Gut microbiome in impulsively violent female convicts.

Introduction Impulsivity and aggression are often interlinked behavioral traits that have major implications for our society. Therefore, the study of this phenomenon and derivative interventions that could lead to better control of impulsive aggression are of interest. Methods We analyzed the composition and diversity of the gut bacterial microbiome of 33 impulsively violent female convicts with dissocial personality disorder and 20 non-impulsive age-matched women. Further, levels of assorted neurotransmitters and short-chain fatty acids (SCFA) were analyzed in serum and stool samples. We also assessed all participants using a battery of psychological questionnaires and tested possible correlations between the collected clinical data and the composition and diversity of their microbiomes and metabolites. Results We identified four bacterial amplicon sequencing variants that were differentially abundant in non-impulsive vs. impulsive women - the genera Bacteroides, Barnesiella, and the order Rhodospirillales were more abundant in impulsive women. In contrast, the genus Catenisphaera was more abundant in non-impulsive women. Fecal tryptophan levels were significantly higher in impulsive women. Association analysis revealed a strong positive intercorrelation between most fecal short-chain fatty acids in the entire dataset. Conclusions Our study demonstrated possible associations between gut microbiomes and their metabolites and impulsive behavior in a unique cohort of prisoners convicted of violent assaults and a matched group of non-impulsive women from the same prison. Genus Bacteroides, which was differentially abundant in the two groups, encoded enzymes that affect serotonin pathways and could contribute to this maladaptive behavior. Similarly, increased fecal tryptophan levels in impulsive individuals could affect neuronal circuits in the brain.

Aztreonam-avibactam versus meropenem for the treatment of serious infections caused by Gram-negative bacteria (REVISIT): a descriptive, multinational, open-label, phase 3, randomised trial.

BACKGROUND: There is a need for additional therapeutic options for serious infections caused by Gram-negative pathogens. In the phase 3, descriptive REVISIT study, we investigated the safety and efficacy of aztreonam-avibactam in the treatment of complicated intra-abdominal infections or hospital-acquired pneumonia or ventilator-associated pneumonia (HAP-VAP) caused, or suspected to be caused, by Gram-negative bacteria. METHODS: This prospective, multinational, open-label, central assessor-masked study enrolled adults who were hospitalised with a complicated intra-abdominal infection or HAP-VAP. Patients were randomly allocated via block randomisation using interactive response technology stratified by infection type in a 2:1 ratio to aztreonam-avibactam (with metronidazole for complicated intra-abdominal infection) or meropenem with or without colistin for 5-14 days for complicated intra-abdominal infection or 7-14 days for HAP-VAP. The primary endpoint was clinical cure at the test-of-cure visit (within 3 days before or after day 28) in the intention-to-treat (ITT) population. Secondary endpoints included 28-day mortality in the ITT population and safety in patients in the ITT population who received study drug (safety analysis set). No formal hypothesis testing was planned. The study was registered with ClinicalTrials.gov (NCT03329092) and EudraCT (2017-002742-68) and is complete. FINDINGS: Between April 5, 2018, and Feb 23, 2023, we screened 461 patients. 422 patients were enrolled and randomly allocated (282 in the aztreonam-avibactam group and 140 in the meropenem group, forming the ITT analysis set), of whom ten patients (seven in the aztreonam-avibactam group and three in the meropenem group) were randomly allocated but did not receive study treatment. 271 (64%) of 422 patients had at least one Gram-negative pathogen from an adequate specimen identified at baseline. The most frequent baseline pathogens were Enterobacterales (252 [93%] of 271). Overall, 19 (24%) of 80 isolates tested for carbapenemases were carbapenemase-positive (serine, metallo-ß-lactamase, or both). 193 (68·4%) of 282 patients in the aztreonam-avibactam group and 92 (65·7%) of 140 in the meropenem group had clinical cure at the test-of-cure visit (treatment difference 2·7% [95% CI -6·6 to 12·4]). For patients with complicated intra-abdominal infection, the adjudicated clinical cure rate was 76·4% (159 of 208) for the aztreonam-avibactam group and 74·0% (77 of 104) for the meropenem group. Cure rates in patients with HAP-VAP were 45·9% (34 of 74) for aztreonam-avibactam and 41·7% (15 of 36) for meropenem. 28-day all-cause mortality rates were 4% (12 of 282) for aztreonam-avibactam and 7% (ten of 140) for meropenem; in patients with complicated intra-abdominal infection, mortality was 2% (four of 208) and 3% (three of 104) for aztreonam-avibactam and meropenem, respectively, and in patients with HAP-VAP, mortality was 11% (eight of 74) and 19% (seven of 36), respectively. Aztreonam-avibactam was generally well tolerated, and safety findings were consistent with the known safety profile of aztreonam monotherapy. There were no treatment-related serious adverse events in the aztreonam-avibactam group. INTERPRETATION: These phase 3 efficacy and safety data provide support for aztreonam-avibactam as a potential therapeutic option for complicated intra-abdominal infection or HAP-VAP caused by Gram-negative bacteria. FUNDING: Pfizer.

Microplastics meet micropollutants in a central european river stream: Adsorption of pollutants to microplastics under environmentally relevant conditions.

Microplastics have emerged as pervasive pollutants in aquatic environments, and their interaction with organic contaminants poses a significant environmental challenge. This study aimed to explore the adsorption of micropollutants onto microplastics in a river, examining different plastic materials and the effect of aging on adsorption capacity. Microplastics (low-density polyethylene (LDPE), polyethylene terephthalate (PET), and polyvinyl chloride (PVC)) were introduced into a river stream, and a comprehensive analysis involving 297 organic pollutants was conducted. Passive samplers were deployed to monitor micropollutant presence in the river. Sixty-four analytes were identified in the river flow, with telmisartan being the most prevalent. Nonaged PVC showed the highest telmisartan concentration at 279 ng/g (168 ng/m2 regarding the microplastic surface), while aged PVC exhibited a fourfold decrease. Conversely, aged LDPE preferentially adsorbed metoprolol and tramadol, with concentrations increasing 12- and 3-fold, respectively, compared to nonaged LDPE. Azithromycin and clarithromycin, positively charged compounds, exhibited higher sorption to PET microplastics, regardless of aging. Diclofenac showed higher concentrations on nonaged PVC compared to aged PVC. Aging induced structural changes in microplastics, including color alterations, smaller particle production, and increased specific surface area. These changes influenced micropollutant adsorption, with hydrophobicity, dissociation constants, and the ionic form of pollutants being key factors. Aged microplastics generally showed different sorption properties. A comparison of microplastics and control sand particles indicated preferential micropollutant sorption to microplastics, underscoring their role as vectors for contaminant transport in aquatic ecosystems. Analysis of river sediment emphasized the significance of contact time in pollutant accumulation. Overall, this study provides insights into the complex interactions between microplastics and organic pollutants under environmental conditions and contributes to a better understanding of the fate and behavior of these two types of contaminants in aquatic ecosystems.

Ceftobiprole for Treatment of Complicated Staphylococcus aureus Bacteremia.

BACKGROUND: Ceftobiprole is a cephalosporin that may be effective for treating complicated Staphylococcus aureus bacteremia, including methicillin-resistant S. aureus. METHODS: In this phase 3, double-blind, double-dummy, noninferiority trial, adults with complicated S. aureus bacteremia were randomly assigned in a 1:1 ratio to receive ceftobiprole at a dose of 500 mg intravenously every 6 hours for 8 days and every 8 hours thereafter, or daptomycin at a dose of 6 to 10 mg per kilogram of body weight intravenously every 24 hours plus optional aztreonam (at the discretion of the trial-site investigators). The primary outcome, overall treatment success 70 days after randomization (defined as survival, bacteremia clearance, symptom improvement, no new S. aureus bacteremia-related complications, and no receipt of other potentially effective antibiotics), with a noninferiority margin of 15%, was adjudicated by a data review committee whose members were unaware of the trial-group assignments. Safety was also assessed. RESULTS: Of 390 patients who underwent randomization, 387 (189 in the ceftobiprole group and 198 in the daptomycin group) had confirmed S. aureus bacteremia and received ceftobiprole or daptomycin (modified intention-to-treat population). A total of 132 of 189 patients (69.8%) in the ceftobiprole group and 136 of 198 patients (68.7%) in the daptomycin group had overall treatment success (adjusted difference, 2.0 percentage points; 95% confidence interval [CI], -7.1 to 11.1). Findings appeared to be consistent between the ceftobiprole and daptomycin groups in key subgroups and with respect to secondary outcomes, including mortality (9.0% and 9.1%, respectively; 95% CI, -6.2 to 5.2) and the percentage of patients with microbiologic eradication (82.0% and 77.3%; 95% CI, -2.9 to 13.0). Adverse events were reported in 121 of 191 patients (63.4%) who received ceftobiprole and 117 of 198 patients (59.1%) who received daptomycin; serious adverse events were reported in 36 patients (18.8%) and 45 patients (22.7%), respectively. Gastrointestinal adverse events (primarily mild nausea) were more frequent with ceftobiprole. CONCLUSIONS: Ceftobiprole was noninferior to daptomycin with respect to overall treatment success in patients with complicated S. aureus bacteremia. (Funded by Basilea Pharmaceutica International and the U.S. Department of Health and Human Services; ERADICATE ClinicalTrials.gov number, NCT03138733.).

In vitro toxicity assessment of polyethylene terephthalate and polyvinyl chloride microplastics using three cell lines from rainbow trout (Oncorhynchus mykiss).

The RTgill-W1 (gill), RTG-2 (gonad), and RTL-W1 (liver) cell lines derived from a freshwater fish rainbow trout (Oncorhynchus mykiss), were used to assess the toxicity of polyethylene terephthalate (PET) and two forms of polyvinyl chloride (PVC). Two size fractions (25-µm and 90-µm particles) were tested for all materials. The highest tested concentration was 1 mg/ml, corresponding to from 70 000 ± 9000 to 620 000 ± 57 000 particles/ml for 25-µm particles and from 2300 ± 100 to 11 000 ± 1000 particles/ml for 90-µm particles (depending on the material). Toxicity differences between commercial PVC dry blend powder and secondary microplastics created from a processed PVC were newly described. After a 24-h exposure, the cells were analyzed for changes in viability, 7-ethoxyresorufin-O-deethylase (EROD) activity, and reactive oxygen species (ROS) generation. In addition to the microplastic suspensions, leachates and particles remaining after leaching resuspended in fresh exposure medium were tested. The particles were subjected to leaching for 1, 8, and 15 days. The PVC dry blend (25 µm and 90 µm) and processed PVC (25 µm) increased ROS generation, to which leached chemicals appeared to be the major contributor. PVC dry blend caused substantially higher ROS induction than processed PVC, showing that the former is not suitable for toxicity testing, as it can produce different results from those of secondary PVC. The 90-µm PVC dry blend increased ROS generation only after prolonged leaching. PET did not induce any changes in ROS generation, and none of the tested polymers had any effect on viability or EROD activity. The importance of choosing realistic extraction procedures for microplastic toxicity experiments was emphasized. Conducting long-term experiments is crucial to detect possible environmentally relevant effects. In conclusion, the tested materials showed no acute toxicity to the cell lines.

Magnetic nanoprecipitates and interfacial spin disorder in zero-field-annealed Ni50Mn45In5 Heusler alloys as seen by magnetic small-angle neutron scattering.

Shell ferromagnetism is a new functional property of certain off-stoichiometric Ni-Mn-In Heusler alloys, with a potential application in non-volatile magnetic memories and recording media. One key challenge in this field remains the determination of the structural and magnetic properties of the nanoprecipitates that are the result of an annealing-induced segregation process. Thanks to its unique mesoscopic length scale sensitivity, magnetic small-angle neutron scattering appears to be a powerful technique to disclose the microstructure of such annealing-induced nanoprecipitates. In this study, the microstructure of a zero-field-annealed off-stoichiometric Ni50Mn45In5 Heusler alloy is investigated by unpolarized magnetic small-angle neutron scattering. The neutron data analysis reveals a significant spin-misalignment scattering, which is mainly related to the formation of annealing-induced ferromagnetic nanoprecipitates in an antiferromagnetic matrix. These particles represent a source of perturbation which, due to dipolar stray fields, gives rise to canted spin moments in the surroundings of the particle-matrix interface. The presence of anticorrelations in the computed magnetic correlation function reflects the spatial perturbation of the magnetization vector around the nanoprecipitates. The magnetic field dependence of the zero crossing and the minima of the magnetic correlation function are qualitatively explained using the law of approach to ferromagnetic saturation for inhomogeneous spin states. More specifically, at remanence, the nanoprecipitates act magnetically as one superdefect with a correlation length that lies outside the experimental q range, whereas near saturation the magnetization distribution follows each individual nanoprecipitate. Analysis of the neutron data yields an estimated size of 30 nm for the spin-canted region and a value of about 75 nm for the magnetic core of the individual nanoprecipitates.

Uniaxial polarization analysis of bulk ferromagnets: theory and first experimental results.

On the basis of Brown's static equations of micromagnetics, the uniaxial polarization of the scattered neutron beam of a bulk magnetic material is computed. The approach considers a Hamiltonian that takes into account the isotropic exchange interaction, the antisymmetric Dzyaloshinskii-Moriya interaction, magnetic anisotropy, the dipole-dipole interaction and the effect of an applied magnetic field. In the high-field limit, the solutions for the magnetization Fourier components are used to obtain closed-form results for the spin-polarized small-angle neutron scattering (SANS) cross sections and the ensuing polarization. The theoretical expressions are compared with experimental data on a soft magnetic nanocrystalline alloy. The micromagnetic SANS theory provides a general framework for polarized real-space neutron methods, and it may open up a new avenue for magnetic neutron data analysis on magnetic microstructures.

Polycyclic aromatic hydrocarbon accumulation in aged and unaged polyurethane microplastics in contaminated soil.

The interaction of microplastics (MPs) and common environmental organic pollutants has been a frequently discussed topic in recent years. Although the estimated contamination caused by MPs in terrestrial ecosystems is one order of magnitude higher than that in the oceans, experiments have been conducted solely in an aqueous matrix. Therefore, an experiment was carried out with two soils differing in their concentrations of polycyclic aromatic hydrocarbons (PAHs) and polyurethane foams used for scent fences along roads and crop fields. Two types of polyurethane foam (biodegradable and conventional in aged and unaged form) were exposed to soils containing PAHs that originated from historically contaminated localities. The exposure lasted 28 days, and a newly developed three-step procedure to separate MPs from soil was then applied. Biodegradable polyurethane MPs exhibited a strong tendency to accumulate PAHs after 7 days, and their concentrations significantly grew over time. In contrast, the sorption of PAHs on conventional polyurethane MPs was substantially lower (a maximum of 3.6 times higher concentration than that in the soil). Neither type of foam changed their sorption behaviors after the aging procedure. The results indicate that the flexibility of the polyurethane polymeric network could be the main driving factor for the sorption.

A Randomized, Double-blind, Multicenter Trial Comparing Efficacy and Safety of Imipenem/Cilastatin/Relebactam Versus Piperacillin/Tazobactam in Adults With Hospital-acquired or Ventilator-associated Bacterial Pneumonia (RESTORE-IMI 2 Study).

BACKGROUND: Imipenem combined with the ß-lactamase inhibitor relebactam has broad antibacterial activity, including against carbapenem-resistant gram-negative pathogens. We evaluated efficacy and safety of imipenem/cilastatin/relebactam in treating hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP). METHODS: This was a randomized, controlled, double-blind phase 3 trial. Adults with HABP/VABP were randomized 1:1 to imipenem/cilastatin/relebactam 500 mg/500 mg/250 mg or piperacillin/tazobactam 4 g/500 mg, intravenously every 6 hours for 7-14 days. The primary endpoint was day 28 all-cause mortality in the modified intent-to-treat (MITT) population (patients who received study therapy, excluding those with only gram-positive cocci at baseline). The key secondary endpoint was clinical response 7-14 days after completing therapy in the MITT population. RESULTS: Of 537 randomized patients (from 113 hospitals in 27 countries), the MITT population comprised 264 imipenem/cilastatin/relebactam and 267 piperacillin/tazobactam patients; 48.6% had ventilated HABP/VABP, 47.5% APACHE II score ≥15, 24.7% moderate/severe renal impairment, 42.9% were ≥65 years old, and 66.1% were in the intensive care unit. The most common baseline pathogens were Klebsiella pneumoniae (25.6%) and Pseudomonas aeruginosa (18.9%). Imipenem/cilastatin/relebactam was noninferior (P < .001) to piperacillin/tazobactam for both endpoints: day 28 all-cause mortality was 15.9% with imipenem/cilastatin/relebactam and 21.3% with piperacillin/tazobactam (difference, -5.3% [95% confidence interval {CI}, -11.9% to 1.2%]), and favorable clinical response at early follow-up was 61.0% and 55.8%, respectively (difference, 5.0% [95% CI, -3.2% to 13.2%]). Serious adverse events (AEs) occurred in 26.7% of imipenem/cilastatin/relebactam and 32.0% of piperacillin/tazobactam patients; AEs leading to treatment discontinuation in 5.6% and 8.2%, respectively; and drug-related AEs (none fatal) in 11.7% and 9.7%, respectively. CONCLUSIONS: Imipenem/cilastatin/relebactam is an appropriate treatment option for gram-negative HABP/VABP, including in critically ill, high-risk patients. CLINICAL TRIALS REGISTRATION: NCT02493764.

Magnetic Guinier law.

Small-angle scattering of X-rays and neutrons is a routine method for the determination of nanoparticle sizes. The so-called Guinier law represents the low-q approximation for the small-angle scattering curve from an assembly of particles. The Guinier law has originally been derived for nonmagnetic particle-matrix-type systems and it is successfully employed for the estimation of particle sizes in various scientific domains (e.g. soft-matter physics, biology, colloidal chemistry, materials science). An important prerequisite for it to apply is the presence of a discontinuous interface separating particles and matrix. Here, the Guinier law is introduced for the case of magnetic small-angle neutron scattering and its applicability is experimentally demonstrated for the example of nanocrystalline cobalt. It is well known that the magnetic microstructure of nanocrystalline ferromagnets is highly nonuniform on the nanometre length scale and characterized by a spectrum of continuously varying long-wavelength magnetization fluctuations, i.e. these systems do not manifest sharp interfaces in their magnetization profile. The magnetic Guinier radius depends on the applied magnetic field, on the magnetic interactions (exchange, magnetostatics) and on the magnetic anisotropy-field radius, which characterizes the size over which the magnetic anisotropy field is coherently aligned into the same direction. In contrast to the nonmagnetic conventional Guinier law, the magnetic version can be applied to fully dense random-anisotropy-type ferromagnets.

Inverse barocaloric effect in the giant magnetocaloric La-Fe-Si-Co compound.

Application of hydrostatic pressure under adiabatic conditions causes a change in temperature in any substance. This effect is known as the barocaloric effect and the vast majority of materials heat up when adiabatically squeezed, and they cool down when pressure is released (conventional barocaloric effect). There are, however, materials exhibiting an inverse barocaloric effect: they cool when pressure is applied, and they warm when it is released. Materials exhibiting the inverse barocaloric effect are rather uncommon. Here we report an inverse barocaloric effect in the intermetallic compound La-Fe-Co-Si, which is one of the most promising candidates for magnetic refrigeration through its giant magnetocaloric effect. We have found that application of a pressure of only 1 kbar causes a temperature change of about 1.5 K. This value is larger than the magnetocaloric effect in this compound for magnetic fields that are available with permanent magnets.