Youngcollier2034

In the developing brain, the death of immature oligodendrocytes (OLs) has been proposed to explain a developmental window for vulnerability to white matter injury (WMI). However, in neonatal mice, chronic sublethal intermittent hypoxia (IH) recapitulates the phenotype of diffuse WMI without affecting cellular viability. This work determines whether, in neonatal mice, a developmental window of WMI vulnerability exists in the absence of OLs lineage cellular death.

Neonatal mice were exposed to cell-nonlethal early or late IH stress. The presence or absence of WMI phenotype in their adulthood was defined by the extent of sensorimotor deficit and diffuse cerebral hypomyelination. A separate cohort of mice was examined for markers of cellular degeneration and OLs maturation.

Compared to normoxic littermates, only mice exposed to early IH stress demonstrated arrested OLs maturation, diffuse cerebral hypomyelination, and sensorimotor deficit. No cellular death associated with IH was detected.

Neonatal subletmia exists even in the absence of excessive OLs and other cells death. This is an important finding because the existence of the developmental window of vulnerability to WMI has been explained by a lethal-selective sensitivity of immature OLs to hypoxic and ischemic stress, which coincided with their differentiation. Thus, our study expands mechanistic explanation of a developmental window of sensitivity to WMI by showing the existence of cell-nonlethal pathways responsible for this biological phenomenon.

Cerebral autoregulation mechanisms help maintain adequate cerebral blood flow (CBF) despite changes in cerebral perfusion pressure. Impairment of cerebral autoregulation, during and after cardiopulmonary bypass (CPB), may increase risk of neurologic injury in neonates undergoing surgery. In this study, alterations of cerebral autoregulation were assessed in a neonatal swine model probing four perfusion strategies.

Neonatal swine (n = 25) were randomized to continuous deep hypothermic cardiopulmonary bypass (DH-CPB, n = 7), deep hypothermic circulatory arrest (DHCA, n = 7), selective cerebral perfusion (SCP, n = 7) at deep hypothermia, or normothermic cardiopulmonary bypass (control, n = 4). The correlation coefficient (LDx) between laser Doppler measurements of CBF and mean arterial blood pressure was computed at initiation and conclusion of CPB. Alterations in cerebral autoregulation were assessed by the change between initial and final LDx measurements.

Cerebral autoregulation became more impaired (LDHCA) or selective cerebral perfusion (SCP), but it was altered in piglets that underwent deep hypothermic CBP.

Approximately half of the patients who survive neonatal heart surgery with cardiopulmonary bypass (CPB) experience neurodevelopmental delays. This preclinical investigation takes steps to elucidate and isolate potential perioperative risk factors of neurologic injury, such as impairment of cerebral autoregulation, associated with cardiac surgical procedures involving CPB. We demonstrate a method to characterize cerebral autoregulation during CPB pump flow changes in a neonatal swine model of cardiac surgery. Cerebral autoregulation was not altered in piglets that underwent deep hypothermic circulatory arrest (DHCA) or selective cerebral perfusion (SCP), but it was altered in piglets that underwent deep hypothermic CBP.Colonization by the microbiota provides one of our most effective barriers against infection by pathogenic microbes. The microbiota protects against infection by priming immune defenses, by metabolic exclusion of pathogens from their preferred niches, and through direct antimicrobial antagonism. Disruption of the microbiota, especially by antibiotics, is a major risk factor for bacterial pathogen colonization. Restoration of the microbiota through microbiota transplantation has been shown to be an effective way to reduce pathogen burden in the intestine but comes with a number of drawbacks, including the possibility of transferring other pathogens into the host, lack of standardization, and potential disruption to host metabolism. More refined methods to exploit the power of the microbiota would allow us to utilize its protective power without the drawbacks of fecal microbiota transplantation. To achieve this requires detailed understanding of which members of the microbiota protect against specific pathogens and the mechanistic basis for their effects. In this review, we will discuss the clinical and experimental evidence that has begun to reveal which members of the microbiota protect against some of the most troublesome antibiotic-resistant pathogens Klebsiella pneumoniae, vancomycin-resistant enterococci, and Clostridioides difficile.A Correction to this paper has been published https//doi.org/10.1038/s41477-021-00924-y.The SARS-COV-2 pandemic has led to strict and generalized transmission prevention measures that may have changed the epidemiological landscape of common seasonal respiratory virus (CSRV). Through a prospective CSRV survey program conducted from 2016 onwards in allogeneic stem cell transplant (allo-HSCT) recipients with respiratory symptoms, we aimed to analyze and compare the epidemiology and characteristics of CSRV over three consecutive periods [from February 1 to September 30 of 2018 (P1), 2019 (P2), and 2020 (P3)]. CSRV screening was performed through multiplex PCR assays during the study period. We identified 188 consecutive allo-HSCT recipients with 406 episodes screened for CSRV during the study period, of which 147 developed 300 CSRV. In P1 and P2 we diagnosed 115 (38.3%) and 145 (48.3%) CSRV episodes, respectively, whereas in P3 only 40 (13.3%) episodes were detected (p  less then  0.001). During P3, we observed a reduction of 80.2% in Ev/Rh, 93.3% in RSV, 80% in hIV, 96.3% HPIV, 68.4% in hMPV, 77.7% in ADV, 100% in HBoV, and 53.6% in HCoV as compared to P1 and P2. Consequently, we also observed a decline in absolute numbers of lower respiratory tract disease (68.1%), co-infections (91.7%), and hospitalizations (72.6%) during P3. We diagnosed SARS-COV-2 in nine allo-HSCT recipients, representing 23% of all CSRV detections in that period. VU0463271 In conclusion, we provide evidence of a significant drop in CSRV circulation during the SARS-COV-2 pandemic in our allo-HSCT recipients, indicating that prevention measures in the general population are highly effective in reducing CSRV prevalence and its complications in immunocompromised patients.