Evaluation of an interphalangeal-joint prosthetic hand in trans-radial prosthesis users.

BACKGROUND: A body-powered functional and cosmetically appeasing hand with moving interphalangeal joints (IPJ-Hand) was created. Function and satisfaction with the IPJ-Hand, conventional hand (CH) and functional hook (FH) in trans-radial prosthesis users were evaluated. METHODS: Eight participants with trans-radial amputations were provided with three prosthetic hands and performed the Nine Hole Peg Test (NHPT), Brief Activity Measure of Upper Limb Amputees (BAM-ULA) and Quebec User Evaluation of Satisfaction with Assistive Technology QUEST). RESULTS: The data are shown as the median and interquartile range (IQR) due to skewed data distribution. Differences across hands were seen in NHPT with CH 57 (13.3), FH 49.5 (26.5), IPJ-H and 49 (14.8) seconds respectively. BAM-ULA, 10 (1.5), FH 10 (0.7), and IPJ-Hand 10 (1.7). QUEST scores, FH 28.5 (7.2) with the highest score, IPJ-Hand 26 (6.8), and lastly CH 25.5 (9.2). CONCLUSION: Individual participant results varied, with some participants performing better on the NHPT when using the IPJ-Hand when compared to the CH and FH. No differences between hands on the BAM-ULA were seen, and although no large differences in QUEST were observed, users performed best using IPJ-Hand.Key messagesAn interphalangeal joint prosthetic hand (IPJ-Hand) offers the similar function of a prosthetic hook, and the appearance of a conventional hand, but with improved dexterity.Minimal resources are needed to create the IPJ-Hand for prosthesis wearers.

High-Level Mobility of Trans-Tibial Prosthesis Users Wearing Commercial and sPace Energy-Storing Prosthetic Feet.

Outcomes of users provided with a commercial ESR Vari-Flex foot (Össur, Reykjavik, Iceland) and a locally designed sPace foot were investigated. Step activity with users' own prosthetic foot compared to the sPace foot was explored. METHODS: Eleven individuals with unilateral trans-tibial amputation participated and were provided with an sPace and Vari-Flex foot. Ten- and twenty-meter walk tests (10/20MWT) at comfortable and fast walking speeds (CWS/FWS), the two-minute walk test (2-MWT) and Comprehensive High-Level Activity Mobility Predictor (CHAMP) were administered. A subgroup was provided a pedometer to record their steps over a 7-day period in their own foot and later the sPace. RESULTS: The sPace foot performed well in a battery of high-level mobility outcome measures. On CHAMP, participants scored 16.94 ± 5.41 and 16.72 ± 6.09 with the sPace and Vari-Flex feet, respectively. Subgroup testing of step activity showed 4490 ± 3444 steps in users' own feet and 3115 ± 1967 in the sPace foot, p = 0.176. CONCLUSIONS: Participants using the sPace foot were capable of performing walking, high-level mobility and activity outcome measures.

Assessment of Socket Pressure during Walking in Rapid Fit Prosthetic Sockets.

(1) Background: A sustainable casting system that combines the use of a polystyrene bag, a prosthetic liner and a vacuum system was developed to reduce fabrication time while maintaining comfort for the trans-tibial prosthesis user. (2) Methods: Eight prosthetists (28.7 ± 8.25 years old) fit ten trans-tibial prosthesis wearers (46 ± 12.4 years old) with two types of total surface bearing (TSB) prostheses; a polystyrene bead (PS) prosthesis and a plaster of paris (POP) prosthesis. Duration of casting and combined mean peak pressure was measured at six locations on the residual limb using Force Sensing Resistors (FSR). A pressure uniformity score (%) was determined. Socket Comfort Scale (SCS) was also measured. (3) Results: Duration of casting for the POP method was 64.8 ± 9.53 min and 7.8 ± 2 min for the PS method, (p = 0.006). Pressure uniformity in the POP prosthesis was 79.3 ± 6.54 and 81.7 ± 5.83 in the PS prosthesis (p = 0.027). SCS in both prosthesis types were equivalent. (4) Conclusion: A rapid fit PS prosthesis was developed, with significantly shorter duration than the traditional POP method. Socket pressure uniformity was confirmed and improved in the PS method. Socket comfort was equal between the two prothesis types.

Sustainable, affordable and functional: reimagining prosthetic liners in resource limited environments.

PURPOSE: The purpose of this study was to evaluate function and performance of unilateral trans-tibial prosthesis users wearing an affordable liner in three types of socket designs. METHODS: Five unilateral trans-tibial amputees participated, were provided an Affordable Ethyl-Vinyl-Acetate Roll-On liner (AERO) roll-on liner with patella tendon bearing (PTB) prosthesis, PE-Lite liner with PTB prosthesis, and an (AERO) liner with total-surface bearing (TSB) prosthesis. A battery of outcome measures; step-counts, socket comfort score (SCS), orthotics prosthetics user survey (OPUS) and socket pressure measurement during walking were administered. RESULTS: Comparisons of step-counts indicated that PTB-AERO (3604 ± 815) was not significantly different than PTB-PE-Lite (3386 ± 942). Mean SCS was 9.2 ± .83 and 7.2 ± 2.1 for PTB-AERO and PTB-PE-Lite. A 6.6% decrease in mean peak pressure was observed between PTB-PE-Lite and TSB-AERO, and 3.2% difference between PTB-PE-Lite and PTB-AERO. CONCLUSION: An affordable ($20 USD) and sustainably fabricated prosthesis liner was created and evaluated in trans-tibial prosthesis users. These initial results garner preliminary support for use of the AERO prosthetic liner and continued research.Implications for rehabilitationLower limb prosthetics in less-resourced settings can leverage locally sourced and affordable materials to fabricate roll-on liners for use in modern prosthetic sockets.The cost of the AERO liner is markedly lower than current standard of care gel liners, yet still facilitates use of current prosthetic sockets.

Imaging Mass Microscopy of Kidneys from Azithromycin-Treated Rats with Phospholipidosis.

Drug-induced phospholipidosis is a lysosomal storage disorder characterized by the excess accumulation of tissue phospholipids. Although azithromycin can be used to induce phospholipidosis, no experimental studies evaluating the relationship between drug accumulation and phospholipid localization have been performed. In this study, azithromycin was orally administered to rats for 7 days, and the relationship between drug and phospholipid accumulation was performed using imaging mass microscopy. The administration of azithromycin induced tubular epithelial vacuolation in the inner stripe of the outer medulla of the kidney, consistent with the lamellar bodies that are typical manifestations of drug-induced phospholipidosis. Azithromycin and phospholipid tissue levels were extensively elevated in the kidneys of azithromycin-treated rats. Imaging mass microscopy revealed that both azithromycin and its metabolites were found in the kidneys of azithromycin-treated rats but not in control animals. The vacuolated areas of the kidneys were primarily found in the inner stripe of the outer medulla, consistent with the areas of high azithromycin concentration. Azithromycin was colocalized with several phospholipids-phosphatidylinositol (18:0/20:4), phosphatidylethanolamine (18:0/20:4 and 16:0/20:4), and possibly didocosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate, a putative biomarker of drug-induced phospholipidosis. In summary, we found correlations between regions of kidney damage and the accumulation of azithromycin, its metabolites, and phospholipids using imaging mass microscopy. Such analyses may help reveal the mechanism and identify putative biomarkers of drug-induced phospholipidosis.

The reversible adjustable coupling: A lightweight and low-cost alignment component for the lower limb prosthesis.

BACKGROUND: The alignment of the lower limb prosthesis is an integral part of the prosthetic fitting. A properly aligned prosthesis contributes to optimal gait and overall function of the patient. The current offering of alignment componentry is expensive for low-income countries. The purpose of this study was to develop a lightweight and low-cost alignment coupler for the lower limb prosthesis. METHODS: An alignment coupler called the reversible adjustable coupling was designed and manufactured. Measurements of total anterior/posterior and medial/lateral and rotation in prostheses were recorded and mechanical testing performed. Swiftness and difficulty of use was also recorded. RESULTS: The reversible adjustable coupling permitted acceptable ranges of anterior/posterior and medial/lateral translation and 30° of internal and external rotation of prosthetic componentry. Repetitive loading of the coupling at a speed of 1 Hz under 1.28 kN load for 2000 cycles was successful, as were static and strength tests. DISCUSSION: The coupler provided acceptable ranges of anterior/posterior and medial/lateral and rotation adjustment and is acceptable for potential use in the alignment of both exoskeletal and endoskeletal prosthesis. The final weight of the component was 166 g and cost of $55.00 USD is affordable for low-income countries for use in clinical and educational settings.

The development and testing of a modified natural rubber CR solid ankle-cushion heel prosthetic foot for developing countries.

BACKGROUND: Durable and locally fabricated prosthetic feet are important for developing countries. Modifications to the current CR solid ankle-cushion heel prosthetic foot could enhance current foot characteristics and reduce costs. The goal of this project was to modify the keel and rubber outer foot shell to enhance features and reduce costs of the current CR solid ankle-cushion heel offering. METHODS: The prosthetic foot was designed, fabricated and then tested mechanically for strain and displacement in a cyclic testing machine according to a component of the ISO-10328 testing protocol. Dynamic cyclic testing of both forefoot and heel portions of the foot was conducted. FINDINGS: Dynamic mechanical cyclic testing of the forefoot and heel at 1.28 kN for two million cycles at a rate of 1 Hz was successfully achieved. The final cost of producing the foot was roughly $16 USD. Limitations include the inability to perform the full battery of ISO-10328 foot testing, UV testing and a limitation to laboratory testing. Clinical studies examining practical application of the modified foot should be conducted.

Plasma substance P levels in patients with persistent cough.

BACKGROUND: Substance P (SP) is involved in the pathogenesis of cough in animal models. However, few studies in humans have been reported and the roles of SP in clinical cough remain obscure. OBJECTIVES: To clarify the relevance of plasma levels of SP in patients with persistent cough. METHODS: We studied 82 patients with cough persisting for at least 3 weeks and 15 healthy controls. Patients were classified as having asthmatic cough (cough-variant asthma and cough-predominant asthma; n = 61) or nonasthmatic cough (n = 21; postinfectious cough, n = 6; gastroesophageal reflux disease, n = 5; idiopathic cough, n = 5, and others, n = 5). Correlations were evaluated between plasma SP levels as measured with ELISA and methacholine airway hyperresponsiveness (airway sensitivity and airway reactivity), capsaicin cough sensitivity, sputum eosinophil and neutrophil counts, and pulmonary function. RESULTS: Plasma SP levels were significantly elevated in patients with both asthmatic and nonasthmatic cough compared with controls [31.1 pg/ml (range 18.0-52.2) and 30.0 pg/ml (range 15.1-50.3) vs. 15.4 pg/ml (range 11.3-23.7); p = 0.003 and p = 0.038, respectively] but did not differ between the two patient groups (p = 0.90). Plasma SP levels correlated with airway sensitivity (threshold dose of methacholine) in the patients with asthmatic cough (r = -0.37, p = 0.005) but not with airway reactivity, cough sensitivity, FEV1 values, or sputum eosinophil and neutrophil counts in either group. CONCLUSIONS: Increased levels of SP in plasma are associated with persistent cough in humans and might be related to airway sensitivity in asthmatic cough.

Regulation of dopamine-induced Na+ current response by small G-protein RhoB or C and phospholipase D in Aplysia neurons.

A family of GTP-binding proteins, Rho, plays critical roles in cell migration, morphological change, cytokinesis, and smooth muscle contraction. Furthermore, evidence has recently been accumulating for an involvement in regulation of receptor-operated ionic channels. We previously reported that stimulation of D1-like receptor by dopamine (DA) induces a slow Na+ current response in the identified neurons of Aplysia under voltage-clamp. To further study a regulatory mechanism of the DA-induced response, we examined possible involvement of small G-proteins and subsequent enzymes. The Na+ current response to DA was gradually and irreversibly depressed after the intracellular injection of either Clostridium difficile toxin B, an inhibitor for all Rho family G-proteins, or Clostridium botulinum C3 exoenzyme, a specific blocker for RhoA-C. Intacellular injection of active RhoA had no significant effect on the response. However, injection of GAP domain of p50RhoGAP significantly depressed the DA-induced response, while application of GEF domain of RhoGEF Dbs increased the response. In addition, either intracellular injection of alpha-synuclein or extracellular application of 1-butanol, inhibitors for phospholipase D (PLD), significantly depressed the DA-induced response. These results suggest that the DA-induced Na+ current response may be facilitated by the activation of Rho family G-protein RhoB or C but not RhoA, and subsequent PLD.

Regulatory roles of Ca2+/calmodulin-dependent protein kinase II and protein phosphatase 2A on the quisqualic acid-induced K+-current response in identified neurons of Aplysia.

In identified B6 neurons of Aplysia buccal ganglia under voltage-clamp, application of quisqualic acid (QA) induces a unique slow K(+)-current response independent of G-protein. The response was augmented by raising the temperature in a similar fashion to the Phe-Met-Arg-Phe-NH(2)-induced K(+)-current response mediated by Gi/o. The QA-induced K(+)-current response markedly increased during the perfusion with Ca(2+)-free solution or after the application of W-7, a calmodulin (CaM) inhibitor. It was also enhanced by intracellular application either of H-7, a serine/threonine protein kinase inhibitor, or of KN-93, a Ca(2+)/CaM-dependent kinase II (CaMKII) inhibitor. Furthermore, the QA-induced response was markedly augmented by pre-treatment with 2,3-butanedione monoxime, an inorganic phosphatase. Intracellular application of protein phosphatase 2A (PP2A) significantly augmented the QA-induced response although neither protein phosphatase 1 nor protein phosphatase 2B altered the response. Application of either okadaic acid or calyculin A, protein phosphatase inhibitors, only slightly depressed the QA-induced response. Surprisingly, W-7 had no augmenting effect on the QA-induced response when examined after the application of either okadaic acid or calyculin A. These results suggest that the K(+)-current response is reciprocally but sequentially regulated by PP2A and CaMKII, the response of which the former is facilitating and the latter is inhibiting.

Augmenting effect of serotonin on the voltage-dependent Ca2+ current and subsequently activated K+ current in Aplysia neurons.

Receptor-induced activation of protein kinase C (PKC) plays an important role in modulation of various types of ionic channels in neurons. For example, PKC causes facilitation or long-lasting activation of certain ionic channels involved in spike firing after the receptor stimulation. We investigated the effect of serotonin (5-HT) on the voltage-dependent Ca(2+) channels in RB and RC neurons of Aplysia ganglia under voltage clamp. An outward current response was induced by voltage change of the cell membrane from -60 mV to +10 mV. Application of 5-HT significantly augmented the outward current response to the voltage change. Both the outward current and the augmenting effect of 5-HT markedly decreased when examined in either Ca(2+)-free, 10 mM tetraethylammonium, or 0.3 mM Cd(2+)-solution, indicating the current to be Ca(2+)-activated K(+) current produced by Ca(2+) entry. Intracellular application of either guanosine 5'-O-(2-thiodiphosphate) or cholera toxin (CTX), reagents for G-proteins, irreversibly blocked the augmenting effect of 5-HT. Application of phorbol dibutylate (PDBu), an activator of PKC, augmented the outward current and the effect of 5-HT was occluded after PDBu application. Staurosporine, a specific inhibitor of PKC, markedly suppressed the augmenting effects of both 5-HT and PDBu on the outward current. However, either 5-HT or PDBu did not augment the Ca(2+)-activated K(+) current induced by intracellular injection of Ca(2+) but rather depressed it. These results suggest that stimulation of 5-HT receptor may activate a novel type of CTX-sensitive G-protein and subsequent PKC, and that phosphorylation of voltage-dependent Ca(2+) channels may result in the increase in Ca(2+) entry and subsequent Ca(2+)-activated K(+) current. The mechanism may contribute to retain the long-lasting activation without broadening of the spike width during the excitatory response to 5-HT in these neurons.

Electrophysiological and pharmacological characterization of the K(ATP) channel involved in the K+-current responses to FSH and adenosine in the follicular cells of Xenopus oocyte.

The follicular cells surrounding Xenopus oocyte under voltage clamp produce K(+)-current responses to follicle-stimulating hormone (FSH), adenosine (Ade), and intracellularly applied cAMP. We previously reported that these responses are suppressed by the stimulation of P2Y receptor through phosphorylation by PKC presumably of the ATP-sensitive K(+) (K(ATP)) channel. This channel comprises sulfonylurea receptors (SURs) and K(+) ionophores (Kirs) having differential sensitivities to K(+) channel openers (KCOs) depending on the SURs. To characterize the K(+) channels involved in the FSH- and Ade-induced responses, we investigated the effects of various KCOs and SUR blockers on the agonist-induced responses. The applications of PCO400, cromakalim (Cro), and pinacidil, but not diazoxide, produced K(+)-current responses similar to the FSH- and Ade-induced responses in the magnitude order of PCO400 > Cro >> pinacidil in favor of SUR2A. The application of glibenclamide, phentolamine, and tolbutamide suppressed all the K(+)-current responses to FSH, Ade, cAMP, and KCOs. Furthermore, both the FSH- and Ade-induced responses were markedly augmented during the KCO-induced responses, or vice versa. The I-V curves for the K(+)-current responses induced by Cro, Ade, and FSH showed outward rectification in normal [K(+)](o), but weak inward rectification in 122 mM [K(+)](o). Also, stimulations of P2Y receptor by UTP or PKC by PDBu markedly depressed the K(+)-current response to KCOs in favor of Kir6.1, as previously observed with the responses to FSH and Ade. These results suggest that the K(+)-current responses to FSH and Ade may be produced by the opening of a novel type of K(ATP) channel comprising SUR2A and Kir6.1.

The small GTP-binding protein RhoA regulates serotonin-induced Na+-current response in the neurons of Aplysia.

Application of serotonin (5-HT) induces a slow inward current response in identified neurons of Aplysia ganglia under voltage clamp. The 5-HT-induced current response was depressed in Na+-free media, but augmented in Ca2+-free media, and unaffected by a change in external K+. The 5-HT-induced response was markedly blocked by intracellular injection of guanosine 5'-O-(2-thiodiphosphate) (GDPbetaS). After the injection of guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS), the responses to 5-HT gradually and significantly increased at the initial period, reached its plateau, and finally decreased. Intracellular injection of Clostridium difficile toxin B, a blocker of small G-protein Rho family members such as Rho (RhoA, RhoB and RhoC), Rac and Cdc42, markedly depressed the 5-HT-induced response. Intracellular injection of Clostridium botulinum C3 exoenzyme, a specific blocker of RhoA, RhoB, RhoC, exhibited a similar depressing effect observed with toxin B. In contrast, intracellular injection of recombinant L63RhoA, a constitutively active form of RhoA, significantly augmented the 5-HT-induced response without affecting the resting membrane. These results suggested that the 5-HT-induced Na+-current response might be facilitated by the activation of Aplysia Rho which is closely homologous to RhoA, RhoB or RhoC in mammalian neuron.

Development of automatic immediate fitting socket system for artificial leg socket modeling using fuzzy control.

Automatic immediate fitting socket (AIFS) system was developed to shorten the long length of time for making an artificial leg, by applying powder technology. AIFS is constructed of an outer shell, a particle containing bag, which the rigidity can be controlled by the application of negative air pressure and three airbags between the outer shell and the particle bag to adjust the shape by controlling the compression. A fuzzy controller was applied for the real-time automatic control of the shape based on the subjective evaluation of the amputee. The surface contact pressure was evaluated during AIFS walking as well as the walking with the conventional socket. The peak pressure at the tibia end was 30 kPa in AIFS walking while 90 kPa with conventional socket. The pressure distribution among medial condyle, fibula head and tibia end was more uniform with AIFS. The shape modeling performance was evaluated by measuring the circumferences of four amputees' stumps. The modeling error was 6%. The shape modeling including test walking was completed in 10 minutes in all four amputees and practical shapes were obtained.

The role of rho and rho-dependent kinase in serotonin-induced contraction observed in bovine middle cerebral artery.

The current study was designed to characterize the role of Rho and Rho-dependent kinase (Rho-kinase) in isometric contractile responses induced by serotonin (5-HT) and a solution containing 40 mM K(+) (high K(+)) in ring preparations of the middle cerebral artery of bovine. Application of W-7, a Ca(2+)-calmodulin inhibitor, reversibly and equally attenuated the amplitudes of contractions produced by both 5-HT and high K(+). Similar effects were observed with ML-7, an inhibitor of myosin light chain kinase. Surprisingly, the protein kinase C inhibitors, calphostin C and Ro-31-8220, had no effect on the 5-HT-induced contraction. Incubation of preparations with Clostridium difficile toxin A and B or with Clostridium botulinum C3 exoenzyme for 48 hours attenuated the 5-HT-induced response but not the high K(+)-induced response. Application of the Rho-kinase inhibitor, Y-27632, resulted in marked inhibition of the 5-HT-induced response but had negligible effect on the high K(+)-induced response. These results suggest that the activation of Rho and Rho-kinase may be involved in the generation of the contraction produced by 5-HT in the bovine middle cerebral artery, while protein kinase C plays, if any, an insignificant role on the contraction.

In vitro inhibition of adrenal catecholamine secretion by steroidal metabolites of ginseng saponins.

We reported previously that the protopanaxatriol saponins in Panax ginseng greatly reduce the secretion of catecholamines from bovine adrenal chromaffin cells stimulated by acetylcholine (ACh). However, protopanaxadiol saponins showed only slight inhibitory effects. Recent studies have demonstrated that oligosaccharides connected to the hydroxyl groups of the aglycone in ginseng saponins (ginsenosides) are in turn hydrolyzed in the digestive tract and absorbed into the circulation following oral administration of ginseng. Therefore, the present study was performed to investigate the effects of the major ginsenoside metabolites (M1, M2, M3, M4, M5, M11, and M12) on catecholamine secretion. All of these metabolites were shown to be potent inhibitors of ACh-evoked secretion, and M4 was the most effective. M4 blocked not only the ACh-induced Na(+) influx into the chromaffin cells but also the ACh-induced inward current into Xenopus oocytes expressing human alpha 3 beta 4 neuronal nicotinic ACh receptors. M4 reduced the secretion induced by high K(+), an activator of voltage-sensitive Ca(2+) channels, to a much lesser extent than that evoked by ACh. M1, M2, M3, M5, and M12 are protopanaxadiol saponin-derived metabolites. Therefore, these results imply that the protopanaxadiol saponins are prodrugs, and they show more potent inhibitory activity following metabolism in the digestive tract. The results further suggest that the metabolites act on nicotinic ACh receptors, blocking Na(+) influx through the receptors, and consequently reduce the catecholamine secretion from bovine adrenal chromaffin cells. The inhibitory effect of ginsenoside metabolites is probably one of the mechanisms of action responsible for the pharmacological effects of ginseng.

Blockade of ionotropic receptor responses by progesterone in the ganglion cells of Aplysia.

To compare nongenomic effects of progesterone on various receptor responses of neurons, Aplysia ganglion cells were pretreated with 30 microM progesterone for 5 min and various receptor responses were tested using a conventional voltage-clamp method. Progesterone reduced nicotinic receptor-activated Na(+)-currents, nicotinic receptor-activated Cl(-)-currents, gamma-aminobutyric acid receptor-activated Cl(-)-currents, and dopamine receptor-activated Na(+)-currents. These depressant effects are similar at two different agonist concentrations. On the other hand, progesterone affected neither muscarinic receptor-activated K(+)-currents nor dopamine receptor-activated K(+)-currents. The former four types of receptors are known to be ionotropic while the latter two types of receptors are known to be metabotropic. Therefore, progesterone selectively inhibited all the types of ionotropic receptor responses, presumably in a noncompetitive manner.