Acute effects of different types of cannabis on young adult and adolescent resting-state brain networks.

Adolescence is a time of rapid neurodevelopment and the endocannabinoid system is particularly prone to change during this time. Cannabis is a commonly used drug with a particularly high prevalence of use among adolescents. The two predominant phytocannabinoids are Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which affect the endocannabinoid system. It is unknown whether this period of rapid development makes adolescents more or less vulnerable to the effects of cannabis on brain-network connectivity, and whether CBD may attenuate the effects of THC. Using fMRI, we explored the impact of vaporized cannabis (placebo, THC: 8 mg/75 kg, THC + CBD: 8 mg/75 kg THC & 24 mg/75 kg CBD) on resting-state networks in groups of semi-regular cannabis users (usage frequency between 0.5 and 3 days/week), consisting of 22 adolescents (16-17 years) and 24 young adults (26-29 years) matched for cannabis use frequency. Cannabis caused reductions in within-network connectivity in the default mode (F[2,88] = 3.97, P = 0.022, η² = 0.018), executive control (F[2,88] = 18.62, P < 0.001, η² = 0.123), salience (F[2,88] = 12.12, P < 0.001, η² = 0.076), hippocampal (F[2,88] = 14.65, P < 0.001, η² = 0.087), and limbic striatal (F[2,88] = 16.19, P < 0.001, η² = 0.102) networks compared to placebo. Whole-brain analysis showed cannabis significantly disrupted functional connectivity with cortical regions and the executive control, salience, hippocampal, and limbic striatal networks compared to placebo. CBD did not counteract THC's effects and further reduced connectivity both within networks and the whole brain. While age-related differences were observed, there were no interactions between age group and cannabis treatment in any brain network. Overall, these results challenge the assumption that CBD can make cannabis safer, as CBD did not attenuate THC effects (and in some cases potentiated them); furthermore, they show that cannabis causes similar disruption to resting-state connectivity in the adolescent and adult brain.

Women and men with distressing low sexual desire exhibit sexually dimorphic brain processing.

Distressing low sexual desire, termed Hypoactive Sexual Desire Disorder (HSDD), affects approximately 10% of women and 8% of men. In women, the 'top-down' theory of HSDD describes hyperactivity in higher-level cognitive brain regions, suppressing lower-level emotional/sexual brain areas. However, it is unknown how this neurofunctional disturbance compares to HSDD in men. To investigate this, we employed task-based functional MRI in 32 women and 32 men with HSDD to measure sexual-brain processing during sexual versus non-sexual videos, as well as psychometric questionnaires to assess sexual desire/arousal. We demonstrate that women had greater activation in higher-level and lower-level brain regions, compared to men. Indeed, women who had greater hypothalamic activation in response to sexual videos, reported higher psychometric scores in the evaluative (r = 0.55, P = 0.001), motivational (r = 0.56, P = 0.003), and physiological (r = 0.57, P = 0.0006) domains of sexual desire and arousal after watching the sexual videos in the scanner. By contrast, no similar correlations were observed in men. Taken together, this is the first direct comparison of the neural correlates of distressing low sexual desire between women and men. The data supports the 'top-down' theory of HSDD in women, whereas in men HSDD appears to be associated with different neurofunctional processes.

Mitochondrial complex I density is associated with IQ and cognition in cognitively healthy adults: an in vivo [18F]BCPP-EF PET study.

BACKGROUND: Mitochondrial function plays a key role in regulating neurotransmission and may contribute to general intelligence. Mitochondrial complex I (MC-I) is the largest enzyme of the respiratory chain. Recently, it has become possible to measure MC-I distribution in vivo, using a novel positron emission tomography tracer [18F]BCPP-EF, thus, we set out to investigate the association between MC-I distribution and measures of cognitive function in the living healthy brain. RESULTS: Analyses were performed in a voxel-wise manner and identified significant associations between [18F]BCPP-EF DVRCS-1 in the precentral gyrus and parietal lobes and WAIS-IV predicted IQ, WAIS-IV arithmetic and WAIS-IV symbol-digit substitution scores (voxel-wise Pearson's correlation coefficients transformed to Z-scores, thresholded at Z = 2.3 family-wise cluster correction at p < 0.05, n = 16). Arithmetic scores were associated with middle frontal and post-central gyri tracer uptake, symbol-digit substitution scores were associated with precentral gyrus tracer uptake. RAVLT recognition scores were associated with [18F]BCPP-EF DVRCS-1 in the middle frontal gyrus, post-central gyrus, occipital and parietal regions (n = 20). CONCLUSIONS: Taken together, our findings support the theory that mitochondrial function may contribute to general intelligence and indicate that interindividual differences in MC-I should be a key consideration for research into mitochondrial dysfunction in conditions with cognitive impairment.

Drug resistant Mycobacterium tuberculosis strains have altered cell envelope hydrophobicity that influences infection outcomes in human macrophages.

Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis (TB), is considered one of the top infectious killers in the world. In recent decades, drug resistant (DR) strains of M.tb have emerged that make TB even more difficult to treat and pose a threat to public health. M.tb has a complex cell envelope that provides protection to the bacterium from chemotherapeutic agents. Although M.tb cell envelope lipids have been studied for decades, very little is known about how their levels change in relation to drug resistance. In this study, we examined changes in the cell envelope lipids [namely, phthiocerol dimycocerosates (PDIMs)], glycolipids [phosphatidyl-myo-inositol mannosides (PIMs)], and the PIM associated lipoglycans [lipomannan (LM); mannose-capped lipoarabinomannan (ManLAM)] of 11 M.tb strains that range from drug susceptible (DS) to multi-drug resistant (MDR) to pre-extensively drug resistant (pre-XDR). We show that there was an increase in the PDIMs:PIMs ratio as drug resistance increases, and provide evidence of PDIM species only present in the DR-M.tb strains studied. Overall, the LM and ManLAM cell envelope levels did not differ between DS- and DR-M.tb strains, but ManLAM surface exposure proportionally increased with drug resistance. Evaluation of host-pathogen interactions revealed that DR-M.tb strains have decreased association with human macrophages compared to DS strains. The pre-XDR M.tb strain with the largest PDIMs:PIMs ratio had decreased uptake, but increased intracellular growth rate at early time points post-infection when compared to the DS-M.tb strain H37Rv. These findings suggest that PDIMs may play an important role in drug resistance and that this observed increase in hydrophobic cell envelope lipids on the DR-M.tb strains studied may influence M.tb-host interactions.

Plant-Derived Phenolic Acids Limit the Pathogenesis of Salmonella Typhimurium and Protect Intestinal Epithelial Cells during Their Interactions.

The incidence of gastrointestinal illness attributable to Salmonella enterica serovar Typhimurium (ST) remains a concern for public health worldwide, as it can progress into systemic infections mediated by the type-three secretion system (T3SS), which allows for adherence and invasion to intestinal epithelial cells. The current study evaluates the ability of gallic acid (GA), protocatechuic acid (PA), and vanillic acid (VA) to impair the adhesion and invasion abilities of ST to a human epithelial (INT-407) cell monolayer while also assessing their cytotoxicity. GA, PA, and VA inhibited detectable ST growth at specific concentrations but showed cytotoxicity against INT-407 cells (>20% reduction in viability) after 3 h of treatments. Adjusting the pH of the solutions had a neutralizing effect on cytotoxicity, though it did reduce their antimicrobial potency. Adhesion of ST was reduced significantly when the cells were treated with 4.0 mg/mL of VA, whereas invasion was reduced in all treatments, with GA requiring the lowest concentration (0.5 mg/mL). Relative gene expression of virulence genes after treatment with GA showed downregulation in the T3SS regulator and effector hilA and sipA, respectively. These findings suggest further use of phenolic acids in reducing the activity of key virulence factors critical during ST infection.

Outcomes after bioprosthetic versus mechanical mitral valve replacement for infective endocarditis in the United States.

Objective: In patients who underwent mitral valve replacement for infectious endocarditis, we evaluated the association of prosthesis choice with readmission rates and causes (the primary outcomes), as well as with in-hospital mortality, cost, and length of stay (the secondary outcomes). Methods: Patients with infectious endocarditis who underwent isolated mitral valve replacement from January 2016 to December 2018 were identified in the United States Nationwide Readmissions Database and stratified by valve type. Propensity score matching was used to compare adjusted outcomes. Results: A weighted total of 4206 patients with infectious endocarditis underwent bioprosthetic mitral valve replacement (n = 3132) and mechanical mitral valve replacement (n = 1074) during the study period. Patients in the bioprosthetic mitral valve replacement group were older than those in the mechanical mitral valve replacement group (median 57 vs 46 y, P < .001). After propensity matching, the bioprosthetic mitral valve replacement group (n = 1068) had similar in-hospital mortality, length of stay, and costs compared with the mechanical mitral valve replacement group (n = 1056). Overall, 90-day readmission rates were high (28.9%) and comparable for bioprosthetic mitral valve replacement (30.5%) and mechanical mitral valve replacement (27.5%, P = .4). Likewise, there was no difference in readmissions over a calendar year by prosthesis type. Readmissions for infection and bleeding were common for both bioprosthetic mitral valve replacement and mechanical mitral valve replacement groups. Conclusions: Outcomes and readmission rates were similar for mechanical mitral valve replacement and bioprosthetic mitral valve replacement in infectious endocarditis, suggesting that valve choice should not be determined by endocarditis status. Additionally, strategies to mitigate readmission for infection and bleeding are needed for both groups.

The acute effects of cannabis, with and without cannabidiol, on attentional bias to cannabis related cues: a randomised, double-blind, placebo-controlled, cross-over study.

RATIONALE: Attentional bias to drug-related stimuli is hypothesised to contribute towards addiction. However, the acute effects of Δ9-tetrahydrocannabinol (THC) on attentional bias to cannabis cues, the differential response in adults and adolescents, and the moderating effect of cannabidiol (CBD) are unknown. OBJECTIVES: Our study investigated (1) the acute effects of vaporised cannabis on attentional bias to cannabis-related images in adults and adolescents and (2) the moderating influences of age and CBD. METHODS: We conducted a randomised, double-blind, placebo-controlled, cross-over study where three weight-adjusted vaporised cannabis preparations: 'THC' (8 mg THC for a 75-kg person), 'THC + CBD' (8 mg THC and 24 mg CBD for a 75-kg person) and PLA (matched placebo). Cannabis was administered on 3 separate days to 48 participants, who used cannabis 0.5-3 days/week: 24 adolescents (12 females, aged 16-17) and 24 adults (12 females, aged 26-29). Participants completed a visual probe task with cannabis cues. Our primary outcome was attentional bias to cannabis stimuli, measured using the differential reaction time to a cannabis vs. neutral probe, on 200-ms trials. RESULTS: In contrast to hypotheses, attention was directed away from cannabis cues on placebo, and there was a main effect of the drug (F(2,92) = 3.865, p = 0.024, η2p = 0.077), indicating THC administration eliminated this bias. There was no significant impact of CBD nor an age-by-drug interaction. CONCLUSIONS: Acute THC intoxication eliminated attentional bias away from cannabis cues. There was no evidence of differential response in adolescents compared to adults and no evidence that a moderate vaporised dose of CBD altered the impact of cannabis on attentional bias. TRIAL REGISTRATION: This study was listed with the US National Library of Medicine and registered on ClinicalTrials.gov, URL: Do Adolescents and Adults Differ in Their Acute Response to Cannabis?-Full Text View-ClinicalTrials.gov, registration number: NCT04851392.

Development of a Sensor Technology to Objectively Measure Dexterity for Cardiac Surgical Proficiency.

BACKGROUND: Technical skill is essential for good outcomes in cardiac surgery. However, no objective methods exist to measure dexterity while performing surgery. The purpose of this study was to validate sensor-based hand motion analysis (HMA) of technical dexterity while performing a graft anastomosis within a validated simulator. METHODS: Surgeons at various training levels performed an anastomosis while wearing flexible sensors (BioStamp nPoint, MC10 Inc) with integrated accelerometers and gyroscopes on each hand to quantify HMA kinematics. Groups were stratified as experts (n = 8) or novices (n = 18). The quality of the completed anastomosis was scored using the 10 Point Microsurgical Anastomosis Rating Scale (MARS10). HMA parameters were compared between groups and correlated with quality. Logistic regression was used to develop a predictive model from HMA parameters to distinguish experts from novices. RESULTS: Experts were faster (11 ± 6 minutes vs 21 ± 9 minutes; P = .012) and used fewer movements in both dominant (340 ± 166 moves vs 699 ± 284 moves; P = .003) and nondominant (359 ± 188 moves vs 567 ± 201 moves; P = .02) hands compared with novices. Experts' anastomoses were of higher quality compared with novices (9.0 ± 1.2 MARS10 vs 4.9 ± 3.2 MARS10; P = .002). Higher anastomosis quality correlated with 9 of 10 HMA parameters, including fewer and shorter movements of both hands (dominant, r = -0.65, r = -0.46; nondominant, r = -0.58, r = -0.39, respectively). CONCLUSIONS: Sensor-based HMA can distinguish technical dexterity differences between experts and novices, and correlates with quality. Objective quantification of hand dexterity may be a valuable adjunct to training and education in cardiac surgery training programs.

Cognitive Dysfunction in Patients Treated with Androgen Deprivation Therapy: A Multimodality Functional Imaging Study to Evaluate Neuroinflammation.

Background: Androgen deprivation therapy (ADT) for prostate cancer is implicated as a possible cause of cognitive impairment (CI). CI in dementia and Alzheimer's disease is associated with neuroinflammation. In this study, we investigated a potential role of neuroinflammation in ADT-related CI. Methods: Patients with prostate cancer on ADT for ≥3 months were categorized as having ADT-emergent CI or normal cognition (NC) based on self-report at interview. Neuroinflammation was evaluated using positron emission tomography (PET) with the translocator protein (TSPO) radioligand [11C]-PBR28. [11C]-PBR28 uptake in various brain regions was quantified as standardized uptake value (SUVR, normalized to cerebellum) and related to blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) choice-reaction time task (CRT) activation maps. Results: Eleven patients underwent PET: four with reported CI (rCI), six with reported NC (rNC), and one status unrecorded. PET did not reveal any between-group differences in SUVR regionally or globally. There was no difference between groups on brain activation to the CRT. Regardless of the reported cognitive status, there was strong correlation between PET-TSPO signal and CRT activation in the hippocampus, amygdala, and medial cortex. Conclusions: We found no difference in neuroinflammation measured by PET-TSPO between patients with rCI and rNC. However, we speculate that the strong correlation between TSPO uptake and BOLD-fMRI activation in brain regions involved in memory and known to have high androgen-receptor expression mediating plasticity (hippocampus and amygdala) might reflect inflammatory effects of ADT with compensatory upregulated/increased synaptic functions. Further studies of this imaging readout are warranted to investigate ADT-related CI.

Neuroimaging in psychedelic drug development: past, present, and future.

Psychedelic therapy (PT) is an emerging paradigm with great transdiagnostic potential for treating psychiatric disorders, including depression, addiction, post-traumatic stress disorder, and potentially others. 'Classic' serotonergic psychedelics, such as psilocybin and lysergic acid diethylamide (LSD), which have a key locus of action at the 5-HT2A receptor, form the main focus of this movement, but substances including ketamine, 3,4-Methylenedioxymethamphetamine (MDMA) and ibogaine also hold promise. The modern phase of development of these treatment modalities in the early 21st century has occurred concurrently with the wider use of advanced human neuroscientific research methods; principally neuroimaging. This can potentially enable assessment of drug and therapy brain effects with greater precision and quantification than any previous novel development in psychiatric pharmacology. We outline the major trends in existing data and suggest the modern development of PT has benefitted greatly from the use of neuroimaging. Important gaps in existing knowledge are identified, namely: the relationship between acute drug effects and longer-term (clinically-relevant) effects, the precise characterisation of effects at the 5-HT2A receptor and relationships with functional/clinical effects, and the possible impact of these compounds on neuroplasticity. A road-map for future research is laid out, outlining clinical studies which will directly address these three questions, principally using combined Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) methods, plus other adjunct techniques. Multimodal (PET/MRI) studies using modern PET techniques such as the 5-HT2A-selective ligand [11 C]Cimbi-36 (and other ligands sensitive to neuroplasticity changes) alongside MRI measures of brain function would provide a 'molecular-functional-clinical bridge' in understanding. Such results would help to resolve some of these questions and provide a firmer foundation for the ongoing development of PT.

Acute effects of Δ9-tetrahydrocannabinol (THC) on resting state connectivity networks and impact of COMT genotype: A multi-site pharmacological fMRI study.

BACKGROUND: Cannabis produces various acute psychotropic effects, with marked individual differences. Cannabis use is a risk factor for developing psychotic disorders. The main component responsible for these effects is Δ9-tetrahydrocannabinol (THC). Here we investigated the neural basis of acute THC effects and its modulation by catechol-methyl-transferase (COMT) Val158Met genotype. METHODS: Resting state functional MRI data of healthy occasional cannabis users were combined and re-analyzed from three double-blind, placebo-controlled, within-subject pharmacological functional magnetic resonance imaging studies (total N=87). Functional connectivity after placebo and THC was compared in three functional networks (salience, executive and default mode network) and a network implicated in psychosis (the hippocampus-midbrain-striatum network). COMT genotype modulation of subjective effects and connectivity was examined. RESULTS: THC reduced connectivity in the salience network, specifically from the right insula to both the left insula and anterior cingulate cortex. We found a trend towards decreased connectivity in the hippocampus-midbrain-striatum network after THC. COMT genotype modulated subjective effects of THC, with strongest dysphoric reactions in Met/Met individuals. In addition, reduced connectivity after THC was demonstrated in the hippocampus-midbrain-striatum network of Met/Met individuals only. CONCLUSIONS: In this large multisite study we found that THC robustly decreases connectivity in the salience network, involved in processing awareness and salient information. Connectivity changes in the hippocampus-midbrain-striatum network may reflect the acute psychotic-like effects of THC. COMT genotype modulation of THC's impact on subjective effects and functional connectivity provides further evidence for involvement of prefrontal dopamine levels in the acute effects of cannabis.

Assessment of the prevalence, serotype, and antibiotic resistance pattern of Salmonella enterica in integrated farming systems in the Maryland-DC area.

Implementation of organic/pasture farming practices has been increasing in the USA regardless of official certification. These practices have created an increasingly growing demand for marketing safe products which are produced through these systems. Products from these farming systems have been reported to be at greater risk of transmitting foodborne pathogens because of current trends in their practices. Salmonella enterica (SE) is a ubiquitous foodborne pathogen that remains a public health issue given its prevalence in various food products, but also in the environment and as part of the microbial flora of many domestic animals. Monitoring antibiotic resistance and identifying potential sources contamination are increasingly important given the growing trend of organic/pasture markets. This study aimed to quantify prevalence of SE at the pre- and post-harvest levels of various integrated farms and sites in Maryland-Washington D.C. area, as well as identify the most prevalent serovars and antibiotic resistance patterns. Samples from various elements within the farm environment were collected and screened for SE through culture and molecular techniques, which served to identify and serotype SE, using species and serovar-specific primers, while antibiotic resistance was evaluated using an antibiogram assay. Results showed a prevalence of 7.80% of SE pre-harvest and 1.91% post-harvest. These results also showed the main sources of contamination to be soil (2.17%), grass (1.28%), feces (1.42%) and unprocessed produce (1.48%). The most commonly identified serovar was Typhimurium (11.32%) at the pre-harvest level, while the only identified serovar from post-harvest samples was Montevideo (4.35%). With respect to antibiotic resistance, out of the 13 clinically relevant antibiotics tested, gentamycin and kanamycin were the most effective, demonstrating 78.93 and 76.40% of isolates, respectively, to be susceptible. However, ampicillin, amoxicillin and cephradine had the lowest number of susceptible isolates with them being 10.95, 12.36, and 9.83%, respectively. These results help inform farms striving to implement organic practices on how to produce safer products by recognizing areas that pose greater risks as potential sources of contamination, in addition to identifying serotypes of interest, while also showcasing the current state of antibiotic efficacy and how this can influence antibiotic resistance trends in the future.

Associations between regular cannabis use and brain resting-state functional connectivity in adolescents and adults.

BACKGROUND/AIM: Cannabis use is highly prevalent in adolescents; however, little is known about its effects on adolescent brain function. METHOD: Resting-state functional magnetic resonance imaging was used in matched groups of regular cannabis users (N = 70, 35 adolescents: 16-17 years old, 35 adults: 26-29 years old) and non-regular-using controls (N = 70, 35 adolescents/35 adults). Pre-registered analyses examined the connectivity of seven major cortical and sub-cortical brain networks (default mode network, executive control network (ECN), salience network, hippocampal network and three striatal networks) using seed-based analysis methods with cross-sectional comparisons between user groups and age groups. RESULTS: The regular cannabis use group (across both age groups), relative to controls, showed localised increases in connectivity only in the ECN analysis. All networks showed localised connectivity differences based on age group, with the adolescents generally showing weaker connectivity than adults, consistent with the developmental effects. Mean connectivity across entire network regions of interest (ROIs) was also significantly decreased in the ECN in adolescents. However, there were no significant interactions found between age group and user group in any of the seed-based or ROI analyses. There were also no associations found between cannabis use frequency and any of the derived connectivity measures. CONCLUSION: Regular cannabis use is associated with changes in connectivity of the ECN, which may reflect allostatic or compensatory changes in response to regular cannabis intoxication. However, these associations were not significantly different in adolescents compared to adults.

Reward processing in schizophrenia and its relation to Mu opioid receptor availability and negative symptoms: A [11C]-carfentanil PET and fMRI study.

BACKGROUND: Reward processing deficits are a core feature of schizophrenia and are thought to underlie negative symptoms. Pre-clinical evidence suggests that opioid neurotransmission is linked to reward processing. However, the contribution of Mu Opioid Receptor (MOR) signalling to the reward processing abnormalities in schizophrenia is unknown. Here, we examined the association between MOR availability and the neural processes underlying reward anticipation in patients with schizophrenia using multimodal neuroimaging. METHOD: 37 subjects (18 with Schizophrenia with moderate severity negative symptoms and 19 age and sex-matched healthy controls) underwent a functional MRI scan while performing the Monetary Incentive Delay (MID) task to measure the neural response to reward anticipation. Participants also had a [11C]-carfentanil PET scan to measure MOR availability. RESULTS: Reward anticipation was associated with increased neural activation in a widespread network of brain regions including the striatum. Patients with schizophrenia had both significantly lower MOR availability in the striatum as well as striatal hypoactivation during reward anticipation. However, there was no association between MOR availability and striatal neural activity during reward anticipation in either patient or controls (Pearson's Correlation, controls df = 17, r = 0.321, p = 0.18, patients df = 16, r = 0.295, p = 0.24). There was no association between anticipation-related neural activation and negative symptoms (r = -0.120, p = 0.14) or anhedonia severity (social r = -0.365, p = 0.14 physical r = -0.120, p = 0.63). CONCLUSIONS: Our data suggest reduced MOR availability in schizophrenia might not underlie striatal hypoactivation during reward anticipation in patients with established illness. Therefore, other mechanisms, such as dopamine dysfunction, warrant further investigation as treatment targets for this aspect of the disorder.

Penetrating cardiac injury: a narrative review.

Background and Objective: Penetrating cardiac trauma is rare but can cause life-threatening complications. Survival is dependent on prompt diagnosis and treatment. Given the low incidence and life-threatening implications, it is difficult to study in large prospective studies. The current literature regarding penetrating cardiac trauma comes primarily from large, experienced trauma centers and military sources. Understanding the history, current literature and even expert opinion can help with effectively treating injury promptly to maximize survival after penetrating cardiac trauma. We aimed to review the etiology and history of penetrating cardiac trauma. We review the prehospital treatment and initial diagnostic modalities. We review the incisional approaches to treatment including anterolateral thoracotomy, median sternotomy and subxiphoid window. The repair of atrial, ventricular and coronary injuries are also addressed in our review. The purpose of this paper is to perform a narrative review to better describe the history, etiology, presentation, and management of penetrating cardiac trauma. Methods: A narrative review was preformed synthesizing literature from MEDLINE and bibliographic review from identified publications. Studies were included based on relevance without exclusion to time of publication or original publication language. Key Content and Findings: Sonographic identification of pericardial fluid can aid in diagnosis of patients too unstable for CT. Anterolateral thoracotomy should be used for emergent repairs and initial stabilization. A median sternotomy can be used for more stable patients with known injuries. Carefully placed mattress sutures can be useful for repair of injuries surrounding coronary vessels to avoid devascularization. Conclusions: Penetrating cardiac trauma is life threatening and requires prompt workup and treatment. Trauma algorithms should continue to refine and be clear on which patients should undergo an emergency department (ED) thoracotomy, median sternotomy and further imaging.

Psychedelic therapy in the treatment of addiction: the past, present and future.

Psychedelic therapy has witnessed a resurgence in interest in the last decade from the scientific and medical communities with evidence now building for its safety and efficacy in treating a range of psychiatric disorders including addiction. In this review we will chart the research investigating the role of these interventions in individuals with addiction beginning with an overview of the current socioeconomic impact of addiction, treatment options, and outcomes. We will start by examining historical studies from the first psychedelic research era of the mid-late 1900s, followed by an overview of the available real-world evidence gathered from naturalistic, observational, and survey-based studies. We will then cover modern-day clinical trials of psychedelic therapies in addiction from first-in-human to phase II clinical trials. Finally, we will provide an overview of the different translational human neuropsychopharmacology techniques, including functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), that can be applied to foster a mechanistic understanding of therapeutic mechanisms. A more granular understanding of the treatment effects of psychedelics will facilitate the optimisation of the psychedelic therapy drug development landscape, and ultimately improve patient outcomes.

Combined effect of metabolites produced by a modified Lactobacillus casei and berry phenolic extract on Campylobacter and microbiome in chicken cecum contents.

Campylobacter is one of the most common foodborne bacterial pathogens causing illness, known as campylobacteriosis, in the United States. More than 70% of the campylobacteriosis cases have direct or indirect relation with poultry/poultry products. Currently, both conventional and organic/pasture poultry farmers are searching for sustainable alternative to antibiotics which can reduce colonization and cross-contamination of poultry products with Campylobacter and promote poultry health and growth. Probiotic and their nutritional supplement, known as prebiotic, have become consumers' preferences as alternatives to antibiotics/chemicals. In this study, we evaluated the combined effect of plant-derived prebiotic and probiotic-derived metabolites in reducing growth of Campylobacter in cecum contents, a simulated chicken gut condition. Cecum contents were collected from chickens pre-inoculated with kanamycin-resistant Campylobacter (CJRMKm), were incubated over 48 h time period, while being supplemented with either berry phenolic extract (BPE), cell free cultural supernatant from an engineered probiotic, Lactobacillus casei, or their combination. It was found that combine treatments were able to reduce both inoculated and naturally colonized Campylobacter more effectively. Microbiome analysis using 16S rRNA sequencing also revealed that combine treatments were capable to alter natural microflora positively within chicken cecum contents. Differences were observed in bacterial abundance at both phylum and genus level but did not show significant alteration in alpha diversity due to this treatment. PRACTICAL APPLICATION: The results of this study provide critical information for understanding the potential of synbiotic as an alternative in sustainable poultry farming. The outcomes of this study will lead future direction of using combination of probiotic-derived metabolites and BPE in poultry farming.

Purified Plant-Derived Phenolic Acids Inhibit Salmonella Typhimurium without Alteration of Microbiota in a Simulated Chicken Cecum Condition.

Salmonella enterica serovar Typhimurium (ST) remains a predominant zoonotic pathogen because of its colonization in poultry, survivability in the environment, and increasing antibiotic-resistance pattern. Plant-derived phenolics, gallic acid (GA), protocatechuic acid (PA), and vanillic acids (VA) have demonstrated antimicrobial activity in vitro; therefore, this study collected chicken cecal fluid and supplemented it with these phenolics to evaluate their potential for eliminating ST and mod-ulating the microbiota of complex environments. ST was quantified through plating, while micro-biome analysis was performed through pair-end 16S-rRNA gene sequencing. CFU/mL of ST in cecal fluid with GA was significantly reduced by 3.28 and 2.78 log at 24 h and 48 h, while PA only had a slight numerical decrease. VA significantly reduced ST by 4.81 and 5.20 log at 24 h and 48 h. Changes in relative abundance of major phyla were observed at 24 h for samples with GA and VA as Firmicute levels increased 8.30% and 20.90%, while Proteobacteria decreased 12.86% and 18.48%, respectively. Significant changes in major genre were observed in Acinetobacter (3.41% for GA) and Escherichia (13.53% for VA), while Bifidobacterium increased (3.44% for GA) and Lactobacillus remained unchanged. Results suggest that phenolic compounds exert different effects on certain pathogens, while supporting some commensal bacteria.

Coronary artery bypass grafting at safety-net versus non-safety-net hospitals.

Objectives: Safety-net hospitals (SNHs) provide essential services to predominantly underserved patients regardless of their ability to pay. We hypothesized that patients who underwent coronary artery bypass grafting (CABG) would have inferior observed outcomes at SNHs compared with non-SNHs but that matched cohorts would have comparable outcomes. Methods: We queried the Nationwide Readmissions Database for patients who underwent isolated CABG from 2016 to 2018. We ranked hospitals by the percentage of all admissions in which the patient was uninsured or insured with Medicaid; hospitals in the top quartile were designated as SNHs. We used propensity-score matching to mitigate the effect of confounding factors and compare outcomes between SNHs and non-SNHs. Results: A total of 525,179 patients underwent CABG, including 96,133 (18.3%) at SNHs, who had a greater burden of baseline comorbidities (median Elixhauser score 8 vs 7; P = .04) and more frequently required urgent surgery (57.1% vs 52.8%; P < .001). Observed in-hospital mortality (2.1% vs 1.8%; P = .004) and major morbidity, length of stay (9 vs 8 days; P < .001), cost ($46,999 vs $38,417; P < .001), and readmission rate at 30 (12.4% vs 11.3%) and 90 days (19.0% vs 17.7%) were greater at SNHs (both P < .001). After matching, none of these differences persisted except length of stay (9 vs 8 days) and cost ($46,977 vs $39,343) (both P < .001). Conclusions: After matching, early outcomes after CABG were comparable at SNHs and non-SNHs. Improved discharge resources could reduce length of stay and curtail cost, improving the value of CABG at SNHs.

Increased low-frequency brain responses to music after psilocybin therapy for depression.

BACKGROUND: Psychedelic-assisted psychotherapy with psilocybin is an emerging therapy with great promise for depression, and modern psychedelic therapy (PT) methods incorporate music as a key element. Music is an effective emotional/hedonic stimulus that could also be useful in assessing changes in emotional responsiveness following PT. METHODS: Brain responses to music were assessed before and after PT using functional Magnetic Resonance Imaging (fMRI) and ALFF (Amplitude of Low Frequency Fluctuations) analysis methods. Nineteen patients with treatment-resistant depression underwent two treatment sessions involving administration of psilocybin, with MRI data acquired one week prior and the day after completion of psilocybin dosing sessions. RESULTS: Comparison of music-listening and resting-state scans revealed significantly greater ALFF in bilateral superior temporal cortex for the post-treatment music scan, and in the right ventral occipital lobe for the post-treatment resting-state scan. ROI analyses of these clusters revealed a significant effect of treatment in the superior temporal lobe for the music scan only. Voxelwise comparison of treatment effects showed relative increases for the music scan in the bilateral superior temporal lobes and supramarginal gyrus, and relative decreases in the medial frontal lobes for the resting-state scan. ALFF in these music-related clusters was significantly correlated with intensity of subjective effects felt during the dosing sessions. LIMITATIONS: Open-label trial. Relatively small sample size. CONCLUSIONS: These data suggest an effect of PT on the brain's response to music, implying an elevated responsiveness to music after psilocybin therapy that was related to subjective drug effects felt during dosing.