Live donor study – implications of kidney donation on cardiovascular risk with a focus on lipid parameters including lipoprotein a

In this prospective observational cohort study, we evaluate the change in cardiovascular risk parameters, with a focus on lipids, in live kidney donors 1 year post donation. Body mass index, systolic/diastolic blood pressure, kidney function (chromium-51 ethylenediaminetetraacetic acid estimated glomerular filtration) and lipid parameters were measured at baseline and 1 year. Data on 87 live kidney donors were collected. Body mass index increased from 26.5 ± 2.7 pre to 27.4 ± 3.0 kg/m post donation (p < 0.0001). Chromium-51 ethylenediaminetetraacetic acid estimated glomerular filtration decreased from 111.8 ± 20.0 pre to 72.1 ± 13.1 mL/min/1.73 m post donation (p < 0.0001). Serum triglyceride levels increased from 0.8 (interquartile range 0.6–1.3) pre to 1.0 mmol/L (interquartile range 0.7–1.6) post donation (p = 0.0004). Statin use increased from 11.5% pre to 21% post donation (p < 0.005). Low-density lipoprotein remained stable, and other lipids (high-density lipoprotein, apolipoprotein B and lipoprotein a) did not change post donation

Thrombotic Microangiopathy Associated with Pazopanib in a Kidney Transplant Recipient

Thrombotic microangiopathy (TMA) is characterised by abnormalities in the walls of arterioles and capillaries, precipitated by hereditary or acquired characteristics, and culminating in microvascular thrombosis because of dysregulated complement activity. A number of drugs can precipitate TMA, including vascular endothelial growth factor (VEGF) inhibitors, because of their effects on endothelial repair. Pazopanib is a VEGF inhibitor used for the treatment of renal cell carcinoma (RCC); it is uncommonly associated with TMA. A 52-year-old male, 5 years post his second kidney transplant secondary to immunoglobulin (Ig) A nephropathy, presented with hypertension, fluid overload, and worsening graft function (peak creatinine 275 μmol/L, baseline 130–160 μmol/L) and nephrotic range proteinuria 2 months after commencing pazopanib for metastatic RCC. His maintenance immunosuppression included ciclosporin, mycophenolate, and prednisolone. Haematological parameters were unremarkable. Allograft biopsy demonstrated glomerular and arteriolar changes consistent with chronic active TMA, with overlying features of borderline cellular rejection. He was treated with intravenous methylprednisolone 250 mg for 3 days and commenced on irbesartan 75 mg daily. Drug-induced TMA from pazopanib was suspected, particularly given the documented association with other tyrosine kinase inhibitors (TKIs). In consultation with his medical oncologist, pazopanib was ceased, and an alternate TKI cabozantinib was commenced. Serum creatinine remained &lt;200 μmol/L 3 months after admission. This is the first reported biopsy-proven case of TMA attributed to pazopanib in a kidney transplant recipient. With increasing clinical indications for and availability of TKIs, clinicians need to be aware of their association with TMA events in kidney transplant recipients, who are already susceptible to TMA due to abnormal vasculature, infectious triggers, ischaemia-reperfusion injury, and use of calcineurin inhibitor

Auditory spatial representations of the world are compressed in blind humans

Compared to sighted listeners, blind listeners often display enhanced auditory spatial abilities such as localization in azimuth. However, less is known about whether blind humans can accurately judge distance in extrapersonal space using auditory cues alone. Using virtualization techniques, we show that auditory spatial representations of the world beyond the peripersonal space of blind listeners are compressed compared to those for normally sighted controls. Blind participants overestimated the distance to nearby sources, and underestimated the distance to remote sound sources, in both reverberant and anechoic environments, and for speech, music and noise signals. Functions relating judged and actual virtual distance were well fitted by compressive power functions, indicating that the absence of visual information regarding the distance of sound sources may prevent accurate calibration of the distance information provided by auditory signals

Franchises lost and gained: post-coloniality and the development of women’s rights in Canada

The Canadian constitution is to some extent characterised by its focus on equality, and in particular gender equality. This development of women’s rights in Canada and the greater engagement of women as political actors is often presented as a steady linear process, moving forwards from post-enlightenment modernity. This article seeks to disturb this ‘discourse of the continuous,’ by using an analysis of the pre-confederation history of suffrage in Canada to both refute a simplistic linear view of women’s rights development and to argue for recognition of the Indigenous contribution to the history of women’s rights in Canada. The gain of franchise and suffrage movements in Canada in the late nineteenth and early twentieth century are, rightly, the focus of considerable study (Pauker 2015), This article takes an alternative perspective. Instead, it examines the exercise of earlier franchises in pre-confederation Canada. In particular it analyses why franchise was exercised more widely in Lower Canada and relates this to the context of the removal of franchises from women prior to confederation

The SUN Protein Mps3 Is Required for Spindle Pole Body Insertion into the Nuclear Membrane and Nuclear Envelope Homeostasis

The budding yeast spindle pole body (SPB) is anchored in the nuclear envelope so that it can simultaneously nucleate both nuclear and cytoplasmic microtubules. During SPB duplication, the newly formed SPB is inserted into the nuclear membrane. The mechanism of SPB insertion is poorly understood but likely involves the action of integral membrane proteins to mediate changes in the nuclear envelope itself, such as fusion of the inner and outer nuclear membranes. Analysis of the functional domains of the budding yeast SUN protein and SPB component Mps3 revealed that most regions are not essential for growth or SPB duplication under wild-type conditions. However, a novel dominant allele in the P-loop region, MPS3-G186K, displays defects in multiple steps in SPB duplication, including SPB insertion, indicating a previously unknown role for Mps3 in this step of SPB assembly. Characterization of the MPS3-G186K mutant by electron microscopy revealed severe over-proliferation of the inner nuclear membrane, which could be rescued by altering the characteristics of the nuclear envelope using both chemical and genetic methods. Lipid profiling revealed that cells lacking MPS3 contain abnormal amounts of certain types of polar and neutral lipids, and deletion or mutation of MPS3 can suppress growth defects associated with inhibition of sterol biosynthesis, suggesting that Mps3 directly affects lipid homeostasis. Therefore, we propose that Mps3 facilitates insertion of SPBs in the nuclear membrane by modulating nuclear envelope composition

‘Beyond policy tourism’: the international lived experience of cycling in the Netherlands and Canada

ABSTRACTAs more cities implement cycling infrastructure, there is a growing need to both learn best practices from other places through a detailed understanding of the lived and embodied experiences of cycling. However, this is rarely the case. On the one hand, planners and policymakers rely on incomplete (quantitative) data and policy tours that are unable to document the full extent of cycling or how it is experienced. While recent studies have expanded to include qualitative methods, they are predominantly conducted in one place, limiting our ability to draw international comparisons. The Netherlands is a popular destination for such tours and is generally regarded as one of the best places in the world for cycling. But what about people who, for a variety of reasons, have lived in different countries? Their knowledge, experiences and reflections on cycling are rarely featured in planning. To redress this, we interviewed participants who have international experience, capturing beyond aspects of policy tourism, illuminating how: (1) mixed land-use patterns, (2) incentivizing cycling as a mode choice, and (3) cycle networks and safety are vital to cycling participation. We advance the cycling research agenda by examining these findings and proposing changes best suited to low-cycling cities