Small-cell lung cancer (SCLC), an aggressive neuroendocrine tumor with early dissemination and dismal prognosis, accounts for 15-20% of lung cancer cases and ∼200,000 deaths each year. Most cases are ...inoperable, and biopsies to investigate SCLC biology are rarely obtainable. Circulating tumor cells (CTCs), which are prevalent in SCLC, present a readily accessible 'liquid biopsy'. Here we show that CTCs from patients with either chemosensitive or chemorefractory SCLC are tumorigenic in immune-compromised mice, and the resultant CTC-derived explants (CDXs) mirror the donor patient's response to platinum and etoposide chemotherapy. Genomic analysis of isolated CTCs revealed considerable similarity to the corresponding CDX. Most marked differences were observed between CDXs from patients with different clinical outcomes. These data demonstrate that CTC molecular analysis via serial blood sampling could facilitate delivery of personalized medicine for SCLC. CDXs are readily passaged, and these unique mouse models provide tractable systems for therapy testing and understanding drug resistance mechanisms.
Foot Function Index (FFI) is a valid and reliable outcome measure, which is widely used to measure the foot and ankle functional level and disorders. Until now, no validated Arabic version of the FFI ...is available. This study was conducted at a tertiary care hospital in Riyadh, Saudi Arabia. The purpose of this project was to translate and adapt the FFI into Arabic and to evaluate its psychometric properties of validity and reliability.
The study consisted of two phases. The first phase was the translation and cultural adaptation of the FFI to Arabic. The next phase involved, testing the psychometric properties of the Arabic version of the FFI on a sample of 50 consecutive participants which included internal consistency, test-retest reliability, floor and ceiling effects and construct validity.
The mean age of the study participants was 38 ± 12.94 years. Both the genders were evenly enrolled with 50% of the participants as male and 50% as female. Majority of them complained of plantar fasciopathy (32%) followed by pes planus (22%) and ankle sprain (18%). The scores of FFI-Ar were normally distributed, confirmed by a significant Shapiro-Wilk test. The mean value of FFI-Ar total score was 47.73 ± 19.85. There were no floor or ceiling effects seen in any of the subscales and total score. The internal consistency was good with the Cronbach's alpha value of 0.882, 0.936 and 0.850 for the pain, disability and activity limitation subscales, respectively. The reproducibility of the FFI-Ar was analysed by intra-class correlation coefficient which revealed good to excellent test-retest reliability. A significant correlation was found between FFI-Ar and SF-36 and numeric rating scale (NRS) confirming its construct validity.
The FFI-Arabic version showed good validity and reliability in patients with foot and ankle problems. This tool can be used in usual practice and research for analysing foot and ankle disorders in Arabic-speaking people.
Although profiling of RNA in single cells has broadened our understanding of development, cancer biology and mechanisms of disease dissemination, it requires the development of reliable and flexible ...methods. Here we demonstrate that the EpiStem RNA-Amp™ methodology reproducibly generates microgram amounts of cDNA suitable for RNA-Seq, RT-qPCR arrays and Microarray analysis.
Initial experiments compared amplified cDNA generated by three commercial RNA-Amplification protocols (Miltenyi μMACS™ SuperAmp™, NuGEN Ovation® One-Direct System and EpiStem RNA-Amp™) applied to single cell equivalent levels of RNA (25-50 pg) using Affymetrix arrays. The EpiStem RNA-Amp™ kit exhibited the highest sensitivity and was therefore chosen for further testing. A comparison of Affymetrix array data from RNA-Amp™ cDNA generated from single MCF7 and MCF10A cells to reference controls of unamplified cDNA revealed a high degree of concordance. To assess the flexibility of the amplification system single cell RNA-Amp™ cDNA was also analysed using RNA-Seq and high-density qPCR, and showed strong cross-platform correlations. To exemplify the approach we used the system to analyse RNA profiles of small populations of rare cancer initiating cells (CICs) derived from a NSCLC patient-derived xenograft. RNA-Seq analysis was able to identify transcriptional differences in distinct subsets of CIC, with one group potentially enriched for metastasis formation. Pathway analysis revealed that the distinct transcriptional signatures demonstrated in the CIC subpopulations were significantly correlated with published stem-cell and epithelial-mesenchymal transition signatures.
The combined results confirm the sensitivity and flexibility of the RNA-Amp™ method and demonstrate the suitability of the approach for identifying clinically relevant signatures in rare, biologically important cell populations.
The use of a marker ball in digital templating for hip arthroplasty is a well-established method of preoperative planning and is used to overcome the inherent magnification in plain film radiographs. ...Our hospital policy is to place a marker ball in all anteroposterior pelvic films taken in the emergency department (ED) which have been requested for suspected neck of femur fractures. We carried out a baseline measurement followed by three Plan-Do-Study-Act cycles for all pelvic films taken in ED during July 2016, November 2016, February 2017 and November 2017. Interventions between the baseline measurement and cycle 1 were to educate the lead radiographer and publish the results in the radiology newsletter, and between cycles 1 and 2 was to run a teaching session for radiographers, display posters in the X-ray department and place an electronic prompt on the X-ray machine to alert them of the need to place a marker ball in the X-ray field. Cycle 3 looked to see if improvements were sustained. 16/81 (20%) radiographs complied with the policy in our baseline measurement; 25/51 (46%, p=0.002) in cycle 1; 40/54 (74%, p=0.0056) in cycle 2; and 48/63 (76%) in cycle 3. Our quality improvement project led to large improvements in clinical practice through straightforward, small, but appropriately targeted interventions. Stakeholder management is key to successfully implementing change. The next step is to switch from the VoyantMark to the KingMark marker ball, as it has greater accuracy of templating and is also easier to place within the field of an X-ray.
This paper examines the processes involved in a participatory inclusive research project in Liverpool and Merseyside, UK. The project involved 25 people with learning difficulties - the Heritage ...Forum - visiting 13 cultural and heritage sites on more than 50 occasions across a 15-month period. The research provides a much needed resource at a time when there is a lack of provision for, and research into, the intellectual accessibility of cultural and heritage sites in the UK and globally. This paper details the research approach taken by the Heritage Forum, providing a flexible protocol about ways of working with groups and individuals with learning difficulties. It also reports on the Heritage Forum's general findings about the cultural and heritage sites, providing some initial guidance about how to best include this diverse population.
This thesis examines the role of national defence in British parliamentary politics between 1794 and 1812. It suggests that previous analyses of the late eighteenth-century political milieu ...insufficiently explore the impact of war on the structure of the state. Work by J.E. Cookson, Linda Colley, J.C.D. Clark, and Paul Langford depicts a decentralised state that had little direct involvement in developing a popular “British” patriotism. Here I argue that the threat of a potential French invasion during the wars against Revolutionary and Napoleonic France provoked a drive for centralisation. Nearly all the defence measures enacted during the period gave the government a much greater degree of control over British manpower and resources. The readiness of successive governments to involve large sections of the nation in the war effort through military service, financial contributions, and appeals to the British “spirit”, resulted in a much more inclusive sense of citizenship in which questions of national participation and political franchise were unlinked. National identity was also affected, and the focus on military defence of the British Isles influenced political attitudes towards the regular army. By 1810, however, the nation was disillusioned by the lengthy struggle with France. The result of lingering political weakness was that attention shifted from national defence onto domestic corruption and venality. The aftermath of the Irish Act of Union, too, demonstrated the limits of attempts to centralise the policy of the whole United Kingdom. Significantly, however, the debates over the relationship between the centre and the localities in the 1830s and 1840s, and the response to a new French invasion threat in the 1850s and 1860s, revived themes addressed during the 1790s and 1800s. The political reaction to the invasion threats between 1794 and 1812 ultimately had more in common with a Victorian state bureaucracy than an eighteenth-century ancien régime.
Purpose
Elective operations including surgeries for breast cancer were significantly reduced during the height of the surge of COVID-19 cases in Massachusetts. The safety of performing breast ...reconstruction during the pandemic was unknown. This study aims to review the safety of performing mastectomy with immediate breast reconstruction during the first COVID-19 surge in Massachusetts.
Methods
A retrospective chart review of patients who underwent mastectomy with immediate breast reconstruction by Massachusetts General Hospital breast and plastic surgeons immediately preceding and during the COVID-19 pandemic was performed.
Results
Thirty patients (34 breasts) underwent mastectomies with immediate breast reconstruction during the COVID-19 restriction period in Massachusetts. Most reconstructions were unilateral. All reconstructions were performed with implants or expanders, and no autologous reconstructions were performed. Two patients (2 breasts) had operative complications. The complication rate during the pandemic was similar to the complication rate pre-pandemic. No patients or surgeons experienced symptoms or positive COVID-19 tests. Over 90% of patients were discharged the same day.
Conclusion
Prosthetic breast reconstruction was able to be performed safely during the height of the COVID-19 pandemic surge in Massachusetts. Strict screening protocols, proper use of personal protective equipment, and same-day discharge when possible are essential for patient and surgeon safety during the pandemic.
Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination ...complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens. Here, we report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail 'triplex' strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 p53(++), causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli.
This study investigated the predictive role of psychological flexibility on long-term mTBI outcomes.
Adults with mTBI (N = 147) completed a context specific measure of psychological flexibility, ...(AAQ-ABI), psychological distress, and mTBI outcomes at less than three months post injury (M = 6.02 weeks after injury) and 6 months later (N = 102). Structural equation modelling examined the mediating effects of psychological flexibility on psychological distress and mTBI outcomes at six months. The direct effect of psychological flexibility at less than three months on mTBI outcomes at six months was entered into the model, plus pre-injury and injury risk factors.
The theoretically derived model had good overall fit (χ2 = 1.42; p = 0.09; NFI = 0.95; TLI = 0.95; CFI = 0.98 and RMSEA = 0.06). Psychological flexibility at less than 3 months was directly significantly related to psychological distress and post-concussion symptoms at six months. Psychological flexibility at 6 months significantly mediated the relationship between psychological distress and functional disability but not post-concussion symptoms at six months post injury.
The exploratory findings suggest that a context specific measure of psychological flexibility assessed acutely and in the chronic phase of recovery may predict longer-term mTBI outcomes.
Implications for Rehabilitation
Persistent post-concussion symptoms (PPCS) after mild traumatic brain injury (mTBI) can have a significant impact on wellbeing, functional status, and quality of life.
In this study, psychological flexibility early in recovery, was associated with higher levels of psychological distress and more severe post-concussion symptoms six months later.
Psychological flexibility at six months post-injury also mediated the relationship between psychological distress and functional disability.
A context specific measure of psychological flexibility may predict poorer long-term outcomes following mTBI.
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