Mechanisms underlying the association between maternal mental illness in pregnancy and adverse offspring outcomes still remain uncertain. Therefore, this study investigated the relationship between maternal antenatal psychopathology and child outcomes in middle childhood, and whether infant development might explain this relationship. 253 women comprising healthy controls, n=103; women with history only Major Depressive Disorder (MDD) (n=32); women with MDD in current pregnancy (n=67); and women at risk of Postpartum Psychosis (PP), n=51, were recruited in pregnancy and followed up, with their children until 6-8 years. Infant development was assessed at 12 months postpartum across all four groups, and children's psychopathology at 6-8 years across all groups except "at risk of PP", who have yet to be assessed. Infants of mothers "at risk of PP" scored lower than "healthy controls" for cognitive development (p=.015), and lower than all groups for motor development (p=.004). Infants of mothers "at risk of PP" also scored lower for language development than "healthy controls" and "MDD in pregnancy" (p=<.001). At 6-8 years, more children of "history-only MDD" had clinically significant peer problems compared to "healthy controls" (34.4% difference). Finally, infant cognitive scores were negatively correlated with clinically significant peer problems at 6-8 years (p=.002). Maternal antenatal psychopathology is associated with less optimal infant development, and more peer problems in middle childhood. Furthermore, infant cognitive development is associated with later psychopathology. Future regression models will test whether these associations represent mechanistic pathways.

Nine plant essential oils (EOs), including those from Artemisia sieberi, Cuminum cyminum, Foeniculum vulgare, Heracleum persicum, Menta spicata, Nigella sativa, Rosmarinus officinalis, Zataria multiflora and Ziziphora clinopodioides, were evaluated for their anti-dermatophytic properties.The tested dermatophytes included Trichophyton mentagrophytes (No. 32), T. rubrum (No. 29), Epidermophyton floccosum (No. 19), Microsporum gypseum (No. 11) and M. canis (No. 42). The susceptibility tests of plant oils in terms of minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were performed by the broth microdilution technique as described by the Clinical Laboratory Standard Institute.All EOs studied were active against the dermatophytes. The MICs recorded for the plant oils tested ranged from 0.25 to 4 mg·mL−1. The most significant activity was observed with A. sieberi, showing a lower MIC against dermatophytes than other plant oils (P < 0.05).Data from this study indicated that several Iranian medicinal plant oils, mainly A. sieberi, are active in vitro against different dermatophyte species, suggesting their potential use for the topical treatment of dermatophytoses.

We aimed to evaluate the efficacy and safety of mepolizumab (MEP) in the management of hypereosinophilic syndrome (HES). A systematic search was performed, and articles published until March 2021 were analyzed. The primary efficacy results evaluated were hospitalization rate related to HES, morbidity (new or worsening), relapses/failure, treatment-related adverse effects, prednisone dosage ≤10 mg/day for ≥8 weeks, and eosinophil count <600/μL for ≥8 weeks. A meta-analysis was conducted, when appropriate. Three randomized controlled trials (RCTs), with a total of 255 patients, were included. The studies contemplated the use of MEP 300 mg/SC or 750 mg/IV. According to the evaluation of the proposed outcomes, when relapse rates/therapeutic failures were assessed, there was a 26% reduction with MEP 300 mg/SC (RD=-0.26; 95% CI: -0.44 to -0.08; p=0.04) and 48% reduction with MEP 750 mg/IV (RD=-0.48; 95% CI: -0.67, -0.30; p<0.00001). For the outcomes, prednisone dosage ≤10 mg/day for ≥8 weeks was 48% (RD=0.48; 95% CI: 0.35 to 0.62; p<0.00001), and the eosinophil count <600/μL for ≥8 weeks was 51% (RD=0.51; 95% CI: 0.38 to 0.63; p<0.00001), both showed a reduction with MEP 300 mg/IV and 750 mg/IV. No statistically significant differences in treatment-related adverse effects outcomes were observed for either dosage (RD=0.09; 95% CI: -0.05 to 0.24; p=0.20; RD=0.09; 95% CI: -0.11 to 0.29; p=0.39). Despite the positive effects observed for the studied outcomes, the exact significance remains unclear.

There is a substantial body of literature that links psychological stress to adverse pregnancy outcomes, particularly preterm birth. Comparatively few studies have examined potential biologic mechanisms that explain these associations. Attention to inflammatory processes is warranted. This article describes emerging studies that demonstrate that, as in nonpregnant humans and animals, psychological stress and distress (ie, depressive symptoms) predict dysregulation of inflammatory processes in human pregnancy. This includes elevations in circulating inflammatory cytokines, exaggerated inflammatory responses to in vivo biologic challenges, and more robust inflammatory responses to psychological challenges. Continued research in this area is needed to determine the implications of such stress-induced immune dysregulation for birth outcomes and for maternal health and fetal development.

We aimed to examine neonatal behaviour and cortisol reactivity in neonates born to women at risk of postpartum psychosis (AR) who had a psychiatric relapse within 4 weeks post-delivery (AR-unwell), compared with neonates of women at risk who stayed well (AR-well) and those born to healthy women (HC). We assessed neonatal behaviour using the Neonatal Behavioral Assessment Scale (NBAS), performed on 105 neonates (AR-unwell=17; AR-well=27; HC=61). Neonatal cortisol was measured pre-, immediately post- and 30-minutes post-NBAS. Neonates born to AR women did not differ from those born to HCs in behaviour or cortisol reactivity. There was also no difference in behaviour between neonates born to AR-unwell women and those born to AR-well women. However, neonates born to AR-unwell women had significantly lower pre-NBAS cortisol compared with neonates of AR-well women (t(38)=2.3, p=.02). Neonates of AR-unwell women also had a greater increase in cortisol from pre- to post-NBAS, though the difference did not reach statistical significance (p=.12), and a greater increase from pre- to 30 minutes post-NBAS (t(32)=2.7, p=.01). Maternal postpartum symptoms appear to disrupt the stress response of neonates whose mothers are at risk of postpartum psychosis.

Exaggerated pro-inflammatory cytokine production by primed microglia is thought to mediate pathology during stress, aging, and neurodegeneration. Recently, it was demonstrated that beta-adrenergic receptor (β-AR) antagonism prevents priming of microglia in mice exposed to chronic stress. To determine if β-AR stimulation is sufficient to prime microglia, rats were intra-cerebroventricularly administered isoproterenol (β-AR agonist) or vehicle and 24 h later hippocampal microglia were placed in culture with media or LPS. Prior isoproterenol treatment significantly enhanced IL-1β and IL-6, but not TNF-α production following LPS stimulation. These data suggest that central β-AR stimulation is sufficient to prime microglia cytokine responses.

Antenatal depression is associated with heightened infant stress reactivity, but how long-lasting these changes are, what factors might protect against them, and what the impact is on psychiatric risk is unknown. The Psychiatry Research and Motherhood-Depression study recruited antenatally depressed women, and controls, who are now being followed at child age 7-9 years. Children completed the Depression Self-Rating Scale and the State-Trait Anxiety Inventory. Salivary cortisol output was calculated as AUC from before, to 40 minutes after, the Cold Pressor Task. Children born of antenatally depressed and control mothers did not differ on their self-reported depression (z=0.32, p=0.75), state (z=-1.10, p=0.27) or trait anxiety (z=1.19, p=0.24), or cortisol output (t(39)=-1.82, p=0.076). Cortisol output was significantly correlated with child trait anxiety (r=0.34, p=0.030). These data indicate that, in this cohort, antenatal depression was not associated with child outcomes at 7-9 years. Instead, child cortisol output was associated with concurrent trait anxiety. This may suggest either that age 7-9 is too early, or, more encouragingly, that protective factors are present in this cohort which break the mother-child transmission cycle.

Considering the rapid antidepressant action of ketamine, we aimed to investigate its anti-inflammatory effect. As part of a randomised double-blind placebo-controlled study plasma samples from 31 healthy remitted depressed were collected before and 1.5 hours after ketamine (0.5 mg/kg) and saline (placebo) administration in a two-period cross-over design. Meso Scale Discovery was used to measure cytokines concentrations. Significant interaction effect between the treatment and time were found for IL-1beta (F=8.35, p=0.008), TNF-alpha (F=5.17, p=0.032), IFN-gamma (F=8.78, p=0.006) and GM-CSF (F=5.19, p=0.031). Following ketamine administration, there was a significant decrease in the levels of IFN-gamma (p<0.001) and GM-CSF (p=0.021); but not after placebo infusion (p>0.05). Delta for changes in cytokine concentration in response to ketamine showed statistical significance for IL-1beta, TNF-alpha, and IFN-gamma (p<0.05), and a trend for GM-CSF (p=0.072). Ketamine exhibits anti-inflammatory properties by the effect on the major proinflammatory cytokines including IL-1beta, TNF-alpha, IFN-gamma and GM-CSF. Ketamine could be useful for treatment resistant depression or suicidal thoughts, and our findings suggest that rapid changes in inflammatory markers to be studied as potential mediators of these effects, especially in patients with higher levels of inflammation.

Previous cross-sectional studies have found clozapine to N-desmethylclozapine (CLZ:NDMC) ratio to be negatively correlated with cognition in clozapine-treated patients with schizophrenia. However, no work has examined the association between CLZ:NDMC ratio and cognition using a within-subjects design. Here, we investigate the longitudinal effects of changes in the clozapine load and the CLZ:NDMC ratio on cognition whilst controlling for a range of independent factors. We analyzed data from a cohort of seventeen clozapine-treated patients who have been repeatedly assessed with the Brief Assessment of Cognition for Schizophrenia (BACS). The Positive symptoms sub-score of the Clinical Global Impression for Schizophrenia (CGI-P) was used to assess severity of psychosis. Blood samples were collected to measure the plasmatic levels of clozapine (CLZ) and of N-desmethylclozapine, allowing calculation of the CLZ:NDMC ratio. Our analyses included bivariate and partial correlations, along with a mediation model analysis. We found that both plasmatic levels of CLZ and the CLZ:NDMC ratio were negatively correlated with cognitive performance, and that these associations were independent of changes in both daily clozapine dose and severity of psychotic symptoms. Mediation analyses further revealed the association between CLZ concentration and cognition to be partially mediated by changes in the CLZ:NDMC ratio. This is the first longitudinal analysis of the influence of CLZ concentration and CLZ:NDMC ratio on cognition. Our findings suggest that reduction of CLZ concentration and the CLZ:NDMC ratio might favorably affect cognition. Thus, the CLZ:NDMC ratio may represent a promising target for novel therapeutic strategies aiming to ameliorate cognitive impairment in clozapine-treated patients.

Depression is associated with peripheral inflammation, but its link with brain microglial activity remains unclear. In seven healthy males, we used repeated translocator protein-Positron Emission Tomography (TSPO-PET) dynamic scans with [11C]PBR28 to image brain microglial activation before and 24 h after the immune challenge interferon (IFN)-α. We also investigated the association between changes in peripheral inflammation, changes in microglial activity, and changes in mood. IFN-α administration decreased [11C]PBR28 PET tissue volume of distribution (Vt) across the brain (−20 ± 4%; t6 = 4.1, p = 0.01), but after correction for radioligand free-plasma fraction there were no longer any changes (+23 ± 31%; t = 0.1, p = 0.91). IFN-α increased serum IL-6 (1826 ± 513%, t6 = −7.5, p < 0.001), IL-7 (39 ± 12%, t6 = −3.6, p = 0.01), IL-10 (328 ± 48%, t6 = −12.8, p < 0.001), and IFN-γ (272 ± 64%, t6 = −7.0, p < 0.001) at 4–6 h, and increased serum TNF-α (49 ± 7.6%, t6 = −7.5, p < 0.001), IL-8 (39 ± 12%, t6 = −3.5, p = 0.013), and C-reactive protein (1320 ± 459%, t6 = −7.2, p < 0.001) at 24 h. IFN-α induced temporary mood changes and sickness symptoms after 4–6 h, measured as an increase in POMS-2 total mood score, confusion and fatigue, and a decrease in vigor and friendliness (all p ≤ 0.04). No association was found between changes in peripheral inflammation and changes in PET or mood measures. Our work suggests that brain TSPO-PET signal is highly dependent of inflammation-induced changes in ligand binding to plasma proteins. This limits its usefulness as a sensitive marker of neuroinflammation and consequently, data interpretation. Thus, our results can be interpreted as showing either that [11C]PBR28 is not sensitive enough under these conditions, or that there is simply no microglial activation in this model.

Buildings consume a considerable share of global energy, mostly from non-renewable sources, and emit a substantial amount of CO2. As this is not aligned with sustainable development goals one of the main changes needed is to make buildings more energy efficient by insulating them from the ambient environment. This article discusses the factors affecting the type and quantity of insulating materials in a residential building made using prefabricated Structural Insulated Panels (SIPs), and designed to require near zero space conditioning. A life cycle assessment approach is used to find the most effective level of insulation. The analysis shows it is not appropriate to use the same type of SIPs in different locations, as some relevant factors are context-dependent. The factors considered in this analysis were the design goals, climate characteristics, and most importantly the current and projected profile of the energy used for manufacturing materials and for operating the building. It is important these factors are studied together, as individual investigations can be misleading.

Matching pedestrians across disjoint camera views, known as person re-identification (re-id), is a challenging problem that is of importance to visual recognition and surveillance. Most existing methods exploit local regions with spatial manipulation to perform matching in local correspondences. However, they essentially extract fixed representations from pre-divided regions for each image and then perform matching based on these extracted representations. For models in this pipeline, local finer patterns that are crucial to distinguish positive pairs from negative ones cannot be captured, and thus making them underperformed. In this paper, we propose a novel deep multiplicative integration gating function, which answers the question of what-and-where to match for effective person re-id. To address what to match, our deep network emphasizes common local patterns by learning joint representations in a multiplicative way. The network comprises two Convolutional Neural Networks (CNNs) to extract convolutional activations, and generates relevant descriptors for pedestrian matching. This leads to flexible representations for pair-wise images. To address where to match, we combat the spatial misalignment by performing spatially recurrent pooling via a four-directional recurrent neural network to impose spatial dependency over all positions with respect to the entire image. The proposed network is designed to be end-to-end trainable to characterize local pairwise feature interactions in a spatially aligned manner. To demonstrate the superiority of our method, extensive experiments are conducted over three benchmark data sets: VIPeR, CUHK03 and Market-1501.

Immunological dysregulation has been suggested to be involved in the pathogenesis of schizophrenia. Accumulating evidences further implicate that activated inflammatory processes may be particularly relevant for the precipitation of negative and cognitive symptoms of schizophrenia. Toll-like receptor 2 (TLR2) plays an important role in innate immunity by sensing a variety of pathogens and inducing an acquired immunity. In the present study, we investigated whether the coding region of single nucleotide polymorphisms (SNPs) of the TLR2 gene was associated with schizophrenia as well as with clinical symptoms in schizophrenia patients. The study population consisted of 286 Korean schizophrenia patients and 305 Korean control subjects. The assessment of the Scale for the Assessment of Negative Symptoms was used to evaluate the negative symptoms of schizophrenia; the operational criteria checklist was used to measure general psychopathology. We selected two cSNPs [rs3804099 (Asn199Asn) and rs3804100 (Ser450Ser)] considering their heterozygosity and minor allele frequency. SNP genotyping was conducted using direct sequencing. We did not find any significant associations between SNPs and schizophrenia in the genotype and allelic frequencies. On the other hand, in the analysis of cognitive symptoms, rs3804099 showed significant differences in schizophrenia patients with poor concentration in the dominant model (TC/CC vs. TT, p = 0.0099). Also, rs3804100 showed a significant association with poor concentration in the co-dominant (TC vs. TT, p = 0.014) and the dominant models (TC/CC vs. TT, p = 0.0035). We obtained no significant support for the association of the TLR2 gene with susceptibility to schizophrenia in the Korean population. However, our results provide possibility that C allele of rs3804099 and rs3804100 may be associated with poor concentration in schizophrenia patients. Further studies with larger samples are required to confirm our results.