Glimepiride, a novel sulfonylurea, does not abolish myocardial protection afforded by either ischemic preconditioning or diazoxide

Background: The sulfonylurea glibenclamide (Glib) abolishes the cardioprotective effect of ischemic preconditioning (IP), presumably by inhibiting mitochondrial KATP channel opening in myocytes. Glimepiride (Glim) is a new sulfonylurea reported to affect nonpancreatic KATP channels less than does Glib. We examined the effects of Glim on IP and on the protection afforded by diazoxide (Diaz), an opener of mitochondrial KATP channels. Methods and results: Rat hearts were Langendorff-perfused, subjected to 35 minutes of regional ischemia and 120 minutes of reperfusion, and assigned to 1 of the following treatment groups: (1) control; (2) IP of 2x 5 minutes each of global ischemia before lethal ischemia; or pretreatment with (3) 30 µmol/L Diaz, (4) 10 µmol/L Glim, (5) 10 µmol/L Glib, (6) IP+Glim, (7) IP+Glib, (8) Diaz+Glim, or (9) Diaz+Glib. IP limited infarct size (18.5±1% vs 43.7±3% in control, P<0.01) as did Diaz (22.2±4.7%, P<0.01). The protective actions of IP or Diaz were not abolished by Glim (18.5±3% in IP+Glim, 22.3±3% in Diaz+Glim; P<0.01 vs control). However, Glib abolished the infarct-limiting effects of IP and Diaz. Patch-clamp studies in isolated rat ventricular myocytes confirmed that both Glim and Glib (each at 1 µmol/L) blocked sarcolemmal KATP currents. However, in isolated cardiac mitochondria, Glim (10 µmol/L) failed to block the effects of KATP opening by GTP, in contrast to the blockade caused by Glib. Conclusions: Although it blocks sarcolemmal currents in rat cardiac myocytes, Glim does not block the beneficial effects of mitochondrial KATP channel opening in the isolated rat heart. These data may have significant implications for the treatment of type 2 diabetes in patients with ongoing ischemic heart disease

Two Wrongs Make a Right: Deficits in Reversal Learning after Orbitofrontal Damage Are Improved by Amygdala Ablation

Impaired cognitive flexibility after orbitofrontal damage has informed theories of orbitofrontal function and prefrontal cortex function generally. In this issue of Neuron, Stalnaker et al. demonstrate that reversal learning deficits after orbitofrontal damage in rats are eliminated by additional lesions of the basolateral amygdala. The involvement of orbitofrontal cortex in cognitive flexibility is via its interaction with the amygdala, and perhaps other brain areas, rather than an intrinsic property of this cortical region

Transfer Matrices and Partition-Function Zeros for Antiferromagnetic Potts Models. V. Further Results for the Square-Lattice Chromatic Polynomial

We derive some new structural results for the transfer matrix of square-lattice Potts models with free and cylindrical boundary conditions. In particular, we obtain explicit closed-form expressions for the dominant (at large |q|) diagonal entry in the transfer matrix, for arbitrary widths m, as the solution of a special one-dimensional polymer model. We also obtain the large-q expansion of the bulk and surface (resp. corner) free energies for the zero-temperature antiferromagnet (= chromatic polynomial) through order q^{-47} (resp. q^{-46}). Finally, we compute chromatic roots for strips of widths 9 <= m <= 12 with free boundary conditions and locate roughly the limiting curves.Comment: 111 pages (LaTeX2e). Includes tex file, three sty files, and 19 Postscript figures. Also included are Mathematica files data_CYL.m and data_FREE.m. Many changes from version 1: new material on series expansions and their analysis, and several proofs of previously conjectured results. Final version to be published in J. Stat. Phy

Glauber Dynamics for the mean-field Potts Model

We study Glauber dynamics for the mean-field (Curie-Weiss) Potts model with $q\geq 3$ states and show that it undergoes a critical slowdown at an inverse-temperature $\beta_s(q)$ strictly lower than the critical $\beta_c(q)$ for uniqueness of the thermodynamic limit. The dynamical critical $\beta_s(q)$ is the spinodal point marking the onset of metastability. We prove that when $\beta<\beta_s(q)$ the mixing time is asymptotically $C(\beta, q) n \log n$ and the dynamics exhibits the cutoff phenomena, a sharp transition in mixing, with a window of order $n$. At $\beta=\beta_s(q)$ the dynamics no longer exhibits cutoff and its mixing obeys a power-law of order $n^{4/3}$. For $\beta>\beta_s(q)$ the mixing time is exponentially large in $n$. Furthermore, as $\beta \uparrow \beta_s$ with $n$, the mixing time interpolates smoothly from subcritical to critical behavior, with the latter reached at a scaling window of $O(n^{-2/3})$ around $\beta_s$. These results form the first complete analysis of mixing around the critical dynamical temperature --- including the critical power law --- for a model with a first order phase transition.Comment: 45 pages, 5 figure

The Ising Susceptibility Scaling Function

We have dramatically extended the zero field susceptibility series at both high and low temperature of the Ising model on the triangular and honeycomb lattices, and used these data and newly available further terms for the square lattice to calculate a number of terms in the scaling function expansion around both the ferromagnetic and, for the square and honeycomb lattices, the antiferromagnetic critical point.Comment: PDFLaTeX, 50 pages, 5 figures, zip file with series coefficients and background data in Maple format provided with the source files. Vs2: Added dedication and made several minor additions and corrections. Vs3: Minor corrections. Vs4: No change to eprint. Added essential square-lattice series input data (used in the calculation) that were removed from University of Melbourne's websit

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

Effect of radiofrequency catheter ablation on the biochemical marker ischemia modified albumin

Ischemia-modified albumin (IMA) levels were measured after radiofrequency (RF) catheter ablation to evaluate the effect of direct myocardial necrosis on IMA formation. IMA levels have been shown to increase in patients after RF catheter ablation compared with those who undergo diagnostic electrophysiologic studies. The results of this study suggest that IMA may be a marker of myocardial injury