Social and clinical predictors of perianal colonisation by multidrug-resistant bacteria for geriatric patients in the internal medicine service.

BACKGROUND: Colonisation by multidrug-resistant (MDR) bacteria is a global health issue. The identification of patients with a higher risk of colonisation is essential. Patients admitted to internal medicine services might represent a vulnerable population with a high risk of colonisation. This study was the first to assess social and clinical variables associated with a higher risk of perianal colonisation by MDR bacteria in a Spanish cohort of patients admitted to internal medicine service. METHODS: Patients admitted to an internal medicine service during 12 months of recruitment (1 March 2022 to 1 March 2023) were included in the study. Perianal swabs were performed at admission to identify the presence of MDR bacteria. Social and clinical variables were collected following a directed acyclic graph. A cluster analysis was performed to identify clinical profiles of higher risk. Bivariate analyses and multivariable logistic regression models were fitted to identify potential predictors of MDR bacteria colonisation. RESULTS: A total of 245 patients, according to the required sample size, were included. Of them, 46 (18.8%) were colonised by MDR bacteria in perianal swabs. Female sex, age > 80 years, dependency on activities of daily living, cognitive deterioration and living in long-term care facilities constituted the highest risk clinical profile. After adjustments, living in long-term care facilities and malnutrition remained the main risk factors identified. CONCLUSION: Patients admitted to internal medicine services presented a high frequency of perianal colonisation by MDR bacteria. Social and clinical variables associated with bio-psycho-social susceptibility were associated with colonisation. Special surveillance is needed in internal medicine services to control the transmission.

Trihydrogen Cation Helium Clusters: A New Potential Energy Surface.

We present a new analytical potential energy surface (PES) for the interaction between the trihydrogen cation and a He atom, H 3 + - H e ${{H}_{3}^{+}-He}$ , in its electronic ground state. The proposed PES has been built as a sum of two contributions: a polarization energy term due to the electric field generated by the molecular cation at the position of the polarizable He atom, and an exchange-repulsion and dispersion interactions represented by a sum of "atom-bond" potentials between the three bonds of H 3 + ${{H}_{3}^{+}}$ and the He atom. All parameters of this new PES have been chosen and fitted from data obtained from high-level ab-initio calculations. Using this new PES plus the Aziz-Slaman potential for the interaction between Helium atoms and assuming pair-wise interactions, we carry out classical Basin-Hopping (BH) global optimization, semiclassical BH with Zero Point Energy corrections, and quantum Diffusion Monte Carlo simulations. We have found the minimum energy configurations of small He clusters doped with H 3 + ${{H}_{3}^{+}}$ , H 3 + H e N ${{H}_{3}^{+}{\left(He\right)}_{N}}$ , with N=1-16. The study of the energies of these clusters allows us to find a pronounced anomaly for N=12, in perfect agreement with previous experimental findings, which we relate to a greater relative stability of this aggregate.

Forecasting levels of serum 25-hydroxyvitamin D based on dietary intake, lifestyle and personal determinants in a sample of Southern Europeans.

Vitamin D is an essential nutrient to be consumed in the habitual dietary intake, whose deficiency is associated with various disturbances. This study represents a validation of vitamin D status estimation using a semi-quantitative FFQ, together with data from additional physical activity and lifestyle questionnaires. This information was combined to forecast the serum vitamin D status. Different statistical methods were applied to estimate the vitamin D status using predictors based on diet and lifestyle. Serum vitamin D was predicted using linear regression (with leave-one-out cross-validation) and random forest models. Intraclass correlation coefficients, Lin's agreement coefficients, Bland-Altman plots and other methods were used to assess the accuracy of the predicted v. observed serum values. Data were collected in Spain. A total of 220 healthy volunteers aged between 18 and 78 years were included in this study. They completed validated questionnaires and agreed to provide blood samples to measure serum 25-hydroxyvitamin D (25(OH)D) levels. The common final predictors in both models were age, sex, sunlight exposure, vitamin D dietary intake (as assessed by the FFQ), BMI, time spent walking, physical activity and skin reaction after sun exposure. The intraclass correlation coefficient for the prediction was 0·60 (95 % CI: 0·52, 0·67; P < 0·001) using the random forest model. The magnitude of the correlation was moderate, which means that our estimation could be useful in future epidemiological studies to establish a link between the predicted 25(OH)D values and the occurrence of several clinical outcomes in larger cohorts.

Correction: Helium nanodroplets as an efficient tool to investigate hydrogen attachment to alkali cations.

Correction for 'Helium nanodroplets as an efficient tool to investigate hydrogen attachment to alkali cations' by Siegfried Kollotzek et al., Phys. Chem. Chem. Phys., 2023, 25, 462-470, https://doi.org/10.1039/D2CP03841B.

Antimicrobial potential of new diclofenac hydrogels for disinfection in regenerative endodontics: An in vitro and ex vivo study.

AIM: There is a need to explore new alternatives for root canal disinfection in regenerative endodontics, since the current strategies are far from ideal. Currently, the potential use of diclofenac (DC) is being investigated for controlling root canal infections. The objective was to evaluate the antimicrobial efficacy of novel DC-based hydrogels (DCHs) against polymicrobial biofilms grown in radicular dentine and root canals and to compare results with triantibiotic (TAH) and diantibiotic (DAH) hydrogels, and calcium hydroxide (Ca[OH]2 ). METHODOLOGY: The in vitro antimicrobial activity of intracanal medicaments was evaluated against 3-week-old polymicrobial root canal biofilms grown on human radicular dentine. Dentine samples were obtained and randomly divided into the study groups (n = 4/group): (1) 1 mg/ml TAH; (2) 1 mg/ml DAH; (3) 5% diclofenac (DCH); (4) 2.5% DCH; (5) 1.25% DCH; (6) 1 mg/ml DAH + 5% DCH; (7) Ca(OH)2 paste; (8) positive control. The microbial viability, in terms of percentage of intact cell membranes, was assessed after 7 days by confocal scanning laser microscopy (CSLM). The ex vivo efficacy of intracanal medications was evaluated in root canals infected with a polymicrobial suspension. Intracanal microbiological samples at baseline (S1) and 7 days post-treatment (S2) were taken; microbial quantification and cell viability were assessed by quantitative polymerase chain reaction (qPCR) and flow cytometry (FC). The mean Log10 of bacterial DNA copies in root canal samples before (S1) and the Log10 reduction of DNA copies S1-S2 in qPCR were recorded. The absolute value of total cells stained, and the percentage reduction of intact membrane cells after treatment (S1-S2), were analysed by FC. Global comparison was done using the Kruskal-Wallis test, whilst the Mann-Whitney U test was used for pair-by-pair comparison. RESULTS: Confocal scanning laser microscopy analysis indicated that the greatest effectiveness was obtained with 5% DCH, showing significant differences with respect to the other groups (p < .001). In root canals, the highest Log10 DNA reduction S1-S2 was obtained with 5% DCH and TAH, with no differences between them. The results of FC showed that only 5% DCH proved significantly superior to the other treatments. CONCLUSIONS: Sodium DC hydrogels demonstrate antimicrobial efficacy against endodontic biofilms.

Alcohol and early mortality (before 65 years) in the 'Seguimiento Universidad de Navarra' (SUN) cohort: does any level reduce mortality?

The aim of this study was to assess the association between alcohol intake and premature mortality (younger than 65 years) and to explore the effect of potential alcohol underreporting by heavy drinkers. We followed-up 20 272 university graduates. Four categories of alcohol intake were considered (abstainer, light, moderate and heavy consumption). Repeated measurements of alcohol intake and updated information on confounders were used in time-dependent Cox models. Potential underreporting of alcohol intake by some heavy drinkers (likely misclassified as light or moderate drinkers) was explicitly addressed in an attempt to correct potential underreporting by using indirect information. During 12·3 years of median follow-up (interquartile range: 6·8-15·0), 226 participants died before their 65th birthday. A higher risk of early mortality was found for the highest category of alcohol intake (≥50 g/d) in comparison with abstention (multivariable-adjusted hazard ratio (HR) = 2·82, 95 % CI 1·38, 5·79). In analyses of alcohol as a continuous variable, the multivariable-adjusted HR was 1·17 (95 % CI 1·08, 1·26), for each 10 g/d of alcohol. This harmful linear association was present both in uncorrected models and in models corrected for potential underreporting. No significant inverse association between light or moderate alcohol intake and premature mortality was observed, even after correcting for potential misclassification. Alcohol intake exhibited a harmful linear dose-response association with premature mortality (<65 years) in this young and highly educated Mediterranean cohort. Our attempts to correct for potential misclassification did not substantially change these results.

Helium nanodroplets as an efficient tool to investigate hydrogen attachment to alkali cations.

We report a novel method to reversibly attach and detach hydrogen molecules to positively charged sodium clusters formed inside a helium nanodroplet host matrix. It is based on the controlled production of multiply charged helium droplets which, after picking up sodium atoms and exposure to H2 vapor, lead to the formation of Nam+(H2)n clusters, whose population was accurately measured using a time-of-flight mass spectrometer. The mass spectra reveal particularly favorable Na+(H2)n and Na2+(H2)n clusters for specific "magic" numbers of attached hydrogen molecules. The energies and structures of these clusters have been investigated by means of quantum-mechanical calculations employing analytical interaction potentials based on ab initio electronic structure calculations. A good agreement is found between the experimental and the theoretical magic numbers.

Ca+ Ions Solvated in Helium Clusters.

We present a combined experimental and theoretical investigation on Ca+ ions in helium droplets, HeNCa+. The clusters have been formed in the laboratory by means of electron-impact ionization of Ca-doped helium nanodroplets. Energies and structures of such complexes have been computed using various approaches such as path integral Monte Carlo, diffusion Monte Carlo and basin-hopping methods. The potential energy functions employed in these calculations consist of analytical expressions following an improved Lennard-Jones formula whose parameters are fine-tuned by exploiting ab initio estimations. Ion yields of HeNCa+ -obtained via high-resolution mass spectrometry- generally decrease with N with a more pronounced drop between N=17 and N=25, the computed quantum HeNCa+ evaporation energies resembling this behavior. The analysis of the energies and structures reveals that covering Ca+ with 17 He atoms leads to a cluster with one of the smallest energies per atom. As new atoms are added, they continue to fill the first shell at the expense of reducing its stability, until N=25, which corresponds to the maximum number of atoms in that shell. Behavior of the evaporation energies and radial densities suggests liquid-like cluster structures.

Snowball formation for Cs+ solvation in molecular hydrogen and deuterium.

Interactions of atomic cations with molecular hydrogen are of interest for a wide range of applications in hydrogen technologies. These interactions are fairly strong despite being non-covalent, hence one can ask whether hydrogen molecules would form dense, solid-like, solvation shells around the ion (snowballs) or rather a more weakly bound compound. In this work, the interactions between Cs+ and H2 are studied both experimentally and computationally. Isotopic substitution of H2 by D2 is also investigated. On the one hand, helium nanodroplets doped with cesium and hydrogen or deuterium are ionized by electron impact and the (H2/D2)nCs+ (up to n = 30) clusters formed are identified via mass spectrometry. On the other hand, a new analytical potential energy surface, based on ab initio calculations, is developed and used to study cluster energies and structures by means of classical and quantum-mechanical Monte Carlo methods. The most salient features of the measured ion abundances are remarkably mimicked by the computed evaporation energies, particularly for the clusters composed of deuterium. This result supports the reliability of the present potential energy surface and allows us to recommend its use in related systems. Clusters with either twelve H2 or D2 molecules stand out for their stability and quasi-rigid icosahedral structures. However, the first solvation shell involves thirteen or fourteen molecules for hydrogenated or deuterated clusters, respectively. This shell retains its internal structure when extra molecules are added to the second shell and is nearly solid-like, especially for the deuterated clusters. The role played by three-body induction interactions as well as the rotational degrees of freedom is analyzed and they are found to be significant (up to 15% and 18%, respectively) for the molecules belonging to the first solvation shell.

A combined experimental and theoretical investigation of Cs+ ions solvated in HeN clusters.

Solvation of Cs+ ions inside helium droplets has been investigated both experimentally and theoretically. On the one hand, mass spectra of doped helium clusters ionized with a crossed electron beam, HeNCs+, have been recorded for sizes up to N = 60. The analysis of the ratio between the observed peaks for each size N reveals evidences of the closure of the first solvation shell when 17 He atoms surround the alkali ion. On the other hand, we have obtained energies and geometrical structures of the title clusters by means of basin-hopping, diffusion Monte Carlo (DMC), and path integral Monte Carlo (PIMC) methods. The analytical He-Cs+ interaction potential employed in our calculations is represented by the improved Lennard-Jones expression optimized on high level ab initio energies. The weakness of the existing interaction between helium and Cs+ in comparison with some other alkali ions such as Li+ is found to play a crucial role. Our theoretical findings confirm that the first solvation layer is completed at N = 17 and both evaporation and second difference energies obtained with the PIMC calculation seem to reproduce a feature observed at N = 12 for the experimental ion abundance. The analysis of the DMC probability distributions reveals the important contribution from the icosahedral structure to the overall configuration for He12Cs+.

Mediterranean diet, physical activity and their combined effect on all-cause mortality: The Seguimiento Universidad de Navarra (SUN) cohort.

The health benefits of the Mediterranean diet (MedDiet) and of physical activity (PA) have been widely documented. However, no longitudinal studies have investigated their combined effect on mortality. We assessed the individual and combined effects of adherence to the MedDiet and PA on all-cause mortality. We used data from 19,467 participants from a prospective cohort of Spanish university graduates, the SUN cohort, followed-up between December 1999 and February 2016. Adherence to the MedDiet was assessed using four different dietary scores, categorizing the quantitative scores into tertiles of adherence. To assess multiple dimensions of PA, an 8-item score was built. Multivariable Cox regression models were used to study the individual and combined relationship of adherence to the MedDiet and PA with all-cause mortality. During a median follow-up of 10.3years, we registered 305 deaths. Compared with the lowest adherence to the MedDiet (<20 in the modified Mediterranean diet score), better adherence (23-30 points) was associated with lower mortality (multivariable-adjusted hazard ratio [HR]=0.66, 95% confidence interval [CI]: 0.46-0.96). Engaging in moderate or high levels of PA (versus lower levels) was associated with 44% and 52% relative reductions in mortality, respectively. High adherence to the MedDiet combined with engaging in higher amounts of PA showed a HR=0.36 (95% CI: 0.19-0.67). We documented that the combined effect of better adherence to the MedDiet and increased PA had multiplicative effects on mortality risk reduction.

Lithium ions solvated in helium.

We report on a combined experimental and theoretical study of Li+ ions solvated by up to 50 He atoms. The experiments show clear enhanced abundances associated with HenLi+ clusters where n = 2, 6, 8, and 14. We find that classical methods, e.g. basin-hopping (BH), give results that qualitatively agree with quantum mechanical methods such as path integral Monte Carlo, diffusion Monte Carlo and quantum free energy, regarding both energies and the solvation structures that are formed. The theory identifies particularly stable structures for n = 4, 6 and 8 which line up with some of the most abundant features in the experiments.

Adsorption of molecular hydrogen on coronene with a new potential energy surface.

Benchmark interaction energies between coronene, C24H12, and molecular hydrogen, H2, have been computed by means of high level electronic structure calculations. Binding energies, equilibrium distances and strengths of the long range attraction, evaluated for the basic configurations of the H2-C24H12 complex, indicate that the system is not too affected by the relative orientations of the diatom, suggesting that its behavior can be approximated to that of a pseudoatom. The obtained energy profiles have confirmed the noncovalent nature of the bonding and serve to tune-up the parameters of a new force field based on the atom-bond approach which correctly describes the main features of the H2-coronene interaction. The structure and binding energies of (para-H2)N-coronene clusters have been investigated with an additive model for the above mentioned interactions and exploiting basin-hopping and path integral Monte Carlo calculations for N = 1-16 at T = 2 K. Differences with respect to the prototypical (rare gas)N-coronene aggregates have been discussed.

Comparative investigation of pure and mixed rare gas atoms on coronene molecules.

Clusters formed by the combination of rare gas (RG) atoms of He, Ne, Ar, and Kr on coronene have been investigated by means of a basin-hopping algorithm and path integral Monte Carlo calculations at T = 2 K. Energies and geometries have been obtained and the role played by the specific RG-RG and RG-coronene interactions on the final results is analysed in detail. Signatures of diffuse behavior of the He atoms on the surface of the coronene are in contrast with the localization of the heavier species, Ar and Kr. The observed coexistence of various geometries for Ne suggests the motion of the RG atoms on the multi-well potential energy surface landscape offered by the coronene. Therefore, the investigation of different clusters enables a comparative analysis of localized versus non-localized features. Mixed Ar-He-coronene clusters have also been considered and the competition of the RG atoms to occupy the docking sites on the molecule is discussed. All the obtained information is crucial to assess the behavior of coronene, a prototypical polycyclic aromatic hydrocarbon clustering with RG atoms at a temperature close to that of interstellar medium, which arises from the critical balance of the interactions involved.

Examination of the Feynman-Hibbs Approach in the Study of NeN-Coronene Clusters at Low Temperatures.

Feynman-Hibbs (FH) effective potentials constitute an appealing approach for investigations of many-body systems at thermal equilibrium since they allow us to easily include quantum corrections within standard classical simulations. In this work we apply the FH formulation to the study of NeN-coronene clusters (N = 1-4, 14) in the 2-14 K temperature range. Quadratic (FH2) and quartic (FH4) contributions to the effective potentials are built upon Ne-Ne and Ne-coronene analytical potentials. In particular, a new corrected expression for the FH4 effective potential is reported. FH2 and FH4 cluster energies and structures-obtained from energy optimization through a basin-hopping algorithm as well as classical Monte Carlo simulations-are reported and compared with reference path integral Monte Carlo calculations. For temperatures T > 4 K, both FH2 and FH4 potentials are able to correct the purely classical calculations in a consistent way. However, the FH approach fails at lower temperatures, especially the quartic correction. It is thus crucial to assess the range of applicability of this formulation and, in particular, to apply the FH4 potentials with great caution. A simple model of N isotropic harmonic oscillators allows us to propose a means of estimating the cutoff temperature for the validity of the method, which is found to increase with the number of atoms adsorbed on the coronene molecule.

Coronene molecules in helium clusters: Quantum and classical studies of energies and configurations.

Coronene-doped helium clusters have been studied by means of classical and quantum mechanical (QM) methods using a recently developed He-C24H12 global potential based on the use of optimized atom-bond improved Lennard-Jones functions. Equilibrium energies and geometries at global and local minima for systems with up to 69 He atoms were calculated by means of an evolutive algorithm and a basin-hopping approach and compared with results from path integral Monte Carlo (PIMC) calculations at 2 K. A detailed analysis performed for the smallest sizes shows that the precise localization of the He atoms forming the first solvation layer over the molecular substrate is affected by differences between relative potential minima. The comparison of the PIMC results with the predictions from the classical approaches and with diffusion Monte Carlo results allows to examine the importance of both the QM and thermal effects.

Spectroradiometry with sub-microsecond time resolution using multianode photomultiplier tube assemblies.

Accurate and precise measurements of spectroradiometric temperature are crucial for many high pressure experiments that use diamond anvil cells or shock waves. In experiments with sub-millisecond timescales, specialized detectors such as streak cameras or photomultiplier tubes are required to measure temperature. High accuracy and precision are difficult to attain, especially at temperatures below 3000 K. Here, we present a new spectroradiometry system based on multianode photomultiplier tube technology and passive readout circuitry that yields a 0.24 µs rise-time for each channel. Temperature is measured using five color spectroradiometry. During high pressure pulsed Joule heating experiments in a diamond anvil cell, we document measurement precision to be ±30 K at temperatures as low as 2000 K during single-shot heating experiments with 0.6 µs time-resolution. Ambient pressure melting tests using pulsed Joule heating indicate that the accuracy is ±80 K in the temperature range 1800-2700 K.

Surgical Treatment in Post-Stroke Spastic Hands: A Systematic Review.

Background: For more than two decades, the surgical treatment of post-stroke spastic hands has been displaced by botulinum toxin therapy and is currently underutilized. Objectives: This article aimed to assess the potential of surgery for treating a post-stroke spastic upper extremity through a systematic review of the literature on surgical approaches that are adopted in different profiles of patients and on their outcomes and complications. Methods: Medline PubMed, Web of Science, SCOPUS, and Cochrane Library databases were searched for observational and experimental studies published in English up to November 2022. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) system. Results: The search retrieved 501 abstracts, and 22 articles were finally selected. The GRADE-assessed quality of evidence was low or very low. The results of the reviewed studies suggest that surgery is a useful, safe, and enduring treatment for post-stroke spastic upper extremities, although most studied patients were candidates for hygienic improvements alone. Patients usually require an individualized combination of techniques. Over the past ten years, interest has grown in procedures that act on the peripheral nerve. Conclusions: Despite the lack of comparative studies on the effectiveness, safety, and cost of the treatments, botulinum toxin has displaced surgery for these patients. Studies to date have found surgery to be an effective and safe approach, but their weak design yields only poor-quality evidence, and clinical trials are warranted to compare these treatment options.

Virtual indentation of the empty capsid of the minute virus of mice using a minimal coarse-grained model.

A minimal coarse-grained model for T=1 viral capsids assembled from 20 protein rigid trimers has been designed by extending a previously proposed form of the interaction energy written as a sum of anisotropic pairwise interactions between the trimeric capsomers. The extension of the model has been performed to properly account for the coupling between two internal coordinates: the one that measures the intercapsomer distance and the other that gives the intercapsomer dihedral angle. The model has been able to fit with less than a 10% error the atomic force microscopy (AFM) indentation experimental data for the empty capsid of the minute virus of mice (MVM), providing in this way an admissible picture of the main mechanisms behind the capsid deformations. In this scenario, the bending of the intercapsomer dihedral angle is the angular internal coordinate that can support larger deformations away from its equilibrium values, determining important features of the AFM indentation experiments as the elastic constants along the three symmetry axes of the capsid and the critical indentations. From the value of one of the parameters of our model, we conclude that trimers in the MVM must be quite oblate tops, in excellent agreement with their known structure. The transition from the linear to the nonlinear regimes sampled in the indentation process appears to be an interesting topic for future research in physical virology.

A point mutation in the ubiquitin-associated domain of SQSMT1 is sufficient to cause a Paget's disease-like disorder in mice.

Mutations of SQSTM1 occur in about10% of patients with Paget's disease of bone (PDB), but it is unclear whether they play a causal role or regulate susceptibility to an environmental trigger. Here we show that mice with a proline to leucine mutation at codon 394 of mouse sqstm1 (P394L), equivalent to the P392L SQSTM1 mutation in humans, develop a bone disorder with remarkable similarity to PDB. The P394L mutant mice developed focal bone lesions with increasing age and by 12 months, 14/18 (77%) heterozygotes and 20/21 (95%) homozygotes had lesions, compared with 0/18 (0%) wild-type littermates (P< 0.001). Lesions predominantly affected the lower limbs in an asymmetric manner and were characterized by focal increases in bone turnover, with increased bone resorption and formation, disruption of the normal bone architecture and accumulation of woven bone. Osteoclasts within lesions were larger and more nucleated than normal and some contained nuclear inclusions similar to those observed in human PDB. Osteoclast precursors from P394L mutant mice had increased sensitivity to RANKL in vitro resulting in the generation of osteoclasts that were larger and more nucleated than those generated from wild-type littermates. There was increased expression of sqstm1, autophagy-related gene 5 (atg5) and light chain 3 gene (lc3) in osteoclast precursors and increased LC3-II protein levels in Bafilomycin-treated osteoclasts from P394L mutant mice compared with wild-type suggesting dysregulation of autophagy and enhanced autophagosome formation. These studies demonstrate that SQSTM1 mutations can cause a PDB-like skeletal disorder in the absence of an additional trigger and provide a new disease model for PDB.