Developing a dialysis centre foot screening culture

Foot lesions are common in the dialysis population and contribute to increased morbidity and mortality (Broersma 2004). lmportantly, patients on dialysis with and without diabetes are at increased risk of foot ulcers (Jones et al. 2012) and lower limb amputation (Kaminski, Frescos & Tucker 2012). Simple foot screening in dialysis centres can identify those at risk of foot complications and the presence of foot ulcers (Ahmad 2009; Ng et al. 2003). Valid and reliable foot screening tools have been developed in the dialysis context to identify those at risk and those with actual ulcers (Murphy et al. 2012).ln 2011, following the completion of a Diabetes and Renal Pilot Study and staff education, Moorabbin Haemodialysis Unit and Southern Health, identified the need to formalise foot screening for all patients and increase the rate at which these were conducted. The aim of this report is to present a summary of the audit evaluation of foot health screens and referrals in our dialysis centre.

Short term aerobic exercise training in young males does not alter sensitivity to a central serotonin agonist

An increase in the concentration of serotonin in the brain has been shown to cause fatigue during exercise in humans and experimental animals. This type of fatigue is referred to as central fatigue and is likely to be mediated by the concentration of serotonin as well as serotonin receptor sensitivity. Serotonin (5-HT) receptor antagonism in humans and experimental animals has been shown to improve endurance performance. A previous report has shown decreased receptor sensitivity in athletes compared to sedentary controls. It is unclear whether this is due to a training adaptation or if individuals are predisposed to enhanced athletic performance due to their inherent decreased receptor sensitivity. The present study investigated changes in 5-HT receptor sensitivity in response to aerobic exercise. Subjects completed 3 × 30 min of stationary cycling at 70% of their peak aerobic power (V̇O2,peak) for 9 weeks. Serotonin receptor sensitivity was assessed indirectly by measuring the neuroendocrine response following administration of a serotonin agonist (buspirone hydrochloride). The neuroendocrine response following administration of a placebo was also investigated in a blind crossover design. A group of sedentary control subjects was also recruited to control for seasonal variations in central receptor sensitivity. The training caused a significant increase in V̇O2,peak (3.1 ± 0.16 to 3.6 ± 0.15 l min−1, P < 0.05) and endurance capacity (93 ± 8 to 168 ± 11 min, P < 0.05), but there was no change (P > 0.05) in the neuroendocrine response in the presence of a serotonin agonist. However, one-quarter of the subjects in the training group demonstrated decreases in receptor sensitivity. These results suggest that despite increases in V̇O2,peak and endurance performance, there was no measurable change in 5-HT receptor sensitivity in the presence of a serotonin agonist. In addition, it is possible that changes in receptor sensitivity may take longer to occur, that the training stimulus used in the present investigation was inadequate and/or that changes occurred in receptor subtypes that were not probed by the agonist used in the present investigation.

Endurance training in Wistar rats decreases receptor sensitivity to a serotonin agonist

There is mounting evidence that increased brain serotonin during exercise is associated with the onset of CNS-mediated fatigue. Serotonin receptor sensitivity is likely to be an important determinant of this fatigue. Alterations in brain serotonin receptor sensitivity were examined in Wistar rats throughout 6 weeks of endurance training, running on a treadmill four times a week with two exercise tests per week to exhaustion. Receptor sensitivity was determined indirectly as the reduction in exercise time in response to a dose of a serotonin (1A) agonist, m-chlorophenylpiperazine (m-CPP). The two groups of controls were used to examine (i) the effect of the injection per se on exercise performance and (ii) changes in serotonin receptor sensitivity associated with maturation. In the test group, undrugged exercise performance significantly improved by 47% after 6 weeks of training (4518 ± 729 to 6640 ± 903 s, P=0.01). Drugged exercise performance also increased significantly from week 1 to week 6 (306 ± 69–712 ± 192 s, P = 0.04). Control group results indicated that the dose of m-CPP alone caused fatigue during exercise tests and that maturation was not responsible for any decrease in receptor sensitivity. Improved resistance to the fatiguing effects of the serotonin agonist suggests desensitization of central serotonin receptors, probably the 5-HT1A receptors. Endurance training appears to stimulate an adaptive response to the fatiguing effects of increased brain serotonin, which may enhance endurance exercise performance.

Allosteric Modulation of the HIV-1 gp120-gp41 Association Site by Adjacent gp120 Variable Region 1 (V1) N-Glycans Linked to Neutralization Sensitivity

The HIV-1 gp120-gp41 complex, which mediates viral fusion and cellular entry, undergoes rapid evolution within its external glycan shield to enable escape from neutralizing antibody (NAb). Understanding how conserved protein determinants retain functionality in the context of such evolution is important for their evaluation and exploitation as potential drug and/ or vaccine targets. In this study, we examined how the conserved gp120-gp41 association site, formed by the N- and Cterminal segments of gp120 and the disulfide-bonded region (DSR) of gp41, adapts to glycan changes that are linked to neutralization sensitivity. To this end, a DSR mutant virus (K601D) with defective gp120-association was sequentially passaged in peripheral blood mononuclear cells to select suppressor mutations. We reasoned that the locations of suppressors point to structural elements that are functionally linked to the gp120-gp41 association site. In culture 1, gp120 association and viral replication was restored by loss of the conserved glycan at Asn136 in V1 (T138N mutation) in
conjunction with the L494I substitution in C5 within the association site. In culture 2, replication was restored with deletion of the N139INN sequence, which ablates the overlapping Asn141-Asn142-Ser-Ser potential N-linked glycosylation sequons in
V1, in conjunction with D601N in the DSR. The 136 and 142 glycan mutations appeared to exert their suppressive effects by altering the dependence of gp120-gp41 interactions on the DSR residues, Leu593, Trp596 and Lys601. The 136 and/or 142
glycan mutations increased the sensitivity of HIV-1 pseudovirions to the glycan-dependent NAbs 2G12 and PG16, and also pooled IgG obtained from HIV-1-infected individuals. Thus adjacent V1 glycans allosterically modulate the distal gp120-
gp41 association site. We propose that this represents a mechanism for functional adaptation of the gp120-gp41 association site to an evolving glycan shield in a setting of NAb selection.

Dichloroacetate inhibits aerobic glycolysis in multiple myeloma cells and increases sensitivity to bortezomib

Background:
Dichloroacetate (DCA), through the inhibition of aerobic glycolysis (the ‘Warburg effect’) and promotion of pyruvate oxidation, induces growth reduction in many tumours and is now undergoing several clinical trials. If aerobic glycolysis is active in multiple myeloma (MM) cells, it can be potentially targeted by DCA to induce myeloma growth inhibition.

Methods:
Representative multiple myeloma cell lines and a myeloma-bearing mice were treated with DCA, alone and in combination with bortezomib.

Results:
We found that aerobic glycolysis occurs in approximately half of MM cell lines examined, producing on average 1.86-fold more lactate than phorbol myristate acetate stimulated-peripheral blood mononuclear cells and is associated with low-oxidative capacity. Lower doses of DCA (5–10 mM) suppressed aerobic glycolysis and improved cellular respiration that was associated with activation of the pyruvate dehydrogenase complex. Higher doses of DCA (10–25 mM) induced superoxide production, apoptosis, suppressed proliferation with a G0/1 and G2M phase arrest in MM cell lines. In addition, DCA increased MM cell line sensitivity to bortezomib, and combinatorial treatment of both agents improved the survival of myeloma-bearing mice.

Conclusion:
Myeloma cells display aerobic glycolysis and DCA may complement clinically used MM therapies to inhibit disease progression.

Discovering consumer personality clusters in prestige sensitivity and fashion consciousness context

This article aims to discover the differences among consumer personality clusters in regard to their extent of fashion consciousness and prestige sensitivity. Data were collected from 251 undergraduate students using self-administered questionnaires. Cluster analysis and MANOVA were employed to assess whether significant differences exist among four personality clusters. The study used the Big Five scale items to measure consumer personality and found that respondents who score low on the “openness to experience” dimension tend to be less prestige sensitive, and those who score high on “extraversion,” “agreeableness,” and “conscientiousness” tend to be highly fashion conscious.