Associations between diabetes, body mass index and frailty: The Western Australian Health In Men Study.

OBJECTIVES: To investigate whether diabetes and obesity are associated with frailty independently, and to determine the proportion of frailty cases attributable to each factor. STUDY DESIGN: Prospective cohort study of 4219 older men assessed in 2001-04 (time-point 1, T1), of whom 1939 were reassessed in 2008-09 (time-point 2, T2). Frailty was defined as positive responses on three or more of the five domains on the FRAIL scale: fatigue, difficulty climbing a flight of stairs (resistance), difficulty walking 100 m (ambulation), >5 illnesses, or >5% weight loss. We explored associations of diabetes and obesity with frailty using binary logistic regression, and estimated population attributable fractions for diabetes and obesity as risk factors for frailty. MAIN OUTCOME MEASURES: Associations of obesity and diabetes with frailty. RESULTS: At T1, 15.5% of participants (n = 652) were frail, 15.4% (n = 651) had diabetes, and 15.1% (n = 636) were obese (BMI ≥ 30 kg/m2). At T2, 22.9% (n = 444) were frail, 19.8% (n = 383) had diabetes and 9.1% (n = 176) were obese. In multivariable models, diabetes was associated with frailty at T1 (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.7-2.6) and T2 (OR = 2.1, CI = 1.6-2.8). Obesity was associated with frailty at T1 (OR = 1.7, CI = 1.3-2.2) only. Both diabetes (OR = 1.5, CI = 1.1-2.2) and obesity (OR = 1.9, CI = 1.3-2.9) at T1 were independently associated with the development of frailty between T1 and T2. Approximately the same proportion (5%) of new frailty cases were attributable to diabetes or to obesity. CONCLUSIONS: Diabetes and obesity are modifiable risk factors which independently carry equal risk for the development of frailty in older men. Interventions targeting these risk factors may have the potential to reduce frailty risk.

Conducting polymer hydrogels with electrically-tuneable mechanical properties as dynamic cell culture substrates.

Hydrogels are a popular substrate for cell culture due to their mechanical properties closely resembling natural tissue. Stimuli-responsive hydrogels are a good platform for studying cell response to dynamic stimuli. Poly(N-isopropylacrylamide) (pNIPAM) is a thermo-responsive polymer that undergoes a volume-phase transition when heated to 32 °C. Conducting polymers can be incorporated into hydrogels to introduce electrically responsive properties. The conducting polymer, polypyrrole (PPy), has been widely studied as electrochemical actuators due to its electrochemical stability, fast actuation and high strains. We determine the volume-phase transition temperature of pNIPAM hydrogels with PPy electropolymerised with different salts as a film within the hydrogel network. We also investigate the electro-mechanical properties at the transition temperature (32 °C) and physiological temperature (37 °C). We show statistically significant differences in the Young's modulus of the hybrid hydrogel at elevated temperatures upon electrochemical stimulation, with a 5 kPa difference at the transition temperature. Furthermore, we show a three-fold increase in actuation at transition temperature compared to room temperature and physiological temperature, attributed to the movement of ions in/out of the PPy film that induce the volume-phase transition of the pNIPAM hydrogel. Furthermore, cell adhesion to the hybrid hydrogel was demonstrated with mouse articular chondrocytes.

Acute herpes zoster radiculopathy mimicking cervical radiculopathy after ChAdOx1 nCoV-19/AZD1222 vaccination.

This case report describes an 84-year-old man who presented with 3 weeks of gradually worsening right arm weakness associated with a painful vesicular rash across his arm. This occurred 3 days after his first dose of the ChAdOx1 nCoV-19/AZD1222 (University of Oxford, AstraZeneca and the Serum Institute of India) vaccine. The diagnosis was complicated by the presence of right C5-C6 foraminal stenosis compressing on the C6 nerve root sheath on non-contrast MRI, leading to an initial diagnosis of cervical radiculopathy. However, a positive varicella zoster virus-PCR test and findings of abnormal contrast enhancement of his right C5-C7 nerve roots on gadolinium-enhanced MRI resulted in a revision of his diagnosis to zoster radiculopathy. He was subsequently commenced on oral valacilovir and made significant recovery. This report aims to highlight the diagnostic dilemma between cervical radiculopathy secondary to spondylosis and zoster radiculopathy and how an erroneous diagnosis could result in inappropriate, aggressive surgical intervention and delayed treatment with antiviral therapy.

Biomechanical responses of encysted zoospores of the oomycete Achlya bisexualis to hyperosmotic stress are consistent with an ability to turgor regulate.

Zoospores are motile, asexual reproductive propagules that enable oomycete pathogens to locate and infect new host tissue. While motile, they have no cell wall and maintain tonicity with their external media using water expulsion vacuoles. Once they locate host tissue, they encyst and form a cell wall, enabling the generation of turgor pressure that will provide the driving force for germination and invasion of the host. It is not currently known how these spores respond to the osmotic stresses that might arise due to different environments on and around their hosts that have different osmotic strengths. We have made microaspiration (MA) measurements on > 800 encysted zoospores and atomic force microscopy (AFM) measurements on 12 encysted zoospores to determine their mechanical properties and how these change after hyperosmotic stress. Two types of encysted zoospores (Type A and Type B) were produced from the oomycete Achlya bisexualis, that differed in their morphology and response. With a small hyperosmotic stress (using 0.1 and 0.2 M sorbitol to give media osmolality changes of 155.4 and 295.6 mOsmol/kg), Type A zoospores initially became stiffer, with an increase in the Young's modulus (E) over 30 mins from 0.16 MPa to 0.25 and 0.22 MPa respectively. E then returned to its original value after 120 min. With a greater osmotic stress (using 0.3, 0.4 and 0.5 M sorbitol to give media osmolality changes of 438.2, 587.2 and 787.6 mOsmol/kg) the reverse occurred, with an initial decrease in E over 30 - 60 mins to values of 0.1, 0.08 and 0.09 MPa respectively, before recovery to the original value after 120 min. In 0.5 M sorbitol this recovery was only observed with AFM, but not with MA. Type B zoospores, which may be primary/secondary spores about to release secondary/tertiary spores, or else spores that were damaged during encystment, initially stiffened in response to the lower hyperosmotic stresses with a slight increase in E (from 0.077 to 0.1 MPa after 15 min (with both 0.1 and 0.2 M sorbitol) before recovering to the original value after 60 min. These spores showed no change in response to the higher osmotic stresses. The responses of the Type A spores are consistent with rapid changes in cell wall thickness and a turgor regulation mechanism. Turgor regulation is further supported by microscopic observations of the Type A spores showing protoplast retraction from the cell wall followed by deplasmolysis, coupled with measurements of spore volume. As far as we are aware this is the first demonstration of turgor regulation, not just in encysted zoospores, but in oomycetes in general.

Modulation of hydrogel stiffness by external stimuli: soft materials for mechanotransduction studies.

Mechanotransduction is an important process in determining cell survival, proliferation, migration and differentiation. The extracellular matrix (ECM) is the component of natural tissue that provides structural support and biochemical signals to adhering cells. The ECM is dynamic and undergoes physical and biochemical changes in response to various stimuli and there is an interest in understanding the effect of dynamic changes in stiffness on cell behaviour and fate. Therefore, stimuli-responsive hydrogels have been developed to mimic the cells' microenvironment in a controlled fashion. Herein, we review strategies for dynamic modulation of stiffness using various stimuli, such as light, temperature and pH. Special emphasis is placed on conducting polymer (CP) hydrogels and their fabrication procedures. We believe that the redox properties of CPs and hydrogels' biological properties make CPs hydrogels a promising substrate to investigate the effect of dynamic stiffness changes and mechanical actuation on cell fate in future studies.

Familial Dysalbuminemic Hyperthyroxinemia as a Cause for Discordant Thyroid Function Tests.

INTRODUCTION: Discordant thyroid function tests are routinely encountered in clinical practice. Differential diagnoses include acute thyroxine (T4) ingestion, laboratory interference from heterophilic antibodies, thyroid hormone resistance, thyroid-stimulating hormone (TSH)-secreting pituitary adenomas, and T4 protein binding abnormalities. The impact of abnormal binding proteins may be less recognized since widespread use of free T4 (FT4) assays compared to older total T4 assays. CASE REPORT: A 69-year-old female was referred for assessment of discordant thyroid function tests. Biochemistry since July 2015 showed persistently elevated FT4 levels by immunoassay ranging between 25 to 34 pmol/L with normal or slightly decreased TSH ranging between 0.05 to 2.74 mU/L. The patient was clinically euthyroid on 100 mcg daily of levothyroxine for Hashimoto's thyroiditis. FT4 measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was 19.5 pmol/L. Exome sequencing (confirmed by Sanger sequencing) detected a guanine to adenine substitution at residue 725 of the ALB gene previously associated with dysalbuminemic hyperthyroxinemia. The patient's daughter had similar thyroid function tests and the same genetic variant. FT4 results from 3 different automated immunoassays showed the Roche Cobas and Siemens Centaur platforms to be most affected by the variant, and Abbott Architect had the best agreement with LC-MS/MS. CONCLUSION: Familial dysalbuminemic hyperthyroxinemia is a potential cause of discordant thyroid function tests. Clinicians suspecting protein-binding abnormalities may further investigate using reference methods such as LC-MS/MS and equilibrium dialysis if available. The increasing accessibility of exome sequencing offers a cost-effective method of diagnosing genetic variants that cause discordant thyroid function tests.

A comparative study of tough hydrogen bonding dissipating hydrogels made with different network structures.

Hydrogels are excellent soft materials to interface with biological systems. Precise control and tunability of dissipative properties of gels are particularly interesting in tissue engineering applications. In this work, we produced hydrogels with tunable dissipative properties by photopolymerizing a second polymer within a preformed cross-linked hydrogel network of poly(acrylamide). We explored second networks made with different structures and capacity to hydrogen bond with the first network, namely linear poly(acrylic acid) and branched poly(tannic acid). Gels incorporating a second network made with poly(tannic acid) exhibited excellent stiffness (0.35 ± 0.035 MPa) and toughness (1.64 ± 0.26 MJ m-3) compared to the poly(acrylic acid) counterparts. We also demonstrate a strategy to fabricate hydrogels where the dissipation (loss modulus) can be tuned independently from the elasticity (storage modulus) suitable for cell culture applications. We anticipate that this modular design approach for producing hydrogels will have applications in tailored substrates for cell culture studies and in load bearing tissue engineering applications.

Mechanical Characterization for Cellular Mechanobiology: Current Trends and Future Prospects.

Accurate mechanical characterization of adherent cells and their substrates is important for understanding the influence of mechanical properties on cells themselves. Recent mechanobiology studies outline the importance of mechanical parameters, such as stress relaxation and strain stiffening on the behavior of cells. Numerous techniques exist for probing mechanical properties and it is vital to understand the benefits of each technique and how they relate to each other. This mini review aims to guide the reader through the toolbox of mechanical characterization techniques by presenting well-established and emerging methods currently used to assess mechanical properties of substrates and cells.