Increased rate of parental postpartum depression and traumatization in moderate and late preterm infants is independent of the infant's motor repertoire

Background

Moderately and late preterm infants represent a considerable and increasing proportion of infants cared for in neonatal departments worldwide. Parents of preterm infants are at risk of postpartal depression (PPD) and posttraumatic stress disorder (PTSD), and preterm infants are at risk of developmental impairment.

Aim

This study aimed to assess (1) the incidence of parental PPD and PTSD in moderate to late preterm infants in comparison to full-term infants and (2) the influence of infants' motor repertoire assessed by Prechtl's general movements and illness severity on parental PPD and PTSD.

Subjects

We studied 60 mothers and 56 fathers of 69 preterm infants (born at 32 to 37 weeks of gestation) and 32 mothers and 29 fathers of 34 full-term infants.

Outcome measures

We assessed the incidence of parental PPD, PTSD and perceived social support as well as infants' illness severity and motor repertoire at birth, term and 3 months corrected age.

Results

Preterm mothers and fathers had significant higher depression scores after birth compared to full-term parents (p = 0.033 and 0.021). Preterm fathers also had higher traumatization scores compared to full-term fathers (p = 0.007). Probable or possible PPD/PTSD was not associated with infant's illness severity or quality of motor repertoire. No differences in motor development were found between preterm and full-term infants.

Conclusion

Moderate to late preterm infants' parents are at increased risk for PPD irrespective of infants' motor repertoire or illness severity.     

Evidence of a local intestinal immunomodulatory effect of sulfasalazine in rheumatoid arthritis

Objective. To analyze whether the intestinal mucosa in rheumatoid arthritis (RA) is immnunologically abnormal and whether sulfasalazine (SSZ) possesses any local intestinal immunoregulatory effect. Methods. Lymphocyte subpopulations and HLA—DR expression were evaluated in biopsy specimens from the duodenal—jejunal mucosa and in peripheral blood samples obtained from 17 patients with RA, both before and after 16 weeks of SSZ treatment. The same mucosal assays were also performed in 7 controls. Results. The mucosa of the small intestine in RA patients showed no differences in morphology, HLA—DR expression, or the amounts and distribution of CD3+, CD4+, CD8+, and γ/δ+ lymphocytes compared with the control group. However, there was a reduction in mucosal CD3+ and γ/δ+ lymphocyte numbers after SSZ therapy, which did not correspond to a change in peripheral blood CD3+ lymphocyte number. SSZ treatment also tended to diminish the peripheral blood CD4+:CD8+ cell ratio (P = 0.05). Conclusion. No signs of inflammation or immunologic abnormalities were seen in RA duodenal-jejunal mucosa. In this part of the intestine, however, SSZ exerted immunoregulatory effects that were not encountered in the peripheral blood.     

Biperiden and mepazine effectively inhibit MALT1 activity and tumor growth in pancreatic cancer

MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.     

Reflection of neuroblastoma intratumor heterogeneity in the new OHC-NB1 disease model

Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80–540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with four clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system.     

An H3F3A K27M‐mutation in a sonic hedgehog medulloblastoma

Medulloblastomas are malignant embryonal brain tumours that may harbour mutations in histone‐modifying genes, while mutations in histone genes have not been detected to date. We here describe the first SHH medulloblastoma with H3 K27M mutation. This may have diagnostic implications as H3 K27M mutations are the hallmark of diffuse midline gliomas, H3 K27M mutant, WHO grade IV. Medulloblastomas arise in midline structures and thus must not be mistaken for DMG when using an antibody detecting the H3 K27M mutation.     

Circulating delta‐like Notch ligand 1 is correlated with cardiac allograft vasculopathy and suppressed in heart transplant recipients on everolimus‐based immunosuppression

Cardiac allograft vasculopathy (CAV) causes heart failure after heart transplantation (HTx), but its pathogenesis is incompletely understood. Notch signaling, possibly modulated by everolimus (EVR), is essential for processes involved in CAV. We hypothesized that circulating Notch ligands would be dysregulated after HTx. We studied circulating delta‐like Notch ligand 1 (DLL1) and periostin (POSTN) and CAV in de novo HTx recipients (n = 70) randomized to standard or EVR‐based, calcineurin inhibitor‐free immunosuppression and in maintenance HTx recipients (n = 41). Compared to healthy controls, plasma DLL1 and POSTN were elevated in de novo (P < .01; P < .001) and maintenance HTx recipients (P < .001; P < .01). Use of EVR was associated with a treatment effect for DLL1. For de novo HTx recipients, a change in DLL1 correlated with a change in CAV at 1 (P = .021) and 3 years (P = .005). In vitro, activation of T cells increased DLL1 secretion, attenuated by EVR. In vitro data suggest that also endothelial cells and vascular smooth muscle cells (VSMCs) could contribute to circulating DLL1. Immunostaining of myocardial specimens showed colocalization of DLL1 with T cells, endothelial cells, and VSMCs. Our findings suggest a role of DLL1 in CAV progression, and that the beneficial effect of EVR on CAV could reflect a suppressive effect on DLL1. Trial registration numbers— SCHEDULE trial: ClinicalTrials.gov NCT01266148; NOCTET trial: ClinicalTrials.gov NCT00377962.