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•Age and baseline HAI titers were associated with immune response to egg-free influenza vaccine.•HAI response differed by antigen level contained in prior season’s influenza vaccine.•The ideal sequence of vaccine formulations across influenza seasons remains unknown. Immune responses to influenza vaccination tend to be lower among older, frequently vaccinated adults. Use of egg-free influenza vaccines is increasing, but limited data exist on factors associated with their immunogenicity in older adults. Community-dwelling older adults ≥ 56 years of age were enrolled in a prospective, observational study of immunogenicity of 2018–2019 influenza vaccine. Hemagglutination inhibition (HAI) antibody titers were measured pre-vaccination (Day 0) and four weeks after vaccination (Day 28) to calculate geometric mean titers, seropositivity (HAI titers ≥ 1:40), seroconversion (fourfold rise in HAI titer with post-vaccination titer ≥ 1:40) and geometric mean fold rise (GMFR). Linear regression models assessed the association of predictors of GMFR for each vaccine antigen. Among 91 participants who received egg-free influenza vaccines, 84 (92.3 %) received quadrivalent recombinant influenza vaccine (RIV4, Flublok, Sanofi Pasteur), and 7 (7.7 %) received quadrivalent cell culture-based influenza vaccine (ccIIV4, Flucelvax, Seqirus). Pre-vaccination seropositivity was 52.8 % for A(H1N1), 94.5 % for A(H3N2), 61.5 % for B/Colorado and 48.4 % for B/Phuket. Seroconversion by antigen ranged from 16.5 % for A(H1N1) and B/Colorado to 37.4 % for A(H3N2); 40 participants failed to seroconvert to any antigen. Factors independently associated with higher GMFR in multivariable models included lower pre-vaccination HAI antibody titer for A(H1N1), B/Colorado and B/Phuket, and younger age for A(H1N1). Overall pre-vaccination seropositivity was high and just over half of the cohort seroconverted to ≥ 1 vaccine antigen. Antibody responses were highest among participants with lower pre-vaccination titers. Among older adults with high pre-existing antibody titers, approaches to improve immune responses are needed.

Hemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children’s and young adults’ HAI titers against the 2019–2020 LAIV4 and ccIIV4. Participants aged 4–21 years were randomized 1:1 to receive ccIIV4 (n = 100) or LAIV4 (n = 98). Blood was drawn prevaccination and on day 28 (21–35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Primary outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers. GMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p < 0.05). The GMFR range was 2.4–3.0 times higher for ccIIV4 than for LAIV4 (p < 0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p < 0.05) than cell-grown GMTs [ccIIV4 day 28: egg = 205 (95% CI: 178–237); cell = 136 (95% CI:113–165); LAIV4 day 28: egg = 96 (95% CI: 83–112); cell = 63 (95% CI: 58–74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR. The HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. Lower prevaccination titers were associated with greater GMFR in both vaccine groups.

Thin coatings of crosslinked poly(vinylphosphonic acid), PVPA, display good adhesion and excellent intumescent, fire-retardant barrier properties when applied to the surfaces of a typical thermoplastic, such as poly(methyl methacrylate), but perform relatively poorly in water-soak tests. To strengthen and further improve the barrier properties of the intumescent char and to make the coating more hydrophobic, PVPA has been complexed with various inorganic and organic species. The chars formed from coatings of some of these hybrid materials are less friable than chars from coatings synthesized from crosslinked PVPA alone, and show higher levels of water tolerance with no significant reduction in dry adhesion to the substrate.

Older adults (age ≥ 65) are at high risk of influenza morbidity and mortality. This study evaluated the impact of a hypothetical two-dose influenza vaccine regimen per season to reduce symptomatic flu cases by providing preseason (first dose) and mid-season (second dose) protection to offset waning vaccine effectiveness (VE). The Framework for Reconstructing Epidemiological Dynamics (FRED), an agent-based modeling platform, was used to compare typical one-dose vaccination to a two-dose vaccination strategy. Primary models incorporated waning VE of 10% per month and varied influenza season timing (December through March) to estimate cases and hospitalizations in older adults. Additional scenarios modeled reductions in uptake and VE of the second dose, and overall waning. In seasons with later peaks, two vaccine doses had the largest potential to reduce cases (14.4% with February peak, 18.7% with March peak) and hospitalizations (13.1% with February peak, 16.8% with March peak). Reductions in cases and hospitalizations still resulted but decreased when 30% of individuals failed to receive a second dose, second dose VE was reduced, or overall waning was reduced to 7% per month. Agent-based modeling indicates that two influenza vaccine doses could decrease cases and hospitalizations in older individuals. The highest impact occurred in the more frequently observed late-peak seasons. The beneficial impact of the two-dose regimen persisted despite model scenarios of reduced uptake of the second dose, decreased VE of the second dose, or overall VE waning.

Objectives. To estimate the effect of influenza vaccination disparities. Methods. We compared symptomatic influenza cases between Black and White races in 2 scenarios: (1) race- and age-specific vaccination coverage and (2) equal vaccination coverage. We also compared differences in household composition between races. We used the Framework for Reconstructing Epidemiological Dynamics, an agent-based model that assigns US Census‒based age, race, households, and geographic location to agents (individual people), in US counties of varying racial and age composition. Results. Influenza cases were highest in counties with higher proportions of children. Cases were up to 30% higher in Black agents with both race-based and race-equal vaccination coverage. Compared with corresponding categories of White households, cases in Black households without children were lower and with children were higher. Conclusions. Racial disparities in influenza cases persisted after equalizing vaccination coverage. The proportion of children in the population contributed to the number of influenza cases regardless of race. Differences in household composition may provide insight into racial differences and offer an opportunity to improve vaccination coverage to reduce influenza burden for both races. ( Am J Public Health. 2025;115(2):209–216. https://doi.org/10.2105/AJPH.2024.307878 )

The aim was to determine if persistent c-peptide in long duration childhood onset (<17 years) type 1 diabetes (T1D) related to microvascular complications. Pittsburgh Epidemiology of Diabetes Complications (EDC) participants (n = 185) had serum c-peptide levels measured by Mercodia ultra-sensitive ELISA at the 25-year follow-up exam. Microvascular complications between those with and without detectable c-peptide were compared. Eighteen (9.7%) participants had detectable median c-peptide levels of 3.8 (2.6, 12.2) pmol/L and did not differ from those without detectable levels. No differences in microalbuminuria, confirmed distal symmetric polyneuropathy, renal failure, or between those with one or more complications were found between the two groups. Proliferative retinopathy (PR) was marginally lower in those with detectable c-peptide (33.3% vs 55.1%, p = 0.08). However, those with c-peptide were somewhat less likely to have fasted for a full 8-h (66.7% vs. 84.9%, p = 0.09). Excluding those not fully fasted, PR no longer approached significance but macroalbuminuria became marginally lower in those with detectable levels (23.4% vs 0%, p = 0.07). Low levels of c-peptide in T1D patients of long duration were detected but were not strongly related to microvascular complications.

Aims/hypothesisThe risk for coronary artery disease (CAD) is substantially increased in type 1 diabetes and it has been postulated that insulin resistance may contribute to this risk. The current study measured insulin resistance in type 1 diabetes with vs without CAD and with a focus upon skeletal muscle, to test the hypothesis that insulin resistance is more severe in participants who have type 1 diabetes and CAD. Additionally, in type 1 diabetes, we examined the hypothesis that insulin resistance is more severe in soleus (an oxidative type muscle) vs tibialis anterior (a more glycolytic type of muscle).MethodsInsulin resistance was measured in participants with type 1 diabetes with (n = 9, CAD+) and without CAD (n = 10, CAD−) using euglycaemic insulin infusions combined with positron emission tomography (PET) imaging of [18F]fluorodeoxyglucose (FDG) uptake into soleus and tibialis anterior skeletal muscles. Coronary artery calcium (CAC) score was quantified by electron beam tomography.ResultsCAD+ participants with type 1 diabetes had a >100-fold higher CAC score than did CAD− participants with type 1 diabetes but groups did not differ in HbA1c or insulin dose. During clamp studies, CAD+ and CAD− groups had similar glucose disposal but were insulin resistant compared with historical non-diabetic participants (n = 13). FDG uptake by soleus muscle was similarly reduced, overall, in individuals with type 1 diabetes with or without CAD compared with non-diabetic individuals. However, FDG uptake by tibialis anterior muscle was not reduced in CAD− participants with type 1 diabetes while in CAD+ participants with type 1 diabetes it was 75% greater (p < 0.01). Across all participants with type 1 diabetes, FDG uptake by tibialis anterior muscle correlated positively with CAC severity.Conclusions/interpretationOur study confirms that systemic and skeletal muscle-specific insulin resistance is seen in type 1 diabetes but found that it does not appear to be more severe in the presence of CAD. There were, however, sharp differences between soleus and tibialis anterior muscles in type 1 diabetes: while insulin resistance was clearly manifest in soleus muscle, and was of equal severity in CAD+ and CAD− participants, tibialis anterior did not suggest insulin resistance in participants with type 1 diabetes, as FDG uptake by tibialis anterior correlated positively with CAC severity and was significantly increased in participants with type 1 diabetes and clinical CAD.

Though the long-term consequences of celiac disease (CD) in type 1 diabetes are unclear, CD has been associated with increased prevalence of end-stage renal disease (ESRD) independent of type 1 diabetes. We evaluated whether celiac autoimmunity is related to the cumulative incidence of microalbuminuria [albumin excretion rate (AER) 20 to 200 µg/min], macroalbuminuria (AER >200 µg/min), and ESRD. In the prospective follow-up of the Pittsburgh Epidemiology of Diabetes Complications study of childhood-onset type 1 diabetes, 618 participants were screened for tissue transglutaminase (tTG) antibodies with a clinical assay. Nephropathy outcomes were determined at 25 years of diabetes duration. Overall, the 33 subjects (5.3%) with strongly positive tTG levels (≥3 times the upper limit of normal) or a reported clinical history of CD had lower baseline blood pressure and lipid values. At 25 years of diabetes duration, a lower cumulative incidence of macroalbuminuria in strongly positive subjects compared with those with negative serology (3.6% vs 30.0%; P = 0.003) remained significant after adjustment for age, HbA1c, lipid measures, and blood pressure (adjusted P = 0.004). No considerable differences between these subjects and tTG-negative groups were found for microalbuminuria (40.0% vs 57.1%) or ESRD (0 vs 4.1%). These findings show that strongly positive celiac autoimmunity status in individuals with childhood-onset type 1 diabetes is associated with lower baseline blood pressure and cholesterol measurements as well as lower macroalbuminuria risk after 25 years of type 1 diabetes duration with no increase in the risk of microalbuminuria or ESRD.

Can clinical factors estimate insulin resistance in type 1 diabetes? K V Williams , J R Erbey , D Becker , S Arslanian and T J Orchard Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA. williamsky@msx.upmc.edu Abstract An insulin resistance syndrome (IRS) score was developed based on clinical risk factors in adults with childhood-onset type 1 diabetes in the Epidemiology of Diabetes Complications (EDC) Study and was validated using euglycemic-hyperinsulinemic clamp studies. Hypertension, waist-to-hip ratio (WHR), triglyceride and HDL cholesterol levels, family history of type 2 diabetes, and glycemic control were risk factors used to define the score. A score of 1 (lowest likelihood IRS) to 3 (highest likelihood IRS) was assigned for each risk factor. Eligible subjects (n = 24) were recruited from the EDC cohort based on tertile of IRS score. Subjects received an overnight insulin infusion to normalize glucose levels, then underwent a 3-h euglycemic-hyperinsulinemic (60 mU x m(-2) x min(-1)) clamp. Glucose disposal rate (GDR) was determined during the last 30 min of the clamp. The GDR differed significantly by IRS group (9.65 +/- 2.99, 8.02 +/- 1.39, and 5.68 +/- 2.16 mg x kg(-1) x min(-1), P < 0.01). The GDR was inversely correlated with the IRS score (r = -0.64, P < 0.01). Using linear regression, the combination of risk factors that yielded the highest adjusted r2 value (0.57, P < 0.001) were WHR, hypertension, and HbA1. This study found that clinical risk factors can be used to identify subjects with type 1 diabetes who are insulin resistant, and it provides validation of a score based on clinical factors to determine the extent of insulin resistance in type 1 diabetes. This score will be applied to the entire EDC population in future studies to determine the effect of insulin resistance on complications.

Weight Loss-Induced Plasticity of Glucose Transport and Phosphorylation in the Insulin Resistance of Obesity and Type 2 Diabetes Katherine V. Williams 1 , Alessandra Bertoldo 2 , Paul Kinahan 3 , Claudio Cobelli 2 and David E. Kelley 1 1 Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 2 Department of Information Engineering, University of Padova, Padova, Italy 3 Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania Address correspondence and reprint requests to Katherine V. Williams, MD, Instructor of Medicine, University of Pittsburgh School of Medicine, Division of Endocrinology and Metabolism, 810N Montefiore University Hospital, 3459 Fifth Ave., Pittsburgh, PA 15213. E-mail: williamsk{at}msx.dept-med.pitt.edu Abstract We tested the hypothesis that weight loss alleviates insulin resistance in skeletal muscle within the proximal steps of glucose metabolism, namely substrate delivery, glucose transport, and glucose phosphorylation. In obese subjects with and without type 2 diabetes, in vivo skeletal muscle assessments were obtained with dynamic positron emission tomography (PET) imaging performed during euglycemic clamps at moderate hyperinsulinemia (40 mU · min −1 · m −2 ), using [ 15 O]H 2 O and [ 18 F]fluoro-deoxyglucose ([ 18 F]FDG) to quantify tissue perfusion and glucose metabolism. Dynamic [ 18 F]FDG PET data were analyzed using both a novel muscle-specific compartmental model and a compartmental model originally developed for the brain and often used for [ 18 F]FDG muscle image quantification. Weight loss in obese subjects with ( n = 9) and without ( n = 9) type 2 diabetes over a 4-month intervention was substantial (14 ± 2 kg, P < 0.05). Muscle insulin resistance, assessed by insulin-stimulated [ 18 F]FDG uptake, decreased threefold in diabetic subjects and twofold in nondiabetic subjects ( P < 0.001). Kinetic parameters for [ 18 F]FDG transport and phosphorylation improved substantially in both groups, whereas tissue blood flow did not change. In particular, clinically significant weight loss fully corrected insulin resistance in type 2 diabetes at the step of glucose phosphorylation and largely, but incompletely, corrected insulin resistance at the glucose transport step. CT, computed tomography G6P, glucose-6-phosphate [18F]FDG, [18F]fluoro-deoxyglucose 3K, three-compartment/three-rate constant 5K, four-compartment/five-rate constant MBF, muscle blood flow NMR, nuclear magnetic resonance PET, positron emission tomography Footnotes Accepted March 31, 2003. Received December 18, 2002. DIABETES