Hair follicle dermal cells: a morphological, behavioural and molecular study

Anatomy and smooth muscle a-actin expression in hair follicles from a variety of animal species (Mink, Polecat, Meerkat, Grey squirrel and stoat) was investigated. Smooth muscle ɑ-actin expression was related to follicle activity. Expression was greatest during anagen, with a marked reduction in expression during telogen. Follicular dermal cells were cultured from the above animal species. In vitro grey squirrel dermal papilla (DP) and dermal sheath (DS) cells both expressed smooth muscle ɑ -actin. Rat dermal papilla cell in vitro aggregative behaviour was characterized, by proliferation, chemotactic and molecular studies. Aggregation behaviour in these cells was not attributed to focal proliferation. However, fluctuations in cell motility correlated with the aggregation process, with the greatest motility between subconfluent and clumped cells. Motility was terminated within the clumped cells. Furthermore, DP cells in vitro secreted molecules that enhancer! motility in subconfluent DP cells and a variety of other cell types. As yet the type and specificity of this medium borne component is unknown. TGFP, bFGF and aFGF were all used as a comparison to the unknown molecule, however migration was rarely similar in magnitude to the response of the DP cell medium. Mouse cDNA probes of BMP 2 and BMP 4 were used to isolate rat homologues from a cDNA library. Wholemount in situ hybridization of BMP 4 expression was consistent with the data in the mouse, however BMP 4 was also expressed in adult rat telogen vibrissae. Molecular expression within in vitro DP cells was studied using a differential screen of a cDNA library. A number of clumped DP specific clones were differentially expressed, one of which having high homology with migration inhibitory factor. These results are discussed, and a hypothetical model is proposed to describe how DP aggregation occurs with reference to dermal condensation in vivo

Granulocyte macrophage colony-stimulating factor receptor α expression and its targeting in antigen-induced arthritis and inflammation

A Representative FACS plots showing Ly6G and Ly6C staining of CD45+ myeloid populations in the AIA knee joint. F4/80intSSchi eosinophils (Eos), F4/80+CD11c+MHCII+ Mo-DCs (R1), F4/80+CD11c-MHCII+ macrophages (Macs) (R2), F4/80+CD11c-MHCII- macrophages (R3), F4/80-CD11c+ MHCII+ cDCs, F4/80-CD11b+Ly6G+ neutrophils, which are also Ly6C+, and F4/80-CD11b+Ly6G-SScloLy6C+/- monocytes. B Representative FACS plots of CD45+ myeloid populations in the AIA knee joint showing Ly6G+ neutrophils are CD64- and F4/80+ macrophages/Mo-DCs are CD64+. (PDF 235 kb

The association between socioeconomic position and the symptoms and concerns of hospital inpatients seen by specialist palliative care: Analysis of routinely collected patient data

Background: Understanding how socioeconomic position influences the symptoms and concerns of patients approaching the end of life is important for planning more equitable care. Data on this relationship is lacking, particularly for patients with non-cancer conditions. Aim: To analyse the association between socioeconomic position and the symptoms and concerns of older adult patients seen by specialist palliative care. Design: Secondary analysis of cross-sectional, routinely collected electronic patient data. We used multivariable linear regression with robust standard errors, to predict scores on the three subscales of the Integrated Palliative care Outcome Scale (IPOS; physical symptoms, emotional symptoms and communication and practical concerns) based on patient level of deprivation, measured using Index of Multiple Deprivation. Setting/participants: Consecutive inpatients aged 60 years and over, seen by specialist palliative care at two large teaching hospitals in London between 1st January 2016 and 31st December 2019. Results: Seven thousand eight hundred and sixty patients were included, 38.3% had cancer. After adjusting for demographic and clinical characteristics, patients living in the most deprived areas had higher (worse) predicted mean scores on the communication and practical subscale than patients living in the least deprived areas, 5.38 (95% CI: 5.10, 5.65) compared to 4.82 (4.62, 5.02) respectively. This effect of deprivation diminished with increasing age. Deprivation was not associated with scores on the physical or emotional symptoms subscales. Conclusions: Targetting resources to address practical and communication concerns could be a strategy to reduce inequalities. Further research in different hospitals and across different settings using patient centred outcome measures is needed to examine inequalities

Socioeconomic position and use of hospital-based care towards the end of life: a mediation analysis using the English Longitudinal Study of Ageing

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Many patients prefer to avoid hospital-based care towards the end of life, yet hospitalisation is common and more likely for people with low socioeconomic position. The reasons underlying this socioeconomic inequality are not well understood. This study investigated health, service access, and social support as potential mediating pathways between socioeconomic position and receipt of hospital-based care towards the end of life. Methods: For this observational cohort study, we included deceased participants from the nationally representative English Longitudinal Study of Ageing of people aged 50 years or older in England. We used a multiple mediation model with age-adjusted and gender-adjusted probit regression to estimate the direct effect of socioeconomic position (measured by wealth and education) on death in hospital and three or more hospital admissions in the last 2 years of life, and the indirect effects of socioeconomic position via three mediators: health and function, access to health-care services, and social support. Findings: 737 participants were included (314 [42·6%] female, 423 [57·4%] male), with a median age at death of 78 years (IQR 71–85). For death in hospital, higher wealth had a direct negative effect (probit coefficient −0·16, 95% CI −0·25 to −0·06), which was not mediated by any of the pathways tested. For frequent hospital admissions, health and function mediated the effect of wealth (−0·04, −0·08 to −0·01), accounting for 34·6% of the total negative effect of higher wealth (−0·13, −0·23 to −0·02). Higher wealth was associated with better health and function (0·25, 0·18 to 0·33). Education was associated with the outcomes only indirectly via wealth. Interpretation: Our findings suggest that worse health and function could partly explain why people with lower wealth have more hospital admissions, highlighting the importance of socioeconomically driven health differences in explaining patterns of hospital use towards the end of life. The findings should raise awareness about the related risk factors of low wealth and worse health for patients approaching the end of life, and strengthen calls for resource allocation to be made on the basis of health need and socioeconomic profile. Funding: Dunhill Medical Trust Fellowship Grant (RTF74/0116)

Mathematical and computational models of drug transport in tumours

The ability to predict how far a drug will penetrate into the tumour microenvironment within its pharmacokinetic (PK) lifespan would provide valuable information about therapeutic response. As the PK profile is directly related to the route and schedule of drug administration, an in silico tool that can predict the drug administration schedule that results in optimal drug delivery to tumours would streamline clinical trial design. This paper investigates the application of mathematical and computational modelling techniques to help improve our understanding of the fundamental mechanisms underlying drug delivery, and compares the performance of a simple model with more complex approaches. Three models of drug transport are developed, all based on the same drug binding model and parametrized by bespoke in vitro experiments. Their predictions, compared for a ‘tumour cord’ geometry, are qualitatively and quantitatively similar. We assess the effect of varying the PK profile of the supplied drug, and the binding affinity of the drug to tumour cells, on the concentration of drug reaching cells and the accumulated exposure of cells to drug at arbitrary distances from a supplying blood vessel. This is a contribution towards developing a useful drug transport modelling tool for informing strategies for the treatment of tumour cells which are ‘pharmacokinetically resistant’ to chemotherapeutic strategies

The future of mammary stem cell biology: the power of in vivo transplants

The recent review by Smith and Medina [1] of in vivo transplantation models and their role in investigating mammary stem cell (MaSC) biology provides comprehensive coverage of the history and complexity of the ‘gold standard ’ MaSC assay in mice. This includes a description of the pioneering studies that showed that mammary epithelial outgrowths can be generated in cleared mammary fat pads transplanted with explants or admixtures of mammary cells [2]. However, this approach clearly does not lend itself to prospective analysis of isolated subpopulations in order to identify which cells possess in vivo regenerative activity. More recently, success in obtaining complex mammary gland structures from transplanted suspensions of single cells has now made this possible [3-7]. Moreover, the regenerated structures have been shown to contain daughter cells with the same in viv

Socioeconomic position and use of health care in the last year of life: a systematic review and meta-analysis

BACKGROUND: Low socioeconomic position (SEP) is recognized as a risk factor for worse health outcomes. How socioeconomic factors influence end-of-life care, and the magnitude of their effect, is not understood. This review aimed to synthesise and quantify the associations between measures of SEP and use of healthcare in the last year of life. METHODS AND FINDINGS: MEDLINE, EMBASE, PsycINFO, CINAHL, and ASSIA databases were searched without language restrictions from inception to 1 February 2019. We included empirical observational studies from high-income countries reporting an association between SEP (e.g., income, education, occupation, private medical insurance status, housing tenure, housing quality, or area-based deprivation) and place of death, plus use of acute care, specialist and nonspecialist end-of-life care, advance care planning, and quality of care in the last year of life. Methodological quality was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS). The overall strength and direction of associations was summarised, and where sufficient comparable data were available, adjusted odds ratios (ORs) were pooled and dose-response meta-regression performed. A total of 209 studies were included (mean NOS quality score of 4.8); 112 high- to medium-quality observational studies were used in the meta-synthesis and meta-analysis (53.5% from North America, 31.0% from Europe, 8.5% from Australia, and 7.0% from Asia). Compared to people living in the least deprived neighbourhoods, people living in the most deprived neighbourhoods were more likely to die in hospital versus home (OR 1.30, 95% CI 1.23-1.38, p < 0.001), to receive acute hospital-based care in the last 3 months of life (OR 1.16, 95% CI 1.08-1.25, p < 0.001), and to not receive specialist palliative care (OR 1.13, 95% CI 1.07-1.19, p < 0.001). For every quintile increase in area deprivation, hospital versus home death was more likely (OR 1.07, 95% CI 1.05-1.08, p < 0.001), and not receiving specialist palliative care was more likely (OR 1.03, 95% CI 1.02-1.05, p < 0.001). Compared to the most educated (qualifications or years of education completed), the least educated people were more likely to not receive specialist palliative care (OR 1.26, 95% CI 1.07-1.49, p = 0.005). The observational nature of the studies included and the focus on high-income countries limit the conclusions of this review. CONCLUSIONS: In high-income countries, low SEP is a risk factor for hospital death as well as other indicators of potentially poor-quality end-of-life care, with evidence of a dose response indicating that inequality persists across the social stratum. These findings should stimulate widespread efforts to reduce socioeconomic inequality towards the end of life

Factors associated with transition from community settings to hospital as place of death for adults aged 75 years or older: a population-based mortality follow-back survey

Objective: To identify factors associated with end of life (EoL) transition from usual place of care to hospital as place of death for people aged 75 years or older (75+). Design: Population-based mortality follow-back survey. Setting: Deaths over six months in 2012 in two unitary authorities in England, covering 800 square miles with over one million residents. Participants: A random sample of people aged 75+ who died in a care home or hospital and all those who died at home or in a hospice unit. Cases were identified from death registrations. The person who registered the death (a relative for 98.9%) completed the survey. Measurements: Our main outcome was EoL transition to hospital as place of death versus no EoL transition to hospital. We used multivariable modified Poisson regression to examine factors (illness, demographic and environmental) related to EoL transition to hospital. Results: 443/882 (50.2%) responded, describing the care received by people who died from mostly non-malignant conditions (76.3%) at mean age 87.4 years (SD= 6.4). 32.3% transitioned to hospital and died there (n=146). Transition was more likely in respiratory disease compared to cancer (Prevalence Ratio [PR] =2.07, 95%CI 1.42- 3.01) and for people with severe breathlessness (PR=1.96, 95%CI 1.12-3.43). Transition was less likely if EoL preferences had been discussed with a healthcare professional (PR=0.60, 95%CI 0.42-0.88) and when there was a key healthcare professional (PR=0.74, 95%CI 0.58-0.95). Conclusion: To reduce EoL transition to hospital for older people this study suggests a need to improve the symptom management of breathlessness in the community and better access to a key healthcare professional skilled in coordinating care, communication, facilitating complex discussions and in planning for future care

It's all in the details: methods in breast development and cancer

The inaugural European Network for Breast Development and Cancer (ENBDC) meeting on 'Methods in Mammary Gland Development and Cancer' was held in Weggis, Switzerland last April. The goal was to discuss the details of techniques used to study mammary gland biology and tumourigenesis. Highlights of this meeting included the use of four-colour fluorescence for protein co-localisation in tissue microarrays, genome analysis at single cell resolution, technical issues in the isolation of normal and tumour stem cells, and the use of mouse models and mammary gland transplantations to elucidate gene function in mammary development and to study drug resistance in breast cancer