled trial. TRIAL REGISTRATION: ACTRN12610000797077.

Correction: Electron microscope loading and in situ nanoindentation of water ice at cryogenic temperatures.

[This corrects the article DOI: 10.1371/journal.pone.0281703.].

An approach to common sleep presentations in infants and toddlers.

BACKGROUND: Healthy sleep is vital for optimal child development, yet over 30% of Australian parents report having children with disrupted sleep affecting all family members. These sleep difficulties might co-exist with sleep breathing disorders, contributing to morbidity and reduced quality of life. OBJECTIVE: This article aims to provide general practitioners (GPs) with an evidence-based, biopsychosocial approach to managing common sleep problems in infants and preschool-aged children. DISCUSSION: Strategies and techniques are outlined to aid GPs in promoting healthy sleep during infancy, educating parents on typical sleep patterns and supporting families in managing problematic sleep patterns in toddlers. Emphasis is placed on a tailored approach to developing a healthy sleep environment to meet the child's needs and parental values. Valuable resources and indications for specialist consultation are included.

Optimising sleep in adolescents: The challenges.

BACKGROUND: Adolescence is a stage of significant transition as children develop into young adults. Optimal sleep is crucial during this period to ensure physical, emotional and mental wellbeing. However, it is well recognised that insufficient quality and quantity of sleep is common among adolescents worldwide. OBJECTIVE: This article aims to provide general practitioners with an overview of the key issues encountered in adolescent patients relating to sleep and summarises approaches to assessment and evidence-based management of sleep problems in this population. DISCUSSION: This review highlights the physiological changes that affect sleep during adolescence and how other factors, including unhealthy sleep behaviours, influence these. It discusses the importance of healthy sleep and the consequences of sleep disturbance in adolescents. Management strategies are outlined, focusing on the key common issues that affect sleep in the teenage years, and guidance on when to consider co-management with specialist care is provided.

Foot care behaviours and associated factors among patients with type 2 diabetes: A cross-sectional study.

Background: As numerous studies highlighted the importance of maintaining proper foot care (FC) behaviours among individuals with diabetes to prevent complications, we sought to assess FC behaviours among patients with diabetes and to identify the factors associated with the practice of diabetic FC. Methods: We used a cross-sectional design and collected data through self-reported questionnaires administered to a sample of 586 patients from five medical centres. We conducted descriptive and inferential analyses to explore the relationships between potential risk and protective factors and FC behaviours. Results: Overall, 429 individuals (73.2%) had good FC behaviours, while 157 (26.8%) displayed poor FC behaviours. Furthermore, we identified eight influencing factors on FC behaviours, including smoking status, the availability of a caregiver, the presence of diabetic foot ulcers, amputation history, FC knowledge, subjective norms in diabetes self-care behaviour, diabetes-related stress, and quality of life index values. The logistic regression analysis showed that current smokers were 60% less likely to practice good FC compared to non-smokers (odds ratio (OR) = 0.40; 95%; confidence interval (CI) = 0.22-0.73). Having a caregiver decreased the likelihood of practicing good FC by 50% (OR = 0.52; 95% CI = 0.33-0.84), while having diabetic foot ulcers doubled it (OR = 2.65; 95% CI = 1.26-5.54). Additionally, more FC knowledge increased the likelihood by 20% (OR = 1.21; 95% CI = 1.10-1.33), and higher diabetes-related stress increased it by 1.03 times (OR = 1.03; 95% CI = 1.02-1.05). Conclusions: Our findings underscore the interplay of various factors influencing FC behaviours among individuals with diabetes and call for targeted interventions and tailored strategies to improve FC practices in this vulnerable population.

Adiposity and metabolic health in Asian populations: an epidemiological study using dual-energy x-ray absorptiometry in Singapore.

BACKGROUND: Type 2 diabetes, cardiovascular disease, and related cardiometabolic disturbances are increasing rapidly in the Asia-Pacific region. We investigated the contribution of excess adiposity, a key determinant of type 2 diabetes and cardiovascular risk, to unfavourable cardiometabolic profiles among Asian ethnic subgroups. METHODS: The Health for Life in Singapore (HELIOS) Study is a population-based cohort comprising multiethnic Asian men and women living in Singapore, aged 30-84 years. We performed a cross-sectional analysis of data from individuals who had assessment of body composition by dual-energy x-ray absorptiometry and metabolic characterisation. In a subset of participants on no medication for type 2 diabetes, hypertension, and hypercholesterolaemia, we tested the relationship of BMI and visceral fat mass index (vFMI) with cardiometabolic phenotypes (glycaemic indices, lipid levels, and blood pressure), disease outcomes (type 2 diabetes, hypercholesterolaemia, and hypertension), and metabolic syndrome score with multivariable regression analyses. FINDINGS: Between April 2, 2018, and Jan 28, 2022, 10 004 individuals consented to be part of the HELIOS cohort, of whom 9067 were included in the study (5404 [59·6%] female, 3663 [40·4%] male; 6224 [68·6%] Chinese, 1169 [12·9%] Malay, 1674 [18·5%] Indian; mean age 52·8 years [SD 11·8]). The prevalence of type 2 diabetes, hypercholesterolaemia, and hypertension was 8·2% (n=744), 27·2% (n=2469), and 18·0% (n=1630), respectively. Malay and Indian participants had 3-4-times higher odds of obesity and type 2 diabetes, and showed adverse metabolic and adiposity profiles, compared with Chinese participants. Excess adiposity was associated with adverse cardiometabolic health indices including type 2 diabetes (p<0·0001). However, while vFMI explained the differences in triglycerides and blood pressure between the Asian ethnic groups, increased vFMI did not explain higher glucose levels, reduced insulin sensitivity, and increased risk of type 2 diabetes among Indian participants. INTERPRETATION: Visceral adiposity is an independent risk factor for metabolic disease in Asian populations, and accounts for a large fraction of type 2 diabetes cases in each of the ethnic groups studied. However, the variation in insulin resistance and type 2 diabetes risk between Asian subgroups is not consistently explained by adiposity, indicating an important role for additional mechanisms underlying the susceptibility to cardiometabolic disease in Asian populations. FUNDING: Nanyang Technological University-the Lee Kong Chian School of Medicine, National Healthcare Group, and National Medical Research Council, Singapore.

Tuning the mechanical properties of nanoporous hydrogel particles via polymer cross-linking.

Soft hydrogel particles with tunable mechanical properties are promising for next-generation therapeutic applications. This is due to the increasingly proven role that physicochemical properties play in particulate-based delivery vectors, both in vitro and in vivo. The ability to understand and quantify the mechanical properties of such systems is therefore essential to optimize function and performance. We report control over the mechanical properties of poly(methacrylic acid) (PMA) hydrogel particles based on a mesoporous silica templating method. The mechanical properties of the obtained particles can be finely tuned through variation of the cross-linker concentration, which is hereby quantified using a cross-linking polymer with a fluorescent tag. We demonstrate that the mechanical properties of the particles can be elucidated using an atomic force microscopy (AFM) force spectroscopy method, which additionally allows for the study of hydrogel material properties at the nanoscale through high-resolution force mapping. Young's modulus and stiffness of the particles were tuned between 0.04 and 2.53 MPa and between 1.6 and 28.4 mN m(-1), respectively, through control over the cross-linker concentration. The relationship between the concentration of the cross-linker added and the amount of adsorbed polymer was observed to follow a Langmuir isotherm, and this relationship was found to correlate linearly with the particle mechanical properties.

Mechanics of pH-responsive hydrogel capsules.

While soft hydrogel nano- and microstructures hold great potential for therapeutic treatments and in vivo applications, their nanomechanical characterization remains a challenge. In this paper, soft, single-component, supported hydrogel films were fabricated using pendant-thiol-modified poly(methacrylic acid) (PMASH). The influence of hydrogel architecture on deformation properties was studied by fabricating films on particle supports and producing free-standing capsules. The influence of the degree of thiol-based cross-linking on the mechanical properties of the soft hydrogel systems (core-shell and capsules) was studied using a colloidal-probe (CP) AFM technique. It was found that film mechanical properties, stability, and capsule swelling could be finely tuned by controlling the extent of poly(methacrylic acid) thiol modification. Furthermore, switching the pH from 7.4 to 4.0 led to film densification due to increased hydrogen bonding. Hydrogel capsule systems were found to have stiffness values ranging from 0.9 to 16.9 mN m(-1) over a thiol modification range of 5 to 20 mol %. These values are significantly greater than those for previously reported PMASH planar films of 0.7-5.7 mN m(-1) over the same thiol modification range (Best et al., Soft Matter 2013, 9, 4580-4584). Films on particle substrates had comparable mechanical properties to planar films, demonstrating that while substrate geometry has a negligible effect, membrane and tension effects may play an important role in capsule force resistance. Further, when transitioning from solid-supported films to free-standing capsules, simple predictions of shell stiffness based on modulus changes found for supported films are not valid. Rather, additional effects like diameter increases (geometrical changes) as well as tension buildup need to be taken into account. These results are important for research related to the characterization of soft hydrogel materials and control over their mechanical properties.