Symptoms In Healthy Individuals Research Articles

High levels of glycated haemoglobin (HbA1c) are associated with lower knee joint cartilage quality and higher knee joint symptoms in healthy individuals.

In an asymptomatic population, we investigated the relationships between glycated haemoglobin (HbA1c) and cartilage T2 relaxation time at the knee joint level. Fourteen and 17 participants with high and normal levels of HbA1c were recruited, respectively. A blood sample was used to determine the HbA1c level. T2 relaxation time (T2) of the superficial and deep parts of the femoral cartilage in the anterior, central, and posterior topographical sites was calculated using magnetic resonance (1.5T) images. Each participant completed a knee injury and osteoarthritis outcome score questionnaire (KOOS) and a series of biomechanical analyses while running at their self-selected speed. The group with a high level of HbA1c had a lower score of KOOS symptoms than the other group (P < 0.05). HbA1c was found to be negatively related to the KOOS symptoms score. The group with a high level of HbA1c had low T2 values in all of the investigated topographical sites of the knee femoral cartilage (P < 0.05 in all cases). T2 was negatively correlated with HbA1c levels in all investigated knee femoral cartilage regions. Our data suggest that the subjects with high levels of HbA1c were those with low knee joint symptoms and lower values of T2. These results indicate that HbA1c could be correlated with cartilage deterioration due to its ability to dehydrate collagen fibre, possibly acting as a risk factor for the development of osteoarthritis.

Cellular Transformation by Human Cytomegalovirus.

Epstein-Barr virus (EBV), Kaposi sarcoma human virus (KSHV), human papillomavirus (HPV), hepatitis B and C viruses (HBV, HCV), human T-lymphotropic virus-1 (HTLV-1), and Merkel cell polyomavirus (MCPyV) are the seven human oncoviruses reported so far. While traditionally viewed as a benign virus causing mild symptoms in healthy individuals, human cytomegalovirus (HCMV) has been recently implicated in the pathogenesis of various cancers, spanning a wide range of tissue types and malignancies. This perspective article defines the biological criteria that characterize the oncogenic role of HCMV and based on new findings underlines a critical role for HCMV in cellular transformation and modeling the tumor microenvironment as already reported for the other human oncoviruses.

CGAS/STING signaling pathway-mediated microglial activation in the PFC underlies chronic ethanol exposure-induced anxiety-like behaviors in mice

Chronic ethanol consumption is a prevalent condition in contemporary society and exacerbates anxiety symptoms in healthy individuals. The activation of microglia, leading to neuroinflammatory responses, may serve as a significant precipitating factor; however, the precise molecular mechanisms underlying this phenomenon remain elusive. In this study, we initially confirmed that chronic ethanol exposure (CEE) induces anxiety-like behaviors in mice through open field test and elevated plus maze test. The cGAS/STING signaling pathway has been confirmed to exhibits a significant association with inflammatory signaling responses in both peripheral and central systems. Western blot analysis confirmed alterations in the cGAS/STING signaling pathway during CEE, including the upregulation of p-TBK1 and p-IRF3 proteins. Moreover, we observed microglial activation in the prefrontal cortex (PFC) of CEE mice, characterized by significant alterations in branching morphology and an increase in cell body size. Additionally, we observed that administration of CEE resulted in mitochondrial dysfunction within the PFC of mice, accompanied by a significant elevation in cytosolic mitochondrial DNA (mtDNA) levels. Furthermore, our findings revealed that the inhibition of STING by H-151 effectively alleviated anxiety-like behavior and suppressed microglial activation induced by CEE. Our study unveiled a significant association between anxiety-like behavior, microglial activation, inflammation, and mitochondria dysfunction during CEE.

Effects of high-intensity interval training on depressive and anxiety symptoms in healthy individuals: A systematic review and meta-analysis of randomized clinical trials.

Although evidence regarding the effects of high-intensity interval training (HIIT) on mental health has increased in recent years, there is still no consensus regarding the effects of HIIT on the symptoms of depression and anxiety in a healthy population. Therefore, this systematic review aimed to investigate the effects of HIIT on depressive and/or anxiety symptoms in healthy individuals. The following four databases were searched: PubMed, Scopus, Embase, and PsycINFO. Only randomized clinical trials (RCTs) were included. We performed a random-effects meta-analysis based on standardized mean difference (SMD). The risk of bias was assessed using the RoB 2.0 tool, and the certainty of the evidence was evaluated based on recommendations GRADE. Eight RCTs evaluating 471 participants (81% female) were considered eligible for inclusion. The results of the meta-analysis showed that HIIT-based interventions had no significant effect on reducing anxiety (SMD = -0.17; 95% CI: -0.53, 0.19; p = 0.27) and depressive symptoms (SMD = -0.38; 95% CI: -1.06, 0.30; p = 0.17) compared with the passive control group. In conclusion, HIIT does not improve symptoms of depression and anxiety in healthy individuals. This finding is based on evidence of very low certainty. Therefore, the evidence is still not consistent enough to support HIIT as a viable strategy to reduce both outcomes because of the limited number of included studies and the overall quality of evidence.

Association between cytomegalovirus infection and neurological disorders: A systematic review.

Cytomegalovirus (CMV) belongs to the Herpesviridae family and is also known as human herpesvirus type 5. It is a common virus that usually doesn't cause any symptoms in healthy individuals. However, once infected, the virus remains in the host's body for life and can reactivate when the host's immune system weakens. This virus has been linked to several neurological disorders, including Alzheimer's disease, Parkinson's disease, Autism spectrum disorder, Huntington's disease (HD), ataxia, Bell's palsy (BP), and brain tumours, which can cause a wide range of symptoms and challenges for those affected. CMV may influence inflammation, contribute to brain tissue damage, and elevate the risk of moderate-to-severe dementia. Multiple studies suggest a potential association between CMV and ataxia in various conditions, including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, acute cerebellitis, etc. On the other hand, the evidence regarding CMV involvement in BP is conflicting, and also early indications of a link between CMV and HD were challenged by subsequent research disproving CMV's presence. This systematic review aims to comprehensively investigate any link between the pathogenesis of CMV and its potential role in neurological disorders and follows the preferred reporting items for systematic review and meta-analysis checklist. Despite significant research into the potential links between CMV infection and various neurological disorders, the direct cause-effect relationship is not fully understood and several gaps in knowledge persist. Therefore, continued research is necessary to gain a better understanding of the role of CMV in neurological disorders and potential treatment avenues.

Depressive symptoms and visual attention to others’ eyes in healthy individuals

BackgroundEye contact is a fundamental part of social interaction. In clinical studies, it has been observed that patients suffering from depression make less eye contact during interviews than healthy individuals, which could be a factor contributing to their social functioning impairments. Similarly, results from mood induction studies with healthy persons indicate that attention to the eyes diminishes as a function of sad mood. The present screen-based eye-tracking study examined whether depressive symptoms in healthy individuals are associated with reduced visual attention to other persons’ direct gaze during free viewing.MethodsGaze behavior of 44 individuals with depressive symptoms and 49 individuals with no depressive symptoms was analyzed in a free viewing task. Grouping was based on the Beck Depression Inventory using the cut-off proposed by Hautzinger et al. (2006). Participants saw pairs of faces with direct gaze showing emotional or neutral expressions. One-half of the face pairs was shown without face masks, whereas the other half was presented with face masks. Participants’ dwell times and first fixation durations were analyzed.ResultsIn case of unmasked facial expressions, participants with depressive symptoms looked shorter at the eyes compared to individuals without symptoms across all expression conditions. No group difference in first fixation duration on the eyes of masked and unmasked faces was observed. Individuals with depressive symptoms dwelled longer on the mouth region of unmasked faces. For masked faces, no significant group differences in dwell time on the eyes were found. Moreover, when specifically examining dwell time on the eyes of faces with an emotional expression there were also no significant differences between groups. Overall, participants gazed significantly longer at the eyes in masked compared to unmasked faces.ConclusionsFor faces without mask, our results suggest that depressiveness in healthy individuals goes along with less visual attention to other persons’ eyes but not with less visual attention to others’ faces. When factors come into play that generally amplify the attention directed to the eyes such as face masks or emotions then no relationship between depressiveness and visual attention to the eyes can be established.

The relationship between cyberbullying perpetration/victimization and suicidal ideation in healthy young adults: the indirect effects of positive and negative psychotic experiences

BackgroundEven though not all cyber bullies or victims think of (or consider) suicide, they clearly appear to be at an increased risk. One possible strategy to reduce suicide risk is to decrease cyberbullying occurrence; but this approach has its limitations, as it is certainly an illusion to believe that cyberbullying could be controlled or eliminated in a digitalized world. Another alternative and interesting strategy is to consider mediating factors that may indirectly affect suicidality. To this end, our purpose was to test the hypothesis that positive and negative psychotic experiences (PEs) mediate the relationship from cyberbullying perpetration/victimization to suicidal ideation (SI).MethodThe study followed a cross-sectional design, and was conducted during the period from June to September 2022. A total of 3103 healthy community participants from Lebanon were included (mean age 21.73 ± 3.80 years, 63.6% females).ResultsAfter adjusting over potential confounders, mediation analysis models showed that both positive and negative PEs partially mediated the associations between cyberbullying victimization/perpetration and SI. Higher cyberbullying perpetration and victimization were significantly associated with greater positive and negative PEs; more severe positive and negative PEs were significantly associated with higher levels of SI. Higher cyberbullying victimization and perpetration were significantly and directly associated with higher levels of SI.ConclusionIn light of our preliminary findings, there appears to be an urgent need for a new focus on carefully assessing and addressing attenuated psychotic symptoms in healthy individuals engaged in cyberbullying either as victims or bullies and who present with SI. It is important that school counselors and decision-makers consider a holistic approach taking into account both external/environmental (bullying) and internal/individual (PEs) factors in their suicide prevention programs. Future longitudinal research in larger samples are still required to confirm our findings and further elucidate the mechanisms underlying the relationship between cyberbullying and suicide.

Assessing evidence supporting cannabis harm reduction practices for adolescents at clinical high-risk for psychosis: a review and clinical implementation tool.

Cannabis use is consistently associated with both increased incidence of frank psychotic disorders and acute exacerbations of psychotic symptoms in healthy individuals and people with psychosis spectrum disorders. Although there is uncertainty around causality, cannabis use may be one of a few modifiable risk factors for conversion to psychotic disorders in individuals with Clinical High Risk for Psychosis (CHR-P) syndromes, characterized by functionally impairing and distressing subthreshold psychotic symptoms. To date, few recommendations beyond abstinence to reduce adverse psychiatric events associated with cannabis use have been made. This narrative review synthesizes existing scientific literature on cannabis' acute psychotomimetic effects and epidemiological associations with psychotic disorders in both CHR-P and healthy individuals to bridge the gap between scientific knowledge and practical mental health intervention. There is compelling evidence for cannabis acutely exacerbating psychotic symptoms in CHR-P, but its impact on conversion to psychotic disorder is unclear. Current evidence supports a harm reduction approach in reducing frequency of acute psychotic-like experiences, though whether such interventions decrease CHR-P individuals' risk of conversion to psychotic disorder remains unknown. Specific recommendations include reducing frequency of use, lowering delta-9-tetrahydrocannabinol content in favor of cannabidiol-only products, avoiding products with inconsistent potency like edibles, enhancing patient-provider communication about cannabis use and psychotic-like experiences, and utilizing a collaborative and individualized therapeutic approach. Despite uncertainty surrounding cannabis' causal association with psychotic disorders, cautious attempts to reduce acute psychosis risk may benefit CHR-P individuals uninterested in abstinence. Further research is needed to clarify practices associated with minimization of cannabis-related psychosis risk.

Self-compassion is associated with the superior longitudinal fasciculus in the mirroring network in healthy individuals

Self-compassion (SC) involves taking an emotionally positive attitude towards oneself when suffering. Although SC has positive effects on mental well-being as well as a protective role in preventing symptoms in healthy individuals, few studies on white matter (WM) microstructures in neuroimaging studies of SC has been studied. Brain imaging data were acquired from 71 healthy participants. WM regions of mirroring network were analyzed using tract-based spatial statistics. After the WM regions associated with SC were extracted, exploratory correlation analysis with the self-forgiveness scale, the coping scale, and the world health organization quality of life scale abbreviated version was performed. We found that self-compassion scale total scores were negatively correlated with the fractional anisotropy (FA) values of the superior longitudinal fasciculus (SLF) in healthy individuals. The self-kindness and mindfulness subscale scores were also negatively correlated with FA values of the same regions. These FA values were negatively correlated with the total scores of self-forgiveness scale, and self-control coping strategy and confrontation coping strategy. Our findings suggest levels of SC may be associated with WM microstructural changes of SLF in healthy individuals. These lower WM microstructures may be associated with positive personal attitudes, such as self-forgiveness, self-control and active confrontational strategies.

Sleep disturbances and the association with attenuated psychotic symptoms in individuals at ultra high-risk of psychosis

Sleep disturbances are common in individuals at ultra high-risk (UHR) of psychosis and have proven to play a causal role in the occurrence of psychotic symptoms in healthy individuals. Only a few studies have systematically investigated sleep disturbances in UHR individuals. The help-seeking UHR individuals were 18–40 years old, and we included 72 UHR individuals according to the Comprehensive Assessment of At-Risk Mental State criteria (CAARMS) and 36 healthy controls. Sleep was measured with a modified version of the Karolinska Sleep Questionnaire and actigraphy for one night, and melatonin was measured at awakening and bedtime. We compared subjective rated sleep and actigraphy between healthy and UHR individuals (t-test and chi-square test) and examined the association between a CAARMS-composite score (linear regression). UHR individuals subjectively experienced poor sleep, categorised as disturbed sleep- and awakening index compared with healthy controls. We found no differences in actigraphy variables or morning/evening melatonin between UHR and healthy controls (t-test and chi-square). A high CAARMS-composite score was associated with high morning melatonin (B = 0.15, CI 0.02 to 0.27, p = 0.024) and high awakening index (B = 1.86, CI 0.58 to 3.14, p = 0.004) in UHR individuals. The results suggest that UHR individuals with high CAARMS scores have a delayed sleep phase; they have difficulties waking up and feel exhausted at awakening. It might be necessary to evaluate how UHR individuals sleep, and it would be of great interest to follow these patients over time according to the development of psychosis.

Impact of prolonged face mask wearing on tear break-up time and dry eye symptoms in health care professionals.

PurposeTo evaluate the impact of prolonged surgical face mask wearing on dry eye symptoms and tear film break-up time (T-BUT) in health care professionals.Materials and methodsA total of 33 health care professionals were included in the present cross sectional prospective study. In addition to a complete ophthalmological examination T-BUT measurements were performed twice for all participants in the morning (8 am) and in the afternoon (5 pm). The subjects also filled-in the ocular surface disease index (OSDI) questionnaire twice, before and after wearing the face mask, on the same day.ResultsSixty-six eyes of 33 participants (17 female and 16 male) were evaluated. The mean age was 33.6 ± 7.55 (24–48) years and mean total duration with mask on between the two evaluations was 514 ± 12.5 (495–526) minutes. The mean T-BUT was 9.3 ± 1.0 (3–16) seconds at 8 am and 8.3 ± 1.5 (3–14) seconds at 5 pm (p = 0.01). The mean OSDI score was 20.1 ± 8.3 (0–68.75) at 8 am and 27.4 ± 10.4 (0–81.25) at 5 pm (p < 0.01).ConclusionUse of a surgical mask for the entire work-day was seen to worsen T-BUT and increase dry eye symptoms in healthy individuals. Ophthalmologists should be aware of the possibility of worsening of dry eye symptoms with the prolonged use of surgical face masks and consider modifications if necessary.

Effects of 200cH medications on mice bone marrow cells and macrophages

Paracelsus once wrote: "All things are poison and nothing is without poison, only the dose permits something not to be poisonous." Latter Hahnemann formulated the law of similars, preparations which cause certain symptoms in healthy individuals if given in diluted form to patients exhibiting similar symptoms will cure it. Highly diluted natural complexes prepared according to Hahnemann’s ancient techniques may represent a new form of immunomodulatory therapy. The lack of scientific research with highly diluted products led us to investigate the in vivo and in vitro actions of commonly used medications. Here we describe the results of experimental studies aimed at verifying the effects of Mercurius solubilis, Atropa Belladonna, Lachesis muta and Bryonia alba. All medications were at 200cH dilution. Animals were maintained for 7 days and were allowed to drink the medications, which were prepared in a way that the final dilution and agitation (200cH) was performed in drinking water. The medication bottle was changed and sucussed every afternoon. Co-culture of non treated mice bone marrow cells and in vitro treated peritoneal macrophages were also performed. After animal treatment the bone marrow cells were immunophenotyped with hematopoietic lineage markers on a flow cytometer. We have determined CD11b levels on bone marrow cells after culture and co-culture with treated macrophages and these macrophages were processed to scanning electron microscopy. We have observed by morphological changes that macrophages were activated after all treatments. Mercurius solubilis treated mice showed an increase in CD3 expression and in CD11b on nonadherent bone marrow cells after co-culture with in vitro treatment. Atropa Belladonna increased CD45R and decreased Ly-6G expression on bone marrow cells after animal treatment. Lachesis muta increased CD3, CD45R and, CD11c expression and decreased CD11b ex vivo and in nonadherent cells from co-culture. Bryonia alba increased Ly-6G, CD11c and CD11b expression ex vivo and when in co-culture CD11b was increased in adherent cells as well as decreased in nonadherent cells. With these results we have demonstrated that highly diluted medications act on immune cells activating macrophages, and changing the expression profile of hematopoietic lineage markers. Highly diluted medications are less toxic and cheaper than other commonly used medications and based on our observations, it is therefore conceivable that this medications which are able to act on bone marrow and immune cells may have a potential therapeutic use in clinical applications in diseases were the immune system is affected and also as regenerative medicine as it may allow proliferation and differentiation of progenitor cells.

Age-Related Decrease in Abdominal Pain and Associated Structural- and Functional Mechanisms: An Exploratory Study in Healthy Individuals and Irritable Bowel Syndrome Patients.

Introduction: The world population is ageing, resulting in increased prevalence of age-related comorbidities and healthcare costs. Limited data are available on intestinal health in elderly populations. Structural and functional changes, including altered visceroperception, may lead to altered bowel habits and abdominal symptoms in healthy individuals and irritable bowel syndrome (IBS) patients. Our aim was to explore age-related changes in gastrointestinal symptoms and underlying mechanisms. Methods: In total, 780 subjects (IBS patients n = 463, healthy subjects n = 317) from two separate studies were included. Subjects were divided into different age groups ranging from young adult to elderly. Demographics and gastrointestinal symptom scores were collected from all participants using validated questionnaires. A subset of 233 IBS patients and 103 controls underwent a rectal barostat procedure to assess visceral hypersensitivity. Sigmoid biopsies were obtained from 10 healthy young adults and 10 healthy elderly. Expression of the visceral pain-associated receptors transient receptor potential (TRP) Ankyrin 1 (TRPA1) and Vanilloid 1 (TRPV1) genes were investigated by quantitative RT-PCR and immunofluorescence. Results: Both elderly IBS and healthy individuals showed significantly lower scores for abdominal pain (p < 0.001) and indigestion (p < 0.05) as compared to respective young adults. Visceral hypersensitivity was less common in elderly than young IBS patients (p < 0.001). Relative TRPA1 gene transcription, as well as TRPA1 and TRPV1 immunoreactivity were significantly lower in healthy elderly versus healthy young adults (p < 0.05). Conclusions: Our findings show an age-related decrease in abdominal pain perception. This may in part be related to decreased TRPA1 and/or TRPV1 receptor expression. Further studies are needed to reveal precise underlying mechanisms and the associations with intestinal health.

TNF signaling pathway-mediated microglial activation in the PFC underlies acute paradoxical sleep deprivation-induced anxiety-like behaviors in mice

Acute sleep deprivation is a common condition in modern life and increases anxiety symptoms in healthy individuals. The neuroinflammatory response induced by microglial activation could be an important contributing factor, but its underlying molecular mechanisms are still unclear. In the present study, we first found that acute paradoxical sleep deprivation (PSD) induced by the modified multiple platform method (MMPM) for 6 h led to anxiety-like behavior in mice, as verified by the open field test, elevated plus maze test, light–dark box test, and marble burying test. In addition, bioinformatic analysis suggested an important relationship between acute sleep deprivation and brain inflammatory signaling pathways. Key genes enriched in the TNF signaling pathway were confirmed to be altered during acute PSD by qPCR and Western blot analyses, including the upregulation of the prostaglandin-endoperoxide synthase 2 (Ptgs2) and suppressor of cytokine signaling 3 protein (Socs3) genes and the downregulation of the cysteine-aspartic acid protease 3 (Casp3) gene. Furthermore, we found that microglial cells in the prefrontal cortex (PFC) were activated with significant branch structure changes and that the cell body area was increased in the PSD model. Finally, we found that minocycline, a tetracycline with anti-inflammatory properties, may ameliorate the anxiogenic effect and microglial activation. Our study reveals significant correlations of anxiety-like behavior, microglial activation, and inflammation during acute PSD.

"˜Paradoxical pharmacology": therapeutic strategy used by the "˜homeopathic pharmacology" for more than two centuries

Using the empirical or phenomenological research method by observing the effects of drugs in the human physiology, Samuel Hahnemann proposed the homeopathic treatment. He synthesized modern pharmacodynamic in the ‘primary action’ of the drugs and in the consequent and opposite ‘secondary action’ or ‘vital reaction’ of the organism. Noting that drugs with ‘contrary’ primary action to the symptoms of the diseases caused worsening of the symptoms after its withdrawal, as a result of secondary action of the organism, Hahnemann proposed using this vital reaction in a curative way, administering to sick individuals the drugs that caused ‘similar’ symptoms in healthy individuals (therapeutic use of the similitude principle). According to the clinical and experimental pharmacology, this secondary action (vital reaction) of the organism is observed in the ‘rebound effect’ or ‘paradoxical reaction’ of several classes of drugs, which is the scientific basis of the ‘homeopathic pharmacology’. In the last decade, exponents of modern pharmacology have suggested the therapeutic use of the paradoxical reaction (‘paradoxical pharmacology’), proposing the use of drugs that cause an exacerbation of the disease in the short term to treat these same diseases in the long-term. In this review, we compare the various aspects between the ‘homeopathic pharmacology’ and the ‘paradoxical pharmacology’, reinforcing the validity of homeopathic assumptions and expanding the knowledge to optimize both proposals.

Risk of transfusion-transmitted Babesia microti in Canada.

Babesia microti has gained a foothold in Canada as tick vectors become established in broader geographic areas. B. microti infection is associated with mild or no symptoms in healthy individuals but is transfusion-transmissible and can be fatal in immunocompromised individuals. This is the first estimate of clinically significant transfusion-transmitted babesiosis (TTB) risk in Canada. The proportion of B. microti-antibody (AB)/nucleic acid amplification test (NAT)-positive whole blood donations was estimated at 5.5% of the proportion of the general population with reported Lyme Disease (also tick-borne) based on US data. Monte Carlo simulation estimated the number and proportion of infectious red cell units for three scenarios: base, localized incidence (risk in Manitoba only), and donor study informed (prevalence from donor data). The model simulated 1,029,800 donations repeated 100,000 times for each. In the base scenario 0.5 (0.01, 1.75), B. microti-NAT-positive donations would be expected per year, with 0.08 (0, 0.38) recipients suffering clinically significant TTB (1 every 12.5 years). In the localized incidence scenario, there were 0.21(0, 0.7) B. microti-NAT-positive donations, with 0.04 (0, 0.14) recipient infections (about 1 every 25 years). In the donor study informed scenario, there were 4.6 (0.3, 15.8) B. microti-NAT-positive donations expected, and 0.81 (0.05, 3.14) clinically significant TTB cases per year. The likelihood of clinically relevant TTB is low. Testing would have very little utility in Canada at this time. Ongoing pathogen surveillance in tick vectors is important as B. microti prevalence appears to be slowly increasing in Canada.

Reversible Changes in BDNF Expression in MK-801-Induced Hippocampal Astrocytes Through NMDAR/PI3K/ERK Signaling.

Dizocilpine (MK-801), a non-competitive N-methyl-D-aspartic acid receptor (NMDA-R) antagonist, can induce schizophrenia-like symptoms in healthy individuals, implicating NMDA-R hypofunction in disease pathogenesis. Brain-derived neurotrophic factor (BDNF) is also implicated in schizophrenia, and expression is regulated by NMDA-R activity, suggesting a functional link. We previously found that BDNF signaling was upregulated by MK-801 in cultured hippocampal astrocytes, but the underlying mechanism is not clear. To address this issue, the levels of BDNF expression and secretion were evaluated in hippocampal astrocytes incubated with MK-801 by ELISA and qPCR, with and without NMDA co-incubation or pretreatment of either the ERK1/2 inhibitor, PD98059 or the PI3K inhibitor, LY294002. The apoptosis, viability, and proliferation of the astrocytes were also examined. In the current study, we demonstrate that MK-801 treatment (20 μM for 5 days) enhances the proliferation of rat cultured hippocampal astrocytes. Expression of BDNF mRNA was enhanced after 24 h in MK-801, but returned to near baseline over the next 24 h in the continued presence of MK-801. However, two successive 24-h treatments enhanced BDNF expression. These application regimens had no effect on apoptosis or proliferation rate. Co-addition of NMDA significantly inhibited MK-801-induced upregulation of BDNF. Similarly, MK-801-induced BDNF upregulation was blocked by pretreatment with inhibitors of PI3K and ERK1/2, but not by inhibitors of p38 and JNK. These findings suggested that astrocytes may contribute to the acute neurological and behavioral response to MK-801 treatment via a transient increase in BDNF expression involving NMDA-R–PI3K–ERK signaling.

Population Genomic Analysis of Listeria monocytogenes From Food Reveals Substrate-Specific Genome Variation.

Listeria monocytogenes is the major causative agent of the foodborne illness listeriosis. Listeriosis presents as flu-like symptoms in healthy individuals, and can be fatal for children, elderly, pregnant women, and immunocompromised individuals. Estimates suggest that L. monocytogenes results in ∼1,600 illnesses and ∼260 deaths annually in the United States. L. monocytogenes can survive and persist in a variety of harsh environments, including conditions encountered in production of fermented dairy products such as cheese. For instance, microbial growth is often limited in soft cheese fermentation because of harsh pH, water content, and salt concentrations. However, L. monocytogenes has caused a number of deadly listeriosis outbreaks through the contamination of cheese. The purpose of this study was to understand if genetically distinct populations of L. monocytogenes are associated with particular foods, including cheese and dairy. To address this goal, we analyzed the population genetic structure of 504 L. monocytogenes strains isolated from food with publicly available genome assemblies. We identified 10 genetically distinct populations spanning L. monocytogenes lineages 1, II, and III and serotypes 1/2a, 1/2b, 1/2c, 4b, and 4c. We observed an overrepresentation of isolates from specific populations with cheese (population 2), fruit/vegetable (population 2), seafood (populations 5, 8 and 9) and meat (population 10). We used the Large Scale Blast Score Ratio pipeline and Roary to identify genes unique to population 1 and population 2 in comparison with all other populations, and screened for the presence of antimicrobial resistance genes and virulence genes across all isolates. We identified > 40 genes that were present at high frequency in population 1 and population 2 and absent in most other isolates. Many of these genes encoded for transcription factors, and cell surface anchored proteins. Additionally, we found that the virulence genes aut and ami were entirely or partially deleted in population 2. These results indicate that some L. monocytogenes populations may exhibit associations with particular foods, including cheese, and that gene content may contribute to this pattern.

Effects of Saffron Extract Supplementation on Mood, Well-Being, and Response to a Psychosocial Stressor in Healthy Adults: A Randomized, Double-Blind, Parallel Group, Clinical Trial.

Anxiety, stress, and low mood are closely related and may contribute to depressive symptoms. Among non-pharmacological solutions to improve subclinical mood symptoms and resilience to stress, natural products such as saffron—identified as promising following preliminary beneficial effects in major depressive disorder—represent a relevant strategy. This study aimed to assess the efficacy of 8 weeks' supplementation with 30 mg standardized saffron extract on emotional well-being in healthy adults with subclinical feelings of low mood and anxiety and/or stress and evaluate the acute effect of saffron in response to a lab-based psychosocial stressor. The study adopted a double-blind, randomized, parallel groups design in which 56 healthy male and female individuals (18–54 years) received either a saffron extract or a placebo for 8 weeks. Chronic effects of saffron on subjective anxiety, stress, and depressive feelings were assessed using a questionnaire battery [including Profile of Mood State-2, (POMS)] and acute effects in response to a lab-based psychosocial stressor were measured through psychological and physiological parameters. Urinary crocetin levels were quantified. Participants who received the saffron extract reported reduced depression scores and improved social relationships at the end of the study. Urinary crocetin levels increased significantly with saffron supplementation and were correlated with change in depression scores. The typical stress-induced decrease in heart rate variability (HRV) during exposure to the stressor was attenuated following acute saffron intake. Saffron extract appears to improve subclinical depressive symptoms in healthy individuals and may contribute to increased resilience against the development of stress-related psychiatric disorders.Clinical trials number: NCT03639831.

Mapping relationships between ADHD genetic liability, stressful life events, and ADHD symptoms in healthy adults.

Attention‐deficit/hyperactivity disorder (ADHD) symptoms are continuously distributed in the general population, where both genetic and environmental factors play roles. Stressful life events (SLEs) have been associated with ADHD diagnosis, but the relationship between ADHD genetic liability, SLEs, and ADHD symptoms in healthy individuals is less clear. Using a sample of 1,531 healthy adults (average age 26.9 years; 55.8% female), we investigated relationships between ADHD polygenic risk scores (ADHD‐PRSs), SLEs, and ADHD symptoms in a general population sample. Confirming earlier findings in an overlapping sample, all SLE‐measures assessed (lifetime SLEs, recent SLEs, and childhood trauma (CT)) were significantly correlated with total ADHD, inattention (IA), and hyperactivity‐impulsivity (HI) scores (r 2 range = .08–.15; all p < .005). ADHD‐PRSs was associated with HI (R2 best‐fit = .37%), lifetime SLEs (R2 best‐fit = .56%), and CT (R2 best‐fit = .40%). Mediation analyses showed that lifetime SLEs partially mediated the association between ADHD‐PRSs and HI (indirect effect: β = 68.6, bias corrected accelerated 95% confident interval (BCa95%CI) [11.9, 131.0], p = .016, proportion mediated (PM) =19.5%), with strongest effects contributed by CT (β = 34.4, BCa95%CI [0.4, 76.5], p = .040, PM = 9.8%). On the other hand, HI partially mediated the association between the ADHD‐PRSs and lifetime SLEs (β = 42.9, BCa95%CI [7.3, 83.9], p = .014, PM = 18.8%). Our study observed a complex relationship of genetic and environmental risk factors contributing to ADHD symptoms in the healthy adult population.