Blood salvage and autotransfusion during orthotopic liver transplantation for hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a significant cause of oncologic mortality worldwide. Liver transplantation represents a curative option for patients with significant liver dysfunction and absence of metastases. However, this therapeutic option is associated with significant blood loss and frequently requires various transfusions and intraoperative blood salvage for autotransfusion (IBS-AT) with or without a leukocyte reduction filter. This study aimed to analyze available evidence on long-term oncologic outcomes of patients undergoing liver transplantation for HCC with and without IBS-AT. METHODS: Per PRISMA guidelines, a systematic review of keywords "Blood Salvage," "Auto-transfusion," "Hepatocellular carcinoma," and "Liver-transplant" was conducted in PubMed, EMBASE, and SCOPUS. Studies comparing operative and postoperative outcomes were screened and analyzed for review. RESULTS: Twelve studies totaling 1704 participants were included for analysis. Length of stay, recurrence rates, and overall survival were not different between IBS-AT group and non IBS-AT group. CONCLUSION: IBS-AT use is not associated with increased risk of recurrence in liver transplant for HCC even without leukocyte filtration. Both operative and postoperative outcomes are similar between groups. Comparison of analyzed studies suggest that IBS-AT is safe for use during liver transplant for HCC.

Choline supplementation in early life improves and low levels of choline can impair outcomes in a mouse model of Alzheimer's disease.

Maternal choline supplementation (MCS) improves cognition in Alzheimer's disease (AD) models. However, effects of MCS on neuronal hyperexcitability in AD are unknown. We investigated effects of MCS in a well-established mouse model of AD with hyperexcitability, the Tg2576 mouse. The most common type of hyperexcitability in Tg2576 mice, and many other mouse models and AD patients, are generalized EEG spikes (interictal spikes; IIS). Hyperexcitability is also reflected by elevated expression of the transcription factor ΔFosB in the granule cells (GCs) of the dentate gyrus (DG), which are the principal cell type. We also studied the hilus of the DG because hilar neurons regulate GC excitability. We found reduced expression of the neuronal marker NeuN within hilar neurons in Tg2576 mice, which other studies have shown is a sign of oxidative stress or other pathology. Tg2576 breeding pairs received a diet with a relatively low, intermediate or high concentration of choline. After weaning, all mice received the intermediate diet. In offspring of mice fed the high choline diet, IIS frequency declined, GC ΔFosB expression was reduced, and NeuN expression was restored. Spatial memory improved using the novel object location task. In contrast, offspring exposed to the relatively low choline diet had several adverse effects, such as increased mortality. They had the weakest hilar NeuN immunoreactivity and greatest GC ΔFosB. However, their IIS frequency was low, which was surprising. The results provide new evidence that a diet high in choline in early life can improve outcomes in a mouse model of AD, and relatively low choline can have mixed effects. This is the first study showing that dietary choline can regulate hyperexcitability, hilar neurons, ΔFosB and spatial memory in an animal model of AD.

Hyperbaric oxygen therapy as a treatment for erectile dysfunction: a meta-analysis.

INTRODUCTION: Hyperbaric oxygen therapy (HBOT) is a medical treatment in which the patient is exposed to 100% oxygen at a higher than atmospheric pressure. Over the past few decades, HBOT has been used to treat a variety of medical conditions. In recent times, there has been a rising curiosity regarding the potential therapeutic benefits of HBOT in the treatment of erectile dysfunction (ED). AIMS: The study sought to review and meta-analyze available data regarding the use of HBOT for ED, including its potential mechanisms of action and effectiveness. METHODS: We included only articles that evaluated the impact of HBOT on ED symptoms using the International Index of Erectile Function score. Prospective nonrandomized studies or randomized controlled clinical trials were included. Data extraction was performed in duplicate. Data analysis was conducted using Review Manager 5.41, and the presence of heterogeneity between studies was evaluated. The results were presented as the mean difference (MD) with 95% confidence interval (CI). RESULTS: A total of 5 studies that reported outcomes using the International Index of Erectile Function scores were included in this analysis. In patients with post-robotic-assisted laparoscopic prostatectomy-induced ED, the analysis showed a significant MD of -4.13 (95% CI, -6.08 to -2.18; P < .0001) in favor of the control group. Conversely, patients who received HBOT for reasons other than ED exhibited an MD of 4.58 (95% CI, 2.63 to 6.52; P < .00001). In the group that received HBOT for pure vasculogenic ED, the MD was 10.50 (95% CI, 9.92 to 11.08) in favor of HBOT. A meta-analysis of these data revealed a nonsignificant difference in erectile function scores, with an MD of 3.86 (95% CI, -2.13 to 9.86; P = .21). CONCLUSION: The use of HBOT in the treatment of ED appears to be a promising approach. While further research is needed to establish the efficacy and long-term effects of this treatment, preliminary studies have shown encouraging results in terms of improving erectile function in men with vasculogenic ED.

Meditation-induced bloodborne factors as an adjuvant treatment to COVID-19 disease.

The COVID-19 pandemic has resulted in significant morbidity and mortality worldwide. Management of the pandemic has relied mainly on SARS-CoV-2 vaccines, while alternative approaches such as meditation, shown to improve immunity, have been largely unexplored. Here, we probe the relationship between meditation and COVID-19 disease and directly test the impact of meditation on the induction of a blood environment that modulates viral infection. We found a significant inverse correlation between length of meditation practice and SARS-CoV-2 infection as well as accelerated resolution of symptomology of those infected. A meditation "dosing" effect was also observed. In cultured human lung cells, blood from experienced meditators induced factors that prevented entry of pseudotyped viruses for SARS-CoV-2 spike protein of both the wild-type Wuhan-1 virus and the Delta variant. We identified and validated SERPINA5, a serine protease inhibitor, as one possible protein factor in the blood of meditators that is necessary and sufficient for limiting pseudovirus entry into cells. In summary, we conclude that meditation can enhance resiliency to viral infection and may serve as a possible adjuvant therapy in the management of the COVID-19 pandemic.

Effects of L-Carnitine Intake on Exercise-Induced Muscle Damage and Oxidative Stress: A Narrative Scoping Review.

Exercise-induced muscle damage results in decreased physical performance that is accompanied by an inflammatory response in muscle tissue. The inflammation process occurs with the infiltration of phagocytes (neutrophils and macrophages) that play a key role in the repair and regeneration of muscle tissue. In this context, high intensity or long-lasting exercise results in the breakdown of cell structures. The removal of cellular debris is performed by infiltrated phagocytes, but with the release of free radicals as collateral products. L-carnitine is a key metabolite in cellular energy metabolism, but at the same time, it exerts antioxidant actions in the neuromuscular system. L-carnitine eliminates reactive oxygen and nitrogen species that, in excess, alter DNA, lipids and proteins, disturbing cell function. Supplementation using L-carnitine results in an increase in serum L-carnitine levels that correlates positively with the decrease in cell alterations induced by oxidative stress situations, such as hypoxia. The present narrative scoping review focuses on the critical evaluation of the efficacy of L-carnitine supplementation on exercise-induced muscle damage, particularly in postexercise inflammatory and oxidative damage. Although both concepts appear associated, only in two studies were evaluated together. In addition, other studies explored the effect of L-carnitine in perception of fatigue and delayed onset of muscle soreness. In view of the studies analyzed and considering the role of L-carnitine in muscle bioenergetics and its antioxidant potential, this supplement could help in postexercise recovery. However, further studies are needed to conclusively clarify the mechanisms underlying these protective effects.

Is Curcumine Useful in the Treatment and Prevention of the Tendinopathy and Myotendinous Junction Injury? A Scoping Review.

Physical activity in general and sports in particular, is a mechanism that produces stress and generates great force in the tendon and in the muscle-tendon unit, which increases the risk of injury (tendinopathies). Eccentric and repetitive contraction of the muscle precipitates persistent microtraumatism in the tendon unit. In the development of tendinopathies, the cellular process includes inflammation, apoptosis, vascular, and neuronal changes. Currently, treatments with oral supplements are frequently used. Curcumin seems to preserve, and even repair, damaged tendons. In this systematic review, we focus more especially on the benefits of curcumin. The biological actions of curcumin are diverse, but act around three systems: (a) inflammatory, (b) nuclear factor B (NF-κB) related apoptosis pathways, and (c) oxidative stress systems. A bibliographic search is conducted under the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) as a basis for reporting reliable systematic reviews to perform a Scoping review. After analysing the manuscripts, we can conclude that curcumin is a product that demonstrates a significant biological antialgic, anti-inflammatory, and antioxidant power. Therefore, supplementation has a positive effect on the inflammatory and regenerative response in tendinopathies. In addition, curcumin decreases and modulates the cell infiltration, activation, and maturation of leukocytes, as well as the production of pro-inflammatory mediators at the site of inflammation.

Differing Characteristics of Human-Shaped Visual Stimuli Affect Clinicians' Dosage of a Spinal Manipulative Thrust on a Low-Fidelity Model: A Cross-Sectional Study.

OBJECTIVE: The purpose of this study was to determine whether chiropractic clinicians modulate spinal manipulation (SM) thrust characteristics based on visual perception of simulated human silhouette attributes. METHODS: We performed a cross-sectional within-participant design with 8 experienced chiropractors. During each trial, participants observed a human-shaped life-sized silhouette of a mock patient and delivered an SM thrust on a low-fidelity thoracic spine model based on their visual perception. Silhouettes varied on the following 3 factors: apparent sex (male or female silhouette), height (short, average, tall), and body mass index (BMI) (underweight, healthy, obese). Each combination was presented 6 times for a total of 108 trials in random order. Outcome measures included peak thrust force, thrust duration, peak preload force, peak acceleration, time to peak acceleration, and rate of force application. A 3-way repeated measures analysis of variance model was used to for each variable, followed by Tukey's honestly significant difference on significant interactions. RESULTS: Peak thrust force was reduced when apparent sex of the presented silhouette was female (F1,7 = 5.70, P = .048). Thrust duration was largely invariant, except that a BMI by height interaction revealed a longer duration occurred for healthy tall participants than healthy short participants (F4,28 = 4.34, P = .007). Compared to an image depicting obese BMI, an image appearing underweight lead to reduced peak acceleration (F2,5 = 6.756, P = .009). Clinician time to peak acceleration was reduced in short compared to tall silhouettes (t7 = 2.20, P = .032). CONCLUSION: Visual perception of simulated human silhouette attributes, including apparent sex, height, and BMI, influenced SM dose characteristics through both kinetic and kinematic measures. The results suggest that visual information from mock patients affects the decision-making of chiropractic clinicians delivering SM thrusts.

Effect of Vitamin C on Tendinopathy Recovery: A Scoping Review.

Tendinopathies represent 30-50% of all sports injuries. The tendon response is influenced by the load (volume, intensity, and frequency) that the tendon support, resulting in irritability and pain, among others. The main molecular component of tendons is collagen I (60-85%). The rest consist of glycosaminoglycans-proteoglycans, glycoproteins, and other collagen subtypes. This study's aim was to critically evaluate the efficacy of vitamin C supplementation in the treatment of tendinopathies. At the same time, the study aims to determine the optimal conditions (dose and time) for vitamin C supplementation. A structured search was carried out in the SCOPUS, Medline (PubMed), and Web of Science (WOS) databases. The inclusion criteria took into account studies describing optimal tendon recovery when using vitamin C alone or in combination with other compounds. The study design was considered, including randomized, double-blind controlled, and parallel designs in animal models or humans. The main outcome is that vitamin C supplementation is potentially useful as a therapeutic approach for tendinopathy recovery. Vitamin C supplementation, alone or in combination with other products, increases collagen synthesis with a consequent improvement in the patient's condition. On the other hand, vitamin C deficiency is mainly associated with a decrease in procollagen synthesis and reduced hydroxylation of proline and lysine residues, hindering the tendon repair process.

Nitric-Oxide-Inducing Factors on Vitamin D Changes in Older People Susceptible to Suffer from Sarcopenia.

Calcium and magnesium, together with vitamin D and the hormones testosterone and cortisol, are key elements in muscle function, to maintain physical fitness. This study aims to analyze if supplementation with NO precursors (L-arginine, L-citrulline and beetroot extract) modulates the circulating levels of calcium, magnesium, vitamin D and steroid hormones in elders. Sixty-one volunteers (65.1 years old, 164.6 cm of height and 71.2 kg of weight) susceptible to develop sarcopenia participated in a physical activity program for 6 weeks. Participants were divided into four groups: one placebo and three taking one of the indicated supplements. Physical capacity was assessed through the following tests: (a) distance covered in 6 min by walking (endurance indicator); (b) hand grip (upper-body strength indicator); (c) time to cover 4 m by walking (speed indicator); and (d) time to perform five full squats (lower-body strength indicator). We concluded that there is a disparity in the association of steroid hormones, vitamin D levels and physical fitness. However, a significant inverse correlation between speed and endurance indicators was observed. Higher circulating vitamin D levels were observed in the L-arginine- and beetroot-supplemented groups. In conclusion, vasodilators increase vitamin D circulating levels that, in the long term, could maintain mineral homeostasis, improving muscular function.

The Host-Microbiome Response to Hyperbaric Oxygen Therapy in Ulcerative Colitis Patients.

BACKGROUND & AIMS: Hyperbaric oxygen therapy (HBOT) is a promising treatment for moderate-to-severe ulcerative colitis. However, our current understanding of the host and microbial response to HBOT remains unclear. This study examined the molecular mechanisms underpinning HBOT using a multi-omic strategy. METHODS: Pre- and post-intervention mucosal biopsies, tissue, and fecal samples were collected from HBOT phase 2 clinical trials. Biopsies and fecal samples were subjected to shotgun metaproteomics, metabolomics, 16s rRNA sequencing, and metagenomics. Tissue was subjected to bulk RNA sequencing and digital spatial profiling (DSP) for single-cell RNA and protein analysis, and immunohistochemistry was performed. Fecal samples were also used for colonization experiments in IL10-/- germ-free UC mouse models. RESULTS: Proteomics identified negative associations between HBOT response and neutrophil azurophilic granule abundance. DSP identified an HBOT-specific reduction of neutrophil STAT3, which was confirmed by immunohistochemistry. HBOT decreased microbial diversity with a proportional increase in Firmicutes and a secondary bile acid lithocholic acid. A major source of the reduction in diversity was the loss of mucus-adherent taxa, resulting in increased MUC2 levels post-HBOT. Targeted database searching revealed strain-level associations between Akkermansia muciniphila and HBOT response status. Colonization of IL10-/- with stool obtained from HBOT responders resulted in lower colitis activity compared with non-responders, with no differences in STAT3 expression, suggesting complementary but independent host and microbial responses. CONCLUSIONS: HBOT reduces host neutrophil STAT3 and azurophilic granule activity in UC patients and changes in microbial composition and metabolism in ways that improve colitis activity. Intestinal microbiota, especially strain level variations in A muciniphila, may contribute to HBOT non-response.

Midwives' experiences and perceptions in treating victims of sex trafficking: A qualitative study.

AIM: To explore the experiences and perceptions of midwives in the treatment of sex trafficking victims. DESIGN: The study was qualitative with a hermeneutic-phenomenological approach, using semi-structured interviews and focus groups. METHODS: Two focus groups and six interviews were carried out on 14 midwives in primary care, delivery and emergency rooms. Data were collected in three hospitals in Spain in June 2021. ATLAS.ti 9 software was used to conduct a content analysis of the focus group and interview data. RESULTS: The results revealed two primary themes and six subthemes. The two primary themes were (i) sex trafficking: a camouflaged reality on the invisible spectrum, and (ii) a thirst for attention in the aftermath of violence. Representative quotations were used to illustrate both the main themes and the subthemes. CONCLUSIONS: This study provides new insight into midwives' experiences treating sex trafficking victims. Professionals view this type of violence as a silent issue that negatively impacts victims' health and livelihood. However, a number of different factors stand in the way of correctly identifying and treating victims. Therefore, healthcare workers must be provided with practical tools and continuous professional development on this topic. IMPACT: This study indicates the importance of the midwives' key role in identifying and assisting victims of sex. Not only do measures in the healthcare setting, such as on-going specific-related content training or up-to-date protocols, need to be implemented to ensure proper care for those affected by sexual exploitation, but also focusing on suspicious characteristics and reducing obstacles to patient communication will help bring the true situation to light and better respond to patients' priority needs.

Development of a capillary electrophoresis method for the separation of flavonolignans in silymarin complex.

CE method for the baseline separation of structurally similar flavonolignans silybin A, silybin B, isosilybin A, isosilybin B, silychristin, silydianin, and their precursor taxifolin in silymarin complex has been developed and validated. The optimized background electrolyte was 100 mmol/L boric acid (pH 9.0) containing 5 mmol/L heptakis(2,3,6-tri-O-methyl)-ß-CD and 10% (v/v) of methanol. The separation was carried out in an 80.5/72 cm (50 µm id) fused silica capillary at +25 kV with UV detection at 200 nm. Genistein (10 µg/mL) was used as internal standard. The resolution between the diastereomers of silybin and isosilybin was 1.73 and 2.59, respectively. The method was validated for each analyte in a concentration range of 2.5-50 µg/mL. The calibration curves were rectilinear with correlation coefficients ≥0.9972. The method was applied to determine flavonolignans in two dietary supplements containing Silybum marianum extract. The accuracy was evaluated by comparing the results of the CE analyses of the dietary supplements with those of the reference United States Pharmacopeial HPLC method. The unpaired t-test did not show a statistically significant difference between the results of both the proposed CE and the reference method (p > 0.05, n = 3).

L-Citrulline Supplementation and Exercise in the Management of Sarcopenia.

Sarcopenia is a process associated to aging. Persistent inflammation and oxidative stress in muscle favour muscle wasting and decreased ability to perform physical activity. Controlled exercise can optimize blood flux and moderate the production of reactive oxygen species. Therefore, supplements that can work as a vasodilators and control oxidative stress, might be beneficial for active elders. In this context, we have tested citrulline supplementation in a group of 44 participants aged from 60-73 years that followed a physical activity program adapted to their age and capacities. Volunteers were divided in two groups: placebo (n = 22) and citrullline supplemented (n = 22). Different physical tests and blood extractions were performed at the beginning and at the end of intervention (six weeks). Strength and endurance showed a tendency to increase in the citrulline supplemented group, with no significant differences respect to placebo. However, walking speed in the citrulline supplemented group improved significantly compared to placebo. Markers of muscle damage as well as circulating levels of testosterone, cortisol and vitamin D showed no significant changes, but a tendency to improve at the end of intervention in the supplemented group compared to placebo. Additional studies are necessary to confirm the effect of citrulline supplementation in sarcopenia delay.

Deviance detection in physiologically identified cell types in the rat auditory cortex.

Auditory deviance detection is a function of the auditory system that allows reduction of the processing demand for repetitive stimuli while stressing unpredictable ones, which are potentially more informative. Deviance detection has been extensively studied in humans using the oddball paradigm, which evokes an event-related potential known as mismatch negativity (MMN). The same stimulation paradigms are used in animal studies that aim to elucidate the neuronal mechanisms underlying deviance detection. In order to understand the circuitry responsible for deviance detection in the auditory cortex (AC), it is necessary to determine the properties of excitatory and inhibitory neurons separately. Measuring the spike widths of neurons recorded extracellularly from the anaesthetized rat AC, we classified them as fast spiking or regular spiking units. These two neuron types are generally considered as putative inhibitory or excitatory, respectively. In response to an oddball paradigm, we found that both types of units showed similar amounts of deviance detection overall. When considering each AC field separately, we found that only in A1 fast spiking neurons showed higher deviance detection levels than regular spiking neurons, while in the rest of the fields there was no such distinction. Interpreting these responses in the context of the predictive coding framework, we found that the responses of both types of units reflect mainly prediction error signaling (i.e., genuine deviance detection) rather than repetition suppression.

Prediction error signaling explains neuronal mismatch responses in the medial prefrontal cortex.

The mismatch negativity (MMN) is a key biomarker of automatic deviance detection thought to emerge from 2 cortical sources. First, the auditory cortex (AC) encodes spectral regularities and reports frequency-specific deviances. Then, more abstract representations in the prefrontal cortex (PFC) allow to detect contextual changes of potential behavioral relevance. However, the precise location and time asynchronies between neuronal correlates underlying this frontotemporal network remain unclear and elusive. Our study presented auditory oddball paradigms along with "no-repetition" controls to record mismatch responses in neuronal spiking activity and local field potentials at the rat medial PFC. Whereas mismatch responses in the auditory system are mainly induced by stimulus-dependent effects, we found that auditory responsiveness in the PFC was driven by unpredictability, yielding context-dependent, comparatively delayed, more robust and longer-lasting mismatch responses mostly comprised of prediction error signaling activity. This characteristically different composition discarded that mismatch responses in the PFC could be simply inherited or amplified downstream from the auditory system. Conversely, it is more plausible for the PFC to exert top-down influences on the AC, since the PFC exhibited flexible and potent predictive processing, capable of suppressing redundant input more efficiently than the AC. Remarkably, the time course of the mismatch responses we observed in the spiking activity and local field potentials of the AC and the PFC combined coincided with the time course of the large-scale MMN-like signals reported in the rat brain, thereby linking the microscopic, mesoscopic, and macroscopic levels of automatic deviance detection.

Long-term docosahexaenoic acid (DHA) supplementation in cystic fibrosis patients: a randomized, multi-center, double-blind, placebo-controlled trial.

BACKGROUND: Cystic fibrosis (CF) patients have an alteration in fatty acid (FA) metabolism, associated with increased omega-6 and low omega-3 FA. Previous studies on supplementation with omega-3 FA in CF had contradictory results, and to date there is no evidence to recommend routine use of omega-3 supplements in CF patients. We hypothesized that long-term supplementation with docosahexaenoic acid (DHA) will have beneficial effects in these patients, by reducing pulmonary, systemic and intestinal inflammation. METHODS: This was a randomized, double-blind, parallel, placebo-controlled trial. CF patients (age >2 months) were randomized to receive a seaweed DHA oil solution (50 mg/Kg/day) or matching placebo for 48 weeks. Primary outcomes were pulmonary (interleukin [IL]-8), systemic (IL-8) and intestinal (calprotectin) inflammatory biomarkers. Secondary outcomes included other pulmonary (IL-1ß, IL-6, neutrophil elastase, lactate and calprotectin) and systemic (serum-IL-1ß, IL-6) inflammatory biomarkers, as well as clinical outcomes (FEV1, pulmonary exacerbations, antibiotic use, nutritional status and quality of life). RESULTS: Ninety six CF patients, 44 female, age 14.6±11.9 years (48 DHA and 48 placebo) were included. At trial completion, there were no differences in all primary outcomes [serum-IL-8 (p=0.909), respiratory-IL-8 (p=0.384) or fecal calprotectin (p=0.948)], all secondary inflammatory biomarkers, or in any of the clinical outcomes evaluated. There were few adverse events, with similar incidence in both study groups. CONCLUSION: In this study, long-term DHA supplementation in CF patients was safe, but did not offer any benefit on inflammatory biomarkers, or in clinical outcomes compared with placebo. (NCT01783613).

A Systematic Literature Review of Peripheral Nerve Stimulation Therapies for the Treatment of Pain.

OBJECTIVE: To conduct a systematic literature review of peripheral nerve stimulation (PNS) for pain. DESIGN: Grade the evidence for PNS. METHODS: An international interdisciplinary work group conducted a literature search for PNS. Abstracts were reviewed to select studies for grading. Inclusion/exclusion criteria included prospective randomized controlled trials (RCTs) with meaningful clinical outcomes that were not part of a larger or previously reported group. Excluded studies were retrospective, had less than two months of follow-up, or existed only as abstracts. Full studies were graded by two independent reviewers using the modified Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the US Preventative Services Task Force level-of-evidence criteria. RESULTS: Peripheral nerve stimulation was studied in 14 RCTs for a variety of painful conditions (headache, shoulder, pelvic, back, extremity, and trunk pain). Moderate to strong evidence supported the use of PNS to treat pain. CONCLUSION: Peripheral nerve stimulation has moderate/strong evidence. Additional prospective trials could further refine appropriate populations and pain diagnoses.

Dopamine modulates subcortical responses to surprising sounds.

Dopamine guides behavior and learning through pleasure, according to classic understanding. Dopaminergic neurons are traditionally thought to signal positive or negative prediction errors (PEs) when reward expectations are, respectively, exceeded or not matched. These signed PEs are quite different from the unsigned PEs, which report surprise during sensory processing. But mounting theoretical accounts from the predictive processing framework postulate that dopamine, as a neuromodulator, could potentially regulate the postsynaptic gain of sensory neurons, thereby scaling unsigned PEs according to their expected precision or confidence. Despite ample modeling work, the physiological effects of dopamine on the processing of surprising sensory information are yet to be addressed experimentally. In this study, we tested how dopamine modulates midbrain processing of unexpected tones. We recorded extracellular responses from the rat inferior colliculus to oddball and cascade sequences, before, during, and after the microiontophoretic application of dopamine or eticlopride (a D2-like receptor antagonist). Results demonstrate that dopamine reduces the net neuronal responsiveness exclusively to unexpected sensory input without significantly altering the processing of expected input. We conclude that dopaminergic projections from the thalamic subparafascicular nucleus to the inferior colliculus could encode the expected precision of unsigned PEs, attenuating via D2-like receptors the postsynaptic gain of sensory inputs forwarded by the auditory midbrain neurons. This direct dopaminergic modulation of sensory PE signaling has profound implications for both the predictive coding framework and the understanding of dopamine function.

Identification of a Human Skin Commensal Bacterium that Selectively Kills Cutibacterium acnes.

The microbiome represents a vast resource for drug discovery, as its members engage in constant conflict to outcompete one another by deploying diverse strategies for survival. Cutibacterium acnes is one of the most common bacterial species on human skin and can promote the common disease acne vulgaris. By employing a combined strategy of functional screening, genetics, and proteomics we discovered a strain of Staphylococcus capitis (S. capitis E12) that selectively inhibited growth of C. acnes with potency greater than antibiotics commonly used in the treatment of acne. Antimicrobial peptides secreted from S. capitis E12 were identified as four distinct phenol-soluble modulins acting synergistically. These peptides were not toxic to human keratinocytes and the S. capitis extract did not kill other commensal skin bacteria but was effective against C. acnes on pig skin and on mice. Overall, these data show how a member of the human skin microbiome can be useful as a biotherapy for acne vulgaris.

Momentary mood response to natural outdoor environments in four European cities.

Exposure to natural outdoor environments (NOE) has been shown in population-level studies to reduce anxiety and psychological distress. This study investigated how exposure to one's everyday natural outdoor environments over one week influenced mood among residents of four European cities including Barcelona (Spain), Stoke-on-Trent (United Kingdom), Doetinchem (The Netherlands) and Kaunas (Lithuania). Participants (n = 368) wore a smartphone equipped with software applications to track location and mood (using mobile ecological momentary assessment (EMA) software), for seven consecutive days. We estimated random-effects ordered logistic regression models to examine the association between mood (positive and negative affect), and exposure to green space, represented by two binary variables indicating exposure versus no exposure to NOE using GPS tracking and satellite and aerial imagery, 10 and 30 min prior to participants' completing the EMA. Models were adjusted for home city, day of the week, hour of the day, EMA survey type, residential NOE exposure, and sex, age, education level, mental health status and neighbourhood socioeconomic status. In addition, we tested for heterogeneity of effect by city, sex, age, residential NOE exposure and mental health status. Within 10 min of NOE exposure, compared to non-exposure, we found that overall there was a positive relationship with positive affect (OR: 1.39, 95% CI: 1.06, 1.81) of EMA surveys, and non-significant negative association with negative affect (OR: 0.80, 95% CI: 0.58, 1.10). When stratifying, associations were consistently found for Stoke-on-Trent inhabitants and men, while findings by age group were inconsistent. Weaker and less consistent associations were found for exposure 30 min prior to EMA. Our findings support increasing evidence of psychological and mental health benefits of exposure to natural outdoor environments, especially among urban populations such as those included in our study.