Patient involvement in selection of immunosuppressive regimen following transplantation.

Transplantation has made a considerable difference to the lives of many patients. However, feedback from patients indicates that although having a transplant is a hugely positive experience, having to take medications indefinitely is one of the biggest challenges. An ideal scenario would be no medications following a transplant. A compromise would be a minimal number of medications, with minimal restrictions and as simple a regimen as possible. Although there is considerable research going into fine-tuning the management of the immune response to a transplant, to date there is no universal regimen that enables patients to remain free of immunosuppressant medications, making adherence paramount to maintain long-term allograft survival. This paper reviews the available immunosuppressant regimens and factors influencing choice from both the clinician's and the patient's perspective. Factors influencing the decision-making process, such as quality of life for patients, their satisfaction, acceptability, and adherence uptake are reviewed. We conclude with a further assessment of patient choice as a factor in regimen selection, its impact on adherence, and its implications

A phenomenological description of BslA assemblies across multiple length scales

Intrinsically interfacially active proteins have garnered considerable interest recently owing to their potential use in a range of materials applications. Notably, the fungal hydrophobins are known to form robust and well-organized surface layers with high mechanical strength. Recently, it was shown that the bacterial biofilm protein BslA also forms highly elastic surface layers at interfaces. Here we describe several self-assembled structures formed by BslA, both at interfaces and in bulk solution, over a range of length scales spanning from nanometres to millimetres. First, we observe transiently stable and highly elongated air bubbles formed in agitated BslA samples. We study their behaviour in a range of solution conditions and hypothesize that their dissipation is a consequence of the slow adsorption kinetics of BslA to an air–water interface. Second, we describe elongated tubules formed by BslA interfacial films when shear stresses are applied in both a Langmuir trough and a rheometer. These structures bear a striking resemblance, although much larger in scale, to the elongated air bubbles formed during agitation. Taken together, this knowledge will better inform the conditions and applications of how BslA can be used in the stabilization of multi-phase materials. This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’

Integrin-linked kinase can facilitate syncytialization and hormonal differentiation of the human trophoblast-derived BeWo cell line

<p>Abstract</p> <p>Background</p> <p>In the fusion pathway of trophoblast differentiation, stem villous cytotrophoblast cells proliferate and daughter cells differentiate and fuse with existing syncytiotrophoblast to maintain the multi-nucleated layer. Integrin-linked kinase (ILK) is highly expressed in 1st and 2nd trimester villous cytotrophoblast cells, yet barely detectable in syncytiotrophoblast, thus we examined the potential role of ILK in aiding trophoblast fusion.</p> <p>Methods</p> <p>The temporal/spatial expression and activity of ILK were determined in BeWo cells undergoing syncytialization by immunoblot and immunofluorescence analyses. BeWo cells were also transfected with pEGFP expression vectors containing wildtype or two mutant ILK cDNA constructs. The incidence of cell fusion in transfected cells grown under syncytialization conditions was then scored by the presence or absence of E-cadherin immunostaining. Beta-hCG expression in transfected cells, a marker of syncytiotrophoblast hormonal differentiation, was also similarly assessed.</p> <p>Results</p> <p>ILK catalytic activity increased and ILK began to increasingly localize to BeWo cell nuclei during syncytialization in correlation with increased pAkt and Snail protein expression. Syncytialization was also significantly elevated (p < 0.05) in BeWo cells expressing constitutively active (ca)-ILK vs cells containing empty vector or dn-ILK. Furthermore, cytoplasmic Beta-hCG expression markedly increased (p < 0.05) in cells expressing wt- and ca-ILK.</p> <p>Conclusion</p> <p>ILK-facilitated syncytialization is dependent, at least in part, on ILK catalytic activity while hormonal differentiation appears dependent on both ILK-associated protein interactions and catalytic activity. This study demonstrates that ILK plays a novel role in BeWo syncytialization and differentiation, perhaps through an ILK-Akt-Snail pathway, and implicates ILK in the same process in villous cytotrophoblasts in vivo.</p

Optimization of double pulse pumping for Ni-like Sm x-ray lasers

We report a systematic study of double pulse pumping of the Ni-like Sm x-ray laser at 73 Angstrom, currently the shortest wavelength saturated x-ray laser. It is found that the Sm x-ray laser output can change by orders of magnitude when the intensity ratio of the pumping pulses and their relative delay are varied. Optimum pumping conditions are found and interpreted in terms of a simple model. (C) 1999 American Institute of Physics. [S0021-8979(99)07102-9]

Differential involvement of Na(+),K(+)-ATPase isozymes in preimplantation development of the mouse.

Na(+),K(+)-ATPase plays an essential role in mammalian blastocoel formation (cavitation) by driving trans-epithelial sodium transport. Previously, the alpha1 and beta1 subunit isoforms of this enzyme were identified in preimplantation mouse embryos and were assumed to be responsible for this function. Here we show that mRNAs encoding an additional alpha subunit isoform (alpha3) and the remaining two beta subunit isoforms are also present in preimplantation embryos. Whereas alpha3 mRNA accumulates between the four-cell and the blastocyst stages and thus results from embryonic transcription, the same could not be demonstrated for beta2 and beta3 mRNAs. Immunoblot analyses confirmed that these subunits are present in cavitating embryos. Using confocal immunofluorescence microscopy we found that alpha1 and beta1 subunits are concentrated in the basolateral membranes of the trophectoderm while being equally distributed in plasma membranes of the inner cell mass. In contrast, alpha3, beta2, and beta3 subunits were not detected in plasma membranes. Our current assessment, therefore, is that as many as six isozymes of Na(+),K(+)-ATPase could be involved in preimplantation development although it is primarily the alpha1beta1 isozyme that is responsible for blastocoel formation. Our findings imply that the regulation of sodium transport within the preimplantation mouse embryo is more complex than had been appreciated

<i>Bacillus subtilis</i> matrix protein TasA is interfacially active, but BslA dominates interfacial film properties

Microbial growth often occurs within multicellular communities called biofilms, where cells are enveloped by a protective extracellular matrix. Bacillus subtilis serves as a model organism for biofilm research and produces two crucial secreted proteins, BslA and TasA, vital for biofilm matrix formation. BslA exhibits surface-active properties, spontaneously self-assembling at hydrophobic/hydrophilic interfaces to form an elastic protein film which renders B. subtilis biofilm surfaces water-repellent. TasA is traditionally considered a fiber-forming protein with multiple matrix-related functions. In our current study, we investigate whether TasA also possesses interfacial properties and whether it has any impact on BslA’s ability to form an interfacial protein film. Our research demonstrates that TasA indeed exhibits interfacial activity, partitioning to hydrophobic/hydrophilic interfaces, stabilizing emulsions, and forming an interfacial protein film. Interestingly, TasA undergoes interface-induced restructuring similar to BslA, showing an increase in β-strand secondary structure. Unlike BslA, TasA rapidly reaches the interface and forms non-elastic films that rapidly relax under pressure. Through mixed protein pendant drop experiments, we assess the influence of TasA on BslA film formation, revealing that TasA and other surface-active molecules can compete for interface space, potentially preventing BslA from forming a stable elastic film. This raises a critical question: how does BslA self-assemble to form the hydrophobic "raincoat" observed in biofilms in the presence of other potentially surface-active species? We propose a model wherein surface-active molecules, including TasA, initially compete with BslA for interface space. However, under lateral compression or pressure, BslA retains its position, expelling other molecules into the bulk. This resilience at the interface may result from structural rearrangements and lateral interactions between BslA subunits. This combined mechanism likely explains BslA's role in forming a stable film integral to B. subtilis biofilm hydrophobicity

Optical Coherence Tomography Findings After Childhood Lensectomy

Purpose: To explore the impact of childhood lensectomy on posterior segment development. / Methods: Cross-sectional observational study at children's eye clinics at a tertiary referral center in London, UK. We included 45 children age 4 to 16 years with healthy eyes and 38 who had undergone lensectomy. We acquired posterior segment optical coherence tomography scans of both eyes. We used parametric and nonparametric tests in SPSS24 for the comparison of parameters between groups and within individuals; a P value less than 0.05 was considered significant. The main outcome measures were foveal pit depth and subfoveal choroidal thickness (CT). Secondary outcomes were inner and outer ring CT and photoreceptor layer parameters, macular and peripapillary retinal nerve fiber layer thickness. / Results: Foveal pit depth and subfoveal CT are significantly reduced in eyes that have undergone lensectomy compared with nonoperated eyes. Inner ring CT and outer ring CT are reduced. Foveal inner retinal layer thickness is increased. Mean inner retinal and outer nuclear layer thickness are not affected. / Conclusions: Childhood lensectomy is associated with a reduction in developmental foveal pit deepening and lack of developmental thickening of the posterior choroid. Mechanical and optical disruption of foveal and subfoveal choroidal development may affect structural foveal development after childhood lensectomy

Supersonic strain front driven by a dense electron-hole plasma

We study coherent strain in (001) Ge generated by an ultrafast laser-initiated high density electron-hole plasma. The resultant coherent pulse is probed by time-resolved x-ray diffraction through changes in the anomalous transmission. The acoustic pulse front is driven by ambipolar diffusion of the electron-hole plasma and propagates into the crystal at supersonic speeds. Simulations of the strain including electron-phonon coupling, modified by carrier diffusion and Auger recombination, are in good agreement with the observed dynamics.Comment: 4 pages, 6 figure

A realist review of medication optimisation of community dwelling service users with serious mental illness

Background: Severe mental illness (SMI) incorporates schizophrenia, bipolar disorder, non-organic psychosis, personality disorder or any other severe and enduring mental health illness. Medication, particularly antipsychotics and mood stabilisers are the main treatment options. Medication optimisation is a hallmark of medication safety, characterised by the use of collaborative, person-centred approaches. There is very little published research describing medication optimisation with people living with SMI. Objective: Published literature and two stakeholder groups were employed to answer: What works for whom and in what circumstances to optimise medication use with people living with SMI in the community? Methods: A five-stage realist review was co-conducted with a lived experience group of individuals living with SMI and a practitioner group caring for individuals with SMI. An initial programme theory was developed. A formal literature search was conducted across eight bibliographic databases, and literature were screened for relevance to programme theory refinement. In total 60 papers contributed to the review. 42 papers were from the original database search with 18 papers identified from additional database searches and citation searches conducted based on stakeholder recommendations. Results: Our programme theory represents a continuum from a service user’s initial diagnosis of SMI to therapeutic alliance development with practitioners, followed by mutual exchange of information, shared decision-making and medication optimisation. Accompanying the programme theory are 11 context-mechanism-outcome configurations that propose evidence-informed contextual factors and mechanisms that either facilitate or impede medication optimisation. Two mid-range theories highlighted in this review are supported decision-making and trust formation. Conclusions: Supported decision-making and trust are foundational to overcoming stigma and establishing ‘safety’ and comfort between service users and practitioners. Avenues for future research include the influence of stigma and equity across cultural and ethnic groups with individuals with SMI; and use of trained supports, such as peer support workers. PROSPERO registration number: CRD42021280980