Predictors of walking capacity in peripheral arterial disease patients

OBJECTIVE: To estimate walking capacity in intermittent claudication patients through a prediction model based on clinical characteristics and the walking impairment questionnaire. METHODS: The sample included 133 intermittent claudication patients of both genders aged between 30 and 80 years. Data regarding clinical characteristics, the walking impairment questionnaire and treadmill walking test performance were obtained. Multiple regression modeling was conducted to predict claudication onset distance and total walking distance using clinical characteristics (age, height, mass, body mass index, ankle brachial index lower, gender, history of smoking and co-morbid conditions) and walking impairment questionnaire responses. Comparisons of claudication onset distance and total walking distance measured during treadmill tests and estimated by a regression equation were performed using paired t-tests. RESULTS: Co-morbid conditions (diabetes and coronary artery disease) and questions related to difficulty in walking short distances (walking indoors - such as around your house and walking 5 blocks) and at low speed (walking 1 block at average speed - usual pace) resulted in the development of new prediction models high significant for claudication onset distance and total walking distance (p0.05) were observed. CONCLUSION: The current study demonstrated that walking capacity can be adequately estimated based on co-morbid conditions and responses to the walking impairment questionnaire

Remote ischemic preconditioning in patients with intermittent claudication

OBJECTIVE: Remote ischemic preconditioning (RIPC) is a phenomenon in which a short period of sub-lethal ischemia in one organ protects against subsequent bouts of ischemia in another organ. We hypothesized that RIPC in patients with intermittent claudication would increase muscle tissue resistance to ischemia, thereby resulting in an increased ability to walk. METHODS: In a claudication clinic, 52 ambulatory patients who presented with complaints of intermittent claudication in the lower limbs associated with an absent or reduced arterial pulse in the symptomatic limb and/or an ankle-brachial index <0.90 were recruited for this study. The patients were randomly divided into three groups (A, B and C). All of the patients underwent two tests on a treadmill according to the Gardener protocol. Group A was tested first without RIPC. Group A was subjected to RIPC prior to the second treadmill test. Group B was subjected to RIPC prior to the first treadmill test and then was subjected to a treadmill test without RIPC. In Group C (control group), both treadmill tests were performed without RIPC. The first and second tests were conducted seven days apart. Brazilian Clinical Trials: RBR-7TF6TM. RESULTS: Group A showed a significant increase in the initial claudication distance in the second test compared to the first test. CONCLUSION: RIPC increased the initial claudication distance in patients with intermittent claudication; however, RIPC did not affect the total walking distance of the patients

The NMDA receptor activation by D-serine and glycine is controlled by an astrocytic Phgdh-dependent serine shuttle

Astrocytes express the 3-phosphoglycerate dehydrogenase (Phgdh) enzyme required for the synthesis of L-serine from glucose. Astrocytic L-serine was proposed to regulate NMDAR activity by shuttling to neurons to sustain D-serine production, but this hypothesis remains untested. We now report that inhibition of astrocytic Phgdh suppressed the de novo synthesis of L-and D-serine and reduced the NMDAR synaptic potentials and long-term potentiation (LTP) at the Schaffer collaterals-CA1 synapse. Likewise, enzymatic removal of extracellular L-serine impaired LTP, supporting an L-serine shuttle mechanism between glia and neurons in generating the NMDAR coagonist D-serine. Moreover, deletion of serine racemase (SR) in glutamatergic neurons abrogated D-serine synthesis to the same extent as Phgdh inhibition, suggesting that neurons are the predominant source of the newly synthesized D-serine. We also found that the synaptic NMDAR activation in adult SR-knockout (KO) mice requires Phgdh-derived glycine, despite the sharp decline in the postnatal glycine levels as a result of the emergence of the glycine cleavage system. Unexpectedly, we also discovered that glycine regulates D-serine metabolism by a dual mechanism. The first consists of tonic inhibition of SR by intracellular glycine observed in vitro, primary cultures, and in vivo microdialysis. The second involves a transient glycine-induce D-serine release through the Asc-1 transporter, an effect abolished in Asc-1 KO mice and diminished by deleting SR in glutamatergic neurons. Our observations suggest that glycine is a multifaceted regulator of D-serine metabolism and implicate both D-serine and glycine in mediating NMDAR synaptic activation at the mature hippocampus through a Phgdh-dependent shuttle mechanism

Reproducibility of heart rate recovery in patients with intermittent claudication

Background: Postexercise heart rate recovery (HRR) is a non-invasive tool for cardiac autonomic function assessment. Reproducibility of HRR has been established in healthy subjects; however, no study has evaluated this reproducibility in clinical populations who may present autonomic dysfunction. Patients with peripheral artery disease and intermittent claudication (IC) often present altered cardiac autonomic function and HRR could be an interesting tool for evaluating autonomic responses to interventions in this population. Therefore, the reproducibility of HRR should be determined in this specific population. Objective: To determine the reproducibility of HRR indices in patients with IC. Methods: Nineteen men with IC underwent two repeated maximal treadmill tests. Raw HR and relative HRR (difference to exercise peak) indices measured at 30, 60, 120, 180, 240 and 300s of recovery were evaluated. The presence of systematic bias was assessed by comparing test and retest mean values via paired t-test. Reliability was assessed by intraclass correlation coefficient (ICC), and agreement by typical error (TE), coefficient of variation (CV) and minimal detectable difference (MDD). Results: There were no significant differences between the test and retest values of all raw HR and relative HRR indices (P ≥ 0·05), except for HR120s (P = 0·032). All indices exhibited excellent reliability (ICC ≥ 0·78). Raw HR and relative HRR indices showed TEs ≤ 6·4 bpm and MDDs ≤ 17·8 bpm. In addition, all indices showed CVs ≤ 13·2%, except HRR30s (CV = 45·6%). Conclusions: The current results demonstrated that most HRR indices were highly reproducible with no systematic error, excellent reliability and good agreement in patients with IC following maximal graded exercise

The host metabolite D-serine contributes to bacterial niche specificity through gene selection

Escherichia coli comprise a diverse array of both commensals and niche-specific pathotypes. The ability to cause disease results from both carriage of specific virulence factors and regulatory control of these via environmental stimuli. Moreover, host metabolites further refine the response of bacteria to their environment and can dramatically affect the outcome of the host–pathogen interaction. Here, we demonstrate that the host metabolite, D-serine, selectively affects gene expression in E. coli O157:H7. Transcriptomic profiling showed exposure to D-serine results in activation of the SOS response and suppresses expression of the Type 3 Secretion System (T3SS) used to attach to host cells. We also show that concurrent carriage of both the D-serine tolerance locus (dsdCXA) and the locus of enterocyte effacement pathogenicity island encoding a T3SS is extremely rare, a genotype that we attribute to an ‘evolutionary incompatibility’ between the two loci. This study demonstrates the importance of co-operation between both core and pathogenic genetic elements in defining niche specificity

A Genome-Wide Association Study Identifies Susceptibility Variants for Type 2 Diabetes in Han Chinese

To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54×10−10; odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36–1.82), and serine racemase (SRR) (P = 3.06×10−9; OR = 1.28; 95% CI = 1.18–1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65×10−10; OR = 1.29, 95% CI = 1.19–1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations