Comparison of pharmacodynamics between insulin glargine 100 U/mL and insulin glargine 300 U/mL in healthy cats.

Insulin glargine (IGla) is a synthetic human-recombinant insulin analog that is used routinely in people as a q24h basal insulin. The 300 U/mL (U300) formulation of IGla is associated with longer duration of action and less within-day variability, making it a better basal insulin compared with the 100 U/mL (U100) formulation. We hypothesized that in healthy cats, IGlaU300 has a flatter time-action profile and longer duration of action compared with IGlaU100. Seven healthy neutered male, purpose-bred cats were studied in a randomized, crossover design. Pharmacodynamics of IGlaU100 and IGlaU300 (0.8 U/kg, subcutaneous) were determined by the isoglycemic clamp method. The time-action profile of IGlaU300 was flatter compared with IGlaU100 as demonstrated by lower peak (5.6 ± 1.1 mg/kg/min vs 8.3 ± 1.9 mg/kg/min, respectively; P = 0.04) with no difference in total metabolic effect (ME; P = 0.7) or duration of action (16.8 h ± 4.7 h vs 13.4 h ± 2.6 h; P = 0.2). The greater fraction of ME in the 12- to 24-h period postinjection (35 ± 23% vs 7 ± 8% respectively; P = 0.048) and lower intraday GIR% variability (7.8 ± 3.7% vs 17.4 ± 8.2% respectively; P = 0.03) supports a flatter time-action profile of IGlaU300. There were no differences in onset and end of the action. In summary, although both formulations have a similar duration of action that is well below 24 h, the ME of IGlaU300 is more evenly distributed over a 24 h period in healthy cats, making it a better candidate for once-daily injection in diabetics compared with IGlaU100.

The Mars 2020 Engineering Cameras and Microphone on the Perseverance Rover: A Next-Generation Imaging System for Mars Exploration.

The Mars 2020 Perseverance rover is equipped with a next-generation engineering camera imaging system that represents an upgrade over previous Mars rover missions. These upgrades will improve the operational capabilities of the rover with an emphasis on drive planning, robotic arm operation, instrument operations, sample caching activities, and documentation of key events during entry, descent, and landing (EDL). There are a total of 16 cameras in the Perseverance engineering imaging system, including 9 cameras for surface operations and 7 cameras for EDL documentation. There are 3 types of cameras designed for surface operations: Navigation cameras (Navcams, quantity 2), Hazard Avoidance Cameras (Hazcams, quantity 6), and Cachecam (quantity 1). The Navcams will acquire color stereo images of the surface with a 96 ∘ × 73 ∘ field of view at 0.33 mrad/pixel. The Hazcams will acquire color stereo images of the surface with a 136 ∘ × 102 ∘ at 0.46 mrad/pixel. The Cachecam, a new camera type, will acquire images of Martian material inside the sample tubes during caching operations at a spatial scale of 12.5 microns/pixel. There are 5 types of EDL documentation cameras: The Parachute Uplook Cameras (PUCs, quantity 3), the Descent stage Downlook Camera (DDC, quantity 1), the Rover Uplook Camera (RUC, quantity 1), the Rover Descent Camera (RDC, quantity 1), and the Lander Vision System (LVS) Camera (LCAM, quantity 1). The PUCs are mounted on the parachute support structure and will acquire video of the parachute deployment event as part of a system to characterize parachute performance. The DDC is attached to the descent stage and pointed downward, it will characterize vehicle dynamics by capturing video of the rover as it descends from the skycrane. The rover-mounted RUC, attached to the rover and looking upward, will capture similar video of the skycrane from the vantage point of the rover and will also acquire video of the descent stage flyaway event. The RDC, attached to the rover and looking downward, will document plume dynamics by imaging the Martian surface before, during, and after rover touchdown. The LCAM, mounted to the bottom of the rover chassis and pointed downward, will acquire 90 ∘ × 90 ∘ FOV images during the parachute descent phase of EDL as input to an onboard map localization by the Lander Vision System (LVS). The rover also carries a microphone, mounted externally on the rover chassis, to capture acoustic signatures during and after EDL. The Perseverance rover launched from Earth on July 30th, 2020, and touchdown on Mars is scheduled for February 18th, 2021.

AF Classification from a Short Single Lead ECG Recording: the PhysioNet/Computing in Cardiology Challenge 2017.

The PhysioNet/Computing in Cardiology (CinC) Challenge 2017 focused on differentiating AF from noise, normal or other rhythms in short term (from 9-61 s) ECG recordings performed by patients. A total of 12,186 ECGs were used: 8,528 in the public training set and 3,658 in the private hidden test set. Due to the high degree of inter-expert disagreement between a significant fraction of the expert labels we implemented a mid-competition bootstrap approach to expert relabeling of the data, levering the best performing Challenge entrants' algorithms to identify contentious labels. A total of 75 independent teams entered the Challenge using a variety of traditional and novel methods, ranging from random forests to a deep learning approach applied to the raw data in the spectral domain. Four teams won the Challenge with an equal high F1 score (averaged across all classes) of 0.83, although the top 11 algorithms scored within 2% of this. A combination of 45 algorithms identified using LASSO achieved an F1 of 0.87, indicating that a voting approach can boost performance.

Molecular confirmation of nine cases of Cornelia de Lange syndrome diagnosed prenatally.

OBJECTIVES: Cornelia de Lange syndrome (CdLS) is characterized by distinct facial features, growth retardation, upper limb reduction defects, hirsutism, and intellectual disability. NIPBL mutations have been identified in approximately 60% of patients with CdLS diagnosed postnatally. Prenatal ultrasound findings include upper limb reduction defects, intrauterine growth restriction, and micrognathia. CdLS has also been associated with decreased PAPP-A and increased nuchal translucency (NT). We reviewed NIPBL sequence analysis results for 12 prenatal samples in our laboratory to determine the frequency of mutations in our cohort. METHODS: This retrospective study analyzed data from all 12 prenatal cases with suspected CdLS, which were received by The University of Chicago Genetic Services Laboratories. Diagnostic NIPBL sequencing was performed for all samples. Clinical information was collected from referring physicians. RESULTS: NIPBL mutations were identified in 9 out of the 12 cases prenatally (75%). Amongst the NIPBL mutation-positive cases with clinical information available, the most common findings were upper limb malformations and micrognathia. Five patients had NT measurements in the first trimester, of which four were noted to be increased. CONCLUSION: We demonstrate that prenatally-detected phenotypes of CdLS, particularly severe micrognathia and bilateral upper limb defects, are associated with an increased frequency of NIPBL mutations.

Serum amyloid A concentration in healthy periparturient mares and mares with ascending placentitis.

REASONS FOR PERFORMING STUDY: Placentitis is a prevalent cause of abortion, premature delivery and neonatal death in mares. Early diagnosis is paramount for the survival of the fetus and delivery of a live foal. OBJECTIVES: To determine: 1) Serum amyloid A (SAA) profile in healthy mares during late gestation; 2) if placentitis affects SAA concentrations and 3) the effects of therapy on SAA concentrations and pregnancy outcome in mares with placentitis. METHODS: In Experiment I, 15 healthy pregnant mares were evaluated from 280 days of gestation to 60 h post partum. In Experiment II, pregnant mares were inoculated intra-cervically with Streptococcus zooepidemicus (Day 280-295) and assigned to control (n = 5) and treatment (n = 9) groups. Treatment was initiated at the onset of clinical signs. Serum amyloid A concentrations were determined prior to inoculation and then weekly until abortion or delivery. RESULTS: Serum amyloid A remained at low concentrations (95% confidence interval [CI]: 3.2-8.1 mg/l) during late gestation followed by a significant increase within 36 h post partum; SAA returned to basal concentrations by 60 h post partum. In Experiment II, SAA significantly increased within 96 ± 56 h of inoculation in control mares followed by abortion. Therapy was effective (P<0.05) in preventing the rise in SAA in 66% (6/9) of mares and only one out of 3 mares with increased SAA aborted. Overall, the incidence of abortion was higher in mares with increased SAA concentrations (75%; 6/8) compared with mares in which SAA remained at baseline concentrations (0/6). CONCLUSIONS: Mares with placentitis had significant increased SAA within 96 h post inoculation and concentrations remained increased until abortion in untreated mares. Successful treatment either prevented the rise of SAA concentration or decreased its concentration to baseline concentrations, followed by delivery of a live foal. POTENTIAL RELEVANCE: Serum amyloid A may be used as a prognostic indicator in cases of ascending placentitis in the mare.

Expression of VACM-1/cul5 mutant in endothelial cells induces MAPK phosphorylation and maspin degradation and converts cells to the angiogenic phenotype.

Vasopressin-activated calcium mobilizing receptor (VACM-1) is a member of the cullin gene family involved in ubiquitin-proteosome dependent regulation of cellular functions. Expression of VACM-1 cDNA in cos-1 cells in vitro decreases basal cAMP levels and inhibits growth. The expression of (S730A)VACM-1 mutant cDNA, which removes PKA-dependent phosphorylation site in the VACM-1 cDNA sequence, reverses this phenotype. Since the expression of VACM-1 protein in vivo localizes largely to the vascular endothelial cells, in this study, we examined the effects of (S730A)VACM-1 cDNA expression on cellular signaling in the rat endothelial cell line RAMEC. Our results indicate that expression of (S730A)VACM-1 cDNA in RAMEC promotes cellular proliferation and induces angiogenic growth patterns. Western blot analyses indicate that (S730A)VACM-1 cDNA transfected cells express increased levels of Nedd8 modified VACM-1 and have higher levels of phosphorylated MAPK protein when compared to controls. Furthermore, expression of (S730A)VACM-1 cDNA induces translocation of the endogenous early response gene, egr-1, to the nucleus and leads to morphological changes that involve actin rearrangement. Finally, expression of (S730A)VACM-1 cDNA in RAMEC decreases concentration of maspin, a putative anti-angiogenic factor with a tumor suppressor activity. These results show that VACM-1 protein regulates endothelial cell growth and may modulate angiogenesis by a mechanism that involves MAPK phosphorylation, nuclear localization of egr-1, maspin expression, and actin polymerization.

Revealing the topography of cellular membrane domains by combined atomic force microscopy/fluorescence imaging.

Simultaneous atomic force microscopy (AFM) and confocal fluorescence imaging were used to observe in aqueous buffer the three-dimensional landscape of the inner surface of membrane sheets stripped from fixed tumor mast cells. The AFM images reveal prominent, irregularly shaped raised domains that label with fluorescent markers for both resting and activated immunoglobin E receptors (FcepsilonRI), as well as with cholera toxin-aggregated GM1 and clathrin. The latter suggests that coated pits bud from these regions. These features are interspersed with flatter regions of membrane and are frequently surrounded and interconnected by cytoskeletal assemblies. The raised domains shrink in height by approximately 50% when cholesterol is extracted with methyl-beta-cyclodextrin. Based on composition, the raised domains seen by AFM correspond to the cholesterol-enriched dark patches observed in transmission electron microscopy (TEM). These patches were previously identified as sites of signaling and endocytosis based on their localization of activated FcepsilonRI, at least 10 associated signaling molecules, and the presence of clathrin-coated pits. Overall the data suggest that signaling and endocytosis occur in mast cells from raised membrane regions that depend on cholesterol for their integrity and may be organized in specific relationship with the cortical cytoskeleton.

Functional ramifications of FRET-detected nascent chain folding far inside the membrane-bound ribosome.

During protein biosynthesis, nascent protein chains are directed along a long narrow tunnel that spans the large ribosomal subunit. It has recently become clear that this structural feature has evolved to effect regulatory control over aspects of protein synthesis and protein trafficking. Since this control is nascent chain-specific, ribosomal components that form the tunnel must be involved in recognizing selected nascent proteins as they pass by. The present study focuses on one such situation in which nascent secretory proteins and membrane proteins are distinguished by the ribosome-induced folding of the latter's hydrophobic transmembrane sequence far inside the ribosomal tunnel and close to the peptidyltransferase centre.

Organosilicon dental composite restoratives based on 1,3-bis[(p-acryloxymethyl) phenethyl] tetramethyldisiloxane.

OBJECTIVES: The major concern associated with the use of polysiloxanes as polymer matrices in dental restorative materials, is the generally modest mechanical properties of the polymers. However, it has long been demonstrated that thermal stability, and mechanical properties of polysiloxanes can be substantially modified by incorporation of bulkier substituents such as phenyl groups or more polar groups in the chains. The purpose of this research was to evaluate visible light activated dental composites based on the high molecular weight siloxane monomer 1,3-bis[(p-acryloxymethyl) phenethyl] tetramethyldisiloxane (BAPD). METHODS: Hardness, diametral tensile strength (DTS), degree of conversion (DC), water sorption (WS) and polymerization shrinkage of BAPD-based composites and bis-GMA-based composites were determined and compared. RESULTS: Composites based on BAPD exhibited low WS, high DC, low polymerization shrinkage, and had hardness and DTS values that were not significantly lower than those of dental composites based on bis-GMA. SIGNIFICANCE: BAPD is a high molecular weight monomer (MW = 511) with a low viscosity. It did not require the use of low molecular weight diluent monomers in formulating composite resins. The DC of BAPD was high, ranging from 86 to 94%. Although the DC of BAPD was significantly higher than the conventional difunctional dental monomers, the polymerization shrinkage of the siloxane composites (1.70 - 1.81 vol%) was comparable to several composites based on bis-GMA.

Maintaining the permeability barrier during protein trafficking at the endoplasmic reticulum membrane.

Many proteins are translocated across or integrated into a cellular membrane without disrupting its integrity, although it is difficult to imagine how such macromolecular transmembrane movement can occur without simultaneously allowing significant small-molecule and ion diffusion across the bilayer. Recent studies have identified some molecular mechanisms that are involved in maintaining the permeability barrier of the endoplasmic reticulum membrane during co-translational protein translocation and integration. These mechanisms are both simple and direct in concept, but are operationally complex and require the co-ordinated and regulated interaction of several multicomponent complexes.

Glutathione and adenosine triphosphate content of in vivo and in vitro matured porcine oocytes.

Glutathione (GSH) content in mature porcine oocytes is correlated with subsequent fertilization and developmental success. Adenosine triphosphate (ATP) is an important energy source for maintaining cellular activities and protein synthesis. The objective of this study was to compare GSH and ATP concentrations of in vivo and in vitro matured porcine oocytes. Ovulated, in vivo matured oocytes were frozen at -80 degrees C in groups of 10-20 (GSH) or 5-10 (ATP). In vitro oocytes were matured in either tissue culture medium-199 (TCM199) supplemented with polyvinyl alcohol (PVA) or hyaluronic acid (MAP5), or North Carolina State University-23 (NCSU23) supplemented with porcine follicular fluid (pFF) and frozen as described, or fertilized and cultured. GSH content was determined by the dithionitrobenzoic acid-glutathione disulfide (DTNB-GSSG) reductase recycling assay. ATP content was determined by using the Bioluminescent Somatic Cell Assay Kit. Oocytes matured in vitro in defined TCM199 with PVA or hyaluronic acid, or NCSU23 with pFF had significantly lower concentrations (P < 0.05) of GSH (n = 207, 9.82 +/- 0.71 pmol/oocyte; n = 104, 9.73 +/- 0.81 pmol/oocyte; n = 108, 7.89 +/- 0.66 pmol/oocyte, respectively) compared to in vivo matured oocytes (n = 217, 36.26 +/- 11.00 pmol/oocyte). Concentrations of ATP were not different between treatments (in vivo, n = 70, 0.97 +/- 0.07 pmol/oocyte; TCM-PVA, n = 117, 0.81 +/- 0.13 pmol/oocyte; TCM-MAP, n = 107, 1.02 +/- 0.18 pmol/oocyte; NCSU-pFF, n = 134, 0.71 +/- 0.08 pmol/oocyte). Intracellular ATP content does not appear to be related to developmental potential in porcine oocytes. Low intracellular GSH may be responsible, in part, for lower developmental competence observed in in vitro matured porcine oocytes.

Dopamine D(2) receptors and ingestive behavior: brainstem mediates inhibition of intraoral intake and accumbens mediates aversive taste behavior in male rats.

RATIONALE: One of the factors that terminate the ingestion of an intraorally infused solution of sucrose may be an increase in the perceived aversiveness of its taste. OBJECTIVES: We tested the hypothesis that dopamine D(2), as opposed to D(1), receptors in the brainstem or nucleus accumbens inhibit intraoral intake by enhancing the aversiveness of the taste of the infused solution. METHODS: Male rats were infused intraorally with a 2 M sucrose solution (1 ml/min) and intake and the display of gapes and chin rubs, i.e. taste-related aversive behavior, was measured. Gapes and chin rubs were also measured in rats during and 40 s after brief intraoral infusion (1 ml/min during 20 s) of a 0.3 mM solution of quinine HCl. The full D(1) receptor agonist dihydrexidine (0.1-3.0 mg/kg) and antagonist SCH-23390 (0.03-0.1 mg/kg), the D(2) receptor agonist quinpirole (0.3 mg/kg) and antagonist raclopride (1.7 mg/kg) were injected IP. Quinpirole (14-55 microg) and raclopride (5 microg) were also infused into the fourth brain ventricle. In addition, quinpirole (2 or 10 microg) was infused into the shell region of the nucleus accumbens. RESULTS: IP dihydrexidine and quinpirole inhibited the intraoral intake of sucrose and pretreatment with raclopride, but (in the case of dihydrexidine) not SCH-23390, attenuated this effect. Injection of quinpirole into the fourth ventricle produced raclopride-reversible inhibition of intraoral intake but did not stimulate the display of gapes and chin rubs. Infusion of quinpirole into the shell region of the nucleus accumbens had the opposite effects. The intake of sucrose was suppressed by the addition of quinine HCl but this suppression was unaffected by dopamine agonist or antagonist treatment. CONCLUSIONS: It is suggested that brainstem dopamine D(2) receptors mediate suppression of consummatory ingestive behavior and that D(2) receptors in the shell region of the nucleus accumbens mediate the display of gapes and chin rubs, but that neither of these D(2) receptor populations mediate the hedonic evaluation of taste.

Locus coeruleus noradrenergic lesions attenuate intraoral intake.

I.p. injections of DSP-4 in male rats decreased norepinephrine (NE) levels to varying degrees throughout the brain with 66.7% reductions in the hypothalamic paraventricular nucleus. Intake of intraorally infused sucrose was reduced for 14 days but daily pellet intake recovered within 5 days post-injection. Intraventricular NE restored intraoral sucrose intake in DSP-4-lesioned rats without affecting controls. Intraventricular infusion of neuropeptide Y (NPY) reduced intraoral intake in controls but had no effect in DSP-4-lesioned rats. NPY markedly inhibited intraoral intake in DSP-4-treated rats that also received NE. These data confirm studies showing that NPY decreases consummatory ingestive behavior and suggest that this inhibition involves ascending noradrenergic projections from locus coeruleus.

Sequence-specific delivery of a quinone methide intermediate to the major groove of DNA.

Silyl-protected phenol derivatives serve as convenient precursors for generating highly electrophilic quinone methide intermediates under biological conditions. Reaction is initiated by addition of fluoride and has previously exhibited proficiency in DNA alkylation and cross-linking. This approach has now been extended to the modification of duplex DNA through triplex recognition and fluoride-dependent quinone methide induction. Both oligonucleotides of a model duplex were alkylated in a sequence specific manner by an oligonucleotide conjugate that is consistent with triplex association. Optimum reaction required the presence of the two complementary target sequences and a pH of below 6.5. In addition, one guanine in each strand adjacent to the triplex region was the predominant site of alkylation. The yield of modification varied from approximately 20% for the purine-rich strand to only 4% for the pyrimidine-rich strand. This surprising difference indicates that the linker between the recognition and reactive elements may limit productive interaction between the quinone methide and the reactive nucleophiles of DNA. Restricted orientation of this intermediate may also be responsible for the lack of target cross-linking at detectable levels.

Inhibition of protein translocation across the endoplasmic reticulum membrane by sterols.

Cholesterol and related sterols are known to modulate the physical properties of biological membranes and can affect the activities of membrane-bound protein complexes. Here, we report that an early step in protein translocation across the endoplasmic reticulum (ER) membrane is reversibly inhibited by cholesterol levels significantly lower than those found in the plasma membrane. By UV-induced chemical cross-linking we further show that high cholesterol levels prevent cross-linking between ribosome-nascent chain complexes and components of the Sec61 translocon, but have no effect on cross-linking to the signal recognition particle. The inhibiting effect on translocation is different between different sterols. Our data suggest that the protein translocation machinery may be sensitive to changes in cholesterol levels in the ER membrane.

The cholesterol-dependent cytolysins.

In view of the recent studies on the CDCs, a reasonable schematic of the stages leading to membrane insertion of the CDCs can be assembled. As shown in Fig. 3, we propose that the CDC first binds to the membrane as a monomer. These monomers then diffuse laterally on the membrane surface to encounter other monomers or incomplete oligomeric complexes. Presumably, once the requisite oligomer size is reached, the prepore complex is converted into the pore complex and a large membrane channel is formed. During the conversion of the prepore complex to the pore complex, we predict that the TMHs of the subunits in the prepore complex insert into the bilayer in a concerted fashion to form the large transmembrane beta-barrel, although this still remains to be confirmed experimentally. Many intriguing problems concerning the cytolytic mechanism of the CDCs remain unsolved. The nature of the initial interaction of the CDC monomer with the membrane is currently one of the most controversial questions concerning the CDC mechanism. Is cholesterol involved in this interaction, as previously assumed, or do specific receptors exist for these toxins that remain to be discovered? Also, the trigger for membrane insertion and the regions of these toxins that facilitate the [figure: see text] interaction of the monomers during prepore complex formation are unknown. In addition, the temporal sequence of the multiple structural changes that accompany the conversion of the soluble CDC monomer into a membrane-inserted oligomer have yet to be defined or characterized kinetically.

Endoplasmic reticulum proteins involved in glycosylphosphatidylinositol-anchor attachment: photocrosslinking studies in a cell-free system.

Assembly of glycosylphosphatidylinositol (GPtdIns)-anchored proteins requires translocation of the nascent polypeptide chain across the endoplasmic reticulum (ER) membrane and replacement of the C-terminal signal sequence with a GPtdIns moiety. The anchoring reaction is carried out by an ER enzyme, GPtdIns transamidase. Genetic studies with yeast indicate that the transamidase consists of a dynamic complex of at least two subunits, Gaa1p and Gpi8p. To study the GPtdIns-anchoring reaction, we used a small reporter protein that becomes GPtdIns-anchored when the corresponding mRNA is translated in the presence of microsomes, in conjunction with site-specific photocrosslinking to identify ER membrane components that are proximal to the reporter during its conversion to a GPtdIns-anchored protein. We generated variants of the reporter protein such that upon in vitro translation in the presence of Nepsilon-(5-azido-2-nitrobenzoyl)-lysyl-tRNA, photoreactive lysine residues would be incorporated in the protein specifically near the GPtdIns-attachment site. We analyzed photoadducts resulting from UV irradiation of the samples. We show that proproteins can be crosslinked to the transamidase subunit Gpi8p, as well as to ER proteins of molecular mass approximately 60 kDa, approximately 70 kDa, and approximately 120 kDa. The identification of a photoadduct between a proprotein and Gpi8p provides the first direct evidence of an interaction between a proprotein substrate and one of the genetically identified transamidase subunits. The approximately 70-kDa protein that we identified may correspond to the other subunit Gaa1p, while the other proteins possibly represent additional, hitherto unidentified subunits of the mammalian GPtdIns transamidase complex.

Effect of diabetes mellitus and insulin use on survival after acute myocardial infarction in the elderly (the Cooperative Cardiovascular Project).

Using data from a retrospective cohort study of Medicare beneficiaries hospitalized with an acute myocardial infarction (AMI), we evaluated the role of diabetes mellitus on 30-day and 1-year mortality. We classified subjects as nondiabetics, diabetics controlled with diet alone, diabetics receiving an oral hypoglycemic agent, and diabetics on insulin at time of admission. We compared baseline admission characteristics of subgroups using chi-square and Wilcoxon rank-sum tests and evaluated the effect of each diabetic state using sequential logistic models. We identified 80,832 nondiabetic patients, 9,862 diet-controlled diabetic patients, 14,664 diabetics receiving an oral hypoglycemic agent, and 12,241 diabetic patients on insulin therapy. Although mean age was similar among the groups, prevalence of hypertension, prior AMI, prior congestive heart failure, and prior revascularization were higher among diabetic patients, particularly those taking insulin. Diabetic patients, particularly those taking insulin, were less likely to receive aspirin and beta blockers and to undergo coronary revascularization. Diabetic patients had higher 30-day and 1-year mortality than nondiabetic patients. After adjustment for demographics, clinical and hospital characteristics, and treatment strategies, insulin-treated diabetics had the highest risk of mortality, followed by diabetics receiving oral hypoglycemic agents, followed by diet-controlled diabetics. Thus, diabetes is highly prevalent among elderly patients with an AMI. Mortality rates for these patients, particularly insulin-using diabetics, are higher than among their nondiabetic counterparts. Preventive and therapeutic strategies must be developed to ensure improved short- and long-term outcomes for elderly patients with diabetes and AMI.