The objective of this study is to investigate the impact of early life experiences and gut microbiota on neurobehavioral development in preterm infants during neonatal intensive care unit (NICU) ...hospitalization.
Preterm infants were followed from NICU admission until their 28th postnatal day or until discharge. Daily stool samples, painful/stressful experiences, feeding patterns, and other clinical and demographic data were collected. Gut microbiota was profiled using 16S rRNA sequencing, and operational taxonomic units (OTUs) were selected to predict the neurobehaviors. The neurobehavioral development was assessed by the Neonatal Neurobehavioral Scale (NNNS) at 36 to 38 weeks of post-menstrual age (PMA). Fifty-five infants who had NNNS measurements were included in the sparse log-contrast regression analysis.
Preterm infants who experienced a high level of pain/stress during the NICU hospitalization had higher NNNS stress/abstinence scores. Eight operational taxonomic units (OTUs) were identified to be associated with NNNS subscales after controlling demographic and clinical features, feeding patterns, and painful/stressful experiences. These OTUs and taxa belonging to seven genera, i.e.,
,
,
,
,
,
, and
with five belonging to
and two belonging to
phylum. The enriched abundance of
(OTU17) and
(OTU28) were consistently associated with less optimal neurobehavioral outcomes. The other six OTUs were also associated with infant neurobehavioral responses depending on days at NICU stay.
This study explored the dynamic impact of specific OTUs on neurobehavioral development in preterm infants after controlling for early life experiences, i.e., acute and chronic pain/stress and feeding in the NICU. The gut microbiota and acute pain/stressful experiences dynamically impact the neurobehavioral development in preterm infants during their NICU hospitalization.
In this paper, the characteristics of the impact pressure and force of a trimaran section was studied by Computational Fluid Dynamics (CFD). The time domain features of the slamming pressure or force ...showed a strong correlation with the penetration depth regardless of the specific ways of water entry. The effects of velocity and acceleration on the impact pressure and force were analyzed. It was found that the initial impact of the main hull and the wet-deck slamming were predominantly affected by the entry velocities, whilst the acceleration had almost no effect for initial impact. The impact velocity presented a quadratic relation with slamming pressure/forces, and the relation between acceleration and wet-deck slamming pressure/force was linear. These were consistent with the patterns implied by analytical models such as the Wagner or MLM (Modified Logvinovich model) theories.
Background: The current understanding of the venous system in the hippocampus is mostly based on histological and autopsy studies.1 However, the main disadvantage is that it only reveals the anatomy ...of the vascular system at the post-mortem stage and lacks physiological aspects associated with neuronal metabolism. In vivo characterization of the venous system using susceptibility weighted imaging (SWI) at 7 T could provide valuable information on both venous anatomy and blood oxygen saturation, through high-resolution SWI venography2 and quantitative susceptibility mapping (QSM).3 In this study, we aim to elucidate the hierarchical network of the hippocampal venous system and then test the feasibility of using venous susceptibility to characterize venous oxygenation level changes related to neurodegeneration.
Methods: Seven healthy volunteers were recruited for this study. We used high in-plane resolution of flow-compensated dual-echo gradient echo sequence (TE1/TE2/TR=7.5/15/22 ms, voxel size: 0.25*0.25*1 mm). SWI and QSM were then reconstructed using the iterative SWI and mapping (iterative SWIM) algorithm,3 as shown in Figure 1. Hippocampus masks were extracted from the T1-MPRAGE image, which was transformed to SWI space afterwards. To reduce the partial volume effect from the tissue-vessel boundary, we extract the venous susceptibility value from each voxel along the centerline of the vessels.
Results: High-resolution in vivo mapping of hippocampal venous vasculature exhibits a high analogy to Duvernoy’s reference4 for hippocampal vascularization. As shown in Figure 1, there is a shape of venous arch near the fimbria of the hippocampus, and small veins extending through the arch are possibly the intrahippocampal veins. The intrahippocampal veins will eventually reach the inferior ventricular vein (IVV) (anteriorly) and medial atrial vein (MAV) (posteriorly), before joining the basal vein of Rosenthal (BVR). For venous susceptibility quantification, Figure 1 shows the representative color-coded QSM for centerline extraction on BVR.
Conclusions: Our results showed improved visualization of the micro venous system in the hippocampus using high-resolution 7 T SWI data without the contrast agent.5 In summary, the characterization of venous QSM in major tributaries related to the hippocampus offers a novel perspective on oxygen utilization in the hippocampus, which may be useful for studying age-related dementia. We delineated the hierarchical network of the hippocampus venous system using SWI/QSM at 7 T and extract the venous density and venous susceptibility value in hippocampus-related small veins and major venous tributaries, as an overall measure for venous oxygenation level related to the hippocampus, which may be used as an early marker for hippocampal atrophy in Alzheimer’s disease.
Long-term ozone (O3) exposure may lead to non-communicable diseases and increase mortality risk. However, cohort-based studies are relatively rare, and inconsistent exposure metrics impair the ...credibility of epidemiological evidence synthetization. To provide more accurate meta-estimations, this study updates existing systematic reviews by including recent studies and summarizing the quantitative associations between O3 exposure and cause-specific mortality risks, based on unified exposure metrics. Cross-metric conversion factors were estimated linearly by decadal observations during 1990–2019. The Hunter-Schmidt random-effects estimator was applied to pool the relative risks. A total of 25 studies involving 226,453,067 participants (14 unique cohorts covering 99,855,611 participants) were included in the systematic review. After linearly unifying the inconsistent O3 exposure metrics, the pooled relative risks associated with every 10 nmol mol−1 (ppbV) incremental O3 exposure, by mean of the warm-season daily maximum 8-h average metric, were as follows: 1.014 with 95% confidence interval (CI) ranging 1.009–1.019 for all-cause mortality; 1.025 (95% CI: 1.010–1.040) for respiratory mortality; 1.056 (95% CI: 1.029–1.084) for COPD mortality; 1.019 (95% CI: 1.004–1.035) for cardiovascular mortality; and 1.074 (95% CI: 1.054–1.093) for congestive heart failure mortality. Insignificant mortality risk associations were found for ischemic heart disease, cerebrovascular diseases, and lung cancer. Adjustment for exposure metrics laid a solid foundation for multi-study meta-analysis, and widening coverage of surface O3 observations is expected to strengthen the cross-metric conversion in the future. Ever-growing numbers of epidemiological studies supported the evidence for considerable cardiopulmonary hazards and all-cause mortality risks from long-term O3 exposure. However, evidence of long-term O3 exposure-associated health effects was still scarce, so more relevant studies are needed to cover more populations with regional diversity.
Display omitted
•Updated evidence for O3-mortality associations from 25 cohorts has been provided•Adjusting various O3 exposure metrics can provide more accurate risk estimations•Long-term O3 exposure could be associated with increased multi-cause mortality
Since image background is normally composed of congenial regions, it can be represented by a feature dictionary via sparse representation. Based on this theory, the authors propose a novel bottom-up ...saliency detection method that unites the syncretic merits of sparse representation and multi-hierarchical layers. In contrast to most pre-existing sparse-based approaches that only highlight the boundaries of a target, the proposed method highlights the entire object even if it is large. Given a source image, a multi-scale background dictionary is structured with the features form different layers. Each region of the image is then reconstructed by the dictionary to compute its reconstruction error as a saliency score. Although a reconstruction map can be generated by the saliency scores, it is not good enough to be the final result because of low resolution and high error detection rates. Therefore, in middle cue, they propose a multi-scale contour zooming approach to address the error detection across the hierarchical layers. To improve the resolution of the final detection, a pixel-level rectification based on the Bayesian observation likelihood is calculated as the bottom cue. Combining sparse representation and multi-scale correction, the precision of the final saliency map is significantly improved for the detection results.
Aims/hypothesis
Glucagon-stimulated hepatic gluconeogenesis contributes to endogenous glucose production during fasting. Recent studies suggest that TGF-β is able to promote hepatic gluconeogenesis ...in mice. However, the physiological relevance of serum TGF-β levels to human glucose metabolism and the mechanism by which TGF-β enhances gluconeogenesis remain largely unknown. As enhanced gluconeogenesis is a signature feature of type 2 diabetes, elucidating the molecular mechanisms underlying TGF-β-promoted hepatic gluconeogenesis would allow us to better understand the process of normal glucose production and the pathophysiology of this process in type 2 diabetes. This study aimed to investigate the contribution of upregulated TGF-β1 in human type 2 diabetes and the molecular mechanism underlying the action of TGF-β1 in glucose metabolism.
Methods
Serum levels of TGF-β1 were measured by ELISA in 74 control participants with normal glucose tolerance and 75 participants with type 2 diabetes. Human liver tissue was collected from participants without obesity and with or without type 2 diabetes for the measurement of TGF-β1 and glucagon signalling. To investigate the role of Smad3, a key signalling molecule downstream of the TGF-β1 receptor, in mediating the effect of TGF-β1 on glucagon signalling, we generated
Smad3
knockout mice. Glucose levels in
Smad3
knockout mice were measured during prolonged fasting and a glucagon tolerance test. Mouse primary hepatocytes were isolated from
Smad3
knockout and wild-type (WT) mice to investigate the underlying molecular mechanisms. Smad3 phosphorylation was detected by western blotting, levels of cAMP were detected by ELISA and levels of protein kinase A (PKA)/cAMP response element-binding protein (CREB) phosphorylation were detected by western blotting. The dissociation of PKA subunits was measured by immunoprecipitation.
Results
We observed higher levels of serum TGF-β1 in participants without obesity and with type 2 diabetes than in healthy control participants, which was positively correlated with HbA
1c
and fasting blood glucose levels. In addition, hyperactivation of the CREB and Smad3 signalling pathways was observed in the liver of participants with type 2 diabetes. Treating WT mouse primary hepatocytes with TGF-β1 greatly potentiated glucagon-stimulated PKA/CREB phosphorylation and hepatic gluconeogenesis. Mechanistically, TGF-β1 treatment induced the binding of Smad3 to the regulatory subunit of PKA (PKA-R), which prevented the association of PKA-R with the catalytic subunit of PKA (PKA-C) and led to the potentiation of glucagon-stimulated PKA signalling and gluconeogenesis.
Conclusions/interpretation
The hepatic TGF-β1/Smad3 pathway sensitises the effect of glucagon/PKA signalling on gluconeogenesis and synergistically promotes hepatic glucose production. Reducing serum levels of TGF-β1 and/or preventing hyperactivation of TGF-β1 signalling could be a novel approach for alleviating hyperglycaemia in type 2 diabetes.
Graphical abstract
Enterovirus 71 (EV71) has led to recent outbreaks of hand, foot and mouth disease (HFMD) in China, resulting in high mortality. In this study, several monoclonal antibodies were generated by ...immunizing mice with two synthetic peptides, SP55 and SP70, containing amino acids 163–177 and 208–222 of VP1. The specificities of the anti-EV71 peptide monoclonal antibodies were confirmed by Western blot analysis and immunocytochemistry against EV71 virus. Most importantly, we have identified a monoclonal antibody, clone 22A12, which shows strong neutralizing activity against EV71 in an
in vitro neutralization assay. Because there is no vaccine available and treatment is very limited, mouse anti-EV71 monoclonal antibody, clone 22A12, could be a promising candidate to be humanized and used for treatment of EV71 infection.
Whether anesthesia type is associated with the surgical outcome of Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) remains to be determined. This study aims to ...investigate the impact of volatile inhalational anesthesia (INHA) versus total IV anesthesia (TIVA) on the survival outcomes in HCC patients with PVTT.
A cohort of in-patients whom were diagnosed of HCC with PVTT in Eastern Hepatobiliary Surgery Hospital, Shanghai, China, from January 1, 2008 to December 24, 2012 were identified. Surgical patients receiving the INHA and TIVA were screened out. The overall survival (OS), recurrence-free survival (RFS) and several postoperative adverse events were compared according to anesthesia types.
A total of 1513 patients were included in this study. After exclusions are applied, 263 patients remain in the INHA group and 208 in the TIVA group. Patients receiving INHA have a lower 5-year overall survival rate than that of patients receiving TIVA 12.6% (95% CI, 9.0 to 17.3) vs. 17.7% (95% CI, 11.3 to 20.8), P = 0.024. Results of multivariable Cox-regression analysis also identify that INHA anesthesia is significantly associated with mortality and cancer recurrence after surgery compare to TIVA, with HR (95%CI) of 1.303 (1.065, 1.595) and 1.265 (1.040, 1.539), respectively. Subgroup analysis suggested that in more severe cancer patients, the worse outcome related to INHA might be more significant.
This retrospective analysis identifies that TIVA is associated with better outcomes compared with INHA. Future prospective studies clinical and translational studies are required to verify this difference and investigate underlying pathophysiology.
•We characterized the incompatibility issue between CNTs, superplasticizer and air entrainer.•MWCNTs affect concrete slump and air content by interacting with superplasticizer and air entrainer ...(AE).•MWCNTs drops the surface tension, foam index, and air content up to 33%, 42%, 60%.•This incompatibility applies to different water/cement ratio and different type of air entrainer.
Multi-walled carbon nanotubes (MWCNTs) have great potential to improve performance of cementitious material in terms of mechanical, durability and electrical. This study quantitatively investigates the compatibility between MWCNTs, admixtures of superplasticizer and air entrainer (AE) in concrete materials, by performing experimental tests of surface tension, foam index and air content. Through applying various combination of admixtures and MWCNTs in concrete samples, the study finds that for concrete with MWCNTs, superplasticizer and air entrainer (AE), the surface tension, foam index, and air content could decrease up to 33%, 42%, 60%, respectively, and this significant change of air system can damage concrete freeze–thaw resistance. The significant decrease of air void content indicates the interaction between carbon nanotubes, superplasticizer and air entrainer. This interaction is further verified considering various levels of water/cement ratio or different brands of air entrainer. The study discovered the potential conflict during the application of nano materials and traditional admixtures and focused on much complicated concrete material.
Inositol is a bioactive factor that is widely found in nature; however, there are few studies on its use in ruminant nutrition. This study investigated the effects of different inositol doses and ...fermentation times on rumen fermentation and microbial diversity, as well as the levels of rumen and blood metabolites in sheep. Rumen fermentation parameters, microbial diversity, and metabolites after different inositol doses were determined
. According to the
results, six small-tailed Han sheep fitted with permanent rumen fistulas were used in a 3 × 3 Latin square feeding experiment where inositol was injected into the rumen twice a day and rumen fluid and blood samples were collected. The
results showed that inositol could increase
dry matter digestibility,
crude protein digestibility, NH
-N, acetic acid, propionic acid, and rumen microbial diversity and affect rumen metabolic pathways (
< 0.05). The feeding experiment results showed that inositol increased the blood concentration of high-density lipoprotein and IgG, IgM, and IL-4 levels. The rumen microbial composition was significantly affected (
< 0.05). Differential metabolites in the rumen were mainly involved in ABC transporters, biotin metabolism, and phenylalanine metabolism, whereas those in the blood were mainly involved in arginine biosynthesis and glutathione and tyrosine metabolism. In conclusion, inositol improves rumen function, affects rumen microorganisms and rumen and blood metabolites and may reduce inflammation, improving animal health.
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