Comparative Flavivirus-Host Protein Interaction Mapping Reveals Mechanisms of Dengue and Zika Virus Pathogenesis.

Mosquito-borne flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), are a growing public health concern. Systems-level analysis of how flaviviruses hijack cellular processes through virus-host protein-protein interactions (PPIs) provides information about their replication and pathogenic mechanisms. We used affinity purification-mass spectrometry (AP-MS) to compare flavivirus-host interactions for two viruses (DENV and ZIKV) in two hosts (human and mosquito). Conserved virus-host PPIs revealed that the flavivirus NS5 protein suppresses interferon stimulated genes by inhibiting recruitment of the transcription complex PAF1C and that chemical modulation of SEC61 inhibits DENV and ZIKV replication in human and mosquito cells. Finally, we identified a ZIKV-specific interaction between NS4A and ANKLE2, a gene linked to hereditary microcephaly, and showed that ZIKV NS4A causes microcephaly in Drosophila in an ANKLE2-dependent manner. Thus, comparative flavivirus-host PPI mapping provides biological insights and, when coupled with in vivo models, can be used to unravel pathogenic mechanisms.

Chromatin bridges: stochastic breakage or regulated resolution?

Genetic material is organized in the form of chromosomes, which need to be segregated accurately into two daughter cells in each cell cycle. However, chromosome fusion or the presence of unresolved interchromosomal linkages lead to the formation of chromatin bridges, which can induce DNA lesions and genome instability. Persistent chromatin bridges are trapped in the cleavage furrow and are broken at or after abscission, the final step of cytokinesis. In this review, we focus on recent progress in understanding the mechanism of bridge breakage and resolution. We discuss the molecular machinery and enzymes that have been implicated in the breakage and processing of bridge DNA. In addition, we outline both the immediate outcomes and genomic consequences induced by bridge breakage.

2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease" provides recommendations to guide clinicians in the treatment of patients with lower extremity peripheral artery disease across its multiple clinical presentation subsets (ie, asymptomatic, chronic symptomatic, chronic limb-threatening ischemia, and acute limb ischemia). METHODS: A comprehensive literature search was conducted from October 2020 to June 2022, encompassing studies, reviews, and other evidence conducted on human subjects that was published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through May 2023 during the peer review process, were also considered by the writing committee and added to the evidence tables where appropriate. STRUCTURE: Recommendations from the "2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with peripheral artery disease have been developed.

Cerebral hemodynamics underlying ankle force sense modulated by high-definition transcranial direct current stimulation.

This study aimed to investigate the effects of high-definition transcranial direct current stimulation on ankle force sense and underlying cerebral hemodynamics. Sixteen healthy adults (8 males and 8 females) were recruited in the study. Each participant received either real or sham high-definition transcranial direct current stimulation interventions in a randomly assigned order on 2 visits. An isokinetic dynamometer was used to assess the force sense of the dominant ankle; while the functional near-infrared spectroscopy was employed to monitor the hemodynamics of the sensorimotor cortex. Two-way analyses of variance with repeated measures and Pearson correlation analyses were performed. The results showed that the absolute error and root mean square error of ankle force sense dropped more after real stimulation than after sham stimulation (dropped by 23.4% vs. 14.9% for absolute error, and 20.0% vs. 10.2% for root mean square error). The supplementary motor area activation significantly increased after real high-definition transcranial direct current stimulation. The decrease in interhemispheric functional connectivity within the Brodmann's areas 6 was significantly correlated with ankle force sense improvement after real high-definition transcranial direct current stimulation. In conclusion, high-definition transcranial direct current stimulation can be used as a potential intervention for improving ankle force sense. Changes in cerebral hemodynamics could be one of the explanations for the energetic effect of high-definition transcranial direct current stimulation.

Arm and ankle blood pressure indices, and peripheral artery disease, and mortality: a cohort study.

BACKGROUND AND AIMS: Few studies have compared arm and ankle blood pressures (BPs) with regard to peripheral artery disease (PAD) and mortality. These relationships were assessed using data from three large prospective clinical trials. METHODS: Baseline BP indices included arm systolic BP (SBP), diastolic BP (DBP), pulse pressure (arm SBP minus DBP), ankle SBP, ankle-brachial index (ABI, ankle SBP divided by arm SBP), and ankle-pulse pressure difference (APPD, ankle SBP minus arm pulse pressure). These measurements were categorized into four groups using quartiles. The outcomes were PAD (the first occurrence of either peripheral revascularization or lower-limb amputation for vascular disease), the composite of PAD or death, and all-cause death. RESULTS: Among 40 747 participants without baseline PAD (age 65.6 years, men 68.3%, diabetes 50.2%) from 53 countries, 1071 (2.6%) developed PAD, and 4955 (12.2%) died during 5 years of follow-up. Incident PAD progressively rose with higher arm BP indices and fell with ankle BP indices. The strongest relationships were noted for ankle BP indices. Compared with people whose ankle BP indices were in the highest fourth, adjusted hazard ratios (95% confidence interval) for each lower fourth were 1.64 (1.31-2.04), 2.59 (2.10-3.20), and 4.23 (3.44-5.21) for ankle SBP; 1.19 (0.95-1.50), 1.66 (1.34-2.05), and 3.34 (2.75-4.06) for ABI; and 1.41 (1.11-1.78), 2.04 (1.64-2.54), and 3.63 (2.96-4.45) for APPD. Similar patterns were observed for mortality. Ankle BP indices provided the highest c-statistics and classification indices in predicting future PAD beyond established risk factors. CONCLUSIONS: Ankle BP indices including the ankle SBP and the APPD best predicted PAD and mortality.

Health Disparities in Peripheral Artery Disease: A Scientific Statement From the American Heart Association.

Peripheral artery disease (PAD) affects 200 million individuals worldwide. In the United States, certain demographic groups experience a disproportionately higher prevalence and clinical effect of PAD. The social and clinical effect of PAD includes higher rates of individual disability, depression, minor and major limb amputation along with cardiovascular and cerebrovascular events. The reasons behind the inequitable burden of PAD and inequitable delivery of care are both multifactorial and complex in nature, including systemic and structural inequity that exists within our society. Herein, we present an overview statement of the myriad variables that contribute to PAD disparities and conclude with a summary of potential novel solutions.

Gut microbiota and its relationship with early vascular ageing in a Spanish population (MIVAS study).

BACKGROUND: Gut microbiota and its by-products are increasingly recognized as having a decisive role in cardiovascular diseases. The aim is to study the relationship between gut microbiota and early vascular ageing (EVA). METHODS: A cross-sectional study was developed in Salamanca (Spain) in which 180 subjects aged 45-74 years were recruited. EVA was defined by the presence of at least one of the following: carotid-femoral pulse wave velocity (cf-PWV), cardio-ankle vascular index (CAVI) or brachial-ankle pulse wave velocity (ba-PWV) above the 90th percentile of the reference population. All other cases were considered normal vascular ageing (NVA). MEASUREMENTS: cf-PWV was measured by SphygmoCor® System; CAVI and ba-PWV were determined by Vasera 2000® device. Gut microbiome composition in faecal samples was determined by 16S rRNA Illumina sequencing. RESULTS: Mean age was 64.4 ± 6.9 in EVA group and 60.4 ± 7.6 years in NVA (p < .01). Women in EVA group were 41% and 53% in NVA. There were no differences in the overall composition of gut microbiota between the two groups when evaluating Firmicutes/Bacteriodetes ratio, alfa diversity (Shannon Index) and beta diversity (Bray-Curtis). Bilophila, Faecalibacterium sp.UBA1819 and Phocea, are increased in EVA group. While Cedecea, Lactococcus, Pseudomonas, Succiniclasticum and Dielma exist in lower abundance. In logistic regression analysis, Bilophila (OR: 1.71, 95% CI: 1.12-2.6, p = .013) remained significant. CONCLUSIONS: In the studied Spanish population, early vascular ageing is positively associated with gut microbiota abundance of the genus Bilophila. No relationship was found between phyla abundance and measures of diversity.

Suppression of YAP Ameliorates Cartilage Degeneration in Ankle Osteoarthritis via Modulation of the Wnt/ß-Catenin Signaling Pathway.

Ankle osteoarthritis is a relatively understudied condition and the molecular mechanisms involved in its development are not well understood. This investigation aimed to explore the role and underlying molecular mechanisms of Yes-associated protein (YAP) in rat ankle osteoarthritis. The results demonstrated that YAP expression levels were abnormally increased in the ankle osteoarthritis cartilage model. In addition, knockdown of YAP expression was shown to hinder the imbalance in ECM metabolism induced by IL-1ß in chondrocytes, as demonstrated by the regulation of matrix metalloproteinase (MMP)-3, MMP-9, and MMP-13, a disintegrin, metalloprotease with thrombospondin motifs, aggrecan, and collagen II expression. Additional studies revealed that downregulation of YAP expression markedly inhibited the overexpression of ß-catenin stimulated by IL-1ß. Furthermore, inhibition of the Wnt/ß-catenin signaling pathway reversed the ECM metabolism imbalance caused by YAP overexpression in chondrocytes. It is important to note that the YAP-specific inhibitor verteporfin (VP) significantly delayed the progression of ankle osteoarthritis. In conclusion, the findings highlighted the crucial role of YAP as a regulator in modulating the progression of ankle osteoarthritis via the Wnt/ß-catenin signaling pathway. These findings suggest that pharmacological inhibition of YAP can be an effective and critical therapeutic target for alleviating ankle osteoarthritis.

Intrinsic ankle stiffness is associated with paradoxical calf muscle movement but not postural sway or age.

Due to Achilles tendon compliance, passive ankle stiffness is insufficient to stabilise the body when standing. This results in 'paradoxical' muscle movement, whereby calf muscles tend to shorten during forward body sway. Natural variation in stiffness may affect this movement. This may have consequences for postural control, with compliant ankles placing greater reliance upon active neural control rather than stretch reflexes. Previous research also suggests ageing reduces ankle stiffness, possibly contributing to reduced postural stability. Here we determine the relationship between ankle stiffness and calf muscle movement during standing, and whether this is associated with postural stability or age. Passive ankle stiffness was measured during quiet stance in 40 healthy volunteers ranging from 18 to 88 years of age. Medial gastrocnemius muscle length was also recorded using ultrasound. We found a significant inverse relationship between ankle stiffness and paradoxical muscle movement, that is, more compliant ankles were associated with greater muscle shortening during forward sway (r ≥ 0.33). This was seen during both quiet stance as well as voluntary sway. However, we found no significant effects of age upon stiffness, paradoxical motion or postural sway. Furthermore, neither paradoxical muscle motion nor ankle stiffness was associated with postural sway. These results show that natural variation in ankle stiffness alters the extent of paradoxical calf muscle movement during stance. However, the absence of a clear relationship to postural sway suggests that neural control mechanisms are more than capable of compensating for a lack of inherent joint stiffness.

A single-centre experience of 29 total ankle replacement in haemophiliac patients: Therapeutic management, factor consumption and cost.

INTRODUCTION: In patients with haemophilia, repeated bleeding in large joints leads to chronic haemophilic arthropathy, a rare disease that can be managed surgically with ankle arthrodesis or with total ankle replacement (TAR). TAR has been reported to provide good surgical results in the medium/long-term and allow preservation of joint mobility but the medical therapeutic management of the patients has not been described. AIM: To describe the medical therapeutic management of TAR. METHODS: All patients with haemophilia A/B, with haemophilic ankle arthropathy, and who underwent TAR between April 2006 and October 2019 were retrospectively included. Factor consumption, perioperative and early complications, volume of blood lost, and orthopaedic data were collected. RESULTS: A total of 25 patients underwent 29 TAR (mean age was 44.7 years [range: 26-65]). In the 17 patients with HA without history of anti-FVIII inhibitor, the mean ± SD consumption the day of surgery was 116 ± 16 UI/kg when clotting factors were administered by continuous infusion, 106 ± 13 UI/kg when SHL factors were administered by bolus infusion, and 75 ± 22 UI/kg when EHL factors were administered by bolus infusion. During hospitalisation, the mean factor cost was €38,073 (83.7% of the total cost of surgery). Mean blood loss was significantly lower in patients treated with tranexamic acid (164 mL, range: 40-300) than in those not (300 mL, range: 70-800; p = .01). Six patients had haematoma. The 10-year survival free of any prosthesis removal/arthrodesis was estimated to be 92.2% (95% CI [83; 100]). CONCLUSION: The medical therapeutic management of TAR is complex, carried out by a multidisciplinary team but effective in avoiding the occurrence of complications.

Arthroscopic ankle surgery in people with haemophilia.

INTRODUCTION: People with haemophilia (PWH) not administered primary haematological prophylaxis since childhood, that is, those treated haematologically on demand or not treated at all, often experience the degeneration of the ankles, leading to pain and functional impairment. AIM: To analyse the outcomes and complications of arthroscopic ankle surgery performed on PWH. METHODS: For this narrative review of the literature, a search was conducted in PubMed on 2, December 2023, using the keywords "haemophilia", "ankle" and "arthroscopy". Of the 29 articles identified, 15 specifically related to ankle arthroscopy in PWH were selected (inclusion criterion). The remaining articles did not meet this requirement (exclusion criterion) and were therefore eliminated. RESULTS: Arthroscopic procedures (arthroscopic synovectomy, debridement and arthrodesis of the ankle) are increasingly used in the surgical treatment of haemophilic ankle arthropathy. Although arthroscopic ankle surgery offers good outcomes in patients with haemophilia, the procedure is not free of complications, which range from 7.9% for arthroscopic ankle debridement to 13.1% in arthroscopic ankle synovectomy and 17.8% in arthroscopic ankle arthrodesis, respectively. The non-union rate of arthroscopic ankle arthrodesis is 7.1% (2/28). CONCLUSION: Although arthroscopic interventions in the haemophilic ankle (synovectomy, debridement, arthrodesis) offer good functional outcomes, they are associated with a non-negligible rate of complications. Arthroscopic ankle surgery in PWH is major surgery and should be treated as such.

Structural alterations and pain perception at the ankle joint in patients with haemophilia.

BACKGROUND: Patients with haemophilia (PwH) suffer from chronic pain due to joint alterations induced by recurring haemorrhage. OBJECTIVES: This study aimed to investigate the relationship between structural alterations and pain perception at the ankle joint in PwH. PATIENTS/METHODS: Ankle joints of 79 PwH and 57 healthy controls (Con) underwent ultrasound examination (US) and assessment of pain sensitivity via pressure pain thresholds (PPT). US discriminated between joint activity (synovitis) and joint damage (cartilage and/or bone degeneration) applying the HEAD-US protocol. Based on US-findings, five subgroups were built: PwH with activity/damage, PwH with activity/no damage, PwH with no activity/no damage, controls with activity/no damage and controls with no activity/no damage. RESULTS: Joint activity and joint damage were significantly increased in ankles of PwH compared to Con (p ≤.001). Subgroup analysis revealed that structural alterations negatively impact pain perception. This is particularly evident when comparing PwH with both activity/damage to PwH with no activity/no damage at the tibiotalar joint (p = .001). At the fibulotalar joint, no significant differences were observed between PwH subgroups. Further analysis showed that both joint activity and joint damage result in an increase in pain sensitivity (p ≤.001). CONCLUSION: The data suggest a relation between joint activity, joint damage and pain perception in PwH. Even minor changes due to synovitis appear to affect pain perception, with the effect not intensifying at higher levels of inflammation. In terms of joint damage, severe degeneration leads to a sensitised pain state most robustly, whereas initial changes do not seem to significantly affect pain perception.

Tips and Tricks for Simple and Complex Below-the-Ankle Punctures.

CLINICAL IMPACT: When the standard endovascular crossing maneuvers have failed during CLTI recanalization procedures and the distal below-the-knee or proximal below-the-ankle retrograde access is not possible due to chronic occlusion of the vessels, mastering the more distal and complex retrograde BTA punctures may be advantageous.There are scanty reports regarding the retrograde puncture of the mid and forefoot vessels. The aim of this article is to review different tips and tricks related to these techniques to help operators to apply them in specific scenarios to eventually improve procedural success rate.

Surveillance After Surgical and Endovascular Treatment for Peripheral Artery Disease: a Dutch Survey.

OBJECTIVE: At present, there is no clear, optimal approach to surveillance after invasive treatment of peripheral artery disease (PAD) in terms of modality, duration, clinical benefit, and cost effectiveness. The ongoing debate on the clinical benefit and cost effectiveness of standard surveillance creates a clear knowledge gap and may result in overtreatment or undertreatment. In this study, a survey was conducted among vascular surgeons in the Netherlands to assess the currently applied surveillance programmes. METHODS: All vascular surgeons from the Dutch Society for Vascular Surgery received an online survey on follow up after open and endovascular revascularisation in patients with PAD. Surveillance was defined as at least one follow up visit after intervention with or without additional imaging or ankle brachial index (ABI) measurement. Ten types of PAD intervention were surveyed. RESULTS: Surveys were returned by 97 (46.2%) of 210 vascular surgeons, and 76% reported using a routine follow up protocol after an invasive intervention. Clinical follow up only is most commonly performed after femoral endarterectomy (53%). After peripheral bypass surgery, clinical follow up only is applied rarely (4 - 8%). In six of the 10 interventions surveyed, duplex ultrasound (DUS) was the most used imaging modality for follow up. After bypass surgery, 76 - 86% of vascular surgeons perform DUS with or without ABI measurement. After endovascular interventions, 21 - 60% performed DUS surveillance. Lifelong surveillance is most often applied after aortobifemoral bypass (57%). Surveillance frequency and duration vary greatly within the same intervention. Frequencies range from every three or six months to annually. Duration ranges from one time surveillance to lifelong follow up. CONCLUSION: There is significant practice variation in surveillance after surgical and endovascular treatment of patients with PAD in the Netherlands. Prospective studies to evaluate treatment outcomes and to define the clinical need and cost effectiveness of standardised surveillance programmes for patients with PAD are recommended.

Five-year outcomes of the GORE VIABAHN Endoprosthesis for the treatment of complex femoropopliteal lesions from a Japanese postmarket surveillance study.

Introduction: The safety and effectiveness of the GORE VIABAHN Endoprosthesis for treatment of symptomatic patients with peripheral artery disease (PAD) and complex femoropopliteal (FP) lesions was assessed in a real-world Japanese practice setting. Methods: A prospective, multicenter, postmarket surveillance study was conducted from 2016 to 2017 at 64 sites in Japan. Symptomatic patients with PAD and FP lesions ⩾ 10 cm and reference vessel diameters ranging from 4.0 to 7.5 mm were eligible for enrollment. Outcome measures evaluated at 5 years were primary patency (PP), primary-assisted patency (PAP), secondary patency (SP), freedom from target lesion revascularization (fTLR), occurrence of device- or procedure-related serious adverse events (SAEs), and stent fractures. Results: A total of 321 patients were enrolled and were a mean age of 73.9 ± 8.7 years; 77.3% were men and 26.5% had chronic limb-threatening ischemia (CLTI). The mean lesion length was 23.6 ± 6.6 cm and the frequency with TASC II C/D lesions and chronic total occlusions was 86.6% and 70.4%, respectively. The Kaplan-Meier estimated PP, PAP, SP, and fTLR at 5 years was 62.4%, 74.1%, 82.3%, and 75.9%, respectively. The mean ankle-brachial index was 0.92 ± 0.15 and the mean improvement in Rutherford class was 2.3 ± 1.4, which was maintained through 5 years. The rate of cumulative device- or procedure-related SAEs through 5 years was 19.9% with only 9.3% of those occurring after the first year. No stent fractures were observed through 5 years by x-ray evaluation. Conclusion: The 5-year safety and efficacy outcomes of the endoprosthesis were clinically acceptable for treating complex FP lesions in a real-world cohort of Japanese patients with PAD. (ClinicalTrials.gov Identifier: NCT04706273).

Accuracy of maximal acceleration time of pedal arteries to diagnose critical limb-threatening ischemia.

INTRODUCTION: Maximal acceleration time of distal arteries of the foot (ATmax) is correlated to ankle-brachial index (ABI) and toe-brachial index (TBI), and seems very promising in diagnosing severe peripheral artery disease (PAD) and especially critical limb-threatening ischemia (CLTI). Our goal was to confirm the cut-off value of 215 ms to predict a toe pressure (TP) ⩽ 30 mmHg. METHODS: A 4-month retrospective study was conducted on patients addressed for suspicion of PAD. Demographic data, ABI, TBI, and Doppler ultrasound scanning parameters of the dorsal pedis and lateral plantar arteries (DPA and LPA) were recorded. RESULTS: A total of 137 patients with 258 lower limbs were included. ATmax was highly correlated to TBI (r = -0.89, p < 0.001). With the cut-off value of 215 ms, ATmax was effective to diagnose TP ⩽ 30 mmHg with a sensitivity of 93% [95% CI 77-99], a specificity of 96% [95% CI 92-98], a positive predictive value of 73% [95% CI 56-86], a negative predictive value of 99% [95% CI 97-100], and an area under the receiver operating characteristics curve of 0.99 [95% CI 0.98-1.00]. ATmax also showed promising results to rule out PAD in healthy patients. CONCLUSION: ATmax is a reliable diagnostic tool to diagnose low TP and could be a new easily performed hemodynamic criterion for diagnosis of CLTI.

Characteristics and correlation of body fat distribution and brachial-ankle pulse wave velocity in adults aged 20-59 years: a cross-sectional study.

BACKGROUND: Fat distribution is closely related to vascular stiffness. This study aimed to investigate age and sex differences in fat distribution and brachial-ankle pulse wave velocity (baPWV), and the association between fat parameters and baPWV. METHODS: A total of 10,811 participants aged 20-59 years were recruited. Measures included waist and hip circumference, waist-to-hip ratio (WHR), body mass index (BMI), percentage body fat (PBF), subcutaneous fat area (SFA), visceral fat area (VFA), and baPWV. RESULTS: The results confirm that fat accumulates with age and that men tend to carry more abdominal fat than women in the same age group. The findings also indicate that baPWV increases with age and is significantly higher in men than in women in the same age group. In addition, WHR, VFA, and baPWV were more strongly correlated than baPWV and BMI, SFA, and PBF. Finally, the effects of age, PBF, WHR, and VFA on baPWV were greater for the higher quantiles. CONCLUSIONS: There are age and sex differences in fat distribution and baPWV. Abdominal obesity is more closely linked to arterial stiffness than overall obesity, and people with higher baPWV are more affected by obesity parameters.

CAVI (Cardio-Ankle Vascular Index) as an independent predictor of hypertensive response to exercise.

OBJECTIVES: Hypertensive response to exercise (HRE) is related to the development of future hypertension, cardiovascular morbidity, and mortality, independent of resting blood pressure. We hypothesized that arterial stiffness as measured by cardio-ankle vascular index (CAVI) could be an independent predictor of HRE. MATERIALS AND METHODS: Retrospective chart review of patients participated in the preventive health program at the Bangkok Heart Hospital who underwent both CAVI and treadmill stress testing on the same day between June and December 2018 were performed. Variables for the prediction of HRE were analyzed using univariate analysis, and significant variables were entered into multiple logistic regression. An ROC curve was created to test the sensitivity and specificity of CAVI as a predictor of HRE. RESULTS: A total of 285 participants (55.1% female) were enrolled in this study. There were 58 patients (20.4%) who met the HRE definition (SBP > 210 mmHg in males, SBP > 190 mmHg in females, or DBP > 110 mmHg in both males and females), with a mean age of 46.4 12.8 years. In univariate analysis, age, systolic blood pressure at rest, diastolic blood pressure at rest, pulse pressure at rest, diabetes mellitus, hypertension, dyslipidemia, history of beta-blocker, and CAVI results were statistically significant. Multiple logistic regression revealed that CAVI and systolic blood pressure were statistically significant predictors of HRE with OR of 5.8, 95%CI: 2.9-11.7, P < 0.001 and OR 1.07, 95%CI: 1.03-1.10, P = 0.001 respectively. ROC curve analysis of the CAVI revealed an AUC of 0.827 (95%CI: 0.76-0.89, p < 0.001), and the sensitivity and specificity of cut-point CAVI > 8 were 53% and 92%, respectively. CONCLUSION: This study demonstrated that CAVI is an independent predictor of hypertensive response to exercise. Additionally, the findings suggest that CAVI > 8 can be a valuable tool in identifying individuals at risk for hypertensive responses during exercise.

Fasting Blood Glucose: A Mediator of the Association between Estimated Glomerular Filtration Rate and Arterial Stiffness in Japanese Population with Decreased Kidney Function.

INTRODUCTION: Low estimated glomerular filtration rate (eGFR) is associated with an increased risk of arterial stiffness in participants with kidney damage. It is uncertain whether this association is due to eGFR itself or is mediated by the eGFR-associated increases in fasting blood glucose (FBG). METHOD: The cross-sectional study included 865 Japanese participants with decreased kidney function, whose eGFR was less than 90 mL/min/1.73 m2, and recruited individuals who received medical healthcare. The mediating variable was FBG, with eGFR as the independent variable and brachial-ankle pulse wave velocity (baPWV) as the dependent variable. A mediation analysis was used to evaluate the mediating effect of FBG on the association between eGFR and arterial stiffness. RESULTS: The mean age of the participants was 51.69 ± 9.25 years old, with 65.90% individuals being male. The mean values for FBG, eGFR, and baPWV were 5.46 ± 0.79 mmol/L, 68.83 ± 10.05 mL/min/1.73 m2, and 1,423.50 ± 247.78 cm/s, respectively. The mediation analysis revealed that eGFR had a significant direct effect on baPWV (ß = -25.68 95% CI: -46.42, -7.45), and that FBG played a partial mediating role in the indirect effect of eGFR on baPWV (ß = -3.54 95% CI: -11.88, -0.079). Mediation analysis showed that 12.10% of the effect of eGFR on risk of arterial stiffness was mediated through FBG. CONCLUSION: The study indicated that there is a mediating relationship between eGFR and FBG in people with decreased kidney function, which is associated with the risk of arterial stiffness. Therefore, the importance of FBG as a mediator should be acknowledged and taken into consideration.

Controlling flat-foot limit cycle walkers with compliant joints based on local stability variation.

This study investigates local stability of a four-link limit cycle walking biped with flat feet and compliant ankle joints. Local stability represents the behavior along the solution trajectory between Poincare sections, which can provide detailed information about the evolution of disturbances. The effects of ankle stiffness and foot structure on local stability are studied. In addition, we apply a control strategy based on local stability analysis to the limit cycle walker. Control is applied only in the phases with poor local stability. Simulation results show that the energy consumption is reduced without sacrificing disturbance rejection ability. This study may be helpful in motion control of limit cycle bipedal walking robots with flat feet and ankle stiffness and understanding of human walking principles.