Notes

Fragrant hydrocarbon receptors throughout mitochondrial biogenesis and function.
Vagus nerve stimulation (VNS) is being used increasingly to treat a wide array of diseases and disorders. This growth is driven in part by the putative ability to stimulate the nerve non-invasively. Despite decades of use and a rapidly expanding application space, we lack a complete understanding of the acute effects of VNS on human cortical neurophysiology. Here, we investigated cortical responses to sub-perceptual threshold cervical implanted (iVNS) and transcutaneous auricular (taVNS) vagus nerve stimulation using intracranial neurophysiological recordings in human epilepsy patients. To understand the areas that are modulated by VNS and how they differ depending on invasiveness and stimulation parameters, we compared VNS-evoked neural activity across a range of stimulation modalities, frequencies, and amplitudes. Using comparable stimulation parameters, both iVNS and taVNS caused subtle changes in low-frequency power across broad cortical networks, which were not the same across modalities and were highly variable across participants. However, within at least some individuals, it may be possible to elicit similar responses across modalities using distinct sets of stimulation parameters. These results demonstrate that both invasive and non-invasive VNS cause evoked changes in activity across a set of highly distributed cortical networks that are relevant to a diverse array of clinical, rehabilitative, and enhancement applications.
Primary ciliary dyskinesia (PCD) is a heterogeneous disease characterized by the failure of mucociliary clearance. Dynein regulatory complex subunit 1 (DRC1) variants can cause PCD by disrupting the nexin link connecting the outer doublets. In this study, we aimed to investigate the clinical and functional impacts of DRC1 variants on respiratory cilia and sperm.

We identified and validated the DRC1 variant by using whole-exome and Sanger sequencing. High-speed video microscopy analysis (HSVA) was used to measure the nasal ciliary beating frequency and pattern in a patient and a healthy control. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) were applied to analyze the morphological and ultrastructural sperm defects resulting from the DRC1 variant.

NM_145038.5c.1296 G>A, p.(Trp432*), a novel homozygous DRC1 nonsense variant, was identified in a patient from a consanguineous Chinese family. The patient exhibited bronchiectasis, chronic sinusitis, situs solitus, and male infe genetic spectrum of PCD and MMAF, and provide a detailed clinical summary and functional analysis of patients with DRC1 variants.Vitiligo is characterized by the progressive disappearance of melanocytes, resulting in depigmentation. Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs that play an essential role in the regulation of inflammation and immunity. Published reports on the expression profile of lncRNAs in vitiligo cases and the potential biological function of lncRNAs in vitiligo are lacking. We performed RNA-Seq to identify the functions of lncRNAs in vitiligo. In total, 32 upregulated lncRNAs and 78 downregulated lncRNAs were identified in skin lesions with vitiligo. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis demonstrated that mRNAs regulated by abnormally expressed lncRNAs are most relevant to melanocyte function and melanogenesis. We identified 14 aberrantly expressed lncRNAs through the co-expression pattern that regulate the melanogenesis-related genes DCT, TYR, and TYRP1. Therefore, we speculate that these hub genes may be involved in pathological mechanisms in melanocytes in vitiligo. These genes are closely related to melanogenesis in vitiligo. Abnormally expressed lncRNAs directly or indirectly act on these target genes to regulate melanogenesis. Aminocaproic mouse Identifying lncRNAs and clarifying the regulatory roles of the lncRNA-mRNA network may be helpful to develop novel diagnoses or treatment targets for vitiligo.
Castration-resistant prostate cancer (CRPC) patients frequently develop neuroendocrine differentiation, with high mortality and no effective treatment. However, the regulatory mechanism that connects neuroendocrine differentiation and metabolic adaptation in response to therapeutic resistance of prostate cancer remain to be unravelled.

By unbiased cross-correlation between RNA-sequencing, database signatures, and ChIP analysis, combining in vitro cell lines and in vivo animal models, we identified that PCK1 is a pivotal regulator in therapy-induced neuroendocrine differentiation of prostate cancer through a LIF/ZBTB46-driven glucose metabolism pathway.

Upregulation of PCK1 supports cell proliferation and reciprocally increases ZBTB46 levels to promote the expression of neuroendocrine markers that are conducive to the development of neuroendocrine characteristic CRPC. PCK1 and neuroendocrine marker expressions are regulated by the ZBTB46 transcription factor upon activation of LIF signalling. Targeting PCK1 can reduce the neuroendocrine phenotype and decrease the growth of prostate cancer cells in vitro and in vivo.

Our study uncovers LIF/ZBTB46 signalling activation as a key mechanism for upregulating PCK1-driven glucose metabolism and neuroendocrine differentiation of CRPC, which may yield significant improvements in prostate cancer treatment after ADT using PCK1 inhibitors.
Our study uncovers LIF/ZBTB46 signalling activation as a key mechanism for upregulating PCK1-driven glucose metabolism and neuroendocrine differentiation of CRPC, which may yield significant improvements in prostate cancer treatment after ADT using PCK1 inhibitors.Epigenetic mechanisms play instrumental roles in gene regulation during embryonic development and disease progression. However, it is challenging to non-invasively monitor the dynamics of epigenomes and related gene regulation at inaccessible human tissues, such as tumours, fetuses and transplanted organs. Circulating cell-free DNA (cfDNA) in peripheral blood provides a promising opportunity to non-invasively monitor the genomes from these inaccessible tissues. The fragmentation patterns of plasma cfDNA are unevenly distributed in the genome and reflect the in vivo gene-regulation status across multiple molecular layers, such as nucleosome positioning and gene expression. In this review, we revisited the computational and experimental approaches that have been recently developed to measure the cfDNA fragmentomics across different resolutions comprehensively. Moreover, cfDNA in peripheral blood is released following cell death, after apoptosis or necrosis, mainly from haematopoietic cells in healthy people and diseased tissues in patients. Several cfDNA-fragmentomics approaches showed the potential to identify the tissues-of-origin in cfDNA from cancer patients and healthy individuals. Overall, these studies paved the road for cfDNA fragmentomics to non-invasively monitor the in vivo gene-regulatory dynamics in both peripheral immune cells and diseased tissues.
This study examines comprehensive patient and process factors that influence breast milk use in the NICU setting.

We examined the association of maternal, neonatal, and family factors and lactation support systems to identify gaps in breast milk use in a retrospective study of 865 infants born in 23-41 weeks gestation admitted to the NICU.

Breast milk at discharge for all infants was 89.3%, for extremely preterm 82.3%, moderately preterm 91.4%, late preterm 86.5%, and term 92.7%. Prematurity (OR 0.31 [0.17-0.56]), low birth weight, morbidities, Black maternal race (OR 0.20 [0.07-0.57]) and public insurance (OR 0.54 [0.34-0.85]) were associated with decreased breast milk use. Early initiation of feeds was associated with increased breast milk use.

There is a need to increase social as well as hospital support systems to address gaps in breast milk use in the NICU.
There is a need to increase social as well as hospital support systems to address gaps in breast milk use in the NICU.
Evaluate spontaneous closure of the patent ductus arteriosus (PDA) in extremely preterm infants and their respiratory outcomes, especially at <26 weeks gestational age (GA).

Retrospective study in <29 weeks, admitted within 24 h after birth (Feb 2015 and Dec 2019). Infants without any intervention to promote ductal closure, ≥1 echocardiography, and alive at discharge were included.

Two hundred and fourteen infants (average GA 26.3 ± 1.5 weeks) were included; 84 (39%) <26 weeks. PDA closed spontaneously in 194 (91%); 76/84 (90%) for infants <26 weeks. PDA closure was ascertained on an echocardiography performed at a median age of 36.4 [34.4-40.1] weeks. Rate of moderate-to-severe bronchopulmonary dysplasia decreased throughout the study period (OR for year of birth 0.70 [95% CI 0.57-0.87], p = 0.001).

Majority of extremely preterm infants, including <26 weeks, had spontaneous closure of the ductus before term corrected age. There was a concomitant improvement of respiratory outcomes.
Majority of extremely preterm infants, including less then 26 weeks, had spontaneous closure of the ductus before term corrected age. There was a concomitant improvement of respiratory outcomes.
To assess risk factors associated with 30-day hospital readmission after a prolonged neonatal intensive care stay.

Retrospective analysis of 57,035 infants discharged >14 days from the NICU between 2013 and 2016. Primary outcome was 30-day, all-cause hospital readmission. Adjusted likelihood of readmission accounting for demographic and clinical characteristics, including chronic conditions was also estimated.

The 30-day readmission rate was 10.7%. Respiratory problems accounted for most (31.0%) readmissions. In multivariable analysis, shunted hydrocephalus [OR 2.2 (95%CI 1.8-2.7)], gastrostomy tube [OR 2.0 (95%CI 1.8-2.3)], tracheostomy [OR 1.5 (95%CI 1.2-1.8)], and use of public insurance [OR 1.3 (95%CI 1.2-1.4)] had the highest likelihood of readmission. Adjusted hospital readmission rates varied significantly (p < 0.001) across hospitals.

The likelihood of hospital readmission was highest for infants with indwelling medical devices and public insurance. These findings will inform future initiatives to reduce readmission for high risk infants with medical and social complexity.
The likelihood of hospital readmission was highest for infants with indwelling medical devices and public insurance. These findings will inform future initiatives to reduce readmission for high risk infants with medical and social complexity.We retrospectively compared the outcomes of reduced-intensity conditioning (RIC) transplantation from matched related donors (MRD; n = 266), matched unrelated donors (MUD; n = 277), and umbilical cord blood (UCB; n = 513) for mature lymphoid malignancies. The 3-year overall survival rates for the MRD, MUD, and UCB groups were 54%, 59%, and 40%, respectively (P  less then  0.001). Multivariate analysis showed no differences in survival between the MRD group and the MUD or UCB group. However, survival was significantly affected by the conditioning regimen and graft-versus-host disease (GVHD) prophylaxis in the UCB group, but not in the MRD and MUD groups. Notably, multivariate analysis showed that the risk of overall mortality in the UCB recipients who received the optimal conditioning regimen and GVHD prophylaxis (n = 116) was lower than that in the MRD group (relative risk [RR], 0.69; P = 0.03) and tended to be lower than that in the MUD group (RR, 0.75; P = 0.09). Our results suggest that UCB transplantation performed with the optimal conditioning regimen and GVHD prophylaxis is highly effective.
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