Ability of the PM3 Quantum Mechanical Method to Model Intermolecular Hydrogen Bonding between Neutral Molecules

The PM3 semiempirical quantum-mechanical method was found to systematically describe intermolecular hydrogen bonding in small polar molecules. PM3 shows charge transfer from the donor to acceptor molecules on the order of 0.02-0.06 units of charge when strong hydrogen bonds are formed. The PM3 method is predictive; calculated hydrogen bond energies with an absolute magnitude greater than 2 kcal mol-' suggest that the global minimum is a hydrogen bonded complex; absolute energies less than 2 kcal mol-' imply that other van der Waals complexes are more stable. The geometries of the PM3 hydrogen bonded complexes agree with high-resolution spectroscopic observations, gas electron diffraction data, and high-level ab initio calculations. The main limitations in the PM3 method are the underestimation of hydrogen bond lengths by 0.1-0.2 for some systems and the underestimation of reliable experimental hydrogen bond energies by approximately 1-2 kcal mol-l. The PM3 method predicts that ammonia is a good hydrogen bond acceptor and a poor hydrogen donor when interacting with neutral molecules. Electronegativity differences between F, N, and 0 predict that donor strength follows the order F > 0 > N and acceptor strength follows the order N > 0 > F. In the calculations presented in this article, the PM3 method mirrors these electronegativity differences, predicting the F-H- - -N bond to be the strongest and the N-H- - -F bond the weakest. It appears that the PM3 Hamiltonian is able to model hydrogen bonding because of the reduction of two-center repulsive forces brought about by the parameterization of the Gaussian core-core interactions. The ability of the PM3 method to model intermolecular hydrogen bonding means reasonably accurate quantum-mechanical calculations can be applied to small biologic systems.

A strategy combining imaging and laboratory biomarkers in comparison with a simplified clinical score for risk stratification of patients with acute pulmonary embolism

This study aimed to assess the performance of two prognostic models-the European Society of Cardiology (ESC) model and the simplified Pulmonary Embolism Severity Index (sPESI)-in predicting short-term mortality in patients with pulmonary embolism (PE).

Estimation of physiologic ability and surgical stress score does not predict immediate outcome after pancreatic surgery

The Estimation of Physiologic Ability and Surgical Stress score was designed to predict postoperative morbidity and mortality in general surgery. Our study aims to evaluate its use and accuracy in estimating postoperative outcome after elective pancreatic surgery.

Novel positron emission tomography/computed tomography of diffuse parenchymal lung disease combining a labeled somatostatin receptor analogue and 2-deoxy-2[¹⁸F]fluoro-D-glucose

We prospectively investigated the potential of positron emission tomography (PET) using the somatostatin receptor (SSTR) analogue ⁶⁸Ga-DOTATATE and 2-deoxy-2[¹⁸F]fluoro-D-glucose (¹⁸F-FDG) in diffuse parenchymal lung disease (DPLD). Twenty-six patients (mean age 68.9 ± 11.0 years) with DPLD were recruited for ⁶⁸Ga-DOTATATE and ¹⁸F-FDG combined PET/high-resolution computed tomography (HRCT) studies. Ten patients had idiopathic pulmonary fibrosis (IPF), 12 patients had nonspecific interstitial pneumonia (NSIP), and 4 patients had other forms of DPLD. Using PET, the pulmonary tracer uptake (maximum standardized uptake value [SUV(max)]) was calculated. The distribution of PET tracer was compared to the distribution of lung parenchymal changes on HRCT. All patients demonstrated increased pulmonary PET signal with ⁶⁸Ga-DOTATATE and ¹⁸F-FDG. The distribution of parenchymal uptake was similar, with both tracers corresponding to the distribution of HRCT changes. The mean SUV(max) was 2.2 ± 0.7 for ⁶⁸Ga-DOTATATE and 2.8 ± 1.0 (t-test, p  =  .018) for ¹⁸F-FDG. The mean ⁶⁸Ga-DOTATATE SUV(max) in IPF patients was 2.5 ± 0.9, whereas it was 2.0 ± 0.7 (p  =  .235) in NSIP patients. The correlation between ⁶⁸Ga-DOTATATE SUV(max) and gas transfer (transfer factor of the lung for carbon monoxide [TLCO]) was r  =  -.34 (p  =  .127) and r  =  -.49 (p  =  .028) between ¹⁸F-FDG SUV(max) and TLCO. We provide noninvasive in vivo evidence in humans showing that SSTRs may be detected in the lungs of patients with DPLD in a similar distribution to sites of increased uptake of ¹⁸F-FDG on PET.

Spike-triggered reaction-time EEG as a possible assessment tool for driving ability

The impact of interictal epileptic activity (IEA) on driving is a rarely investigated issue. We analyzed the impact of IEA on reaction time in a pilot study. Reactions to simple visual stimuli (light flash) in the Flash test or complex visual stimuli (obstacle on a road) in a modified car driving computer game, the Steer Clear, were measured during IEA bursts and unremarkable electroencephalography (EEG) periods. Individual epilepsy patients showed slower reaction times (RTs) during generalized IEA compared to RTs during unremarkable EEG periods. RT differences were approximately 300 ms (p < 0.001) in the Flash test and approximately 200 ms (p < 0.001) in the Steer Clear. Prior work suggested that RT differences >100 ms may become clinically relevant. This occurred in 40% of patients in the Flash test and in up to 50% in the Steer Clear. When RT were pooled, mean RT differences were 157 ms in the Flash test (p < 0.0001) and 116 ms in the Steer Clear (p < 0.0001). Generalized IEA of short duration seems to impair brain function, that is, the ability to react. The reaction-time EEG could be used routinely to assess driving ability.

Detection of gelatinolytic activity in developing basement membranes of the mouse embryo head by combining sensitive in situ zymography with immunolabeling

Genetic evidence indicates that the major gelatinases MMP-2 and MMP-9 are involved in mammalian craniofacial development. Since these matrix metalloproteinases are secreted as proenzymes that require activation, their tissue distribution does not necessarily reflect the sites of enzymatic activity. Information regarding the spatial and temporal expression of gelatinolytic activity in the head of the mammalian embryo is sparse. Sensitive in situ zymography with dye-quenched gelatin (DQ-gelatin) has been introduced recently; gelatinolytic activity results in a local increase in fluorescence. Using frontal sections of wild-type mouse embryo heads from embryonic day 14.5-15.5, we optimized and validated a simple double-labeling in situ technique for combining DQ-gelatin zymography with immunofluorescence staining. MMP inhibitors were tested to confirm the specificity of the reaction in situ, and results were compared to standard SDS-gel zymography of tissue extracts. Double-labeling was used to show the spatial relationship in situ between gelatinolytic activity and immunostaining for gelatinases MMP-2 and MMP-9, collagenase 3 (MMP-13) and MT1-MMP (MMP-14), a major activator of pro-gelatinases. Strong gelatinolytic activity, which partially overlapped with MMP proteins, was confirmed for Meckel's cartilage and developing mandibular bone. In addition, we combined in situ zymography with immunostaining for extracellular matrix proteins that are potential gelatinase substrates. Interestingly, gelatinolytic activity colocalized precisely with laminin-positive basement membranes at specific sites around growing epithelia in the developing mouse head, such as the ducts of salivary glands or the epithelial fold between tongue and lower jaw region. Thus, this sensitive method allows to associate, with high spatial resolution, gelatinolytic activity with epithelial morphogenesis in the embryo.