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AbstractThe significant increase of periodontitis, chronic kidney disease (CKD), Alzheimer’s disease and cancer can be attributed to an ageing population. Each disease produces a range of biomarkers that can be indicative of disease onset and progression. Biomarkers are defined as cellular (intra/extracellular components and whole cells), biochemical (metabolites, ions and toxins) or molecular (nucleic acids, proteins and lipids) alterations which are measurable in biological media such as human tissues, cells or fluids. An interesting group of biomarkers that merit further investigation are the polyamines. Polyamines are a group of molecules consisting of cadaverine, putrescine, spermine and spermidine and have been implicated in the development of a range of systemic diseases, in part due to their production in periodontitis. Cadaverine and putrescine within the periodontal environment have demonstrated cell signalling interfering abilities, by way of leukocyte migration disruption. The polyamines spermine and spermidine in tumour cells have been shown to inhibit cellular apoptosis, effectively prolonging tumorigenesis and continuation of cancer within the host. Polyamine degradation products such as acrolein have been shown to exacerbate renal damage in CKD patients. Thus, the use of such molecules has merit to be utilized in the early indication of such diseases in patients.

The reduction of bacteria and biofilm formation is important when designing surfaces for use in industry. Molybdenum disulfide surfaces (MoS2SUR) were produced using MoS2particle (MoS2PAR) sizes of 90 nm, 2 μm, and 6 μm containing MoS2PARconcentrations of 5%, 10%, 15%, and 20%. These were tested to determine the efficacy of the MoS2SURto impede bacterial retention and biofilm formation of two different types of bacteria, Staphylococcus aureusand Pseudomonas aeruginosa. The MoS2SURwere characterized using Fourier transform infrared spectroscopy, ion-coupled plasma atomic emission spectroscopy, scanning electron microscopy, optical profilometry, and water contact angles. The MoS2SURmade with the smaller 90 nm MoS2PARsizes demonstrated smaller topographical-shaped features. As the size of the incorporated MoS2PARincreased, the MoS2SURdemonstrated wider surface features, and they were less wettable. The increase in MoS2PARconcentration within the MoS2SURgroups did not affect the surface topography but did increase wettability. However, the increase in MoS2PARsize increased both the surface topography and wettability. The MoS2SURwith the smaller topographical-shaped features influenced the retention of the S. aureusbacteria. Increased MoS2SURtopography and wettability resulted in the greatest reduction in bacterial retention, and the bacteria became more heterogeneously dispersed and less clustered across the surfaces. The surfaces that exhibited decreased bacterial retention (largest particle sizes, largest features, greatest roughness, and most wettable) resulted in decreased biofilm formation. Cytotoxicity testing of the surface using cell viability demonstrated that the MoS2SURwere not toxic against HK-2 cells at MoS2PARsizes of 90 nm and 2 μm. This work demonstrated that individual surface variables (MoS2SURtopographic shape and roughness, MoS2PARsize, and concentration) decreased bacterial loading on the surfaces, which then decreased biofilm formation. By optimizing MoS2SURproperties, it was possible to impede bacterial retention and subsequent biofilm formation.

Background:Progressive chronic kidney disease (CKD) inevitably leads to salt and water retention and disturbances in the macro-and microcirculation. Objectives:We hypothesize that salt and water dysregulation in advanced CKD may be linked to inflammation and microvascular injury pathways. Methods:We studied 23 CKD stage 5 patients and 11 healthy controls (HC). Tissue sodium concentration was assessed using 23Sodium magnetic resonance (MR) imaging. Hydration status was evaluated using bioimpedance spectroscopy. A panel of inflammatory and endothelial biomarkers was also measured. Results:CKD patients had fluid overload (FO) when compared to HC (overhydration index: CKD = 0.5 ± 1.9 L vs. HC = –0.5 ± 1.0 L; p= 0.03). MR-derived tissue sodium concentrations were predominantly higher in the subcutaneous (SC) compartment (median [interquartile range] CKD = 22.4 mmol/L [19.4–31.3] vs. HC = 18.4 mmol/L [16.6–21.3]; p= 0.03), but not the muscle (CKD = 24.9 ± 5.5 mmol/L vs. HC = 22.8 ± 2.5 mmol/L; p= 0.26). Tissue sodium in both compartments correlated to FO (muscle: r= 0.63, p< 0.01; SC: rs = 0.63, p< 0.01). CKD subjects had elevated levels of vascular cell adhesion molecule (p< 0.05), tumor necrosis factor-alpha (p< 0.01), and interleukin (IL)-6 (p= 0.01) and lower levels of vascular endothelial growth factor-C (p= 0.04). FO in CKD was linked to higher IL-8 (r= 0.51, p< 0.05) and inversely associated to E-selectin (r= –0.52, p= 0.01). Higher SC sodium was linked to higher intracellular adhesion molecule (ICAM; rs = 0.54, p= 0.02). Conclusion:Salt and water accumulation in CKD appears to be linked with inflammation and endothelial activation pathways. Specifically IL-8, E-Selectin (in FO), and ICAM (in salt accumulation) may be implicated in the pathophysiology of FO and merit further investigation.

Mindfulness-related meditation practices engage various cognitive skills including the ability to focus and sustain attention, which in itself requires several interacting attentional subfunctions. There is increasing behavioural and neuroscientific evidence that mindfulness meditation improves these functions and associated neural processes. More so than other cognitive training programmes, the effects of meditation appear to generalise to other cognitive tasks, thus demonstrating far transfer effects. As these attentional functions have been linked to age-related cognitive decline, there is growing interest in the question whether meditation can slowdown or even prevent such decline. The cognitive reserve hypothesis builds on evidence that various lifestyle factors can lead to better cognitive performance in older age than would be predicted by the existing degree of brain pathology. We argue that mindfulness meditation, as a combination of brain network and brain state training, may increase cognitive reserve capacity and may mitigate age-related declines in cognitive functions. We consider available direct and indirect evidence from the perspective of cognitive reserve theory. The limited available evidence suggests that MM may enhance cognitive reserve capacity directly through the repeated activation of attentional functions and of the multiple demand system and indirectly through the improvement of physiological mechanisms associated with stress and immune function. The article concludes with outlining research strategies for addressing underlying empirical questions in more substantial ways.

Proteinuria is pathogenic to proximal tubular cells (PTC) and linked with progression to renal failure. The aim of this study was to determine the effects of human serum albumin (HSA) overload on the changes in gene and protein expression stimulated by oxidative stress in PTC and any interaction with ANG II that is pivotal in disease pathogenesis. Markers of oxidative stress, antioxidant defences, transcription factor activation, and the expression of stress-related genes were measured in human PTC (HK-2 cells) overloaded with either globulin-free fatty acid free (GF/FAF) HSA or globulin-free (GF) HSA. The effects of ANG II were also determined. HSA overload in HK-2 cells caused PTC hyperfunction, increased oxidative stress, and an upregulation of adaptive responses and stress-related genes. Some responses were common to both HSAs but others were unique to either HSA and unaffected by addition of ANG II or candesartan (a specific ANG II type 1 receptor blocker). ANG II also independently induced oxidative stress and upregulated other stress-related genes. HSA overload in HK-2 cells stimulated increased oxidative stress and upregulated changes in stress-related gene expression indicating new pathways of PTC injury that are not mediated via ANG II type 1 receptors.

The inhibitory effect of a series of 5'-O-amino acid and oligopeptide derivatives of uridine on rat liver UDP-glucuronosyltransferase (UGT) activities was investigated using two assay systems. A quantitative structure-activity relationship (QSAR) study was performed. The compounds include a lipophilic residue linked to the nucleoside by a variable spacer. More­ over, half of the derivatives have two spacers linked to the uridine moiety. Compound 1, a serine derivative of isopropylideneuridine, was found to be the most potent inhibitor of both 4-nitrophenol (4-NP) and phenolphthalein (PPh) glucuronidation, with an I50of 0.45 m? and 0.22 m? , respectively. Kinetic studies with this substance revealed a mixed type of inhibition towards 4-NP and UDP-glucuronic acid, with apparent Ki values of 150 µ? and 120 µ? , respectively. The dipeptide derivatives 11-14 exhibited a low activity against 4-NP conjuga­ tion. However, a marked suppression of PPh glucuronidation was found with compounds 11 and 13. Generally, compounds with two spacers are more inhibitory against the UGT activi­ties studied. The QSAR analysis outlined the significance of the spacers with a minimum length of 5 atoms and lipophilic residues linked to them for the inhibitory effect of the compounds. The most significant contribution to this effect is given by the six-atom spacer for both, 4-NP and PPh substrates. 4-NP converting UGT isoforms seem to respond more specifically to the inhibitors: a five-atom for the first and a six-atom for the second spacer enhance binding to both 4-NP and PPh conjugating isoenzymes, while a long second spacer contributes to inhibitor binding to UGT isoforms only converting PPh.