Interaction of oxytocin level and past depression may predict postpartum depressive symptom severity

We examined plasma oxytocin concentration and postpartum depression (PPD) symptom severity in women who were not depressed during pregnancy and whether this differed by major depressive disorder (MDD) history. We assessed psychiatric history and plasma oxytocin in 66 healthy pregnant women in the third trimester (M?=?35?±?3 weeks) and depressive symptoms at 6 weeks postpartum (M?=?5.9?±?0.8 weeks). Linear regression analysis was used to examine oxytocin and PPD symptom severity and moderation of oxytocin and PPD by past MDD. Women with (n?=?13) and without (n?=?53) past MDD differed in third trimester depressive symptom severity, but not oxytocin level, demographic factors, or birth outcomes. Controlling for third trimester depressive symptoms, oxytocin level was unrelated to PPD symptom severity [B(SE)?=??.019 (.084); β?=??.025; t?=??.227; p?=?.821]. However, oxytocin level interacted with past MDD to predict PPD symptom severity [B(SE)?=?7.489 (2.429); β?=?.328; t?=?3.084; p?=?.003]. Higher oxytocin predicted greater PPD symptom severity in women with past MDD (p?=?.019), but not in women without (p?=?.216). Replication in a larger sample and methodologic challenges are discussed.     

Combined Ex Vivo 9.4T MRI and Quantitative Histopathological Study in Normal and Pathological Neocortical Resections in Focal Epilepsy

High‐resolution magnetic resonance imaging (MRI) may improve the preoperative diagnosis of focal cortical dysplasia (FCD) in epilepsy. Quantitative 9.4T MRI was carried out (T1, T2, T2* and magnetization transfer ratio) on 13 cortical resections, representing pathologically confirmed FCD (five cases) and normal cortex. Quantitative immunohistochemistry for myelination (myelin basic protein/SMI94), neuronal populations [microtubule‐associated protein 2 (MAP2), neurofilament (SMI31, SMI32), synaptophysin, NeuN, calbindin], reactive glia (GFAP), microglia (CD68) and blood–brain barrier permeability (albumin) was carried out in 43 regions of interest (ROI) from normal and abnormal white matter and cortex. MRI was spatially aligned and quantitative analysis carried out on corresponding ROI. Line profile analysis (LPA) of intensity gradients through the cortex was carried out on MRI and immunostained sections. An inverse correlation was noted between myelin/SMI94 and T1, T2 (P < 0.005) and T2* (P < 0.05; Spearman's correlation) and a positive correlation between neuronal MAP2 and T1 (P < 0.005) and T2* (P < 0.05) over all ROI. Similar pathology–MRI correlations were observed for histologically unremarkable white matter ROI only. LPA showed altered gradient contours in regions of FCD, reflecting abnormal cortical lamination and myelo‐architecture, including a preoperatively undetected FCD case. This study demonstrates the ability of quantitative 9.4T MRI to detect subtle differences in neuronal numbers and myelination in histologically normal appearing white matter and LPA in the evaluation of cortical dyslamination. These methods may be translatable to the in vivo detection of mild cortical malformations.     

Identification of a Large DNAJB2 Deletion in a Family with Spinal Muscular Atrophy and Parkinsonism

In this study, we described the identification of a large DNAJB2 (HSJ1) deletion in a family with recessive spinal muscular atrophy and Parkinsonism. After performing homozygosity mapping and whole genome sequencing, we identified a 3.8 kb deletion, spanning the entire DnaJ domain of the HSJ1 protein, as the disease‐segregating mutation. By performing functional assays, we showed that HSJ1b‐related DnaJ domain deletion leads to loss of HSJ1b mRNA and protein levels, increased HSJ1a mRNA and protein expressions, increased cell death, protein aggregation, and enhanced autophagy. Given the role of HSJ1 proteins in the degradation of misfolded proteins, we speculated that enhanced autophagy might be promoted by the elevated HSJ1a expression seen in HSJ1b‐deficient cells. We also observed a significant reduction in both tau and brain‐derived neurotrophic factor levels, which may explain the dopaminergic deficits seen in one of the affected siblings. We concluded that HSJ1b deficiency leads to a complex neurological phenotype, possibly due to the accumulation of misfolded proteins, caused by the lack of the DnaJ domain activity. We thus expand the phenotypic and genotypic spectrums associated with DNAJB2 disease and suggest relevant disease‐associated mechanisms.     

The Effectiveness of Occupational Therapy Supervised Usage of Adaptive Devices on Functional Outcomes and Independence after Total Hip Replacement in Iranian Elderly: A Randomized Controlled Trial

The aim of this randomized controlled trial was to assess the effect of an occupational therapy protocol of teaching the usage of adaptive devices to older individuals in Iran who have had a total hip replacement as compared with conventional occupational therapy on functional outcomes and independence. Forty individuals diagnosed with osteoarthritis and a total hip replacement aged >60 years were randomly allocated to either control group (n = 20) or experimental (n = 20) group. Pain, disability, independence and hip muscle strength were assessed with visual analogue scale, Western Ontario and McMaster Universities Osteoarthritis and Barthel Index and dynamometer, 2 days before and 6 weeks after the hip operation. Both groups received conventional occupational therapy, but the experimental group was additionally supervised on the use of adaptive devices. Correct use of the devices was instructed during the training session. Both groups significantly improved on all variables post‐operatively. However, the experimental group showed significantly more improvement in all dependent variables post‐operatively. No data were available on the use of the devices by the control group patients. Supervision of the utilization of the adaptive devices during regular home visits by the occupational therapist is recommended. Further research is needed to clarify which aspects of this supervision were most beneficial for the patients. Copyright © 2015 John Wiley & Sons, Ltd.     

Tspan8 is expressed in breast cancer and regulates E-cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles

Tspan8 exhibits a functional role in many cancer types including pancreatic, colorectal, oesophagus carcinoma, and melanoma. We present a first study on the expression and function of Tspan8 in breast cancer. Tspan8 protein was present in the majority of human primary breast cancer lesions and metastases in the brain, bone, lung, and liver. In a syngeneic rat breast cancer model, Tspan8⁺ tumours formed multiple liver and spleen metastases, while Tspan8⁻ tumours exhibited a significantly diminished ability to metastasise, indicating a role of Tspan8 in metastases. Addressing the underlying molecular mechanisms, we discovered that Tspan8 can mediate up-regulation of E-cadherin and down-regulation of Twist, p120-catenin, and β-catenin target genes accompanied by the change of cell phenotype, resembling the mesenchymal–epithelial transition. Furthermore, Tspan8⁺ cells exhibited enhanced cell–cell adhesion, diminished motility, and decreased sensitivity to irradiation. As a regulator of the content and function of extracellular vesicles (EVs), Tspan8 mediated a several-fold increase in EV number in cell culture and the circulation of tumour-bearing animals. We observed increased protein levels of E-cadherin and p120-catenin in these EVs; furthermore, Tspan8 and p120-catenin were co-immunoprecipitated, indicating that they may interact with each other. Altogether, our findings show the presence of Tspan8 in breast cancer primary lesion and metastases and indicate its role as a regulator of cell behaviour and EV release in breast cancer. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Adolescent morphine exposure increases nociceptive behaviors in rat model of formalin test

The number of adolescents who use illicit drugs has increased dramatically. Adolescence is a critical period for brain development and maturation. The importance of the study of pain perception and the possible mechanisms involved is crystal clear. Up until now, there has been no evidence regarding the long-term effect of adolescence morphine administration on pain perception. The objective of the present study was to investigate long-lasting effect of adolescent morphine exposure on pain perception as well as analgesic response to a single dose of morphine injection. Adolescent and adult rats received morphine or saline, and then after 30 days of washout period, formalin test was performed. To evaluate morphine analgesia, in a separate group of animals, formalin test was performed after injection of a single dose of morphine during adulthood. The results demonstrated that the adolescent rats treated by morphine exhibited higher pain-related behaviors compared to the control group, while the same results were not observed in adult rats that had been treated by morphine. Moreover, there was no significant difference in analgesic response to a single dose of morphine between two experimental groups. This study demonstrates enduring effect of morphine exposure during adolescence on pain perception.     

Effect of enriched environment during adolescence on spatial learning and memory,and voluntary consumption of morphine in maternally separated rats in adulthood

This study was designed to examine the effect of environmental enrichment (EE) during adolescence on spatial learning and memory and voluntary morphine consumption in maternally separated (MS) male and female rats in adulthood. Male Wistar rats were allowed to mate with female virgin Wistar rats. Pups were separated from the dams daily for 180 min during postnatal days 2–14. All pups were weaned on day 21. The pups of both sexes were reared in a standard (SE) or enriched (EE) environment during postnatal days 21–50. Then, adulthood rats were tested for spatial learning and memory (Morris Water Maze), and voluntary consumption of morphine using a two-bottle choice paradigm (TBC). We found that the MS/SE rats showed longer escape latencies to find the platform on the third (the male) and fourth (the female) days of training than No MS/SE rats. Also, exposure to EE shortened the latency to escape in the male and female MS rats as training progressed than MS/SE rats. Moreover, the No MS/EE and MS/EE male rats spent significantly more time in the target zone compared with the SE control groups in the probe test. We also found that voluntary morphine consumption was higher in the male and female MS/SE than No MS/SE rats, while it was lower in the male and female MS/EE rats. The present results have shown that EE treatment may have potential therapeutic application for the prevention of the development of drug addiction and recovery from cognitive deficits following neonatal MS during adulthood.     

Generality of genomic findings on blood pressure traits and its usefulness in precision medicine in diverse populations: A systematic review

Remarkable findings from genome-wide association studies (GWAS) on blood pressure (BP) traits have made new insights for developing precision medicine toward more effective screening measures. However, generality of GWAS findings in diverse populations is hampered by some technical limitations. There is no comprehensive study to evaluate source(s) of the non-generality of GWAS results on BP traits, so to fill the gap, this systematic review study was carried out. Using MeSH terms, 1545 records were detected through searching in five databases and 49 relevant full-text articles were included in our review. Overall, 749 unique variants were reported, of those, majority of variants have been detected in Europeans and were associated to systolic and diastolic BP traits. Frequency of genetic variants with same position was low in European and non-European populations (n = 38). However, more than 200 (>25%) single nucleotide polymorphisms were found on same loci or linkage disequilibrium blocks (r² ≥ 80%). Investigating for locus position and linkage disequilibrium of infrequent unique variants showed modest to high reproducibility of findings in Europeans that in some extent was generalizable in other populations. Beyond theoretical limitations, our study addressed other possible sources of non-generality of GWAS findings for BP traits in the same and different origins.     

Intraperitoneal and intraamygdala N-cyclohexyladenosine suppress hippocampal kindled seizures in rats

Effects of intraperitoneal and intraamygdala N⁶-cyclohexyladenosine (CHA), a selective adenosine A₁ receptor agonist, and 1,3-dimethyl-8-cyclopentylxanthine (CPT), a selective adenosine A₁ receptor antagonist, were examined in fully hippocampal kindled rats. Intraperitoneal administration of CHA (0.25, 0.5 and 1 mg/kg) decreased hippocampal secondary afterdischarge duration (SAD) and amygdala afterdischarge duration (ADD). Only the 1 mg/kg dose induced a significant increase in latency to stage 4. Intraperitoneal administration of CPT (0.25, 0.5 and 1 mg/kg) induced a significant increase in stage 5 duration, hippocampal SAD and ADD. Pretreatment of animals with CPT (1 mg/kg), antagonized effects of CHA on seizure parameters. Intraamygdala microinfusion (1 μl over 2 min) of CHA (5 nM–1 mM) significantly reduced hippocampal SAD and amygdala ADD. These effects were antagonized by intraamygdala CPT (1 μM). Results obtained suggest that in hippocampal kindled rats, amygdala may be regarded as a relay point for AD propagation specially in recruit activity of the hippocampus.