Ubiquinol cytochrome c reductase binding protein (UQCRB) is important for mitochondrial complex III stability, electron transport, cellular oxygen sensing and angiogenesis. However, its potential as ...a prognostic marker in colorectal cancer (CRC) remains unclear. The aim of this study was to determine whether UQCRB can be used as a diagnostic molecular marker for CRC. The correlation between the expression of three genes (UQCRB, UQCRFS1 and MT-CYB) in the mitochondrial respiratory chain complex III and clinico-pathological features was determined. Compared to non-tumor tissues, UQCRB gene expression was upregulated in CRC tissues. Gene and protein expression of the genes were positively correlated. Copy number variation (CNV) differences in UQCRB were observed in CRC tissues (1.32-fold) compared to non-tumor tissues. The CNV of UQCRB in CRC tissues increased proportionally with gene expression and clinical stage. Single-nucleotide polymorphisms in the 3'-untranslated region of UQCRB (rs7836698 and rs10504961) were investigated, and the rs7836698 polymorphism was associated with CRC clinical stage. DNA methylation of the UQCRB promoter revealed that most CRC patients had high methylation levels (12/15 patients) in CRC tissues compared to non-tumor tissues. UQCRB overexpression and CNV gain were correlated with specific CRC clinico-pathological features, indicating clinical significance as a prognostic predictor in CRC. Gene structural factors may be more important than gene transcription repression factors with respect to DNA methylation in UQCRB overexpression. Our results provide novel insights into the critical role of UQCRB in regulating CRC, supporting UQCRB as a new candidate for the development of diagnostics for CRC patients.
Studies comparing percutaneous closure of patent ductus arteriosus (PDA) with surgical ligation tend to exclude premature infants and have not assessed procedural charges. We compared our ...contemporary outcomes and charges of device closure to surgical ligation of PDA in preterm infants.
Preterm infants who underwent isolated PDA closure during their newborn hospitalization (January 2014 to September 2017) were grouped based on intention to treat (surgery versus device closure). Patient demographics, procedural details, and immediate postprocedural outcomes were compared. Procedural charges for device closure versus surgical ligation were compared.
Compared with the device group (n = 33), patients undergoing surgical ligation (n = 39) were younger, smaller, and required more preoperative support (P < 0.05). The procedure time was shorter for surgical ligation (P < 0.01). Although there was no procedural mortality in either group, the complication rate was higher for device closure than for surgical ligation (15.2% versus 0%; P = 0.02). The proportion of patients returning to preprocedural respiratory support by 48 h after procedure was similar. There was a higher proportion of surgical patients who required increased inotropic support in the first 24 h after procedure (P = 0.19). The procedural charges for transcatheter device closure were twice as expensive as those for surgical ligation.
In our early experience with percutaneous PDA closure, we found a percutaneous approach in preterm infants feasible and well tolerated. Both surgical ligation and device closure were associated with perioperative or postoperative complications. Procedural charges were higher for percutaneous closure, driven by device charge and catheterization room utilization. Further investigation is needed to establish guidelines for first-line therapy for PDA closure in preterm infants, including cost-benefit analysis.
Marine ecosystems have been used, impacted by, and managed by human populations for millennia. As ecosystem degradation has been a common outcome of these activities, marine management increasingly ...considers ecosystem restoration. Currently, there is no coherent data recording format or framework for marine restoration projects. As a result, data are inconsistently recorded and it is difficult to universally track progress, assess restoration's global effectiveness, reduce reporting bias, collect a holistic suite of metrics, and share information. Barriers to developing a unified system for reporting marine restoration outcomes include: reaching agreement on a framework that meets the needs of all users, funding its development and maintenance, balancing the need for ‘ease of use’ and detail, and demonstrating the value of using the framework. However, there are opportunities to leverage arising from the United Nation Decades of Ecosystem Restoration and Science for Sustainable Development and with existing processes already developed by restoration groups (e.g. Global Mangrove Alliance, Society for Ecological Restoration). Here we provide guidelines and a roadmap for how such a framework could be developed and the potential benefits of such an endeavor. We call on practitioners to collaborate to develop such a framework and on governing bodies to commit to making detailed reporting a requirement for restoration project funding. Using a standardized marine restoration monitoring framework would enable the application of adaptive management when projects are not progressing as expected, advance our understanding of the state of worldwide marine restoration, and generate knowledge to advance restoration methodologies.
•The field of marine ecosystem restoration is growing rapidly.•Currently projects are failing to systematically record the outcomes of restoration.•This gap hinders the field and prevents knowledge sharing and refined methods.•Developing a restoration reporting framework will help address this issue.•We present a roadmap for creating a restoration reporting framework.
Background
Children with chronic kidney disease (CKD) are at risk for abnormalities in pubertal development. We aimed to describe the timing of pubertal onset by luteinizing hormone (LH) levels and ...the association between hormonal onset of puberty with changes in GFR.
Methods
Data from the Chronic Kidney Disease in Children (CKiD) study were collected prospectively. GFR was estimated at annual visits and measured by iohexol clearance every other year. LH was measured from stored repository serum samples in a nested sample of 124 participants. Hormonal onset of puberty was defined as LH level greater than or equal to 0.3 IU/L. A mixed effects model with random intercepts and slopes was used to compare the slope of decline of GFR before and after hormonal onset of puberty. The model was adjusted for age, glomerular disease diagnosis, baseline proteinuria on the log scale, and BMI.
Results
Median age at hormonal onset of puberty was 9.9 years (IQR 8.1, 11.9) in girls and 10.2 years (IQR 9.2, 11.0) in boys. The mixed effects model showed faster decline in both estimated GFR and measured GFR in boys after hormonal onset of puberty (
p
< 0.001), and a similar but attenuated accelerated estimated GFR decline was observed for girls with no difference for measured GFR.
Conclusions
LH levels in the post-pubertal range were observed prior to clinical manifestations of puberty in children with CKD. Hormonal onset of puberty was associated with faster decline in GFR, particularly among boys with CKD.
Graphical abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information
Background
Children with chronic kidney disease (CKD) have delays in normal growth and pubertal development. We describe factors associated with delayed menarche and the association of delayed ...menarche with short stature in girls with CKD.
Methods
Two hundred eighty-seven girls with CKD onset prior to menarche within the Chronic Kidney Disease in Children (CKiD) cohort were studied. Delayed menarche was defined as menarche at age 15 years or older; short stature was defined as last available height 2 standard deviations below projected adult height. Kaplan-Meier cumulative incidence function was used to estimate median age at menarche. Chi-squared and Wilcoxon rank-sum tests were used to assess factors associated with delayed menarche. Chi-squared test was used to evaluate the association between delayed menarche and short stature.
Results
Among 287 girls, 68 enrolled with prevalent menarche, 131 were observed to have incident menarche, and 88 were pre-menarchal at their last study visit. Median age at menarche was 12 years. Ten percent had delayed menarche. African American race, lower estimated glomerular filtration rate, ever corticosteroid use, and longer CKD duration were associated with delayed menarche (
p
< 0.05). Girls with delayed menarche had lower height and weight percentiles at the time of menarche (
p
< 0.05). Sixty-one percent of girls with delayed menarche had short stature compared with only 35% of girls without delayed menarche (
p
= 0.03).
Conclusion
Median age at menarche is similar among girls with CKD and healthy girls. Ten percent of girls with CKD had delayed menarche and may be at risk for short stature.
Background
Blunt thoracic aortic injury (BTAI) is associated with a high mortality and is the second most common cause of death from trauma. The approach to major trauma, imaging technology and ...advancement in endovascular therapy have revolutionised the management of BTAI. Endovascular therapy has now become the gold standard technique replacing surgery with its high mortality and morbidity in unstable patients. We aim to assess the outcomes following management of BTAI.
Method
This is a retrospective study of all patients with BTAI between 1 January 2010 and 1 January 2022. Data were obtained from electronic health records. The grading of BTAI severity was done based on the Society of Vascular Surgery (SVS) Criteria.
Results
Fifty patients were included in the study analysis. The most common cause of BTAI was due to high-speed motor vehicle accidents (MVA) (36 patients, 72%). Grade 1 and grade 3 BTAI injuries were mostly encountered in 40% and 30% of the study cohort, respectively. Twenty-three patients (46%) underwent thoracic endovascular aortic repair (TEVAR). There was no secondary aortic re-intervention, conversion to open surgery or aortic-related deaths at 30 days or at most recent follow-up.
Conclusion
Management of BTAI in our centre compares well with currently published studies. Long-term studies are warranted to guide clinicians in areas of controversy in BTAI management.
Maintaining the integrity of cell membranes is indispensable for cellular viability. Poloxamer 188 (P188), a poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO–PPO–PEO) ...triblock copolymer with a number-average molecular weight of 8700 g/mol and containing 80% by mass PEO, protects cell membranes from various external injuries and has the potential to be used as a therapeutic agent in diverse applications. The membrane protection mechanism associated with P188 is intimately connected with how this block copolymer interacts with the lipid bilayer, the main component of a cell membrane. Here, we report the distribution of P188 in a model lipid bilayer comprising 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) using neutron reflectivity (NR) and atomic force microscopy (AFM). We also investigated the association of a PEO homopolymer (PEO8.4K; M n = 8400 g/mol) that does not protect living cell membranes. These experiments were conducted following incubation of a 4.5 mmol/L polymer solution in a buffer that mimics physiological conditions with supported POPC bilayer membranes followed by washing with the aqueous medium. In contrast to previous reports, which dealt with P188 and PEO in salt-free solutions, both P188 and PEO8.4K penetrate into the inner portion of the lipid bilayer as revealed by NR, with approximately 30% by volume occupancy across the membrane without loss of bilayer structural integrity. These results indicate that PEO is the chemical moiety that principally drives P188 binding to bilayer membranes. No defects or phase-separated domains were observed in either P188- or PEO8.4K-incubated lipid bilayers when examined by AFM, indicating that polymer chains mingle homogeneously with lipid molecules in the bilayer. Remarkably, the breakthrough force required for penetration of the AFM tip through the bilayer membrane is unaffected by the presence of the large amount of P188 and PEO8.4K.
Tryptophan radicals play a significant role in mediating biological electron transfer. We report the photogeneration of a long-lived, neutral tryptophan radical (Az48W•) from the native residue ...tryptophan-48 in the hydrophobic core of azurin. The optical absorption, electron paramagnetic resonance, and resonance Raman spectra strongly support the formation of a neutral radical, and the data are consistent with direct electron transfer between tryptophan and the copper(II) center. Spectra of the long-lived Az48W• species are compared to those of a previously studied, solvent-exposed radical at position 108 to identify signatures of tryptophan radicals that are sensitive to the local environment. The absorption maxima of Az48W• display an ∼23 nm hypsochromic shift in the nonpolar environment. The majority of the resonance Raman frequencies are downshifted by ∼7 cm−1 relative to the solvent-exposed radical, and large changes in intensity are observed for some modes. The resonance Raman excitation profiles for Az48W• exhibit distinct maxima within the absorption envelope. Electron paramagnetic resonance spectroscopy yields spectra with partially resolved lines caused by hyperfine couplings; the differences between the coupling constants for the buried and solvent-exposed radical are primarily caused by variations in structure. The insights gained by electronic, vibrational, and magnetic resonance spectroscopy enhance our fundamental understanding of the effects of protein environment on radical properties. Hypotheses for the proton transfer pathway within azurin and a deprotonation rate of ∼5 × 106 s−1 are proposed.
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