Previous studies have evaluated metagenomic next-generation sequencing (mNGS) of cell-free DNA (cfDNA) for pathogen detection in blood and body fluid samples. However, no study has assessed the diagnostic efficacy of mNGS using cellular DNA.

There is a need for an increased understanding of the way a concomitant medial collateral ligament (MCL) injury may influence outcome after anterior cruciate ligament (ACL) reconstruction.

It has been suggested that actions can provide a fruitful conceptual context for sound symbolism phenomena, and that tight interaction between manual and articulatory processes might cause that hand actions, in particular, are sound-symbolically associated with specific speech sounds. Experiment 1 investigated whether novel words, built from speech sounds that have been previously linked to precision or power grasp responses, are implicitly associated with perceived actions that present precision manipulation or whole-hand grasp tool-use or the corresponding utilisation pantomimes. In the two-alternative forced-choice task, the participants were more likely to match novel words to tool-use actions and corresponding pantomimes that were sound-symbolically congruent with the words. Experiment 2 showed that the same or even larger sound-action symbolism effect can be observed when the pantomimes present unfamiliar utilisation actions. Based on this we propose that the sound-action symbolism might originate from the same sensorimotor mechanisms that process the meaning of iconic gestural signs. The study presents a novel sound-action phenomenon and supports the view that hand-mouth interaction might manifest itself by associating specific speech sounds with grasp-related utilisations.

Nightmare disorder is characterized by dysfunctional emotion regulation and poor subjective sleep quality reflected in pathophysiological features such as abnormal arousal processes and sympathetic influences. Dysfunctional parasympathetic regulation, especially before and during rapid eye movement (REM) phases, is assumed to alter heart rate (HR) and its variability (HRV) of frequent nightmare recallers (NM). We hypothesized that cardiac variability is attenuated in NMs as opposed to healthy controls (CTL) during sleep, pre-sleep wakefulness and under an emotion-evoking picture-rating task. Based on the polysomnographic recordings of 24 NM and 30 CTL participants, we examined HRV during pre-REM, REM, post-REM and slow wave sleep, separately. Additionally, electrocardiographic recordings of resting state before sleep onset and under an emotionally challenging picture-rating task were also analyzed. Applying repeated measures analysis of variance (rmANOVA), a significant difference was found in the HR of NMs and CTLs during nocturnal segments but not during resting wakefulness, suggesting autonomic dysregulation, specifically during sleep in NMs. As opposed to the HR, the HRV values were not significantly different in the rmANOVA in the two groups, implying that the extent of parasympathetic dysregulation on a trait level might depend on the severeness of dysphoric dreaming. Nonetheless, in the group comparisons, the NM group showed increased HR and reduced HRV during the emotion-evoking picture-rating task, which aimed to model the nightmare experience in the daytime, indicating disrupted emotion regulation in NMs under acute distress. In conclusion, trait-like autonomic changes during sleep and state-like autonomic responses to emotion-evoking pictures indicate parasympathetic dysregulation in NMs.

A better understanding of the endocannabinoid system and a relaxation in regulatory control of cannabis globally has increased interest in the medicinal use of cannabinoid-based products (CBP). We provide a systematic review of the rationale and current clinical trial evidence for CBP in the treatment of neuropsychiatric and neurodevelopmental disorders in children and adolescents. A systematic search of MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Trials was performed to identify articles published after 1980 about CBP for medical purposes in individuals aged 18 years or younger with selected neuropsychiatric or neurodevelopmental conditions. Risk of bias and quality of evidence was assessed for each article. Of 4466 articles screened, 18 were eligible for inclusion, addressing eight conditions (anxiety disorders (n = 1); autism spectrum disorder (n = 5); foetal alcohol spectrum disorder (n = 1); fragile X syndrome (n = 2); intellectual disability (n = 1); mood disorders (n = 2); post-traumatic stress disorder (n = 3); and Tourette syndrome (n = 3)). Only one randomised controlled trial (RCT) was identified. The remaining seventeen articles included one open-label trial, three uncontrolled before-and-after trials, two case series and 11 case reports, thus the risk of bias was high. Despite growing community and scientific interest, our systematic review identified limited and generally poor-quality evidence for the efficacy of CBP in neuropsychiatric and neurodevelopmental disorders in children and adolescents. Large rigorous RCTs are required to inform clinical care. In the meantime, clinicians must balance patient expectations with the limited evidence available.

The underlying mechanism of chronic pain involves the plasticity in synaptic receptors and neurotransmitters. This study aimed to investigate potential roles of Neuroligins (NLs) within the spinal dorsal horn of rats in a newly established Bone Cancer Pain (BCP) model. The objective was to explore the mechanism of neuroligin involved in the occurrence and development of bone cancer pain.

When patients lose decision-making capacity, others must make surrogate decisions on their behalf. What counts as a surrogate decision might seem self-evident. But as clinician-researchers in the field of advance care planning, we have found that it is not always so clear-cut. In this paper, we describe how and why this is a matter of concern, a novel approach for assessing whether a surrogate decision occurred, and findings from this assessment.

network meta-analysis.

Self-perception of aging is an important psychosocial factor that can influence quality of life in older age. This review aimed to synthesize findings on the association between self-perception of aging and quality of life among older adults aged 60 and above.

Spatial learning is critical for survival and its underlying neuronal mechanisms have been studied extensively. These studies have revealed a wealth of information about the neural representations of space, such as place cells and boundary cells. While many studies have focused on how these representations emerge in the brain, their functional role in driving spatial learning and navigation has received much less attention. We extended an existing computational modeling tool-chain to study the functional role of spatial representations using closed-loop simulations of spatial learning. At the heart of the model agent was a spiking neural network that formed a ring attractor. This network received inputs from place and boundary cells and the location of the activity bump in this network was the output. This output determined the movement directions of the agent. We found that the navigation performance depended on the parameters of the place cell input, such as their number, the place field sizes, and peak firing rate, as well as, unsurprisingly, the size of the goal zone. The dependence on the place cell parameters could be accounted for by just a single variable, the overlap index, but this dependence was nonmonotonic. By contrast, performance scaled monotonically with the Fisher information of the place cell population. Our results therefore demonstrate that efficiently encoding spatial information is critical for navigation performance.

This study is to evaluate the safety and pharmacokinetics (PK) of larsucosterol (DUR-928 or 25HC3S) in subjects with alcohol-associated hepatitis (AH), a devastating acute illness without US Food and Drug Administration-approved therapies.

This integrative review aimed to summarise existing best evidence practice for preventing malnutrition within the First 1000 Days of Life in under-resourced communities. BioMed Central, EBSCOHOST (Academic Search Complete, CINAHL and MEDLINE), Cochrane Library, JSTOR, Science Direct and Scopus were searched as well as Google Scholar and relevant websites for grey literature. Most recent versions of strategies, guidelines, interventions and policies; published in English, focussing on preventing malnutrition in pregnant women and in children less than 2 years old in under-resourced communities, from January 2015 to November 2021 were searched for. Initial searches yielded 119 citations of which 19 studies met inclusion criteria. Johns Hopkins Nursing Evidenced-Based Practice Evidence Rating Scales for appraising research evidence and non-research evidence were used. Extracted data were synthesised using thematic data analysis. Five themes were derived from extracted data: 1. Improving social determinants of health using a multisector approach; 2. Enhancing infant and toddler feeding; 3. Managing healthy nutrition and lifestyle choices in pregnancy; 4. Improving personal and environmental health practices; and 5. Reducing low-birthweight incidence. Further exploration regarding preventing malnutrition in the First 1000 Days in under-resourced communities is required using high-quality studies. Systematic review registration number: H18-HEA-NUR-001 (Nelson Mandela University).

Integrating insights from interdependence theory with the narcissistic admiration and rivalry concept, we propose that a pivotal obstacle for narcissistic leaders is their inability to sustain benevolent perceptions over time. As people strive to interpret social behavior in terms of self- or other-interest, the narcissistic tendency of prioritizing self-interests over the collective may become apparent and eventually taint their reputation as a leader. We examined how interpersonal motive perceptions-based on attributions of self- and other-interest-would clarify the leadership paradox of narcissism. We tracked 472 participants in 119 teams across four time-points. Narcissistic rivalry (but not admiration) corresponded to increasingly negative leader effectiveness ratings. The extent to which individuals were perceived as self-maximizing and lacking concern for other interests was tightly connected to declines in leader effectiveness across time. Altogether, these results offer insight into how perceived interpersonal motives may explain the downfall of narcissistic leadership.

Burning mouth syndrome (BMS) is defined by a burning sensation or pain in the tongue or other oral sites despite the presence of normal mucosa on inspection. Both psychiatric and neuroimaging investigations have examined BMS; however, there have been no analyses using the neurite orientation dispersion and density imaging (NODDI) model, which provides detailed information of intra- and extracellular microstructures. Therefore, we performed voxel-wise analyses using both NODDI and diffusion tensor imaging (DTI) models and compared the results to better comprehend the pathology of BMS.

Postmenopausal osteoporosis is caused by estrogen deficiency, which impairs bone homeostasis, resulting in increased osteoclastic resorption without a corresponding increase in osteoblastic activity. Postbiotics have several therapeutic properties, including anti-obesity, anti-diabetic, anti-inflammatory, and anti-osteoporotic effects. However, the beneficial effects of the postbiotic MD35 of Lactobacillus plantarum on bone have not been studied. In this study, we demonstrated that the postbiotic L. plantarum MD35, isolated from young radish water kimchi, influences osteoclast differentiation in mouse bone marrow-derived macrophage (BMM) culture. In addition, it was effective protecting against estrogen deficiency-induced bone loss in ovariectomized (OVX) mice, an animal model of postmenopausal osteoporosis. In BMM cells, postbiotic MD35 inhibited the receptor activator of nuclear factor-kappa B of NF-κB ligand (RANKL)-induced osteoclast differentiation by attenuating the phosphorylation of extracellular signal-related kinase, significantly suppressing the resorption activity and down-regulating the expression of RANKL-mediated osteoclast-related genes. In the animal model, the oral administration of postbiotic MD35 remarkably improved OVX-induced trabecular bone loss and alleviated the destruction of femoral plate growth. Therefore, postbiotic MD35 could be a potential therapeutic candidate for postmenopausal osteoporosis by suppressing osteoclastogenesis through the regulation of osteoclast-related molecular mechanisms.

Metabolic conditions such as hypoxia, nutrient starvation, and media acidification, together with interactions with stromal cells are critical drivers of metastasis. Since these conditions arise deep within tumor tissues with poor access to the bloodstream, the observation of nascent metastases in vivo is exceedingly challenging. On the other hand, conventional cell culture studies cannot capture the complex nature of metastatic processes. We thus designed and implemented an ex vivo model of the tumor microenvironment to study the emergence of metastatic features in tumor cells in their native 3-dimensional (3D) context. In this system, named 3MIC, tumor cells spontaneously create ischemic-like conditions, and it allows the direct visualization of tumor-stroma interactions with high spatial and temporal resolution. We studied how 3D tumor spheroids evolve in the 3MIC when cultured under different metabolic environments and in the presence or absence of stromal cells. Consistent with previous experimental and clinical data, we show that ischemic environments increase cell migration and invasion. Importantly, the 3MIC allowed us to directly observe the emergence of these pro-metastatic features with single-cell resolution allowing us to track how changes in tumor motility were modulated by macrophages and endothelial cells. With these tools, we determined that the acidification of the extracellular media was more important than hypoxia in the induction of pro-metastatic tumor features. We also illustrate how the 3MIC can be used to test the effects of anti-metastatic drugs on cells experiencing different metabolic conditions. Overall, the 3MIC allows us to directly observe the emergence of metastatic tumor features in a physiologically relevant model of the tumor microenvironment. This simple and cost-effective system can dissect the complexity of the tumor microenvironment to test perturbations that may prevent tumors from becoming metastatic.

The research aims to give new insights on the effect of administering selected bacterial strains, isolated from honey bee gut, and/or a commercial plant extract blend (HiveAlive®) on Nosema ceranae. Analyses were first performed under laboratory conditions such as different infective doses of N. ceranae, the effect of single strains and their mixture and the influence of pollen administration. Daily survival and feed consumption rate were recorded and pathogen development was analysed using qPCR and microscope counts. Biomarkers of immunity and physiological status were also evaluated for the different treatments tested using one bacterial strain, a mixture of all the bacteria and/or a plant extract blend as treatments. The results showed an increase of abaecin transcript levels in the midgut of the honey bees treated with the bacterial mixture and an increased expression of the protein vitellogenin in the haemolymph of honey bees treated with two separate bacterial strains (Bifidobacterium coryneforme and Apilactobacillus kunkeei). A significant effectiveness in reducing N. ceranae was shown by the bacterial mixture and the plant extract blend regardless of the composition of the diet. This bioactivity was seasonally linked. Quantitative PCR and microscope counts showed the reduction of N. ceranae under different experimental conditions. The antiparasitic efficacy of the treatments at field conditions was studied using a semi-field approach which was adapted from research on insecticides for the first time, to analyse antiparasitic activity against N. ceranae. The approach proved to be reliable and effective in validating data obtained in the laboratory. Both the mixture of beneficial bacteria and its association with Hive Alive® are effective in controlling the natural infection of N. ceranae in honey bee colonies.

Lack of sexual consent forms the foundation of unwanted (and nonconsensual) sexual experiences (USEs), yet research suggests it is not well understood amongst university students. While the prevalence of USEs has been well documented within the university context, less is known about how sexual consent is defined or measured. This review aims to identify a consistent sexual consent definition and how current research examining USEs defines and measures sexual consent amongst university students. A systematic review of nine electronic databases (2000-2022) was conducted, and the results were assessed against inclusion criteria (e.g., studies had to focus exclusively on university students). Thirty-three articles were identified and reviewed against the study aims. Sexual consent was more often implicitly defined across measures and articles. Four themes were identified (incapacitation, use of force, use of threats, and lack of wantedness) across the implicit definitions but varied by study with some implicitly defining sexual consent within the context of a relationship. Only three studies explicitly defined sexual consent, referring to it as a willingness to engage in sexual behavior. Measures assessed sexual consent communication or, attitudes and behaviors that might predict sexual aggression. Two studies examined students' individual sexual consent conceptualizations. Sexual consent appears to be contextual so future research should examine the variability of sexual consent in student samples. Students may indeed rely on implicit sexual consent definitions (rather than explicit) but more research is needed. Lastly, researchers should take care to be clear on their sexual consent definitions, both in text and within measures.

Attitudes towards individuals with sexual convictions play a major role in the formation of legislative action, including sentencing policies and registration and notification procedures. However, there is little research about stigmatization directed at those who are accused of such offenses prior to conviction. In this work we explored this gap by comparing stigmatization (e.g., a desire for social distance, and negative personality attributions) towards people accused of a range of crimes (sexual, violent, and acquisitive), and whether this was further impacted by whether or not allegations led to a conviction. We recruited 403 community-based participants for a between-subjects experimental survey. We found support for the conclusion that people accused of and convicted for sexual offenses are more heavily stigmatized than allegations related to other crime types, and especially so when allegations involved child victims. Stigmatization took the form of greater levels of support for police-initiated notifications about allegations before conviction, increased desires for social distance, and attributions of negative personality traits. We discuss the theoretical and applied implications of these findings in relation to stigma research and issues related to anonymity for those accused of sexual offenses.

Myocardial injury is a serious complication in sepsis with high mortality. Zero-valent iron nanoparticles (nanoFe) displayed novel roles in cecal ligation and puncture (CLP)-induced septic mouse model. Nonetheless, its high reactivity makes it difficult for long-term storage.