Contemporary Outcomes of Transfemoral Amputation After Total Knee Arthroplasty.

BACKGROUND: Transfemoral amputation (TFA) is a salvage procedure for unreconstructable failed total knee arthroplasty (TKA). Prior studies have reported poor outcomes, patient survival, and prosthetic use. The purpose of this study was to analyze patient outcomes and prosthetic utilization in a contemporary group of patients undergoing TFA in the setting of a TKA. METHODS: We reviewed 112 patients undergoing TFA with a prior TKA. Indications for amputation and postoperative functional measures were captured through chart review. Patients were contacted by survey to assess the quality of life. The mean follow-up after TFA was 4 years. RESULTS: Amputations were performed for a chronically infected TKA (n = 87, 78%) and an ischemic limb without signs of an infected TKA (n = 22, 20%). The 10-year survival after TFA was 21%. Of the patients not lost to follow-up, 53 (47%) patients were fitted for a prosthesis. Patients who underwent a TFA after the year 2000 were more likely to be fit for a prosthesis (odds ratio 7.27, P < .01); however, patients were likely to be ambulatory before TFA than after TFA (odds ratio 3.68, P < .01). After TFA, the mean 12-Item Short Form Survey scores for the mental and physical components were 54 ± 13 and 34 ± 7, with no difference in scores between patients fitted for a prosthesis and those who were not (P > .05). CONCLUSION: Patients undergoing a TFA after TKA due to failure of the TKA are more likely to be fit for a prosthesis; however, they reported no better quality of life and satisfaction compared with patients not fit for a prosthesis. LEVELS OF EVIDENCE: Level III, Therapeutic.

Effects of high- and low-dose aspirin on adaptive immunity and hypertension in the stroke-prone spontaneously hypertensive rat.

Despite its well-known antithrombotic properties, the effect of aspirin on blood pressure (BP) and hypertension pathology is unclear. The hugely varying doses used clinically have contributed to this confusion, with high-dose aspirin still commonly used due to concerns about the efficacy of low-dose aspirin. Because prostaglandins have been shown to both promote and inhibit T-cell activation, we also explored the immunomodulatory properties of aspirin in hypertension. Although the common preclinical high dose of 100 mg/kg/d improved vascular dysfunction and cardiac hypertrophy, this effect was accompanied by indices of elevated adaptive immunity, renal T-cell infiltration, renal fibrosis, and BP elevation in stroke-prone spontaneously hypertensive rats and in angiotensin II-induced hypertensive mice. The cardioprotective effects of aspirin were conserved with a lower dose (10 mg/kg/d) while circumventing heightened adaptive immunity and elevated BP. We also show that low-dose aspirin improves renal fibrosis. Differential inhibition of the COX-2 isoform may underlie the disparate effects of the 2 doses. Our results demonstrate the efficacy of low-dose aspirin in treating a vast array of cardiovascular parameters and suggest modulation of adaptive immunity as a novel mechanism underlying adverse cardiovascular profiles associated with COX-2 inhibitors. Clinical studies should identify the dose of aspirin that achieves maximal cardioprotection with a new awareness that higher doses of aspirin could trigger undesired autoimmunity in hypertensive individuals. This work also warrants an evaluation of high-dose aspirin and COX-2 inhibitor therapy in sufferers of inflammatory conditions who are already at increased risk for cardiovascular disease.-Khan, S. I., Shihata, W. A., Andrews, K. L., Lee, M. K. S., Moore, X.-L., Jefferis, A.-M., Vinh, A., Gaspari, T., Dragoljevic, D., Jennings, G. L., Murphy, A. J., Chin-Dusting, J. P. F. Effects of high- and low-dose aspirin on adaptive immunity and hypertension in the stroke-prone spontaneously hypertensive rat.

Chronic sympathetic driven hypertension promotes atherosclerosis by enhancing hematopoiesis.

Hypertension is a major, independent risk factor for atherosclerotic cardiovascular disease. However, this pathology can arise through multiple pathways, which could influence vascular disease through distinct mechanisms. An overactive sympathetic nervous system is a dominant pathway that can precipitate in elevated blood pressure. We aimed to determine how the sympathetic nervous system directly promotes atherosclerosis in the setting of hypertension. We used a mouse model of sympathetic nervous system-driven hypertension on the atherosclerotic-prone apolipoprotein E-deficient background. When mice were placed on a western type diet for 16 weeks, we showed the evolution of unstable atherosclerotic lesions. Fortuitously, the changes in lesion composition were independent of endothelial dysfunction, allowing for the discovery of alternative mechanisms. With the use of flow cytometry and bone marrow imaging, we found that sympathetic activation caused deterioration of the hematopoietic stem and progenitor cell niche in the bone marrow, promoting the liberation of these cells into the circulation and extramedullary hematopoiesis in the spleen. Specifically, sympathetic activation reduced the abundance of key hematopoietic stem and progenitor cell niche cells, sinusoidal endothelial cells and osteoblasts. Additionally, sympathetic bone marrow activity prompted neutrophils to secrete proteases to cleave the hematopoietic stem and progenitor cell surface receptor CXCR4. All these effects could be reversed using the ß-blocker propranolol during the feeding period. These findings suggest that elevated blood pressure driven by the sympathetic nervous system can influence mechanisms that modulate the hematopoietic system to promote atherosclerosis and contribute to cardiovascular events.

Y-chromosome lineage determines cardiovascular organ T-cell infiltration in the stroke-prone spontaneously hypertensive rat.

The essential role of the Y chromosome in male sex determination has largely overshadowed the possibility that it may exert other biologic roles. Here, we show that Y-chromosome lineage is a strong determinant of perivascular and renal T-cell infiltration in the stroke-prone spontaneously hypertensive rat, which, in turn, may influence vascular function and blood pressure (BP). We also show, for the first time to our knowledge, that augmented perivascular T-cell levels can directly instigate vascular dysfunction, and that the production of reactive oxygen species that stimulate cyclo-oxygenase underlies this. We thus provide strong evidence for the consideration of Y-chromosome lineage in the diagnosis and treatment of male hypertension, and point to the modulation of cardiovascular organ T-cell infiltration as a possible mechanism that underpins Y- chromosome regulation of BP.-Khan, S. I., Andrews, K. L., Jackson, K. L., Memon, B., Jefferis, A.-M., Lee, M. K. S., Diep, H., Wei, Z., Drummond, G. R., Head, G. A., Jennings, G. L., Murphy, A. J., Vinh, A., Sampson, A. K., Chin-Dusting, J. P. F. Y-chromosome lineage determines cardiovascular organ T-cell infiltration in the stroke-prone spontaneously hypertensive rat.

Cyclo-Oxygenase (COX) Inhibitors and Cardiovascular Risk: Are Non-Steroidal Anti-Inflammatory Drugs Really Anti-Inflammatory?

Cyclo-oxygenase (COX) inhibitors are among the most commonly used drugs in the western world for their anti-inflammatory and analgesic effects. However, they are also well-known to increase the risk of coronary events. This area is of renewed significance given alarming new evidence suggesting this effect can occur even with acute usage. This contrasts with the well-established usage of aspirin as a mainstay for cardiovascular prophylaxis, as well as overwhelming evidence that COX inhibition induces vasodilation and is protective for vascular function. Here, we present an updated review of the preclinical and clinical literature regarding the cardiotoxicity of COX inhibitors. While studies to date have focussed on the role of COX in influencing renal and vascular function, we suggest an interaction between prostanoids and T cells may be a novel factor, mediating elevated cardiovascular disease risk with NSAID use.

Y Chromosome, Hypertension and Cardiovascular Disease: Is Inflammation the Answer?

It is now becomingly increasingly evident that the functions of the mammalian Y chromosome are not circumscribed to the induction of male sex. While animal studies have shown variations in the Y are strongly accountable for blood pressure (BP), this is yet to be confirmed in humans. We have recently shown modulation of adaptive immunity to be a significant mechanism underpinning Y-chromosome-dependent differences in BP in consomic strains. This is paralleled by studies in man showing Y chromosome haplogroup is a significant predictor for coronary artery disease through influencing pathways of immunity. Furthermore, recent studies in mice and humans have shown that Y chromosome lineage determines susceptibility to autoimmune disease. Here we review the evidence in animals and humans that Y chromosome lineage influences hypertension and cardiovascular disease risk, with a novel focus on pathways of immunity as a significant pathway involved.

Plantar Ulcers and Neuropathic Arthropathies: Associated Diseases, Polyneuropathy Correlates, and Risk Covariates.

OBJECTIVE: To evaluate the associated diseases, polyneuropathy correlates, and risk covariates of neuropathic plantar ulcers (PUs) and neuropathic arthropathies (NAs). DESIGN: The authors conducted a retrospective, observational study over 3.5 years of 69 patients with neuropathy, NA, or PU seen in a wound clinic who also had a comprehensive neurologic evaluation and neurophysiologic testing. Comparisons were made to a population representative cohort of patients with diabetes mellitus (DM; n = 259). RESULTS: Of the 69 wound clinic patients, 32 had PUs, 14 had NAs, and 23 had both. Of the 61 adequately assessed patients, 37 (61%) had DM, 22 (36%) had no known associated disease, and 2 (3%) had hereditary sensory and autonomic neuropathy. Of the 37 patients with DM, 35 had distal polyneuropathy, and 2 did not. In 22 patients with chronic idiopathic axonal polyneuropathy, 20 had distal polyneuropathy. CONCLUSIONS: Although DM was the disease most commonly associated with PUs and NAs, chronic hyperglycemia may not have been the major underlying risk factor. The major risk covariates are sensation loss from polyneuropathy, old age, obesity, repetitive foot injury, and inadequate foot care or treatment. Physicians and other healthcare providers can help by identifying patients at risk and instituting measures such as adequate foot care to decrease these risks.

Vascular dysfunction in the stroke-prone spontaneously hypertensive rat is dependent on constrictor prostanoid activity and Y chromosome lineage.

Vascular dysfunction is a hallmark of hypertension and the strongest risk factor to date for coronary artery disease. As Y chromosome lineage has emerged as one of the strongest genetic predictors of cardiovascular disease risk to date, we investigated if Y chromosome lineage modulated this important facet in the stroke-prone spontaneously hypertensive rat (SHRSP) using consomic strains. Here, we show that vascular dysfunction in the SHRSP is attributable to differential cyclooxygenase (COX) activity with nitric oxide (NO) levels playing a less significant role. Measurement of prostacyclin, the most abundant product of COX in the vasculature, confirmed the augmented COX activity in the SHRSP aorta. This was accompanied by functional impairment of the vasodilatory prostacyclin (IP) receptor, while inhibition of the thromboxane (TP) receptor significantly ameliorated vascular dysfunction in the SHRSP, suggesting this is the downstream target responsible for constrictor prostanoid activity. Importantly, Y chromosome lineage was shown to modulate vascular function in the SHRSP through influencing COX activity, prostacyclin levels and IP dysfunction. Vascular dysfunction in the renal and intrarenal arteries was also found to be prostanoid and Y chromosome dependent. Interestingly, despite no apparent differences in agonist-stimulated NO levels, basal NO levels were compromised in the SHRSP aorta, which was also Y chromosome dependent. Thus, in contrast with the widely held view that COX inhibition is deleterious for the vasculature due to inhibition of the vasodilator prostacyclin, we show that COX inhibition abolishes vascular dysfunction in three distinct vascular beds, with IP dysfunction likely being a key mechanism underlying this effect. We also delineate a novel role for Y chromosome lineage in regulating vascular function through modulation of COX and basal NO levels.

Nitroxyl (HNO) reduces endothelial and monocyte activation and promotes M2 macrophage polarization.

Nitroxyl anion (HNO) donors are currently being assessed for their therapeutic utility in several cardiovascular disorders including heart failure. Here, we examine their effect on factors that precede atherosclerosis including endothelial cell and monocyte activation, leucocyte adhesion to the endothelium and macrophage polarization. Similar to the NO donor glyceryl trinitrate (GTN), the HNO donors Angeli's salt (AS) and isopropylamine NONOate (IPA/NO) decreased leucocyte adhesion to activated human umbilical vein endothelial cells (HUVECs) and mouse isolated aorta. This reduction in adhesion was accompanied by a reduction in intercellular adhesion molecule-1 (ICAM-1) and the cytokines monocyte chemoattractant protein 1 (MCP-1) and interleukin 6 (IL-6) which was inhibitor of nuclear factor κB (NFκB) α (IκBα)- and subsequently NFκB-dependent. Intriguingly, the effects of AS on leucocyte adhesion, like those on vasodilation, were found to not be susceptible to pharmacological tolerance, unlike those observed with GTN. As well, HNO reduces monocyte activation and promotes polarization of M2 macrophages. Taken together, our data demonstrate that HNO donors can reduce factors that are associated with and which precede atherosclerosis and may thus be useful therapeutically. Furthermore, since the effects of the HNO donors were not subject to tolerance, this confers an additional advantage over NO donors.

Nitroxyl: a vasodilator of human vessels that is not susceptible to tolerance.

Pre-clinical studies have identified nitroxyl (HNO), the reduced congener of nitric oxide (NO•), as a potent vasodilator which is resistant to tolerance development. The present study explores the efficacy of HNO in human blood vessels and describes, for the first time, a vasodilator for humans that is not susceptible to tolerance. Human radial arteries and saphenous veins were obtained from patients undergoing coronary artery graft surgery and mounted in organ baths. Repeated vasodilator responses to the HNO donor Angeli's salt (AS) and NO• donor glyceryl trinitrate (GTN) were determined. AS- and GTN-induced concentration-dependent vasorelaxation of both human radial arteries (AS pEC50: 6.5 ± 0.2; -log M) and saphenous veins (pEC50: 6.7 ± 0.1) with similar potency. In human radial arteries, GTN-induced relaxation was reduced by the NO• scavenger hydroxocobalamin (HXC; P<0.05) but was unaffected by the HNO scavenger L-cysteine. Alternately, AS was unaffected by HXC but was reduced by L-cysteine (5-fold shift, P<0.05). The sGC (soluble guanylate cyclase) inhibitor ODQ abolished responses to both AS and GTN in arteries and veins (P<0.05). Inhibition of voltage-dependent potassium channels (Kv channels) with 4-AP also significantly reduced responses to AS (pEC50: 5.5) and GTN, suggesting that the relaxation to both redox congeners is cGMP- and Kv channel-dependent. Critically, a concentration-dependent development of tolerance to GTN (1 and 10 µM; P<0.05), but not to AS, was observed in both saphenous veins and radial arteries. Like GTN, the HNO donor AS causes vasorelaxation of human blood vessels via activation of a cGMP-dependent pathway. Unlike GTN, however, it does not develop tolerance in human blood vessels.

NADPH oxidase 1 plays a key role in diabetes mellitus-accelerated atherosclerosis.

BACKGROUND: In diabetes mellitus, vascular complications such as atherosclerosis are a major cause of death. The key underlying pathomechanisms are unclear. However, hyperglycemic oxidative stress derived from NADPH oxidase (Nox), the only known dedicated enzyme to generate reactive oxygen species appears to play a role. Here we identify the Nox1 isoform as playing a key and pharmacologically targetable role in the accelerated development of diabetic atherosclerosis. METHODS AND RESULTS: Human aortic endothelial cells exposed to hyperglycemic conditions showed increased expression of Nox1, oxidative stress, and proinflammatory markers in a Nox1-siRNA reversible manner. Similarly, the specific Nox inhibitor, GKT137831, prevented oxidative stress in response to hyperglycemia in human aortic endothelial cells. To examine these observations in vivo, we investigated the role of Nox1 on plaque development in apolipoprotein E-deficient mice 10 weeks after induction of diabetes mellitus. Deletion of Nox1, but not Nox4, had a profound antiatherosclerotic effect correlating with reduced reactive oxygen species formation, attenuation of chemokine expression, vascular adhesion of leukocytes, macrophage infiltration, and reduced expression of proinflammatory and profibrotic markers. Similarly, treatment of diabetic apolipoprotein E-deficient mice with GKT137831 attenuated atherosclerosis development. CONCLUSIONS: These studies identify a major pathological role for Nox1 and suggest that Nox1-dependent oxidative stress is a promising target for diabetic vasculopathies, including atherosclerosis.

Opinions on noninvasive sensory feedback of upper limb prosthetic users.

BACKGROUND: Restoring touch perception for individuals with upper extremity limb loss is an ambitious task. It is important to understand how persons with upper limb loss think this would be best achieved. METHODS: An anonymous online survey was developed to obtain data from prosthetic users. Participants ranked the perceived acceptability and effectiveness of noninvasive sensory feedback to areas of intact sensation not typically involved in sensory feedback (i.e., the arm). The focus was on 4 main types of haptic information-object contact, proprioception, surface texture, and grasp force-as well as how best to convey those senses with various stimuli. The users were asked to grade themselves in certain tasks and then analyze which tasks would be improved with sensory feedback. Associations were explored between demographic characteristics and interest in sensory feedback. RESULTS: Nationally, prostheses providers sent more than 2000 email invitations to the online survey and received 142 unique responses. Responses indicated interest in sensory feedback through prosthetic limbs by individuals with upper limb loss. The most popular pairing of haptic information with sensory substitution was grasp force paired with gentle vibration. Tasks that most persons taking the survey agreed would benefit from sensory feedback were zipping a jacket, tying shoes, buttoning a shirt, and using a cup. No difference was observed in interest between sex and employment status, but a significant decrease (P = .004) was seen in interest among participants with more years of prosthetic use. DISCUSSION: The results from this national survey of upper extremity prosthetic users can be used to help guide the development of noninvasive sensory feedback options.

High intraluminal pressure promotes vascular inflammation via caveolin-1.

The aetiology and progression of hypertension involves various endogenous systems, such as the renin angiotensin system, the sympathetic nervous system, and endothelial dysfunction. Recent data suggest that vascular inflammation may also play a key role in the pathogenesis of hypertension. This study sought to determine whether high intraluminal pressure results in vascular inflammation. Leukocyte adhesion was assessed in rat carotid arteries exposed to 1 h of high intraluminal pressure. The effect of intraluminal pressure on signaling mechanisms including reactive oxygen species production (ROS), arginase expression, and NFĸB translocation was monitored. 1 h exposure to high intraluminal pressure (120 mmHg) resulted in increased leukocyte adhesion and inflammatory gene expression in rat carotid arteries. High intraluminal pressure also resulted in a downstream signaling cascade of ROS production, arginase expression, and NFĸB translocation. This process was found to be angiotensin II-independent and mediated by the mechanosensor caveolae, as caveolin-1 (Cav1)-deficient endothelial cells and mice were protected from pressure-induced vascular inflammatory signaling and leukocyte adhesion. Cav1 deficiency also resulted in a reduction in pressure-induced glomerular macrophage infiltration in vivo. These findings demonstrate Cav1 is an important mechanosensor in pressure-induced vascular and renal inflammation.

Anti-atherogenic effects of high-density lipoprotein on nitric oxide synthesis in the endothelium.

1. The endothelium is critical in the control of vascular haemodynamics and haemostasis. Endothelial dysfunction, typically characterized by decreased nitric oxide bioavailability and response to endothelium-dependent agonists, is well accepted as a defining characteristic of early atherosclerosis. 2. Numerous epidemiological studies have reported that increased levels of circulating HDL are vasculoprotective and reduce the incidence of adverse cardiovascular events. Traditionally, these effects have been attributed to the ability of HDL to remove cholesterol from cells via reverse cholesterol transport. However, there is increasing evidence that the beneficial effects on the endothelium by HDL encompass its anti-inflammatory, antithrombotic and anti-oxidative properties, which include the release of nitric oxide (NO). 3. This review highlights recent findings on the importance of HDL in reducing atherosclerotic risk. We focus on the beneficial effects of HDL-induced NO release and how this relates to endothelial dysfunction and on the effect of HDL on vascular repair via endothelial progenitor cells.

Nitroxyl (HNO): the Cinderella of the nitric oxide story.

Until recently, most of the biological effects of nitric oxide (NO) have been attributed to its uncharged state (NO*), yet NO can also exist in the reduced state as nitroxyl (HNO or NO(-)). Putatively generated from both NO synthase (NOS)-dependent and -independent sources, HNO is rapidly emerging as a novel entity with distinct pharmacology and therapeutic advantages over its redox sibling, NO*. Thus, unlike NO*, HNO can target cardiac sarcoplasmic ryanodine receptors to increase myocardial contractility, can interact directly with thiols and is resistant to both scavenging by superoxide (*O2-) and tolerance development. HNO donors are protective in the setting of heart failure in which NO donors have minimal impact. Here, we discuss the unique pharmacology of HNO versus NO* and highlight the therapeutic potential of HNO donors in the treatment of cardiovascular disease.

Using a silver-coated polymeric substrate for the management of chronic ulcerations: the initial Mayo Clinic experience.

BACKGROUND: This retrospective observational study was designed to review the use of a silver-coated polymeric substrate on various types of chronic wounds at the Mayo Clinic in Rochester, Minnesota. METHODS: The study was set in a community and referral multidisciplinary vascular wound clinic. The authors identified the first 112 patients treated with a silver dressing in the center. Of these, 15 were lost to follow-up or had incomplete data. Ninety-seven patients were included in the study. Thirty-seven of these 97 patients had multiple wounds; however, 1 wound per person was randomly chosen for analysis. The median age of these patients was 69 years. A wound was considered healed when the wound was completely epithelialized. Of the 97 wounds evaluated, the primary etiologies were as follows: 20 (20.6%) were neurotrophic, 24 (24.7%) were ischemic (arterial, arteriolar, or vasculitic), 20 (20.6%) were venous, 7 (7.2%) were traumatic, and 16 (16.5%) were multifactorial. The silver dressing was the primary wound care product on all wounds. Silverlon (Argentum LLC, Chicago, Illinois) was the silver dressing used for this study. The frequency of dressing changes and use of secondary dressings, to keep the wound moist, were based on the amount of drainage, debris, and slough on the wound. Data pertaining to patient demographics, risk factors, wound etiology, noninvasive arterial vascular studies, frequency of dressing changes, wound discomfort, wound size, and wound duration were collected by retrospective chart review. RESULTS: Thirty-five of the 97 wounds (36.1%) healed. The 62 nonhealed wounds (63.9%) decreased in size by a median of 55.2%. Among the 68 patients who had reported discomfort before the study, 77.9% reported no change in discomfort, 17.7% reported increased pain, and 4.4% reported decreased pain. CONCLUSION: A silver-coated polymeric substrate (Silverlon) can be used as an effective primary wound care dressing in patients with active wounds.

Expedited wound healing with noncontact, low-frequency ultrasound therapy in chronic wounds: a retrospective analysis.

OBJECTIVE: To evaluate the clinical role of noncontact, low-frequency ultrasound therapy (MIST Therapy System; Celleration, Eden Prairie, Minnesota) in the treatment of chronic lower-extremity wounds. DESIGN: A retrospective observational study. SETTING: A multidisciplinary, vascular wound-healing clinic. PATIENTS: One hundred sixty-three patients who received MIST Therapy plus standard of care (treatment group) and 47 patients who received the standard of care alone (control group). INTERVENTIONS: All wounds in the control and treatment groups received the standard of wound care and were followed for 6 months. In the treatment group, MIST Therapy was administered to wounds 3 times per week for 90 days or until healed. MAIN OUTCOME MEASURES: Proportion of wounds healed and wound volume reduction. Rate of healing was also quantified using 1-way analysis of variance to determine the slope of the regression line from starting volume to ending volume, where a steeper slope indicates a faster healing rate. Outcomes were evaluated in all wounds and etiology-specific subgroups. MAIN RESULTS: A significantly greater percentage of wounds treated with MIST Therapy and standard of care healed as compared with those treated with the standard of care alone (53% vs 32%; P = 0.009). The slope of the regression line in the MIST arm (1.4) was steeper than the slope in the control arm (0.22; P = .002), indicating a faster rate of healing in the MIST-treated wounds. CONCLUSION: The rate of healing and complete closure of chronic wounds in patients improved significantly when MIST Therapy was combined with standard wound care.

The Impact of the Immediate Postoperative Prosthesis on Patient Mobility and Quality of Life after Transtibial Amputation.

BACKGROUND: The immediate postoperative prosthesis has been purported to allow early mobilization with potential physical and psychologic benefits to patients. This study used accelerometers and validated questionnaires to prospectively examine activity level and quality of life data for patients receiving an immediate postoperative prosthesis after transtibial amputation. METHODS: A total of 10 patients were included in the study. Mean age was 58 yrs (range, 22-69 yrs), there were 9 men and 1 woman, and reason for amputation was nonhealing gangrenous ulcer in 9 patients and ischemic limb in 1 patient. Patients were followed for 6 wks. Activity data were collected on ActiGraph GT3X accelerometers and analyzed using ActiLife 6 Data Analysis Software. At the 6-wk postoperative visit, an Amputee Mobility Predictor clinician-rated performance evaluation was conducted and a Short Form-36 questionnaire was completed. RESULTS: Patients in the cohort spent an average of 88% (range, 83%-92%) of their time sedentary, 11.5% (range, 7.6%-16.9%) of their time in light physical activity, and 0.3% (range, 0.12%-1.36%) of their time in moderate to vigorous physical activity. No statistically significant relationships were observed between expected level of function and recorded activity level. Patients had low physical and emotional Short Form-36 component scores. CONCLUSIONS: Patients with transtibial amputations were extremely sedentary in the early postoperative period despite their immediate postoperative prosthesis dressings.

Grasp Performance of a Soft Synergy-Based Prosthetic Hand: A Pilot Study.

Current prosthetic hands are frequently rejected in part due to limited functionality and versatility. We assessed the feasibility of a novel prosthetic hand, the SoftHand Pro (SHP), whose design combines soft robotics and hand postural synergies. Able-bodied subjects ( ) tracked cursor motion by opening and closing the SHP and performed a grasp-lift-hold-release (GLHR) task with a sensorized cylindrical object of variable weight. The SHP control was driven by electromyographic (EMG) signals from two antagonistic muscles. Although the time to perform the GLHR task was longer for the SHP than native hand for the first few trials (10.2 ± 1.4 s and 2.13 ± 0.09 s, respectively), performance was much faster on subsequent trials (~5 s). The SHP steady-state grip force was significantly modulated as a function of object weight ( ). For the native hand, however, peak and steady-state grip forces were modulated to a greater extent (+68% and +91%, respectively). These changes were mediated by the modulation of EMG amplitude and co-contraction. These data suggest that the SHP has a promise for prosthetic applications and point-to-design modifications that could improve the SHP.

Caveolae: A Role in Endothelial Inflammation and Mechanotransduction?

Vascular inflammation and disease progression, such as atherosclerosis, are in part a consequence of haemodynamic forces generated by changes in blood flow. The haemodynamic forces, such as shear stress or stretch, interact with vascular endothelial cells, which transduce the mechanical stimuli into biochemical signals via mechanosensors, which can induce an upregulation in pathways involved in inflammatory signaling. However, it is unclear how these mechanosensors respond to shear stress and most significantly what cellular mechanisms are involved in sensing the haemodynamic stimuli. This review explores the transition from shear forces, stretch and pressure to endothelial inflammation and the process of mechanotransduction, specifically highlighting evidence to suggest that caveolae play as a role as mechanosensors.