Recent progress on the chiral unitary approach to meson meson and meson baryon interactions

We report on recent progress on the chiral unitary approach, analogous to the effective range expansion in Quantum Mechanics, which is shown to have a much larger convergence radius than ordinary chiral perturbation theory, allowing one to reproduce data for meson meson interaction up to 1.2 GeV. Applications to physical processes so far unsuited for a standard chiral perturbative approach are presented. Results for the extension of these ideas to the meson baryon sector are discussed, together with applications to kaons in a nuclear medium and $K^-$ atoms.Comment: Contribution to the KEK Tanashi Symposium on Physics of Hadrons and Nuclei, Tokyo, December 1998, 10 pages, 3 postscript figures. To be published as a special issue of Nuclear Physics

The Adolescent Cardio-Renal Intervention Trial (AdDIT): retinal vascular geometry and renal function in adolescents with type 1 diabetes

Aims/hypothesis We examined the hypothesis that elevation in urinary albumin creatinine ratio (ACR) in adolescents with type 1 diabetes is associated with abnormal retinal vascular geometry (RVG) phenotypes. Methods A cross-sectional study at baseline of the relationship between ACR within the normoalbuminuric range and RVG in 963 adolescents aged 14.4 ± 1.6 years with type 1 diabetes (median duration 6.5 years) screened for participation in AdDIT. A validated algorithm was used to categorise log10 ACR into tertiles: upper tertile ACR was defined as ‘high-risk’ for future albuminuria and the lower two tertiles were deemed ‘low-risk’. RVG analysis, using a semi-automated computer program, determined retinal vascular calibres (standard and extended zones) and tortuosity. RVG measures were analysed continuously and categorically (in quintiles: Q1–Q5) for associations with log10 ACR and ACR risk groups. Results Greater log10 ACR was associated with narrower vessel calibres and greater tortuosity. The high-risk group was more likely to have extended zone vessel calibres in the lowest quintile (arteriolar Q1 vs Q2–Q5: OR 1.67 [95% CI 1.17, 2.38] and venular OR 1.39 [0.98, 1.99]) and tortuosity in the highest quintile (Q5 vs Q1–Q4: arteriolar OR 2.05 [1.44, 2.92] and venular OR 2.38 [1.67, 3.40]). The effects of retinal vascular calibres and tortuosity were additive such that the participants with the narrowest and most tortuous vessels were more likely to be in the high-risk group (OR 3.32 [1.84, 5.96]). These effects were independent of duration, blood pressure, BMI and blood glucose control. Conclusions/interpretation Higher ACR in adolescents is associated with narrower and more tortuous retinal vessels. Therefore, RVG phenotypes may serve to identify populations at high risk of diabetes complications during adolescence and well before onset of clinical diabetes complications.This work was supported by the National Health and Medical Research Council of Australia (NHMRC 632521), JDRF (08-2007-902), Diabetes UK (DUK PO NO 2177 BDA:RD06/003341) and the British Heart Foundation

Retinal Arteriolar Dilation Predicts Retinopathy in Adolescents With Type 1 Diabetes

OBJECTIVE—Alterations in retinal vascular caliber may reflect early subclinical microvascular dysfunction. In this study, we examined the association of retinal vascular caliber to incident retinopathy in young patients with type 1 diabetes

Coexisiting type 1 diabetes and celiac disease is associated with lower Hba1c when compared to type 1 diabetes alone: data from the Australasian Diabetes Data Network (ADDN) registry.

AIM: To compare HbA1c and clinical outcomes in adolescents and young adults with type 1 diabetes (T1D), with or without celiac disease (CD). METHODS: Longitudinal data were extracted from ADDN, a prospective clinical diabetes registry. Inclusion criteria were T1D (with or without CD), ≥ 1 HbA1c measurement, age 16-25 years and diabetes duration ≥ 1 year at last measurement. Multivariable Generalised Estimated Equation models were used for longitudinal analysis of variables associated with HbA1c. RESULTS: Across all measurements, those with coexisting T1D and CD had lower HbA1c when compared to those with T1D alone (8.5 ± 1.5% (69.4 ± 16.8 mmol/mol) vs. 8.7 ± 1.8% (71.4 ± 19.8 mmol/mol); p < 0.001); lower HbA1c was associated with shorter diabetes duration (B = - 0.06; 95% CI - 0.07 to - 0.05; p < 0.001), male sex (B = - 0.24; - 0.36 to - 0.11; p < 0.001), insulin pump therapy use (B = - 0.46; - 0.58 to - 0.34; p < 0.001), coexistence of T1D and CD (B = - 0.28; - 0.48 to - 0.07; p = 0.01), blood pressure (B = - 0.16; - 0.23 to - 0.09; p < 0.001) and body mass index (B = -- 0.03; - 0.02 to - 0.04; p = 0.01) in the normal range. At last measurement, 11.7% of the total population had a HbA1c < 7.0% (53.0 mmol/mol). CONCLUSIONS: Across all measurements, coexisting T1D and CD is associated with lower HbA1c when compared to T1D alone. However, HbA1c is above target in both groups

Correction to: Coexisiting type 1 diabetes and celiac disease is associated with lower Hba1c when compared to type 1 diabetes alone: data from the Australasian Diabetes Data Network (ADDN) registry.

Correction to: Acta Diabetologica ‘Australasian Diabetes Data Network Study Group’ should be listed as named authors in the author group. In the abstract, ‘coexistence of T1D and CD’ does not have a listed B value which is now updated as shown below ……coexistence of T1D and CD (B = − 0.28; to − 0.48 to − 0.07…… Body mass index has a small negative value in both the abstract and Table 2, which is now corrected. In Australasian Diabetes Data Network (ADDN) Study Group members: Jenny Batch should be Professor Jenny Batch. There is a ‘2’ incorrectly inserted in Prof Tony Huynh’s affiliation. This should say Queensland Children’s Hospital, Brisbane. The original article has been corrected

Encapsulation-free controlled release: Electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles

Encapsulation of therapeutic molecules within polymer particles is a well-established method for achieving controlled release, yet challenges such as low loading, poor encapsulation efficiency, and loss of protein activity limit clinical translation. Despite this, the paradigm for the use of polymer particles in drug delivery has remained essentially unchanged for several decades. By taking advantage of the adsorption of protein therapeutics to poly(lactic-co-glycolic acid) (PLGA) nanoparticles, we demonstrate controlled release without encapsulation. In fact, we obtain identical, burst-free, extended-release profiles for three different protein therapeutics with and without encapsulation in PLGA nanoparticles embedded within a hydrogel. Using both positively and negatively charged proteins, we show that short-range electrostatic interactions between the proteins and the PLGA nanoparticles are the underlying mechanism for controlled release. Moreover, we demonstrate tunable release by modifying nanoparticle concentration, nanoparticle size, or environmental pH. These new insights obviate the need for encapsulation and offer promising, translatable strategies for a more effective delivery of therapeutic biomolecules

Low-density lipoprotein cholesterol in adolescents and young adults with type 1 diabetes: Data from the Australasian Diabetes Data Network registry.

AIM: To determine low-density lipoprotein cholesterol (LDL-C) screening frequency and levels, and factors associated with elevated LDL-C, in Australasian youth with type 1 diabetes (T1D). METHODS: Data were extracted from the Australasian Diabetes Data Network (ADDN), a prospective clinical quality registry, on all T1D healthcare visits attended by young people aged 16-25 years (with T1D duration of >1 year) between January 2011 and December 2020. The primary outcomes were elevated LDL-C > 2.6 mmol/L (100 mg/dL) and threshold for treatment: >3.4 mmol/L (130 mg/dL), according to consensus guidelines. Multivariable Generalised Estimated Equations (GEE) were used to examine factors associated with elevated LDL-C across all visits. RESULTS: A cohort of 6338 young people (52.6% men) were identified, of whom 1603 (25.3%) had ≥1 LDL-C measurement documented. At last measurement, mean age, age at T1D diagnosis and T1D duration were 18.3 ± 2.4, 8.8 ± 4.5 and 8.9 ± 4.8 years, respectively. LDL-C was elevated in 737 (46.0%) and at the treatment threshold in 250 (15.6%). In multivariable GEE elevated LDL-C continuously was associated with older age (OR = 0.07; 0.01-0.13, p = 0.02), female sex (OR = 0.31; 0.18-0.43; p < 0.001), higher HbA1c (OR = 0.04; 0.01-0.08; p = 0.01) and having an elevated BMI (OR = 0.17, 0.06-0.39, p < 0.001). CONCLUSIONS: LDL-C screening and levels are suboptimal in this cohort, increasing future cardiovascular complication risk. There is an urgent need to understand how healthcare services can support improved screening and management of dyslipidaemia in this population

Quantitative Assessment of Early Diabetic Retinopathy Using Fractal Analysis

OBJECTIVE—Fractal analysis can quantify the geometric complexity of the retinal vascular branching pattern and may therefore offer a new method to quantify early diabetic microvascular damage. In this study, we examined the relationship between retinal fractal dimension and retinopathy in young individuals with type 1 diabetes

High Rate of Regression From Micro-Macroalbuminuria to Normoalbuminuria in Children and Adolescents With Type 1 Diabetes Treated or Not With Enalapril: The influence of HDL cholesterol

OBJECTIVE: To evaluate the frequency of normalization, the persistence of remission, and the impact on normalization of glycemic control and lipid profile, we analyzed data from a retrospective observational cohort study of type 1 diabetic children and adolescents with abnormal urinary albumin excretion (UAE). RESEARCH DESIGN AND METHODS: All diabetic children and adolescents (n = 41) who had persistent abnormal UAE in the period of 1984 to 2008 and followed up until 2009 (follow-up duration = 13.1 \ub1 6.2 years) were included in the study. Nine patients progressed to macroalbuminuria; 24 patients were administered ACE inhibitor treatment. RESULTS: The cumulative prevalence of abnormal UAE was 9%. During follow-up, 14 of 17 untreated and 19 of 24 treated patients reverted to normoalbuminuria. In the remission group compared with the nonremission group, A1C levels during follow-up decreased (7.5 \ub1 1.0 vs. 9.4 \ub1 1.2%, P < 0.0001) and serum HDL cholesterol increased (52.7 \ub1 11.3 vs. 42.7 \ub1 8.6 mg/dL, P < 0.05). The micro-macroalbuminuric patients had lower HDL cholesterol (51.0 \ub1 11.4 vs. 62.4 \ub1 13.6 mg/dL, P < 0.0001) than 134 normoalbuminuric diabetic patients. CONCLUSIONS: Microalbuminuria and macroalbuminuria were not permanent in most of our diabetic children and adolescents. If abnormal UAE values are high and persist for >1 year, only long-lasting treatment with ACE inhibitors seems able to induce persistent remission, especially when associated with good metabolic control and high HDL cholesterol level