Pelvic Lymph Node Dissection may be Limited on the Contralateral Side in Strictly Unilateral Bladder Cancer without Compromising Oncological Radicality.

Results of a dynamic multimodality mapping study showed no lymphatic drainage of the lateral bladder wall to the contralateral internal iliac region. To validate whether pathoanatomical mapping in bladder cancer (BC) patients can confirm these results. Between 01/2000 and 07/2013, 825 BC patients preoperatively staged ≥pT1 and without clinical signs of metastases (cN0 cM0) underwent extended pelvic lymph node dissection (ePLND) and radical cystectomy at our department. Of these patients, 23% (193/825) were lymph node (LN) positive in the pathological specimen; 26% (51/193) of this subgroup had strictly unilateral BC. Pathoanatomical mapping was used to retrospectively validate the distribution of LN involvement in these 51 patients. A median of 35 LNs were removed per patient (range: 13-80 LNs), with a median of 2 positive LNs (range: 1-14 LNs). 27% (14/51) of patients presented with LN metastases on the contralateral side. No positive LNs were found in the contralateral internal iliac region or the contralateral fossa of Marcille. 10% (5/51) of patients had LN metastases only on the contralateral side without evidence of metastases on the tumor-bearing side. Our findings corroborate the data of a dynamic mapping study showing bilateral lymphatic drainage in almost one third of patients with strictly unilateral BC, but no lymphatic drainage from the lateral bladder wall to the contralateral internal iliac region. If prospective studies confirm these results, the contralateral internal iliac region may be omitted during ePLND in patients with strictly unilateral BC

Defining pathways to healthy sustainable urban development

Goals and pathways to achieve sustainable urban development have multiple interlinkages with human health and wellbeing. However, these interlinkages have not been examined in depth in recent discussions on urban sustainability and global urban science. This paper fills that gap by elaborating in detail the multiple links between urban sustainability and human health and by mapping research gaps at the interface of health and urban sustainability sciences. As researchers from a broad range of disciplines, we aimed to: 1) define the process of urbanization, highlighting distinctions from related concepts to support improved conceptual rigour in health research; 2) review the evidence linking health with urbanization, urbanicity, and cities and identify cross-cutting issues; and 3) highlight new research approaches needed to study complex urban systems and their links with health. This novel, comprehensive knowledge synthesis addresses issue of interest across multiple disciplines. Our review of concepts of urban development should be of particular value to researchers and practitioners in the health sciences, while our review of the links between urban environments and health should be of particular interest to those outside of public health. We identify specific actions to promote health through sustainable urban development that leaves no one behind, including: integrated planning; evidence-informed policy-making; and monitoring the implementation of policies. We also highlight the critical role of effective governance and equity-driven planning in progress towards sustainable, healthy, and just urban development

LRP10 interacts with SORL1 in the intracellular vesicle trafficking pathway in non-neuronal brain cells and localises to Lewy bodies in Parkinson's disease and dementia with Lewy bodies

Loss-of-function variants in the low-density lipoprotein receptor-related protein 10 (LRP10) gene have been associated with autosomal-dominant Parkinson's disease (PD), PD dementia, and dementia with Lewy bodies (DLB). Moreover, LRP10 variants have been found in individuals diagnosed with progressive supranuclear palsy and amyotrophic lateral sclerosis. Despite this genetic evidence, little is known about the expression and function of LRP10 protein in the human brain under physiological or pathological conditions. To better understand how LRP10 variants lead to neurodegeneration, we first performed an in-depth characterisation of LRP10 expression in post-mortem brains and human-induced pluripotent stem cell (iPSC)-derived astrocytes and neurons from control subjects. In adult human brain, LRP10 is mainly expressed in astrocytes and neurovasculature but undetectable in neurons. Similarly, LRP10 is highly expressed in iPSC-derived astrocytes but cannot be observed in iPSC-derived neurons. In astrocytes, LRP10 is present at trans-Golgi network, plasma membrane, retromer, and early endosomes. Interestingly, LRP10 also partially co-localises and interacts with sortilin-related receptor 1 (SORL1). Furthermore, although LRP10 expression and localisation in the substantia nigra of most idiopathic PD and DLB patients and LRP10 variant carriers diagnosed with PD or DLB appeared unchanged compared to control subjects, significantly enlarged LRP10-positive vesicles were detected in a patient carrying the LRP10 p.Arg235Cys variant. Last, LRP10 was detected in Lewy bodies (LB) at late maturation stages in brains from idiopathic PD and DLB patients and in LRP10 variant carriers. In conclusion, high LRP10 expression in non-neuronal cells and undetectable levels in neurons of control subjects indicate that LRP10-mediated pathogenicity is initiated via cell non-autonomous mechanisms, potentially involving the interaction of LRP10 with SORL1 in vesicle trafficking pathways. Together with the specific pattern of LRP10 incorporation into mature LBs, these data support an important mechanistic role for disturbed vesicle trafficking and loss of LRP10 function in neurodegenerative diseases

Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes

Stricture of the afferent isoperistaltic tubular segment: a late and rare cause of bilateral dilation of the upper urinary tract after ileal bladder substitution.

To evaluate the etiology and treatment of bilateral hydronephrosis not responding to bladder substitute drainage after ileal bladder substitution using an afferent isoperistaltic tubular segment. A retrospective analysis was performed of a consecutive series of 739 patients who had undergone bladder substitution from April 1985 to August 2012. Of the 739 ileal bladder substitute patients, 10 (1.4%) developed bilateral hydronephrosis unresponsive to complete bladder substitute drainage. The etiology was stenosis of the afferent isoperistaltic tubular segment. The median interval to presentation was 131 months (range 45-192). The incidence of afferent tubular segment stenosis was significantly higher in the 61 ileal bladder substitute patients with recurrent urinary tract infection (9 [15%]) than in the 678 without recurrent urinary tract infection (1 [0.15%]; P <.001). Urine cultures revealed mixed infections (34%), Escherichia coli (18%), Staphylococcus aureus (13%), enterococci (11%), Candida (8%), Klebsiella (8%), and others (8%). Seven patients underwent 10 endourologic interventions, only 1 of which was successful (10%). After failed endourologic treatment, 7 open surgical revisions with resection of the stricture were performed, with all 7 (100%) successful. Bilateral dilation of the upper urinary tract after ileal orthotopic bladder substitution unresponsive to complete bladder substitute drainage is likely to be caused by stenosis of the afferent isoperistaltic tubular segment. The stenosis occurs almost exclusively in patients with long-lasting, recurrent urinary tract infection and can develop many years after the ileal bladder substitution. Minimally invasive endourologic treatment is usually unsuccessful; however, open surgical revision offers excellent results