Association Between Eosinophilia and Late-onset Circulatory Collapse in Preterm Infants: A case-Control Study

Late-onset circulatory collapse (LCC) in preterm infants is presumably caused by relative adrenal insufficiency. Because eosinophilia is known to be associated with adrenal insufficiency, we attempted to clarify the relation-ship between eosinophilia and LCC in preterm infants. We divided the cases of the infants (born at < 28 weeks’ gestation) admitted to our neonatal intensive care unit in 2008-2010 into 2 groups: those diagnosed with LCC that received glucocorticoids (LCC group), and those who did not receive glucocorticoids (control group). We compared eosinophil counts between the 2 groups and between before and after glucocorticoid treatment in the LCC group. A total of 28 infants were examined: LCC group (n = 12); control group (n = 16). The peak eosin-ophil counts of the LCC group were significantly higher than those of the control group (median: 1.392 × 109/L vs. 1.033 × 109/L, respectively; p = 0.02). Additionally, in the LCC group, the eosinophil counts declined significantly after glucocorticoid treatment (0.877 × 109/L vs. 0.271 × 109/L, p = 0.003). Eosinophil counts in the LCC group were significantly higher than in the control group and decreased rapidly after gluco-corticoid treatment. These results indicate that eosinophilia may be a factor associated with LCC caused by adrenal insufficiency

Population-level prokaryotic community structures associated with ferromanganese nodules in the Clarion-Clipperton Zone (Pacific Ocean) revealed by 16S rRNA gene amplicon sequencing

Although deep-sea ferromanganese nodules are a potential resource for exploitation, their formation mechanisms remain unclear. Several nodule-associated prokaryotic species have been identified by amplicon sequencing of 16S rRNA genes and are assumed to contribute to nodule formation. However, the recent development of amplicon sequence variant (ASV)-level monitoring revealed that closely related prokaryotic populations within an operational taxonomic unit often exhibit distinct ecological properties. Thus, conventional species-level monitoring might have overlooked nodule-specific populations when distinct populations of the same species were present in surrounding environments. Herein, we examined the prokaryotic community diversity of nodules and surrounding environments at the Clarion-Clipperton Zone in Japanese licensed areas by 16S rRNA gene amplicon sequencing with ASV-level resolution for three cruises from 2017 to 2019. Prokaryotic community composition and diversity were distinct by habitat type: nodule, nodule-surface mud, sediment, bottom water and water column. Most ASVs (~80%) were habitat-specific. We identified 178 nodule-associated ASVs and 41 ASVs associated with nodule-surface mud via linear discriminant effect size analysis. Moreover, several ASVs, such as members of SAR324 and Woeseia, were highly specific to nodules. These nodule-specific ASVs are promising targets for future investigation of the nodule formation process

Significant association between high serum CCL5 levels and better disease‐free survival of patients with early breast cancer

Analysis of anticancer immunity aids in assessing the prognosis of patients with breast cancer. From 250 operated breast cancers, we focused on serum levels of C-C motif chemokine ligand 5 (CCL5), which is involved in cancer immune reactions. Serum levels of CCL5 were measured using a cytometric bead-based immunoassay kit and CCL5 expression in cancer cells was determined using immunohistochemical staining. In addition, mRNA in cancer and stromal cells was analyzed by microdissection and comparison with the public dataset. Disease-free survival (DFS) of patients with high CCL5 levels (cut-off, 13.87 ng/mL; n = 192) was significantly better than those with low CCL5 levels (n = 58; hazard ratio, 0.20; 95% confidence interval, 0.10- 0.39; P < .0001). An improved overall survival was observed in patients with high CCL5 levels compared to those with low CCL5 levels (P = .024). On the contrary, high immunohistochemical expression of CCL5 in cancer cells was significantly associated with decreased DFS. As serum CCL5 levels did not correlate with CCL5 expression in cancer cells and the relative expression of mRNA CCL5 was elevated in stromal cells in relation to cancer cells, serum CCL5 might be derived not from cancer cells, but from stromal cells. Expression of CCL5 in serum, but not in cancer cells, might contribute to improved patient prognosis mediating through not only immune reaction, but through other mechanisms. Determination of circulating CCL5 levels could be useful for predicting patient prognosis

Transcriptional suppression of nephrin in podocytes by macrophages: Roles of inflammatory cytokines and involvement of the PI3K/Akt pathway

AbstractExpression of nephrin, a crucial component of the glomerular slit diaphragm, is downregulated in patients with proteinuric glomerular diseases. Using conditionally immortalized reporter podocytes, we found that bystander macrophages as well as macrophage-derived cytokines IL-1β and TNF-α markedly suppressed activity of the nephrin gene promoter in podocytes. The cytokine-initiated repression was reversible, observed on both basal and inducible expression, independent of Wilms’ tumor suppressor WT1, and caused in part via activation of the phosphatidylinositol-3-kinase/Akt pathway. These results indicated a novel mechanism by which activated macrophages participate in the induction of proteinuria in glomerular diseases

Postnatal longitudinal analysis of serum nitric oxide and eosinophil counts in extremely preterm infants

Background: Nitric oxide (NO) may be related to the pathogenesis of several morbidities in extremely preterm infants, including late-onset adrenal insufficiency. However, eosinophilia is observed under pathological conditions with adrenal insufficiency. Therefore, this study explored postnatal changes in NO levels and eosinophil counts in extremely preterm infants with and without morbidities. Methods: Nineteen extremely preterm infants with a median gestational age of 27.0 weeks and median birth weight of 888 g were enrolled in this study. Serum levels of nitrogen oxides (NOx) and peripheral blood eosinophil counts were measured at birth and every 2 weeks thereafter. Morbidities of the study group were diagnosed using a single criterion. Results: Serum NOx levels (mean ± standard deviation) were 22.5 ± 14.9 μmol/L, 51.2 ± 23.7 μmol/L, 42.4 ± 15.2 μmol/L, and 33.8 ± 9.4 μmol/L at birth and 2, 4, and 6 weeks of age, respectively. The serum NOx level at 2 weeks of age was significantly higher than that at birth and 6 weeks of age. Eosinophil counts, which increase with adrenal insufficiency, were measured simultaneously and were 145 ± 199/μL, 613 ± 625/μL, 466 ± 375/μL, and 292 ± 228/μL at birth and 2, 4, and 6 weeks of age, respectively. These values showed that the eosinophil count was significantly higher at 2 weeks of age than at birth and 6 weeks of age. The serum NOx level of infants without chorioamnionitis was significantly increased at 4 weeks of age, and the eosinophil count of infants with necrotizing enterocolitis was significantly increased at 2 weeks of age. No correlation with the NOx level or eosinophil count was observed in infants with late-onset circulatory collapse. Conclusion: The postnatal serum NOx level and eosinophil count were significantly correlated with each other and peaked at 2 weeks of age

Host selection of hematophagous leeches (Haemadipsa japonica): Implications for iDNA studies

The development of an efficient and cost‐effective method for monitoring animal populations or biodiversity is urgently needed, and invertebrate‐derived DNA (iDNA) may offer a promising tool for assessing the diversity and other ecological information of vertebrates. We studied the host species of a hematophagous leech (Haemadipsa japonica) in Yakushima by genetic barcoding and compared the results with those for mammal composition revealed by camera trapping. We analyzed 119 samples using two sets of primers by Sanger sequencing and one set of primer by next generation sequencing. The proportion of the samples that were successfully sequenced and identified to at least one species was 11.8–24.3%, depending on the three different methods. In all of these three methods, most of the samples were identified as sika deer (18/20, 6/15 and 16/29) or human (2/20, 7/15 and 21/29). The nonhuman mammal host species composition was significantly different from that estimated by camera trapping. Sika deer was the main host, which may be related with their high abundance, large body size and terrestriality. Ten samples included DNA derived from multiple species of vertebrates. This may be due to the contamination of human DNA, but we also found DNA from deer, Japanese macaque and a frog in the same samples, suggesting the mixture of the two meals in the gut of the leech. Using H. japonica‐derived iDNA would not be suitable to make an inventory of species, but it may be useful to collect genetic information on the targeted species, due to their high host selectivity

NARP-related alterations in the excitatory and inhibitory circuitry of socially isolated mice: developmental insights and implications for autism spectrum disorder

BackgroundSocial isolation during critical periods of development is associated with alterations in behavior and neuronal circuitry. This study aimed to investigate the immediate and developmental effects of social isolation on firing properties, neuronal activity-regulated pentraxin (NARP) and parvalbumin (PV) expression in the prefrontal cortex (PFC), social behavior in juvenile socially isolated mice, and the biological relevance of NARP expression in autism spectrum disorder (ASD).MethodsMice were subjected to social isolation during postnatal days 21–35 (P21–P35) and were compared with group-housed control mice. Firing properties in the PFC pyramidal neurons were altered in P35 socially isolated mice, which might be associated with alterations in NARP and PV expression.ResultsIn adulthood, mice that underwent juvenile social isolation exhibited difficulty distinguishing between novel and familiar mice during a social memory task, while maintaining similar levels of social interaction as the control mice. Furthermore, a marked decrease in NARP expression in lymphoblastoid cell lines derived from adolescent humans with ASD as compared to typically developing (TD) humans was found.ConclusionOur study highlights the role of electrophysiological properties, as well as NARP and PV expression in the PFC in mediating the developmental consequences of social isolation on behavior