Competitive adsorption and reduced mobility: N-octane, CO₂ and H₂S in alumina and graphite pores

Because gas injection into geological formations is a common technology deployed for enhanced oil recovery (EOR), it is important to understand at the molecular level the relations between competitive adsorption and fluid mobility at the single-pore level. To achieve such an understanding, we report here molecular dynamics simulation results to document structural and dynamical properties of n-octane confined in slit-shaped alumina and graphite pores in the presence of CO₂ and H₂S. The substrates are chosen as proxy models for natural hydrophilic and hydrophobic substrates, respectively. It was found that CO₂ and H₂S could displace n-octane from alumina but not from graphite surfaces. Analysis of the results demonstrates that more attractive n-octane – surface and weaker CO₂/H₂S - surface interactions in graphite compared to alumina are responsible for this observation. Regardless of pore type, the results suggest that adding CO₂ or H₂S suppresses the diffusion of n-octane due to pore crowding. However, the mechanisms responsible for this observation are different, wherein preferential adsorption sites are available on the alumina surface for both CO₂ or H₂S, but not on graphite. To contribute to designing advanced EOR technologies, possible molecular mechanisms are proposed to interpret the results

A new technique for transumbilical insertion of central venous silicone catheters in newborn infants

Aim: A new technique allowing placement of umbilical silicone venous catheters (USVC) is described and compared with percutaneous silicone venous catheters (PSVC)

The high mental health burden of "Long COVID" and its association with on-going physical and respiratory symptoms in all adults discharged from hospital

Adults discharged from hospital with COVID-19 may experience 'Long COVID', where mental health symptoms are significant and linked to physical symptoms such as breathlessness. Clinicians should use brief screening questionnaires to support their recovery

Extracellular histones are a target in myocardial ischaemia reperfusion injury.

Acute myocardial infarction causes lethal cardiomyocyte injury during ischaemia and reperfusion (I/R). Histones have been described as important Danger Associated Molecular Proteins (DAMPs) in sepsis. Aims The objective of this study was to establish whether extracellular histone release contributes to myocardial infarction. Methods and results Isolated, perfused rat hearts were subject to I/R. Nucleosomes and histone H4 release was detected early during reperfusion. Sodium-β-O-Methyl cellobioside sulfate (mCBS), a newly developed histone-neutralising compound, significantly reduced infarct size whilst also reducing the detectable levels of histones. Histones were directly toxic to primary adult rat cardiomyocytes in vitro. This was prevented by mCBS, or HIPe, a recently described, histone-H4 neutralizing peptide, but not by an inhibitor of TLR4, a receptor previously reported to be involved in DAMP-mediated cytotoxicity. Furthermore, TLR4-reporter HEK293 cells revealed that cytotoxicity of histone H4 was independent of TLR4 and NF-κB. In an in vivo rat model of I/R, HIPe significantly reduced infarct size. Conclusion Histones released from the myocardium are cytotoxic to cardiomyocytes, via a TLR4-independent mechanism. The targeting of extracellular histones provides a novel opportunity to limit cardiomyocyte death during I/R injury of the myocardium. Translational perspective Acute myocardial infarction causes lethal cardiomyocyte injury during ischaemia and reperfusion (I/R). New approaches are needed to prevent cardiomyocyte injury and limit final infarct size. We show that histones released from damaged cells, and histone-H4 in particular, causes rapid cardiomyocyte death during I/R. mCBS, a compounds targeting histones non-specifically, was cardioprotective in ex vivo rat hearts, while HIPe, a targeting histone H4 specifically, was cardioprotective in an in vivo rat model. HIPe may have potential as a therapeutic agent in the setting of acute myocardial infarction

Association of creatine kinase and skin toxicity in phase I trials of anticancer agents.

BACKGROUND: We investigated the association between skin rash and plasma creatine kinase (CK) levels in oncology phase I trials. METHODS: We analysed data from 295 patients treated at our institution within 25 phase I trials which included CK measurements in the protocol. Trials involved drugs targeting EGFR/HER2, m-TOR, VEGFR, SRC/ABL, aurora kinase, BRAF/MEK, PARP, CDK, A5B1 integrin, as well as oncolytic viruses and vascular disrupting agents. RESULTS: Creatine kinase measurements were available for 278 patients. The highest levels of plasma CK during the trial were seen among patients with Grade (G) 2/3 rash (median 249 U l(-1)) compared with G1 (median 81 U l(-1)) and no rash (median 55 U l(-1)) (P<0.001). There was a significant reduction in CK after the rash resolved (mean 264.2 vs 100.1; P=0.012) in 25 patients, where serial CK values were available. In vitro exposure of human keratinocytes to EGFR, MEK and a PI3Kinase/m-TOR inhibitor led to the increased expression of CK-brain and not CK-muscle or mitochondrial-CK. CONCLUSION: Plasma CK elevation is associated with development of skin rash caused by novel anticancer agents. This should be studied further to characterise different isoforms as this will change the way we report adverse events in oncology phase I clinical trials

Nonlinear Elasticity in Biological Gels

Unlike most synthetic materials, biological materials often stiffen as they are deformed. This nonlinear elastic response, critical for the physiological function of some tissues, has been documented since at least the 19th century, but the molecular structure and the design principles responsible for it are unknown. Current models for this response require geometrically complex ordered structures unique to each material. In this Article we show that a much simpler molecular theory accounts for strain stiffening in a wide range of molecularly distinct biopolymer gels formed from purified cytoskeletal and extracellular proteins. This theory shows that systems of semi-flexible chains such as filamentous proteins arranged in an open crosslinked meshwork invariably stiffen at low strains without the need for a specific architecture or multiple elements with different intrinsic stiffnesses.Comment: 23 pages, 5 figures, submitted to Natur

Congenital anomalies in low- and middle-income countries: the unborn child of global surgery.

Surgically correctable congenital anomalies cause a substantial burden of global morbidity and mortality. These anomalies disproportionately affect children in low- and middle-income countries (LMICs) due to sociocultural, economic, and structural factors that limit the accessibility and quality of pediatric surgery. While data from LMICs are sparse, available evidence suggests that the true human and financial cost of congenital anomalies is grossly underestimated and that pediatric surgery is a cost-effective intervention with the potential to avert significant premature mortality and lifelong disability

More intramedullary nails and arthroplasties for treatment of hip fractures in Sweden: Registry analysis of 144,607 patients, 1998–2007

Background and purpose The surgical methods for treatment of femoral neck fractures and trochanteric hip fractures vary. We describe the changes in Sweden over the period 1998-2007 and the regional differences in treatment. Patients and methods Data on 144,607 patients were drawn from the National Patient Register. Results The proportion of femoral neck fractures treated with arthroplasty increased from 10% in 1998 to 52% in 2007. The use of intramedullary (IM) nails for pertrochanteric fractures increased from 5% to 20%, at the expense of the use of different sliding hip screws. In subtrochanteric fractures, the use of IM nails increased from 32% to 72%. Re-admissions within 180 days due to hip complications were more common after internal fixation for femoral neck fractures than after arthroplasty, and more common after intramedullary nailing of pertrochanteric fractures than after use of sliding hip screws. Treatment varied substantially within Sweden, particularly regarding the use of IM nails. Interpretation An increase in arthroplasties reflects an evidence-based treatment rationale for femoral neck fractures, whereas the increase in use of IM nails in pertrochanteric fractures lacks scientific support. The geographic variations call for national treatment guidelines. Further clinical trials are needed to solve the treatment issues regarding per- and subtrochanteric fractures

Targeted 'Next-Generation' sequencing in anophthalmia and microphthalmia patients confirms SOX2, OTX2 and FOXE3 mutations

<p>Abstract</p> <p>Background</p> <p>Anophthalmia/microphthalmia (A/M) is caused by mutations in several different transcription factors, but mutations in each causative gene are relatively rare, emphasizing the need for a testing approach that screens multiple genes simultaneously. We used next-generation sequencing to screen 15 A/M patients for mutations in 9 pathogenic genes to evaluate this technology for screening in A/M.</p> <p>Methods</p> <p>We used a pooled sequencing design, together with custom single nucleotide polymorphism (SNP) calling software. We verified predicted sequence alterations using Sanger sequencing.</p> <p>Results</p> <p>We verified three mutations - c.542delC in S<it>OX2</it>, resulting in p.Pro181Argfs*22, p.Glu105X in <it>OTX2 </it>and p.Cys240X in <it>FOXE3</it>. We found several novel sequence alterations and SNPs that were likely to be non-pathogenic - p.Glu42Lys in <it>CRYBA4</it>, p.Val201Met in <it>FOXE3 </it>and p.Asp291Asn in <it>VSX2</it>. Our analysis methodology gave one false positive result comprising a mutation in <it>PAX6 </it>(c.1268A > T, predicting p.X423LeuextX*15) that was not verified by Sanger sequencing. We also failed to detect one 20 base pair (bp) deletion and one 3 bp duplication in <it>SOX2</it>.</p> <p>Conclusions</p> <p>Our results demonstrated the power of next-generation sequencing with pooled sample groups for the rapid screening of candidate genes for A/M as we were correctly able to identify disease-causing mutations. However, next-generation sequencing was less useful for small, intragenic deletions and duplications. We did not find mutations in 10/15 patients and conclude that there is a need for further gene discovery in A/M.</p