Longitudinal Problematic Social Media Use in Students and Its Association with Negative Mental Health Outcomes.

Purpose: Social media has become increasingly part of our everyday lives and is influential in shaping the habits, sociability, and mental health of individuals, particularly among students. This study aimed to examine the relationship between changes over time in problematic social media use and mental health outcomes in students. We also investigated whether resilience and loneliness moderated the relationship between social media use and mental health. Patients and Methods: A total of 103 participants completed a baseline virtual study visit, and 78 participants completed a follow-up visit, 4-weeks later. Participants completed a comprehensive set of questionnaires measuring symptoms of depression and anxiety, perceived stress, loneliness, and resilience. Results: Our results showed that problematic social media use at baseline was significantly negatively correlated with resilience and positively correlated with all other mental health outcomes. Furthermore, increases in problematic social media use were significantly associated with increased depressive symptoms and loneliness between visits. Resilience significantly moderated the relationship between increased problematic social media use and heightened perceived stress. Poor mental health at baseline did not predict increased problematic social media use over time. Contrarily to problematic use, frequency of social media use was not significantly correlated with any mental health measures at baseline. Conclusion: This study offers a longitudinal perspective, providing valuable insights into the potential protective role of resilience against the detrimental mental health effects seen with increases in problematic social media use.

Lonely and scrolling during the COVID-19 pandemic: understanding the problematic social media use and mental health link among university students.

Introduction: Undergraduate university students experienced many academic and non-academic stressors during the first year of the coronavirus (COVID-19) pandemic, putting them at a greater risk of negative mental health outcomes. Reports worldwide have shown high incidences of depressive, anxiety, and stress scores among university students at the beginning of the pandemic. Emerging evidence also suggests that to cope with the stress and loneliness of the pandemic, many youth and young adults increased the amount of time they spent on social media platforms. Methods: Undergraduate students participated in an online study aimed to understand the link between time spent on social media, coping through the use of social media and problematic social media use (PSMU) with mental health symptoms, such as stress, depression, anxiety, and loneliness, during the COVID-19 pandemic. Results: While time spent on social media was only weakly associated with stress, depression, anxiety and loneliness scores, PSMU more strongly mapped onto these outcomes. Additionally, students who were coping highly using social media displayed elevated stress, depression, anxiety and loneliness levels in comparison to those reporting low levels of coping with social media. Finally, students who reported high levels of coping using social media displayed higher PSMU scores, with this relationship appearing more pronounced in students who had higher levels of loneliness. Conclusion: These data support evidence that it is not necessarily time spent on social media but rather PSMU that is relevant for mental health symptoms, and that PSMU is exacerbated by loneliness. Moreover, the current results highlight the effects of maladaptive coping on mental health symptoms and PSMU among university students during the COVID-19 pandemic.

Examining Risk Factors in the Cannabis-Suicide Link: Considering Trauma and Impulsivity among University Students.

Cannabis is a commonly used substance among university students that may have several negative health repercussions, including suicidal ideation (SI) and suicide attempts (SA). The factors that contribute to or help explain this relation remain uncertain. Earlier negative experiences, especially trauma encountered during early life, have been associated with the development of psychopathology upon later stressor encounters. In the current study, we examined the associations between SI and SA with problematic cannabis use among young adults and the role of earlier trauma experiences and trait impulsiveness in understanding this link. Among university students (N = 539), problematic cannabis use was moderately related to lifetime and past-12-months suicidal ideation and attempts. Impulsiveness mediated the relationship between problematic cannabis use and lifetime SI and SA. Moreover, previous life trauma moderated the relationship between problematic cannabis use and SA, such that the association between problematic cannabis use and SA was stronger among those who experienced high levels of trauma. These findings highlight behavioral and environmental factors that could predict suicide ideation and attempts among young cannabis users. Accordingly, trait impulsiveness and early trauma experiences should be considered, alongside problematic cannabis use, in suicide-risk detection and prevention strategies among young adults.

Effects of melatonin receptor expression on prognosis and survival in oral squamous cell carcinoma patients.

Melatonin receptors can inhibit breast and prostate cancers; however, little is known regarding their effects on oral squamous cell carcinoma. In this study, we collected specimens from 81 patients with oral squamous cell carcinoma and analysed clinicopathological data retrospectively. In addition, the expression of the melatonin receptor was analysed immunohistochemically. Survival rates were calculated using the Kaplan-Meier method and log-rank test. Multivariate analysis was performed based on the Cox proportional-hazards model. Further, an in vitro study was performed using YD15 cells. The cells were transfected with siRNA targeting melatonin receptor 1A and 1B for evaluating the malignancy of melatonin receptors by western blotting, trypan blue-exclusion, colony-forming, wound-healing, and invasion assays. Survival decreased as melatonin receptor expression and clinical and pathological tumour-node-metastasis stages increased. A Cox proportional-hazard model showed that melatonin receptor 1A may serve as a significant predictor of the survival rate of patients with oral squamous cell carcinoma [hazard ratio = 1.423, 95% confidence interval (CI) = 1.019-1.988, p = 0.038]. Melatonin receptor 1A and 1B knockdown significantly suppressed proliferation, migration ability, and invasion ability of YD15 cells in vitro. Our findings reveal that inhibiting melatonin receptor expression may suppress oral squamous cell carcinoma development.

Flux-pinning behaviors and mechanism according to dopant level in (Fe, Ti) particle-doped [Formula: see text] superconductor.

We have studied flux-pinning effects of [Formula: see text] superconductor by doping (Fe, Ti) particles of which radius is 163 nm on average. 5 wt.% (Fe, Ti) doped [Formula: see text] among the specimens showed the best field dependence of magnetization and 25 wt.% one did the worst at 5 K. The difference of field dependence of magnetization of the two specimens increased as temperature increased. Here we show experimental results of (Fe, Ti) particle-doped [Formula: see text] specimens according to dopant level and the causes of the behaviors. Flux-pinning effect of volume defects-doped superconductor was modeled in ideal state and relative equations were derived. During the study, we had to divide M-H curve of volume defect-dominating superconductor as three discreet regions for analyzing flux-pinning effects, which are diamagnetic increase region after [Formula: see text], [Formula: see text] region, and diamagnetic decrease region. As a result, flux-pinning effects of volume defects decreased as dopant level increased over the optimal dopant level, which was caused by decrease of flux-pinning limit of a volume defect. And similar behaviors are obtained as dopant level decreased below the optimal dopant level, which was caused by the decreased number of volume defects. Comparing the model with experimental results, deviations increased as dopant level increased over the optimal dopant level, whereas the two was well matched on less dopant level. The behavior is considered to be caused by the segregation of the volume defects. On the other hand, the cause that diamagnetic properties of over-doped [Formula: see text] specimens dramatically decreased as temperature increased was the double decreases of flux-pinning limit of a volume defect and the segregation effect, which are caused by over-doping and temperature increase.

Coping With the COVID-19 Pandemic: Examining Gender Differences in Stress and Mental Health Among University Students.

The COVID-19 pandemic has imposed a wide variety of unprecedented challenges, many of which appear to be disproportionately affecting the mental health and well-being of young adults. While there is evidence to suggest university students experience high rates of mental health disorders, less is known about the specific impacts of the COVID-19 pandemic on student mental health and how they are coping with this stress. To address this gap, we conducted an online study among undergraduate students (n = 366) to examine the impact of the COVID-19 pandemic on academics, social isolation, and mental health, as well as the extent to which they have been implementing a variety of coping strategies. The pandemic had a more pronounced negative effect on female students' academics, social isolation, stress and mental health compared to male counterparts. Moreover, for females, frequent use of social media as a coping mechanism was associated with greater perceived negative impacts on their academic performance and stress levels, compared to males. However, frequent social media use related to similar negative mental health effects for both males and females. While male and female students both reported using substances to cope, for males the use of cannabis was associated with greater negative impacts on academic outcomes, stress and mental health compared to females. These findings highlight the need for adequate student support services across the post-secondary sector, and point to the importance of gender informed interventions to address the impacts of the COVID-19 pandemic.

Upper Critical Field Based on a Width of ΔH = ΔB region in a Superconductor.

We studied a method of measuring upper critical field (Hc2) of a superconductor based on a width of ΔH = ΔB region, which appears in a superconductor that volume defects are many and dominant. Here we show basic concepts and details of the method. Although Hc2 of a superconductor is fixed according to a kind of superconductor, it is difficult to measure Hc2 experimentally. Thus, results are different depending on experimental conditions. Hc2 was otained by a theory on a width of ΔH = ΔB region, which is that pinned fluxes at volume defects are picked out and move into an inside of the superconductor when the distance between pinned fluxes is the same as that at Hc2 of the superconductor. Hc2 of MgB2 obtained by the method was 65.4 Tesla at 0 K, which is quite same as that of Ginzburg-Landau theory. The reason that Hc2 obtained by the method is closer to ultimate Hc2 is based on that Fpinning/Fpickout is more than 4 when pinned fluxes at volume defects of 163 nm radius are depinned, which means that the Hc2 is less sensitive to fluctuation. The method will help to find the ultimate Hc2 of volume defect-dominating superconductors.

Tooth bleaching with low-temperature plasma lowers surface roughness and Streptococcus mutans adhesion.

AIM: To evaluate the structural-morphological changes in enamel surface roughness and Streptococcus mutans adhesion after tooth bleaching using plasma in combination with a low concentration of 15% carbamide peroxide (CP). METHODOLOGY: Sixty pairs of premolars were randomly assigned to the treatment groups (n = 30; buccal surface, groups 1A/2A) or controls (n = 30; palatal surface, Groups 1B/2B). Group 1A received a low concentration of 15% CP and low-temperature plasma. Premolars in group 1B were placed in phosphate-buffered saline and served as controls. The buccal surface of Groups 2A was subjected to 15% CP alone, whilst the palatal surface was subsequently immersed in PBS (group 2B). After bleaching, all teeth were soaked for 1 h in artificial saliva at 37 °C. Subsequently, teeth were placed in brain-heart infusion with S. mutans at 37 °C for 24 h. The assessment of the structural-morphological changes was carried out using a biofilm assay, scanning electron microscopy and atomic force microscopy. Statistical analysis of the data was performed with the SPSS (SPSS Inc., Version 18.0, Chicago, IL, USA). The Student's t-test was used to determine whether there was a significant difference in the structural-morphological effects with and without plasma. RESULTS: Significantly less S. mutans adhesion was observed in group 1A compared with the other groups (P < 0.05). Moreover, the surface roughness was significantly greater in group 2A compared with the other groups (P < 0.05). CONCLUSIONS: The application of plasma did not result in any structural-morphological and topographic changes in the enamel. The combined bleaching method using plasma and a low concentration of 15% CP was less destructive, particularly with respect to tooth surface changes.

Retention Improvement in Fluoride Application with Cold Atmospheric Plasma.

This study aimed to apply fluoride formulations to enamel with cold atmospheric plasma (CAP) and analyze the fluoride uptake, retention, and acid resistance quantitatively. Human enamel specimens were divided randomly into 2 groups: group APF1, 1.23% acidulated phosphate fluoride (APF) gel; group APF2, 1.23% APF gel with CAP. Fluoride and CAP were applied to the samples 4 times at 1-wk intervals. The specimens were also stored in artificial saliva for 4 wk to evaluate the retention of fluoride. The fluoride content on the fluoride-treated enamel was measured by an electron probe microanalyzer. To detect the resistance to demineralization, the calcium-to-phosphate ratio of the enamel samples was measured after the application of APF gel with or without CAP, followed by soaking in the demineralization solution. In groups APF1 and APF2, the amount of fluoride detected increased depending on the application frequency, and more fluoride was detected in group APF2 than in group APF1. In the experiment examining the maintenance effect, fluoride was not detected in group APF1, whereas fluoride was detected in group APF2 up to the fourth week. As for the resistance to demineralization, the calcium-to-phosphate ratio of the enamel treated with APF and CAP was higher than that treated with APF alone, and it increased with the frequency of treatment. This study suggests that the combination treatment of CAP and fluoride improves retention of fluoride on the enamel and resistance to demineralization when compared with treatment with fluoride alone.

Skin renewal activity of non-thermal plasma through the activation of ß-catenin in keratinocytes.

For recent years, devices that generate non-thermal plasma (NTP) have been introduced into the field of dermatology. Since NTP has demonstrated strong anti-pathogenic activity with safety of use, NTP was first applied to sterilize the skin surface to aid in the healing of various kinds of skin diseases. However, the effect of NTP on skin regeneration has not yet been fully explored. In this study, the effect of NTP on the growth of keratinocytes was tested using the HaCaT human keratinocyte cell line and HRM2 hairless mice. Treatment with NTP allowed confluent keratinocytes to escape from G1 cell cycle arrest and increased the proportion of cells in S and G2 phases. In particular, NTP treatment immediately dispersed E-cadherin-mediated cell-to-cell interactions, resulting in the translocation of ß-catenin to the nucleus and leading to the enhanced transcription of target genes including c-MYC and cyclin D1. Moreover, repeated treatment of the mice with NTP also stimulated epidermal expansion by activating ß-catenin in the epidermal cells. The symptoms of cellular DNA damage were not detected after NTP treatment. Taken together, these results demonstrate that NTP may be employed as a new type of skin regenerating device.

Exposure to Chronic Mild Stress Differentially Alters Corticotropin-Releasing Hormone and Arginine Vasopressin mRNA Expression in the Stress-Responsive Neurocircuitry of Male and Female Rats Prenatally Exposed to Alcohol.

BACKGROUND: Prenatal alcohol exposure (PAE) results in dysregulation of the offspring hypothalamic-pituitary-adrenal (HPA) axis, increasing sensitivity to stressors and vulnerability to stress-related disorders. We have previously shown that exposure to chronic mild stress (CMS) in adulthood significantly increases anxiety-like behaviors (elevated plus maze) in PAE males and females compared to controls. To explore neurobiological mechanisms linking HPA dysregulation and altered anxiety-like behavior, we investigated neuropeptide (corticotropin-releasing hormone [CRH] and arginine vasopressin [AVP]) expression in brain areas involved in the stress neurocircuitry of animals from this previous behavioral study. METHODS: Adult PAE, pair-fed (PF), and ad libitum fed control (C) male and female offspring exposed to CMS or remaining undisturbed (non-CMS) were terminated 30 minutes following behavioral testing. RESULTS: In the paraventricular nucleus, CMS increased CRH mRNA levels in PAE compared to PF and C males and increased AVP mRNA levels in PAE compared to C males, with no differential effects for CRH or AVP in females. In the central nucleus of the amygdala, there was an increase in CRH mRNA expression overall, regardless of CMS condition or sex, in PAE compared to C animals. Moreover, in PF males, CMS increased AVP mRNA levels in the paraventricular nucleus, resulting in a decreased CRH/AVP ratio compared to PAE males, and decreased amygdala CRH mRNA compared to that in the non-CMS condition. CONCLUSIONS: CMS differentially altered central HPA peptide expression in PAE and PF animals compared to their control counterparts, with a possible shift toward greater CRH mediation of HPA regulation in PAE males, and greater AVP mediation of HPA regulation in PF males. However, changes in CRH and AVP expression do not align fully with the anxiogenic profile observed in our previous behavior study, suggesting that other neuronal substrates and limbic forebrain regions also contribute to increased anxiety-like behavior following CMS.

Superconducting properties of hole doped Ba(0.6)Li(0.4)Fe2As2 single crystal.

We report the emergence of superconductivity in Li doped Ba-122 single crystals grown by the Bridgman method. The superconducting transition temperature Tc,onset is around 19 K. The specific heat capacity C/T shows a weak anomaly near Tc. The value of ΔC/γnTc is smaller than the value predicted in BCS theory indicating a multigap nature of the sample. The magnetic measurements show that the lower critical field Hc1(T) exhibits a linear temperature dependence, with a pronounced change of the Hc1(T) curvature around 0.4Tc and Hc1(0) ≈ 430 Oe in the Ba0.6Li0.4Fe2As2 single crystal. Furthermore, temperature dependence of the penetration depth λ(T) follows a power law (~T(n)) below 0.4Tc which predicts possible S±-wave pairing in a Ba0.6Li0.4Fe2As2 superconductor. Over a wide range of temperatures, the Jc(H) exhibits a relation J(c)[proportionality] H(-α) with α = 0.5 ~ 0.6 for H || c and H || ab which indicates random defects in the sample. We found that the temperature dependence of the critical current density Jc(T) can be fitted well with the δl-type pinning model, whose origin is attributed to spatial variations of charge carrier mean free path l. We suggest that the large mismatch in the ionic radius of Ba and Li can affect the irreversible magnetic properties of the Ba0.6Li0.4Fe2As2 single crystal without any structural transition.

Cord blood mesenchymal stem cells suppress DC-T Cell proliferation via prostaglandin B2.

Immune suppression is a very stable property of multipotent stromal cells also known as mesenchymal stem cells (MSCs). All cell lines tested showed robust immune suppression not affected by a long culture history. Several mechanisms were described to account for this capability. Since several of the described mechanisms were not causing the immune suppression, the expression pattern of cord-blood-derived MSCs by microarray experiments was determined. Dendritic cells cocultured with cord blood MSCs were compared with cord blood MSCs. Putative immune suppressive candidates were tested to explain this inhibition. We find that cord blood MSCs themselves are hardly immunogenic as tested with allogeneic T-cells. Dendritic cells cocultured with second-party T-cells evoked abundant proliferation that was inhibited by third-party cord blood MSCs. Optimal inhibition was seen with one cord blood MSC for every dendritic cell. Blocking human leukocyte antigen G only saw partial recovery of proliferation. Several cytokines, gangliosides, enzymes like arginase, NO synthase, and indole amine 2,3-dioxygenase as well as the induction of Treg were not involved in the inhibition. The inhibiting moiety was identified as prostaglandin B2 by lipid metabolite analysis of the culture supernatant and confirmed with purified prostaglandin B2.

Neurocircuitry underlying stress and emotional regulation in animals prenatally exposed to alcohol and subjected to chronic mild stress in adulthood.

Individuals exposed to alcohol during gestation show higher rates of psychopathologies. The hyperresponsivity to stress induced by prenatal alcohol exposure (PAE) may be related to this increased rate of psychopathologies, especially because this population is more likely to be exposed to stressful environments throughout life. However, alcohol-induced changes in the overlapping neurocircuitries that underlie stress and the expression of psychopathologies are not fully understood. Here, we performed a comprehensive analysis of the neural activity within central areas known to play key roles in both emotional and stress regulation. Adult male and female offspring from PAE, pair-fed, and ad libitum-fed control conditions were exposed to chronic mild stress (CMS). Following CMS, the neural activity (c-fos mRNA) of the amygdala, ventral hippocampal formation, medial prefrontal cortex (mPFC), and paraventricular nucleus of hypothalamus (PVN) was assessed in response to an acute stress (elevated plus maze). Our results demonstrate that, overall, PAE decreased neural activity within the amygdala and hippocampal formation in males and increased neural activity within the amygdala and mPFC in females. CMS reduced neural activity within the mPFC and PVN in PAE males, but reduced activity in all areas analyzed in control males. By contrast, CMS reduced neural activity in the mPFC in PAE females and had no effects in control females. Furthermore, the constrained principal component analysis revealed that these patterns of neural activity resulted in differential activation of the functional neural networks in males compared to females, indicating sexually dimorphic effects of PAE and CMS. Importantly, the altered networks of brain activation in PAE animals may underlie the hyperresponsivity to stress and increased psychopathologies observed among individuals prenatally exposed to alcohol.

Hyaluronidase treatment of acute lymphedema in a mouse tail model.

The purpose of this study was to investigate the impact of hyaluronidase (HAase) on lymphedema using an acute mouse tail lymphedema model. Six-week-old mice served to produce acute lymphedema and were then either treated with HAase injection or used as operative controls. An additional group of unmanipulated normal mice was used for comparison. Tail volumes were measured for 23 days and histological changes examined. Western blot analysis was conducted to quantify lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, podoplanin, CD 44, and vascular endothelial growth factor receptor3 (VEGFR3) expression levels. The operative control group showed an increase in thickness of the dermis and subdermis, microlymphatic dilatation, and an increase in neutrophils. In contrast, the HAase treated group exhibited alleviation of inflammation evidenced by a decline in microlymphatic dilatation and neutrophils and an overall increase in microlymphatic vessels. Western blot analysis demonstrated that TNF-alpha and TGF-beta1 expression declined but CD44 expression increased in the HAase treated group. Levels of LYVE1, podoplanin, and VEGFR3 also increased significantly in the HAase group. Our results indicate that HAase treatment in the acute mouse tail model reduced lymphedema volume possibly through degradation of HA trafficking, which reduced inflammation and fibrosis in tissues and stimulated lymphangiogenesis.

Neurobiology of chronic mild stress: parallels to major depression.

The chronic mild (or unpredictable/variable) stress (CMS) model was developed as an animal model of depression more than 20 years ago. The foundation of this model was that following long-term exposure to a series of mild, but unpredictable stressors, animals would develop a state of impaired reward salience that was akin to the anhedonia observed in major depressive disorder. In the time since its inception, this model has also been used for a variety of studies examining neurobiological variables that are associated with depression, despite the fact that this model has never been critically examined to validate that the neurobiological changes induced by CMS are parallel to those documented in depressive disorder. The aim of the current review is to summarize the current state of knowledge regarding the effects of chronic mild stress on neurobiological variables, such as neurochemistry, neurochemical receptor expression and functionality, neurotrophin expression and cellular plasticity. These findings are then compared to those of clinical research examining common variables in populations with depressive disorders to determine if the changes observed following chronic mild stress are in fact consistent with those observed in major depression. We conclude that the chronic mild stress paradigm: (1) evokes an array of neurobiological changes that mirror those seen in depressive disorders and (2) may be a suitable tool to investigate novel systems that could be disturbed in depression, and thus aid in the development of novel targets for the treatment of depression.

Feasibility of nonthermal atmospheric pressure plasma for intracoronal bleaching.

AIM: To investigate the effect of nonthermal atmospheric pressure plasma on intracoronal tooth bleaching in blood stained human teeth. METHODOLOGY: Forty extracted single-root and blood stained human teeth were used. The teeth were randomly divided into two groups (n=20): group 1 received 30% HP activated by nonthermal atmospheric pressure plasma in the pulp chamber for 30 min, whilst group 2 received 30% HP alone in the pulp chamber for 30 min. The overall colour changes (ΔE) were assessed using the Commission Internationale de L'Eclairage (CIE) Lab Colour System. The data were analysed using Student's t-test to determine the significant differences. RESULTS: The temperature of all teeth was maintained at approximately 37 °C during plasma bleaching. The plasma treatment with 30% HP resulted in significantly higher bleaching efficacy compared to 30% HP alone in discoloured teeth (P<0.05). The average ΔE values of group 1 and group 2 were 9.24 (0.37) and 4.47 (1.62), respectively, at 30 min. CONCLUSIONS: The application of nonthermal atmospheric pressure plasma to intracoronal bleaching could be a novel and efficient therapy in the bleaching of haemorrhagically stained teeth.

Prenatal alcohol exposure and chronic mild stress differentially alter depressive- and anxiety-like behaviors in male and female offspring.

BACKGROUND: Fetal Alcohol Spectrum Disorder (FASD) is associated with numerous neurobehavioral alterations, as well as disabilities in a number of domains, including a high incidence of depression and anxiety disorders. Prenatal alcohol exposure (PAE) also alters hypothalamic-pituitary-adrenal (HPA) function, resulting in increased responsiveness to stressors and HPA dysregulation in adulthood. Interestingly, data suggest that pre-existing HPA abnormalities may be a major contributory factor to some forms of depression, particularly when an individual is exposed to stressors later in life. We tested the hypothesis that exposure to stressors in adulthood may unmask an increased vulnerability to depressive- and anxiety-like behaviors in PAE animals. METHODS: Male and female offspring from prenatal alcohol (PAE), pair-fed (PF), and ad libitum-fed control (C) treatment groups were tested in adulthood. Animals were exposed to 10 consecutive days of chronic mild stress (CMS), and assessed in a battery of well-validated tasks sensitive to differences in depressive- and/or anxiety-like behaviors. RESULTS: We report here that the combination of PAE and CMS in adulthood increases depressive- and anxiety-like behaviors in a sexually dimorphic manner. PAE males showed impaired hedonic responsivity (sucrose contrast test), locomotor hyperactivity (open field), and alterations in affiliative and nonaffiliative social behaviors (social interaction test) compared to control males. By contrast, PAE and, to a lesser extent, PF, females showed greater levels of "behavioral despair" in the forced swim test, and PAE females showed altered behavior in the final 5 minutes of the social interaction test compared to control females. CONCLUSIONS: These data support the possibility that stress may be a mediating or contributing factor in the psychopathologies reported in FASD populations.

Mesenchymal stem cells respond to TNF but do not produce TNF.

Previously, we demonstrated that several TLRs are expressed on cord blood-derived USSC. Stimulation of USSC with TLR agonists resulted in a marked increase of IL-6 and IL-8 production. Interestingly, TNF was undetectable after TLR stimulation, which appeared to be a result of an inactivated TNF promoter in USSC. Here, we elaborate this study by demonstrating that although USSC do not produce TNF, they are susceptible to TNF stimulation, resulting in NF-kappaB translocation and cytokine production. Additionally, we compared different stem cell sources for their ability to produce TNF. Interestingly, we found that the TNF promoter in BM-MSC is inactivated as well. Like USSC, they are able to respond to TNF stimulation, but they are not able to produce TNF, even not after LPS stimulation. This limited cytokine response in combination with the well-studied immunosuppressive properties of MSC makes these cells ideal for immune-suppressive treatment modalities such as graft-versus-host disease.

Circadian phase and sex effects on depressive/anxiety-like behaviors and HPA axis responses to acute stress.

Circadian dysregulation in sleep pattern, mood, and hypothalamic-pituitary-adrenal (HPA) axis activity, often occurring in a sexually dimorphic manner, are characteristics of depression. However, the inter-relationships among circadian phase, HPA function, and depressive-like behaviors are not well understood. We investigated behavioral and neuroendocrine correlates of depressive/anxiety-like responses during diurnal ('light') and nocturnal ('dark') phases of the circadian rhythm in the open field (OF), elevated plus maze (EPM), forced swim (FST), and sucrose contrast (SC) tests. Plasma corticosterone (CORT) was measured after a) acute restraint and OF testing and b) FST. Both phase and sex significantly influenced behavioral responses to stress. Males were more anxious than females on the EPM in the light but not the dark phase. Further, the open:closed arm ratio was lower in the dark for females, but not males. By contrast, in the FST, females showed more "despair" (immobility) when tested in the dark, while phase did not affect males. Acute restraint stress increased OF activity in the light, but not the dark, phase. CORT levels were increased in both sexes following the FST, and in males and light phase females post-OF. As expected, females had higher CORT levels than males, even at rest, and this effect was more pronounced in the dark phase. Together, our data highlight the sexually dimorphic influences of circadian phase and stress on behavioral and hormonal responsiveness.