Cartesian constraints in QM/MM optimizations.

With the rise of quantum mechanical/molecular mechanical (QM/MM) methods, the interest in the calculation of molecular assemblies has increased considerably. The structures and dynamics of such assemblies are usually governed to a large extend by intermolecular interactions. As a result, the corresponding potential energy surfaces are topological rich and possess many shallow minima. Therefore, local structure optimizations of QM/MM molecular assemblies can be challenging, in particular if optimization constraints are imposed. To overcome this problem, structure optimization in normal coordinate space is advocated. To do so, the external degrees of freedom of a molecule are separated from the internal ones by a projector matrix in the space of the Cartesian coordinates. Here we extend this approach to Cartesian constraints. To this end, we devise an algorithm that adds the Cartesian constraints directly to the projector matrix and in this way eliminates them from the reduced coordinate space in which the molecule is optimized. To analyze the performance and stability of the constrained optimization algorithm in normal coordinate space, we present constrained minimizations of small molecular systems and amino acids in gas phase as well as water employing QM/MM constrained optimizations. All calculations are performed in the framework of auxiliary density functional theory as implemented in the program deMon2k.

Infection prevention and control between legal requirements and German Society for Hygiene and Microbiology expert assessments: a cross-sectional study in September-November 2022.

BACKGROUND: In contrast to the beginning of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), pandemic, more and more hospital issues are now regulated by policy. AIM: To identify differences between expert recommendations and legal requirements regarding infection prevention and control (IPC) strategies. METHODS: A cross-sectional study was conducted between 29th September 2022 and 3rd November 2022 addressing 1319 members of the German Society for Hygiene and Microbiology. The response rate was 12%. This paper reports the expert recommendations on different IPC strategies. FINDINGS: The majority (66%) of experts recommended universal mask usage, with 34% recommending it seasonally, even after the SARS-CoV-2 pandemic. Medical microbiology (MM) experts were more likely to recommend continuing to wear the masks indefinitely compared with IPC experts. Concerning the mask type, medical masks were recommended more frequently by IPC experts (47.3%), while FFP2 masks were preferred by MM experts (31.8%). The majority (54.7%) of experts recommended universal screening of employees, mainly in settings with extremely vulnerable patients and if regional incidence rates were high, at a frequency of twice per week. The dominant advice (recommended by at least 50% of experts) for employees exposed to SARS-CoV-2 was daily testing and wearing a mask, regardless of the length of exposure. CONCLUSIONS: Expert recommendations deviate from the legal requirements and appear to be more differentiated and proportional. The influence of specific experience and expertise on mask recommendations should be investigated in more detail. For relevant policy decisions, a quick, focused and broad-based consultation of expertise could be of added value.

Hybrid ADFT Study of the C104 and C106 IPR Isomers.

This work presents a hybrid auxiliary density functional theory (ADFT) study of the neutral and hexaanionic C104 and C106 fullerenes with the aim to determine their ground state structures. To this end, all C104 and C106 fullerene structures that obey the isolated pentagon rule (IPR) were optimized with the Perdew-Burke-Ernzerhof generalized gradient approximation followed by a single-point energy calculation with the PBE0 hybrid functional. Our studies show that this composite approach yields relative energies of giant fullerenes that are accurate to around 1 kcal/mol. As a result, the ground states of C104, C1046-, and C1066- can be assigned to the isomers 234:Cs, 821:D2, and 891:Cs, respectively. On the other hand, the energetically lowest lying IPR isomers of C106, 331:Cs, 1194:C2, 534:C1 are separated by less than 1 kcal/mol which makes an unequivocal ground state assignment by hybrid DFT methods impossible. To guide future experiments, we also report the simulated IR and Raman spectra of the most stable neutral and hexaanionic C104 and C106 fullerenes.

Influence of spin multiplicity on the melting of Na55(+).

The influence of spin multiplicity on the melting of the Na55(+) cluster has been investigated by means of all-electron Kohn-Sham Born-Oppenheimer molecular dynamics simulations. On the basis of the quantitative agreement between the experimental and theoretical melting temperature and latent heat a detailed analysis of the cluster dynamics was performed. This analysis showed a significant structure deformation of the cluster that is inconsistent with the geometrical shell closing concept. In subsequent structure optimizations a high-spin ground state in perfect icosahedral symmetry was found for the Na55(+) cluster. The Born-Oppenheimer molecular dynamics of this high-spin Na55(+) cluster indicates a particular thermal stability of the icosahedral cluster structure. A new electronic mechanism, named subshell closing, is suggested as the origin for this enhanced thermal stability of the icosahedral cluster structure. This mechanism is a natural extension of the common jellium model. By its nature, the subshell closing mechanism is general for finite systems and expected to be found in many other clusters for which the jellium model is applicable.

Double asymptotic expansion of three-center electronic repulsion integrals.

A double asymptotic expansion for the evaluation of three-center electron repulsion integrals (ERIs) in the long-range limit is presented. For the definition of this limit, a natural division of space based on the atomic coordinates and basis function exponents in utilized. The resulting analytical expression for the calculation of three-center ERIs in the long-range limit are implemented in the density functional theory program deMon2k. Validation and benchmark calculations of n-alkanes, hydrogen saturated graphene sheets and hydrogen saturated diamond blocks are discussed. It is shown that for a sufficient large number of long-range ERIs, the linear scaling regime is reached.

Contribution of high-energy conformations to NMR chemical shifts, a DFT-BOMD study.

This paper highlights the relevance of including the high-energy conformational states sampled by Born-Oppenheimer molecular dynamics (BOMD) in the calculation of time-averaged NMR chemical shifts. Our case study is the very flexible glycerol molecule that undergoes interconversion between conformers in a nonrandom way. Along the sequence of structures from one backbone conformer to another, transition states have been identified. The three (13)C NMR chemical shifts of the molecule were estimated by averaging their calculated values over a large set of BOMD snapshots. The simulation time needed to obtain a good agreement with the two signals present in the experimental spectrum is shown to be dependent on the atomic orbital basis set used for the dynamics, with a necessary longer trajectory for the most extended basis sets. The large structural deformations with respect to the optimized conformer geometries that occur along the dynamics are related to a kinetically driven conformer distribution. Calculated conformer type populations are in good agreement with experimental gas phase microwave results.

Structural changes of Pd13 upon charging and oxidation/reduction.

First-principle generalized gradient corrected density functional calculations have been performed to study the stability of cationic and anionic Pd(13) (+∕-), and neutral Pd(13)O(2) clusters. It is found that while cationic Pd(13) (+) favors a C(s) geometry similar to the neutral Pd(13), both anionic Pd(13)(-) and neutral Pd(13)O(2) favor a compact ~I(h) structure. A detailed analysis of the electronic structure shows that the stabilization of the delocalized 1P and 2P cluster orbitals, and the hybridization of the 1D orbitals with the oxygen atomic p orbitals play an important role in the energetic ordering of C(s) and ~I(h) isomers. A structural oscillation is predicted during an oxidation/reduction cycle of Pd(13) in which small energy barriers between 0.3 and 0.4 eV are involved.

Density Functional Study of 2-[(R-Phenyl)amine]-1,4-naphthalenediones.

The molecular and electronic structures of a series of 2-[(R-phenyl)amine]-1,4-naphthalenediones (R = m-Me, p-Me, m-Et, p-CF3, p-Hex, p-Et, m-F, m-Cl, p-OMe, p-COMe, p-Bu, m-COOH, p-Cl, p-COOH, p-Br, m-NO2, m-CN, and p-NO2) and their anions are investigated in the framework of density functional theory. The calculations are of all-electron type using a double zeta valence polarization basis set optimized for density functional theory methods. The theoretical study shows that all compounds are nonplanar. The nonplanarity can be rationalized in terms of occupied π orbitals. A linear correlation between the measured half-wave potentials and the calculated gas-phase electron affinities is found. It holds for local as well as generalized gradient corrected functionals. Structural parameters, harmonic vibrational frequencies, and adiabatic and vertical electron affinities as well as orbital and spin density plots of the studied compounds are presented.

The cognitive development of pre-school children treated for chronic renal failure.

Chronic renal failure in young children is associated with impaired cognitive development, but recent studies present a more optimistic perspective. An important question is whether the earlier initiation of renal replacement therapy (RRT) might prevent the reported developmental retardation. The cognitive development of 31 patients (age < 5 years with a serum creatinine clearance of < 20% of normal) undergoing different treatment modalities was monitored by repeated measurements during a prospective 3-year study. Fifteen patients received conservative treatment and 16 patients were on dialysis treatment at the start of the project. We were able to evaluate the effect of the onset of RRT on 12 patients who were transferred from conservative treatment to dialysis. At the beginning of the study, the cognitive development of the total group was significantly delayed (mean developmental index = 78.5, SD = 19.5) compared with a normal population. Patients undergoing conservative treatment scored significantly higher (P < 0.01) than those on dialysis. The effect of starting dialysis treatment appeared to be positive, but only a significant short-term improvement was observed. Follow-up evaluation of 7 patients on conservative treatment and of 9 dialysis patients over a 2-year period did not show any significant change in a positive or negative direction. The present study revealed that pre-school dialysis patients are at risk with respect to their cognitive development. This is particularly true for the group with concomitant disorders. Less severe disease in the group on conservative treatment may be assumed to be a positive contributing factor to the more normal performance of these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Complement in serum and dialysate in children on continuous ambulatory peritoneal dialysis.

OBJECTIVE: During continuous ambulatory peritoneal dialysis (CAPD), activation of complement in the peritoneal cavity may theoretically occur, with inappropriately high or low levels of certain complement factors in dialysate as a consequence. In a group of children on CAPD, it was tested whether levels of a number of complement factors in dialysate were in the range that was predicted on the basis of their molecular weight. DESIGN: Serum and dialysate levels of C1q, C3, C4, C3d, B, D, and P were measured after a night dwell in children on CAPD. Simultaneously, four non-complement proteins (beta 2-microglobulin, albumin, IgG, and alpha 2-macroglobulin) were also measured in dialysate and serum. Assuming a linear relationship between the log base 10 of the dialysate/serum ratio of these non-complement proteins and the log base 10 of their molecular weight, the expected ratios of all complement factors were determined. The differences between actual and predicted ratios were tested using a modified t-test, taking into account the inaccuracy of the estimate. SETTING: University hospital. PATIENTS: A group of 14 children on CAPD, with a median age of 7.8 years (range 2.1 - 13.2). These children had been on CAPD for a median period of 42.4 months (range 0.4 - 89.1). RESULTS: The ratios of factor D (p < 0.001) and C3d (p = 0.035) were elevated, whereas those of C3 (p < 0.001), C4 (p < 0.001), and factor P (p = 0.012) were decreased. CONCLUSIONS: Relatively low dialysate/serum ratios of C4, C3, and factor P could be caused by intraperitoneal consumption of complement. High levels of C3d are compatible with this. High dialysate/serum ratios of factor D indicate intraperitoneal production of factor D. These results provide evidence for activation of complement in the peritoneal cavity in children on CAPD. A further reduction of already low levels of complement factors in dialysate as a result of this may impair host defense.

Predictors of success with neuromodulation in lower urinary tract dysfunction: results of trial stimulation in 100 patients.

Chronic lower urinary tract dysfunction can be treated by sacral neuro-stimulation. Clinical parameters for selection of patients for this expensive and invasive treatment modality are not well defined to date. Therefore, before implantation of a permanent stimulator, the effect is tested by temporary implantation of a wire electrode connected to an external stimulator. According to the literature, many patients do not respond during temporary implantation and a mean of 25% of the patients with a permanent stimulator implanted fail to respond as well. To improve patient selection, we attempted to define clinical parameters to predict the outcome of sacral neuro-stimulation in 100 consecutive patients who were tested with temporary sacral stimulation. A total of 34 patients achieved a complete cure on trial stimulation. It appeared that detrusor overactivity and urethral instability responded best but they were not predictors of success. We conclude that neither gender, patient age, history nor diagnosis are predictors of success in sacral neuro-stimulation of lower urinary tract dysfunction.

Pharmacokinetics of recombinant human erythropoietin in children treated with continuous ambulatory peritoneal dialysis.

UNLABELLED: In children treated by continuous ambulatory peritoneal dialysis (CAPD) renal anaemia is preferably treated by intraperitoneal administration of erythropoietin, since subcutaneous administration is painful and frightening for the child. Pharmacokinetics of erythropoietin were studied in three groups of children treated by CAPD. In group subcutaneous (SC) (n = 5) erythropoietin was administered subcutaneously, whereas in group intraperitoneal 1 (IP1) (n = 8) and intraperitoneal 2 (IP2) (n = 8) erythropoietin was given intraperitoneally during a 12-h dwell. Group IP1 received erythropoietin in 20 ml/kg of dialysis fluid, while in group IP2 the hormone was added to only 50 ml of dialysate, irrespective of body weight. The median area under the curve (AUC) was 4064 mU.h/ml (range 2647-24357) in group SC, 1698 (570-5514) in group IP1 and 3577 (1225-6555) in group IP2. In comparison to group SC the AUC was significantly lower in group IP1 (Wilcoxon: P = 0.02). The difference between group SC and group IP2 was not statistically significant. CONCLUSION: In children on CAPD the resorption of erythropoietin after intraperitoneal administration, measured as AUC, is similar to subcutaneous administration, when erythropoietin is administered in 50 ml of dialysate. The dose needed to treat renal anaemia with erythropoietin administered intraperitoneally this way will have to be established in a therapeutic study.

Biannual radiographic assessments of hands and feet in a three-year prospective followup of patients with early rheumatoid arthritis.

In a prospective followup study of 147 patients with rheumatoid arthritis of recent onset, we assessed the progression of radiographic evidence of joint damage on films of the patients' hands and feet obtained biannually. Patients were receiving first-line and second-line treatment. Ninety patients were followed up for 3 years, and 57 were followed up for only 2 years. Radiographic damage was determined by a modification of the method described by Sharp, and to ensure comparability of findings, we determined the percentage of damage per joint group (actual score divided by the maximum possible score). After 3 years, radiographic damage was present in 70% of the patients, all of whom could be identified after 1 year of study. Overall, 18-20% of the joints of the hands and feet were affected after 3 years, with relatively little abnormality per joint (approximately 8% of maximum possible score). During the entire followup, more foot joints than hand joints were affected. The rate of progression in the first year was significantly higher than in the second and third years of study, indicating a flattening of the curve of radiographic progression of joint damage.

High CA-125 concentrations in peritoneal fluid of normal cyclic women with various infertility-related factors as demonstrated with two-step immunoradiometric assay.

OBJECTIVE: To determine CA-125 concentrations and total amounts in peritoneal fluid (PF) of women with various infertility-related factors throughout the menstrual cycle. DESIGN: Peritoneal fluid was obtained at laparoscopy. CA-125 was determined using the assessed two-step immunoradiometric assay (IRMA) which, in contrast to the one-step IRMA, gives valid results. SETTING: University Hospital Nijmegen, Nijmegen, The Netherlands. PATIENTS: One hundred six infertile women with a regular and ovulatory cycle were included. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): The mean PF CA-125 concentration and total amount were significantly lower during the luteal phase as compared with other phases of the menstrual cycle. No correlation was found with the presence or absence of endometriosis, adhesions, a male and/or cervical mucus infertility factor, and with patent or closed fallopian tubes. RESULTS: Peritoneal fluid CA-125 concentrations varied from 630 to 12,000 arbitrary units/mL (mean +/- SD = 3,437 +/- 2,286). Total PF CA-125 amounts (concentration x PF volume) varied from 1,760 to 13,300 arbitrary units (mean +/- SD = 30,219 +/- 26,841). CONCLUSIONS: CA-125 secretion into the abdominal cavity varies during the menstrual cycle. Retrograde menstruation is not the main source of CA-125 in PF.