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To examine the characteristics of safety net (sn) and non-sn neonatal intensive care units (NICUs) in California and evaluate whether the site of care is associated with clinical outcomes.
This population-based retrospective cohort study of 34 snNICUs and 104 non-snNICUs included 22 081 infants born between 2014 and 2018 with a birth weight of 401-1500g or gestational age of 22-29weeks. Quality of care as measured by the Baby-MONITOR score and rates of survival without major morbidity were compared between snNICUs and non-snNICUs.
Black and Hispanic infants were cared for disproportionately in snNICUs, where care and outcomes varied widely. We found no significant differences in Baby-Measure Of Neonatal InTensive care Outcomes Research (MONITOR) scores (z-score [SD] snNICUs, -0.31 [1.3]; non-snNICUs, 0.03 [1.1]; P=.1). Among individual components, infants in snNICUs exhibited lower rates of human milk nutrition at discharge (-0.64 [1.0] vs 0.27 [0.9]), lower rates of no health care-associated infection (-0.27 [1.1] vs 0.14 [0.9]), and higher rates of no hypothermia on admission (0.39 [0.7] vs -0.25 [1.1]). We found small but significant differences in survival without major morbidity (adjusted rate, 65.9% [95% CI, 63.9%-67.9%] for snNICUs vs 68.3% [95% CI, 67.0%-69.6%] for non-snNICUs; P=.02) and in some of its components; snNICUs had higher rates of necrotizing enterocolitis (3.8% [3.4%-4.3%] vs 3.1% [95% CI, 2.8%-3.4%]) and mortality (95% CI, 7.1% [6.5%-7.7%] vs 6.6% [6.2%-7.0%]).
snNICUs achieved similar performance as non-snNICUs in quality of care except for small but significant differences in any human milk at discharge, infection, hypothermia, necrotizing enterocolitis, and mortality.
snNICUs achieved similar performance as non-snNICUs in quality of care except for small but significant differences in any human milk at discharge, infection, hypothermia, necrotizing enterocolitis, and mortality.
After kidney transplantation, rejection and drug-related toxicity occur despite tacrolimus whole-blood pre-dose concentrations ([Tac]
) being within the target range. The tacrolimus concentration within peripheral blood mononuclear cells ([Tac]
) might correlate better with clinical outcomes. The aim of this study was to investigate the correlation between [Tac]
and [Tac]
the evolution of [Tac]
and the [Tac]
/[Tac]
ratio, and to assess the relationship between tacrolimus concentrations and the occurrence of rejection.
In this prospective study, samples for the measurement of [Tac]
and [Tac]
were collected on days 3 and 10 after kidney transplantation, and on the morning of a for-cause kidney transplant biopsy. Biopsies were reviewed according to the Banff 2019 update.
Eighty-three [Tac]
samples were measured of 44 kidney transplant recipients. The correlation between [Tac]
and [Tac]
was poor (Pearson's r=0.56 (day 3); r=0.20 (day 10)). Both the dose-corrected [Tac]
and the [Tac]
ation for these results might be related to the low number of patients included in this study and also due to the fact that PBMCs are not a specific enough matrix to monitor tacrolimus concentrations.Aquaporin 4 (AQP4) is a water transporting, transmembrane channel protein that has important regulatory roles in maintaining cellular water homeostasis. Several other AQP proteins exhibit calmodulin (CaM)-binding properties, and CaM has recently been implicated in the cell surface localization of AQP4. The objective of the present study was to assess the CaM-binding properties of AQP4 in detail. Inspection of AQP4 revealed two putative CaM-binding domains (CBDs) in the cytoplasmic N- and C-terminal regions, respectively. The Ca2+-dependent CaM-binding properties of AQP4 CBD peptides were assessed using fluorescence spectroscopy, isothermal titration calorimetry, and two-dimensional 1H, 15N-HSQC NMR with 15N-labeled CaM. The N-terminal CBD of AQP4 predominantly interacted with the N-lobe of CaM with a 11 binding ratio and a Kd of 3.4 μM. The C-terminal AQP4 peptide interacted with both the C- and N-lobes of CaM (21 binding ratio; Kd1 3.6 μM, Kd2 113.6 μM, respectively). A recombinant AQP4 protein domain (recAQP4CT, containing the entire cytosolic C-terminal sequence) bound CaM in a 11 binding mode with a Kd of 6.1 μM. A ternary bridging complex could be generated with the N- and C-lobes of CaM interacting simultaneously with the N- and C-terminal CBD peptides. These data support a unique adapter protein binding mode for CaM with AQP4.Voltage-gated sodium (Nav) channels play critical roles in propagating action potentials and otherwise manipulating ionic gradients in excitable cells. These channels open in response to membrane depolarization, selectively permeating sodium ions until rapidly inactivating. Structural characterization of the gating cycle in this channel family has proved challenging, particularly due to the transient nature of the open state. A structure from the bacterium Magnetococcus marinus Nav (NavMs) was initially proposed to be open, based on its pore diameter and voltage-sensor conformation. However, the functional annotation of this model, and the structural details of the open state, remain disputed. In this work, we used molecular modeling and simulations to test possible open-state models of NavMs. The full-length experimental structure, termed here the α-model, was consistently dehydrated at the activation gate, indicating an inability to conduct ions. Based on a spontaneous transition observed in extended simulations, and sequence/structure comparison to other Nav channels, we built an alternative π-model featuring a helix transition and the rotation of a conserved asparagine residue into the activation gate. Pore hydration, ion permeation, and state-dependent drug binding in this model were consistent with an open functional state. This work thus offers both a functional annotation of the full-length NavMs structure and a detailed model for a stable Nav open state, with potential conservation in diverse ion-channel families.Hybrid polymer/lipid vesicles are self-assembled structures that have been the subject of an increasing number of studies in recent years. They are particularly promising tools in the development of cell membrane models because they offer the possibility to fine-tune their membrane structure by adjusting the distribution of components (presence or absence of "raft-like" lipid domains), which is of prime importance to control their membrane properties. Line tension in multiphase membranes is known to be a key parameter on membrane structuration, but remains unexplored, either experimentally or by computer modeling for hybrid polymer/lipid vesicles. In this study, we were able to measure the line tension on different budded hybrid vesicles, using a micropipette aspiration technique, and show the influence of the molar mass and the architecture of block copolymers on line tension and its consequences for membrane structuration.Cell dispersion from a confined area is fundamental in a number of biological processes, including cancer metastasis. To date, a quantitative understanding of the interplay of single-cell motility, cell proliferation, and intercellular contacts remains elusive. In particular, the role of E- and N-cadherin junctions, central components of intercellular contacts, is still controversial. Combining theoretical modeling with in vitro observations, we investigate the collective spreading behavior of colonies of human cancer cells (T24). The spreading of these colonies is driven by stochastic single-cell migration with frequent transient cell-cell contacts. We find that inhibition of E- and N-cadherin junctions decreases colony spreading and average spreading velocities, without affecting the strength of correlations in spreading velocities of neighboring cells. Based on a biophysical simulation model for cell migration, we show that the behavioral changes upon disruption of these junctions can be explained by reduced repulsive excluded volume interactions between cells. This suggests that in cancer cell migration, cadherin-based intercellular contacts sharpen cell boundaries leading to repulsive rather than cohesive interactions between cells, thereby promoting efficient cell spreading during collective migration.The anterior insular cortex (aIC) plays a critical role in cognitive and motivational control of behavior, but the underlying neural mechanism remains elusive. Here, we show that aIC neurons expressing Fezf2 (aICFezf2), which are the pyramidal tract neurons, signal motivational vigor and invigorate need-seeking behavior through projections to the brainstem nucleus tractus solitarii (NTS). aICFezf2 neurons and their postsynaptic NTS neurons acquire anticipatory activity through learning, which encodes the perceived value and the vigor of actions to pursue homeostatic needs. Correspondingly, aIC → NTS circuit activity controls vigor, effort, and striatal dopamine release but only if the action is learned and the outcome is needed. Notably, aICFezf2 neurons do not represent taste or valence. Moreover, aIC → NTS activity neither drives reinforcement nor influences total consumption. These results pinpoint specific functions of aIC → NTS circuit for selectively controlling motivational vigor and suggest that motivation is subserved, in part, by aIC's top-down regulation of dopamine signaling.PsbX is a 4.1 kDa intrinsic Photosystem II (PS II) protein, found together with the low-molecular-weight proteins, PsbY and PsbJ, in proximity to cytochrome b559. The function of PsbX is not yet fully characterized but PsbX may play a role in the exchange of the secondary plastoquinone electron acceptor QB with the quinone pool in the thylakoid membrane. To study the role of PsbX, we have constructed a PsbX-lacking strain of Synechocystis sp. PCC 6803. Our studies indicate that the absence of PsbX causes sensitivity to high light and impairs electron transport within PS II. In addition to a change in the QB-binding pocket, PsbX-lacking cells exhibited sensitivity to sodium formate, suggesting altered binding of the bicarbonate ligand to the non-heme iron between the sequential plastoquinone electron acceptors QA and QB. Experiments using 35S-methionine revealed high-light-treated PsbX-lacking cells restore PS II activity during recovery under low light by an increase in the turnover of PS II-associated core proteins. These labeling experiments indicate the recovery after exposure to high light requires both selective removal and replacement of the D1 protein and de novo PS II assembly.
Hospital readmission within 30 days of discharge is a well-studied outcome. Predicting readmission after cardiac surgery, however, is notoriously challenging; the best-performing models in the literature have areas under the curve around .65. A reliable predictive model would enable clinicians to identify patients at risk for readmission and to develop prevention strategies.
We analyzed The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database at our institution, augmented with electronic medical record data. Predictors included demographics, preoperative comorbidities, proxies for intraoperative risk, indicators of postoperative complications, and time series-derived variables. We trained several machine learning models, evaluating each on a held-out test set.
Our analysis cohort consisted of 4924 cases from 2011 to 2016. Of those, 723 (14.7%) were readmitted within 30 days of discharge. Saracatinib solubility dmso Our models included 141 STS-derived and 24 electronic medical records-derived variables. A random forest model performed best, with test area under the curve 0.
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