Is PPARγ a Prospective Player in HIV-1-Associated Bone Disease?

Currently infection with the human immunodeficiency virus-1 (HIV-1) is in most instances a chronic disease that can be controlled by effective antiretroviral therapy (ART). However, chronic use of ART has been associated with a number of toxicities; including significant reductions in bone mineral density (BMD) and disorders of the fat metabolism. The peroxisome proliferator-activated receptor gamma (PPARγ) transcription factor is vital for the development and maintenance of mature and developing adipocytes. Alterations in PPARγ expression have been implicated as a factor in the mechanism of HIV-1-associated lipodystrophy. Both reduced BMD and lipodystrophy have been well described as complications of HIV-1 infection and treatment, and a question remains as to their interdependence. Interestingly, both adipocytes and osteoblasts are derived from a common precursor cell type; the mesenchymal stem cell. The possibility that dysregulation of PPARγ (and the subsequent effect on both osteoblastogenesis and adipogenesis) is a contributory factor in the lipid- and bone-abnormalities observed in HIV-1 infection and treatment has also been investigated. This review deals with the hypothesis that dysregulation of PPARγ may underpin the bone abnormalities associated with HIV-1 infection, and treats the current knowledge and prospective developments, in our understanding of PPARγ involvement in HIV-1-associated bone disease

‘I actually know that things will get better’:The many pathways to resilience of LGBTQIA+ youth in out-of-home care

Research on the lives of lesbian, gay, bisexual, transgender, queer, intersex, asexual and other forms of sexual identities and orientations (LGBTQIA+) youth in care has mainly examined their experiences from a risk-based approach, while few studies have explored their resilience experiences. Using in-depth interviews, the present study aims to illuminate the resilience experiences of 13 LGBTQIA+ young people in out-of-home care in the Netherlands. Four themes emerged from their narratives: relationships that support and empower; construction of a positive identity around their sexual orientation and gender identity and expression (SOGIE); community involvement and self-relying strategies. Our findings support the view of resilience as a complex process that shows at an individual, interpersonal and social level

The Explication Defence of Arguments from Reference

In a number of influential papers, Machery, Mallon, Nichols and Stich have presented a powerful critique of so-called arguments from reference, arguments that assume that a particular theory of reference is correct in order to establish a substantive conclusion. The critique is that, due to cross-cultural variation in semantic intuitions supposedly undermining the standard methodology for theorising about reference, the assumption that a theory of reference is correct is unjustified. I argue that the many extant responses to Machery et al.’s critique do little for the proponent of an argument from reference, as they do not show how to justify the problematic assumption. I then argue that it can in principle be justified by an appeal to Carnapian explication. I show how to apply the explication defence to arguments from reference given by Andreasen (for the biological reality of race) and by Churchland (against the existence of beliefs and desires)

Free volume dilatation in polymers by ortho-positronium

The possibility of positronium induced free volume cavity expansion in some polymers above the glass transition temperature was investigated using experimental positron annihilation lifetime data from the literature for polydimethylsiloxane, polyisobutylene, and polybutadiene as function of temperature. The results suggest that free volume sites can expand towards an equilibrium size, determined as the equilibrium Ps-bubble size defined earlier for low-molecular-weight liquids. The expansion can be explained by the increase of molecular mobility and hence decrease of relaxation times, which at the higher temperatures approach the o-Ps lifetimes. Nanoscale viscosities were estimated using Navier-Stokes equation and were found to be several orders of magnitude lower than the macroscopic viscosity at the same temperature

Is the biology of breast cancer changing? A study of hormone receptor status 1984-1986 and 1996-1997

Using archived tumours, those from 1984-1986 and 1996-1997 underwent immunohistochemistry for hormone receptors and grade analysis. A significant shift towards more ER-positive and low-grade disease was found; this appears to reflect screening practices, but could still influence survival

Poor survival outcomes in HER2 positive breast cancer patients with low grade, node negative tumours

We present a retrospective analysis on a cohort of low-grade, node-negative patients showing that human epidermal growth factor receptor 2 (HER2) status significantly affects the survival in this otherwise very good prognostic group. Our results provide support for the use of adjuvant trastuzumab in patients who are typically classified as having very good prognosis, not routinely offered standard chemotherapy, and who as such do not fit current UK prescribing guidelines for trastuzumab

Correction to: Clinical management of ageing people living with HIV in Europe: the view of the care providers.

info:eu-repo/semantics/publishedVersio

Excretion of Vancomycin-Resistant Enterococci by Wild Mammals

A survey of fecal samples found enterococcal excretion in 82% of 388 bank voles (Clethrionomys glareolus), 92% of 131 woodmice (Apodemus sylvaticus), and 75% of 165 badgers (Meles meles). Vancomycin-resistant enterococci, all Enterococcus faecium of vanA genotype, were excreted by 4.6% of the woodmice and 1.2% of the badgers, but by none of the bank voles

Circulating microparticles are increased amongst people presenting with HIV and advanced immune suppression in Malawi and correlate closely with arterial stiffness: a nested case control study

Background: We aimed to investigate whether circulating microparticle (CMPs) subsets were raised amongst people presenting with human immunodeficiency virus (HIV) and advanced immune suppression in Malawi, and whether they associated with arterial stiffness. Methods: Antiretroviral therapy (ART)-naïve adults with a new HIV diagnosis and CD4 <100 cells/µL had microparticle characterisation and carotid femoral Pulse Wave Velocity (cfPWV) at 2 weeks post ART initiation. HIV uninfected controls were matched on age, systolic blood pressure (BP) and diastolic BP in a 1:1 ratio.  Circulating microparticles were identified from platelet poor plasma and stained for endothelial, leucocyte, monocyte and platelet markers. Results: The median (IQ) total CMP count for 71 participants was 1 log higher in HIV compared to those without (p<0.0001) and was associated with arterial stiffness (spearman rho 0.47, p<0.001). In adjusted analysis, every log increase in circulating particles showed a 20% increase in cfPWV (95% confidence interval [CI] 4 – 40%, p=0.02). In terms of subsets, endothelial and platelet derived microparticles were most strongly associated with HIV. Endothelial derived E-selectin+ CMPs were 1.3log-fold higher and platelet derived CD42a+ CMPs were 1.4log-fold higher (both p<0.0001). Endothelial and platelet derived CMPs also correlated most closely with arterial stiffness (spearman rho: E-selectin+ 0.57 and CD42a 0.56, both p<0.0001). Conclusions: Circulating microparticles associate strongly with arterial stiffness among people living with HIV in Malawi. Endothelial damage and platelet microparticles are the predominant cell origin types and future translational studies could consider prioritising these pathways