Quantitative DigitoGraphy: a Comprehensive Real-Time Remote Monitoring System for Parkinson's Disease.

People with Parkinson's disease (PWP) face critical challenges, including lack of access to neurological care, inadequate measurement and communication of motor symptoms, and suboptimal medication management and compliance. We have developed QDG-Care: a comprehensive connected care platform for Parkinson's disease (PD) that delivers validated, quantitative metrics of all motor signs in PD in real time, monitors the effects of adjusting therapy and medication adherence and is accessible in the electronic health record. In this article, we describe the design and engineering of all components of QDG-Care, including the development and utility of the QDG Mobility and Tremor Severity Scores. We present the preliminary results and insights from the first at-home trial using QDG-Care. QDG technology has enormous potential to improve access to, equity of, and quality of care for PWP, and improve compliance with complex time-critical medication regimens. It will enable rapid "Go-NoGo" decisions for new therapeutics by providing high-resolution data that require fewer participants at lower cost and allow more diverse recruitment.

Light-Controlled Fermentations for Microbial Chemical and Protein Production.

Microbial cell factories offer a sustainable alternative for producing chemicals and recombinant proteins from renewable feedstocks. However, overburdening a microorganism with genetic modifications can reduce host fitness and productivity. This problem can be overcome by using dynamic control: inducible expression of enzymes and pathways, typically using chemical- or nutrient-based additives, to balance cellular growth and production. Optogenetics offers a non-invasive, highly tunable, and reversible method of dynamically regulating gene expression. Here, we describe how to set up light-controlled fermentations of engineered Escherichia coli and Saccharomyces cerevisiae for the production of chemicals or recombinant proteins. We discuss how to apply light at selected times and dosages to decouple microbial growth and production for improved fermentation control and productivity, as well as the key optimization considerations for best results. Additionally, we describe how to implement light controls for lab-scale bioreactor experiments. These protocols facilitate the adoption of optogenetic controls in engineered microorganisms for improved fermentation performance.

Optogenetics Illuminates Applications in Microbial Engineering.

Optogenetics has been used in a variety of microbial engineering applications, such as chemical and protein production, studies of cell physiology, and engineered microbe-host interactions. These diverse applications benefit from the precise spatiotemporal control that light affords, as well as its tunability, reversibility, and orthogonality. This combination of unique capabilities has enabled a surge of studies in recent years investigating complex biological systems with completely new approaches. We briefly describe the optogenetic tools that have been developed for microbial engineering, emphasizing the scientific advancements that they have enabled. In particular, we focus on the unique benefits and applications of implementing optogenetic control, from bacterial therapeutics to cybergenetics. Finally, we discuss future research directions, with special attention given to the development of orthogonal multichromatic controls. With an abundance of advantages offered by optogenetics, the future is bright in microbial engineering.

Assessing inertial measurement unit locations for freezing of gait detection and patient preference.

BACKGROUND: Freezing of gait, a common symptom of Parkinson's disease, presents as sporadic episodes in which an individual's feet suddenly feel stuck to the ground. Inertial measurement units (IMUs) promise to enable at-home monitoring and personalization of therapy, but there is a lack of consensus on the number and location of IMUs for detecting freezing of gait. The purpose of this study was to assess IMU sets in the context of both freezing of gait detection performance and patient preference. METHODS: Sixteen people with Parkinson's disease were surveyed about sensor preferences. Raw IMU data from seven people with Parkinson's disease, wearing up to eleven sensors, were used to train convolutional neural networks to detect freezing of gait. Models trained with data from different sensor sets were assessed for technical performance; a best technical set and minimal IMU set were identified. Clinical utility was assessed by comparing model- and human-rater-determined percent time freezing and number of freezing events. RESULTS: The best technical set consisted of three IMUs (lumbar and both ankles, AUROC = 0.83), all of which were rated highly wearable. The minimal IMU set consisted of a single ankle IMU (AUROC = 0.80). Correlations between these models and human raters were good to excellent for percent time freezing (ICC = 0.93, 0.89) and number of freezing events (ICC = 0.95, 0.86) for the best technical set and minimal IMU set, respectively. CONCLUSIONS: Several IMU sets consisting of three IMUs or fewer were highly rated for both technical performance and wearability, and more IMUs did not necessarily perform better in FOG detection. We openly share our data and software to further the development and adoption of a general, open-source model that uses raw signals and a standard sensor set for at-home monitoring of freezing of gait.

Differential Effects of Pathological Beta Burst Dynamics Between Parkinson's Disease Phenotypes Across Different Movements.

Background: Resting state beta band (13-30 Hz) oscillations represent pathological neural activity in Parkinson's disease (PD). It is unknown how the peak frequency or dynamics of beta oscillations may change among fine, limb, and axial movements and different disease phenotypes. This will be critical for the development of personalized closed loop deep brain stimulation (DBS) algorithms during different activity states. Methods: Subthalamic (STN) and local field potentials (LFPs) were recorded from a sensing neurostimulator (Activa® PC + S, Medtronic PLC.) in fourteen PD participants (six tremor-dominant and eight akinetic-rigid) off medication/off STN DBS during 30 s of repetitive alternating finger tapping, wrist-flexion extension, stepping in place, and free walking. Beta power peaks and beta burst dynamics were identified by custom algorithms and were compared among movement tasks and between tremor-dominant and akinetic-rigid groups. Results: Beta power peaks were evident during fine, limb, and axial movements in 98% of movement trials; the peak frequencies were similar during each type of movement. Burst power and duration were significantly larger in the high beta band, but not in the low beta band, in the akinetic-rigid group compared to the tremor-dominant group. Conclusion: The conservation of beta peak frequency during different activity states supports the feasibility of patient-specific closed loop DBS algorithms driven by the dynamics of the same beta band during different activities. Akinetic-rigid participants had greater power and longer burst durations in the high beta band than tremor-dominant participants during movement, which may relate to the difference in underlying pathophysiology between phenotypes.

Optogenetic Control of Microbial Consortia Populations for Chemical Production.

Microbial co-culture fermentations can improve chemical production from complex biosynthetic pathways over monocultures by distributing enzymes across multiple strains, thereby reducing metabolic burden, overcoming endogenous regulatory mechanisms, or exploiting natural traits of different microbial species. However, stabilizing and optimizing microbial subpopulations for maximal chemical production remains a major obstacle in the field. In this study, we demonstrate that optogenetics is an effective strategy to dynamically control populations in microbial co-cultures. Using a new optogenetic circuit we call OptoTA, we regulate an endogenous toxin-antitoxin system, enabling tunability of Escherichia coli growth using only blue light. With this system we can control the population composition of co-cultures of E. coli and Saccharomyces cerevisiae. When introducing in each strain different metabolic modules of biosynthetic pathways for isobutyl acetate or naringenin, we found that the productivity of co-cultures increases by adjusting the population ratios with specific light duty cycles. This study shows the feasibility of using optogenetics to control microbial consortia populations and the advantages of using light to control their chemical production.

Cellulosic biofuel production using emulsified simultaneous saccharification and fermentation (eSSF) with conventional and thermotolerant yeasts.

BACKGROUND: Future expansion of corn-derived ethanol raises concerns of sustainability and competition with the food industry. Therefore, cellulosic biofuels derived from agricultural waste and dedicated energy crops are necessary. To date, slow and incomplete saccharification as well as high enzyme costs have hindered the economic viability of cellulosic biofuels, and while approaches like simultaneous saccharification and fermentation (SSF) and the use of thermotolerant microorganisms can enhance production, further improvements are needed. Cellulosic emulsions have been shown to enhance saccharification by increasing enzyme contact with cellulose fibers. In this study, we use these emulsions to develop an emulsified SSF (eSSF) process for rapid and efficient cellulosic biofuel production and make a direct three-way comparison of ethanol production between S. cerevisiae, O. polymorpha, and K. marxianus in glucose and cellulosic media at different temperatures. RESULTS: In this work, we show that cellulosic emulsions hydrolyze rapidly at temperatures tolerable to yeast, reaching up to 40-fold higher conversion in the first hour compared to microcrystalline cellulose (MCC). To evaluate suitable conditions for the eSSF process, we explored the upper temperature limits for the thermotolerant yeasts Kluyveromyces marxianus and Ogataea polymorpha, as well as Saccharomyces cerevisiae, and observed robust fermentation at up to 46, 50, and 42 °C for each yeast, respectively. We show that the eSSF process reaches high ethanol titers in short processing times, and produces close to theoretical yields at temperatures as low as 30 °C. Finally, we demonstrate the transferability of the eSSF technology to other products by producing the advanced biofuel isobutanol in a light-controlled eSSF using optogenetic regulators, resulting in up to fourfold higher titers relative to MCC SSF. CONCLUSIONS: The eSSF process addresses the main challenges of cellulosic biofuel production by increasing saccharification rate at temperatures tolerable to yeast. The rapid hydrolysis of these emulsions at low temperatures permits fermentation using non-thermotolerant yeasts, short processing times, low enzyme loads, and makes it possible to extend the process to chemicals other than ethanol, such as isobutanol. This transferability establishes the eSSF process as a platform for the sustainable production of biofuels and chemicals as a whole.

Design and Characterization of Rapid Optogenetic Circuits for Dynamic Control in Yeast Metabolic Engineering.

The use of optogenetics in metabolic engineering for light-controlled microbial chemical production raises the prospect of utilizing control and optimization techniques routinely deployed in traditional chemical manufacturing. However, such mechanisms require well-characterized, customizable tools that respond fast enough to be used as real-time inputs during fermentations. Here, we present OptoINVRT7, a new rapid optogenetic inverter circuit to control gene expression in Saccharomyces cerevisiae. The circuit induces gene expression in only 0.6 h after switching cells from light to darkness, which is at least 6 times faster than previous OptoINVRT optogenetic circuits used for chemical production. In addition, we introduce an engineered inducible GAL1 promoter (PGAL1-S), which is stronger than any constitutive or inducible promoter commonly used in yeast. Combining OptoINVRT7 with PGAL1-S achieves strong and light-tunable levels of gene expression with as much as 132.9 ± 22.6-fold induction in darkness. The high performance of this new optogenetic circuit in controlling metabolic enzymes boosts production of lactic acid and isobutanol by more than 50% and 15%, respectively. The strength and controllability of OptoINVRT7 and PGAL1-S open the door to applying process control tools to engineered metabolisms to improve robustness and yields in microbial fermentations for chemical production.

Perspective: Evolution of Control Variables and Policies for Closed-Loop Deep Brain Stimulation for Parkinson's Disease Using Bidirectional Deep-Brain-Computer Interfaces.

A deep brain stimulation system capable of closed-loop neuromodulation is a type of bidirectional deep brain-computer interface (dBCI), in which neural signals are recorded, decoded, and then used as the input commands for neuromodulation at the same site in the brain. The challenge in assuring successful implementation of bidirectional dBCIs in Parkinson's disease (PD) is to discover and decode stable, robust and reliable neural inputs that can be tracked during stimulation, and to optimize neurostimulation patterns and parameters (control policies) for motor behaviors at the brain interface, which are customized to the individual. In this perspective, we will outline the work done in our lab regarding the evolution of the discovery of neural and behavioral control variables relevant to PD, the development of a novel personalized dual-threshold control policy relevant to the individual's therapeutic window and the application of these to investigations of closed-loop STN DBS driven by neural or kinematic inputs, using the first generation of bidirectional dBCIs.

Gender Differences in Modifying Lumbopelvic Motion during Hip Medial Rotation in People with Low Back Pain.

Reducing increased or early lumbopelvic motion during trunk or limb movements may be an important component of low back pain treatment. The ability to reduce lumbopelvic motion may be influenced by gender. The purpose of the current study was to examine the effect of gender on the ability of people with low back pain to reduce lumbopelvic motion during hip medial rotation following physical therapy treatment. Lumbopelvic rotation and hip rotation before the start of lumbopelvic rotation were assessed pre- and posttreatment for 16 females and 15 males. Both men and women decreased lumbopelvic rotation and completed more hip rotation before the start of lumbopelvic rotation post-treatment compared to pre-treatment. Men demonstrated greater lumbopelvic rotation and completed less hip rotation before the start of lumbopelvic rotation than women both pre- and post-treatment. Both men and women reduced lumbopelvic motion relative to their starting values, but, overall, men still demonstrated greater and earlier lumbopelvic motion. These results may have important implications for understanding differences in the evaluation and treatment of men and women with low back pain.

Differences in end-range lumbar flexion during slumped sitting and forward bending between low back pain subgroups and genders.

Patterns of lumbar posture and motion are associated with low back pain (LBP). Research suggests LBP subgroups demonstrate different patterns during common tasks. This study assessed differences in end-range lumbar flexion during two tasks between two LBP subgroups classified according to the Movement System Impairment model. Additionally, the impact of gender differences on subgroup differences was assessed. Kinematic data were collected. Subjects in the Rotation (Rot) and Rotation with Extension (RotExt) LBP subgroups were asked to sit slumped and bend forward from standing. Lumbar end-range flexion was calculated. Subjects reported symptom behaviour during each test. Compared to the RotExt subgroup, the Rot subgroup demonstrated greater end-range lumbar flexion during slumped sitting and a trend towards greater end-range lumbar flexion with forward bending. Compared to females, males demonstrated greater end-range lumbar flexion during slumped sitting and forward bending. A greater proportion of people in the Rot subgroup reported symptoms with each test compared to the RotExt subgroup. Males and females were equally likely to report symptoms with each test. Gender differences were not responsible for LBP subgroup differences. Subgrouping people with LBP provides insight into differences in lumbar motion within the LBP population. Results suggesting potential consistent differences across flexion-related tasks support the presence of stereotypical movement patterns that are related to LBP.

Clinical examination procedures to determine the effect of axial decompression on low back pain symptoms in people with chronic low back pain.

STUDY DESIGN: Observational. OBJECTIVE: To assess the effects of spinal decompression procedures performed during a clinical exam on low back pain (LBP) symptoms. BACKGROUND: Not all patients report an immediate or complete improvement in symptoms when the direction of lumbar motion or alignment is corrected according to principles of the movement system impairment (MSI) model. Axial compression of the spine may be responsible for the remaining symptoms. METHODS: Seventy subjects (mean ± SD age, 41.9 ± 11.5 years; 38 females, 32 males) with chronic LBP were evaluated using a standardized MSI exam. Seven tests assessing the effects of spinal decompression on LBP were added to the exam if the subjects' symptoms were not alleviated with typical standardized corrections of movement and alignment. For each test of decompression, subjects reported their symptoms compared to a reference movement or position. RESULTS: When decompression was performed during lateral bending to the right and left, 21 of 21 (100%) and 16 of 20 (80%) subjects, respectively, reported an improvement. When traction was applied to subjects in right and left sidelying, 6 of 11 (55%) and 7 of 9 (78%), respectively, reported an improvement. When patients performed a push-up in sitting, 36 of 51 (71%) reported an improvement. In subjects who had symptoms in unsupported sitting, 41 of 57 (72%) reported an improvement in supported sitting. In subjects who reported symptoms in standing, 33 of 47 (70%) reported an improvement in hook-lying. CONCLUSION: Patients with chronic LBP consistently reported an improvement in symptoms with tests proposed to decrease the axial load on the spine. These tests are a quick and effective way to assess the contribution of axial decompression to LBP symptoms and potentially could be used as part of the plan of care.

Sex differences in lumbopelvic movement patterns during hip medial rotation in people with chronic low back pain.

OBJECTIVE: To examine sex differences in lumbopelvic motion and symptom behavior during hip medial rotation in people with low back pain (LBP). We hypothesized that men would demonstrate greater and earlier lumbopelvic motion and would be more likely to report increased symptoms compared with women. DESIGN: Cross-sectional observational study. SETTING: University musculoskeletal analysis laboratory. PARTICIPANTS: Persons with chronic LBP (N=59; 30 men, 29 women) were recruited from the community and a university-based physical therapy clinic. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Lumbopelvic rotation range of motion, amount of hip rotation completed before the start of lumbopelvic motion, and provocation of LBP symptoms during the test of prone hip medial rotation were measured. RESULTS: Men demonstrated significantly more lumbopelvic rotation (men, 10.0°±5.1°; women, 4.5°±3.9°; P<.001) and completed less hip rotation before the start of lumbopelvic motion (men, 5.4°±3.8°; women, 16.0°±13.2°; P<.001) compared with women. Additionally, a significantly greater percentage of men (60.0%) than women (34.5%; P=.050) reported increased symptoms with hip medial rotation. CONCLUSIONS: Men could be at greater risk than women for experiencing LBP symptoms related to hip medial rotation as a result of greater and earlier lumbopelvic motion.

Low interrater reliability of examiners performing the prone instability test: a clinical test for lumbar shear instability.

OBJECTIVE: To test the interrater reliability of examiners performing the prone instability test (PIT), a clinical test proposed to identify lumbar shear instability. DESIGN: Cross-sectional test-retest design examining individuals with mechanical low back pain (LBP). SETTING: University-based musculoskeletal analysis laboratory. PARTICIPANTS: Individuals (N=30) with mechanical LBP recruited from community sources in a metropolitan region. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Repeated measures of a clinical examination test proposed to identify lumbar shear instability. RESULTS: Interrater reliability of examiners' judgments of PIT results were indexed with percentage of agreement and κ statistic. Examiners obtained 63% agreement and κ of .10 (95% confidence interval, -.27 to .47). Adjusted κ values based on prevalence and bias indexes were calculated to evaluate the effect on κ. The prevalence index associated with examiner judgments of the PIT was .43, and bias index was .03. The prevalence-adjusted bias-adjusted κ value was slightly higher than the unadjusted κ value (κ=.27; 95% confidence interval, -.08 to .61). CONCLUSIONS: Results of our study are not consistent with those of previous studies examining the reliability of therapists performing the PIT. We conclude that examiners do not attain acceptable interrater reliability when performing procedures for the PIT based on the information currently provided in the literature. Based on our experience, we suggest further exploration, standardization, and clarification of procedural details to improve therapists' ability to conduct the PIT on individuals with LBP.

Effect of classification-specific treatment on lumbopelvic motion during hip rotation in people with low back pain.

Increased and early lumbopelvic motion during trunk and limb movements is thought to contribute to low back pain (LBP). Therefore, reducing lumbopelvic motion could be an important component of physical therapy treatment. Our purpose was to examine the effects of classification-specific physical therapy treatment (Specific) based on the Movement System Impairment (MSI) model and non-specific treatment (Non-Specific) on lumbopelvic movement patterns during hip rotation in people with chronic LBP. We hypothesized that following treatment people in the Specific group would display decreased lumbopelvic rotation and achieve more hip rotation before lumbopelvic rotation began. We hypothesized that people in the Non-Specific group would display no change in these variables. Kinematic data collected before and after treatment for hip lateral and medial rotation in prone were analyzed. The Specific group (N = 16) demonstrated significantly decreased lumbopelvic rotation and achieved greater hip rotation before the onset of lumbopelvic rotation after treatment with both hip lateral and medial rotation. The Non-Specific group (N = 16) demonstrated significantly increased lumbopelvic rotation and no change in hip rotation achieved before the onset of lumbopelvic rotation. People who received treatment specific to their MSI LBP classification displayed decreased and later lumbopelvic motion with hip rotation, whereas people who received generalized non-specific treatment did not.

Differences in activity limitation between 2 low back pain subgroups based on the movement system impairment model.

OBJECTIVE: To examine if activity limitation differs between 2 low back pain (LBP) subgroups in the Movement System Impairment (MSI) model. DESIGN: Cross-sectional observational study. SETTING: University medical center musculoskeletal analysis laboratory. PARTICIPANTS: Convenience sample of 83 subjects with chronic LBP who were subgrouped as rotation (Rot) or rotation with extension (RotExt) according to the MSI model. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASUREMENTS: Subjects completed the modified Oswestry Low Back Pain Disability Questionnaire and the physical function subscale of the 36-Item Short-Form Health survey (SF-36 PFS) to assess activity limitation. Subjects also completed baseline measures related to demographics, LBP history, pain intensity, habitual activity level, general health status, and fear-avoidance behavior. Independent-samples t-tests, χ² tests of independence, and 2-way analysis of variance tests were used to analyze the data. RESULTS: Subjects in the Rot subgroup reported greater activity limitation on the modified Oswestry Questionnaire (P = .02) and SF-36 PFS (P = .03) than subjects in the RotExt subgroup. No other differences between LBP subgroups were significant (P > .05), except gender. More women (71%) than men (29%) were in the RotExt subgroup (P = .03). However, there was no main effect of gender and no interaction effect of gender and LBP subgroup on the modified Oswestry Questionnaire or the SF-36 PFS (P > .05). CONCLUSIONS: These results support that the Rot and RotExt LBP subgroups based on the MSI model differ with regard to variables that index activity limitation, with the Rot subgroup reporting greater limitation on both activity limitation measures. These differences are not the result of differences in other baseline measures.

Minimally invasive surgical ablation of atrial fibrillation: six-month results.

BACKGROUND: A minimally invasive surgery for treatment of atrial fibrillation was developed with bilateral pulmonary vein isolation, mapping, and ablation of the ganglionic plexi and excision of the left atrial appendage. A prospective multicenter registry was created to evaluate the outcomes. METHODS: The procedure was performed through bilateral minithoracotomies with video assistance. It included bilateral pulmonary vein isolation with bipolar radiofrequency with documentation of conduction block, location of ganglionic plexi by high-frequency stimulation, and appropriate ablation and left atrial appendage exclusion/excision. Clinical follow-up at 6 months included monitoring with electrocardiogram, Holter, event monitor, or pacemaker interrogation. RESULTS: One hundred fourteen patients with 60 (52.6%) paroxysmal, 32 (28.1%) persistent, and 22 (19.3%) long-standing persistent atrial fibrillations were treated. The mean age was 59.5 +/- 10.6 years, and 69.3% were men. The mean follow-up period was 204 +/- 41 days (median 195). There were 2 (1.8%) operative mortalities. At 6-month follow-up, with long-term monitoring, 52/60 (86.7%) patients with paroxysmal fibrillations were in normal sinus rhythm and 43/60 (71.7%) were both in normal sinus rhythm and off antiarrhythmic drugs. The patients with persistent atrial fibrillation had a lower success rate, with 18/32 (56.3%) being in normal sinus rhythm and 46.9% both in normal sinus rhythm and off antiarrhythmic drugs; for long-standing persistent cases, 11/22 (50%) were in normal sinus rhythm and 7/22 (31.9%) were also off antiarrhythmic drugs. CONCLUSIONS: Minimally invasive atrial fibrillation surgery is an effective treatment of paroxysmal atrial fibrillation at 6 months. Continuous event monitoring is necessary to accurately assess treatment results. A more extensive lesion set seems to be required for treatment of persistent atrial fibrillation.

High-risk patients referred for transcatheter aortic valve implantation: management and outcomes.

BACKGROUND: Aortic valve replacement (AVR) is the treatment of choice for critical aortic stenosis. Selected patients have not previously been referred for AVR because of excessive risk of mortality and morbidity with surgery. The option of transcatheter aortic valve implantation (TAVI) has increased referral of this high-risk cohort for therapeutic intervention. We report the management and outcomes of these patients. METHODS: Patients referred for TAVI from December 2005 to December 2007 were evaluated and followed up for intermediate-term all cause mortality. Patients received medical management, TAVI, conventional AVR, or balloon valvuloplasty (BAV) based on risk profile, hemodynamic and echocardiographic criteria, physician judgment, or patient choice. Patients were compared for demographics, Society of Thoracic Surgeons predicted risk of mortality score, and outcomes after AVR, TAVI, or BAV. RESULTS: One hundred five patients were referred for TAVI during a 24-month period. Fifty-two patients (49.5%) received medical management, 16 (15.2%) conventional AVR, 21 (20.0%) received TAVI, and 16 (15.2%) received BAV. Patients were classified as medical management because of physician or patient choice, not meeting TAVI criteria, or underevaluation for a possible procedure. For all patients the average length of follow-up was 159 +/- 147 days. Patients receiving BAV had a Society of Thoracic Surgeons predicted risk of mortality score greater than those having medical management, AVR, or TAVI. Thirty-day mortality was 1 of 16 patients (6.3%) for AVR, 2 of 21 patients (9.5%) with TAVI, 2 of 16 patients (12.5%) for BAV, and 7 of 52 patients (13.5%) for the medical management cohort. Overall mortality during follow-up was 42.3% (22 of 52 patients) for medical management, 19.1% (4 of 21 patients) for TAVI, 12.5% (2 of 16 patients) for AVR, and 37.5% (6 of 16 patients) for BAV. CONCLUSIONS: The population of patients screened for transcatheter therapy is complex and heterogeneous. Medical management alone demonstrates a high mortality rate, and BAV, although providing transient symptomatic relief, does not favorably impact survival. The majority of referred patients (65.7%), including those that declined intervention, were candidates for some form of valve replacement therapy, either TAVI or AVR. Transcatheter aortic valve implantation can be performed in appropriately selected patients with good early and immediate-term outcomes.

Effect of metatarsal phalangeal joint extension on plantar soft tissue stiffness and thickness.

BACKGROUND: Plantar soft tissue stiffness and thickness are important biomechanical variables to understand stress concentrations that may contribute to tissue injury. OBJECTIVE: The purpose of this study was to determine the effects of passive metatarsal phalangeal joint (MPJ) extension on plantar soft tissue stiffness and thickness. METHODS: Seventeen healthy participants (7 male, 10 female, mean age 25.3 years, S.D. 4.4 years, mean BMI 24.7 kg/m(2), S.D. 3.2 kg/m(2)) were tested. Plantar soft tissue stiffness and thickness were measured at the metatarsal heads, midfoot and heel using a custom-built indentor device and an ultrasound machine. RESULTS: Indicators of soft tissue stiffness (K1 values) at the metatarsal heads and midfoot showed increases in stiffness of 81-88% (S.D.20-33%) in the MPJ extension position compared with the MPJ neutral position. Soft tissue thickness measures at the metatarsal heads with the MPJ in neutral ranged from a mean of 8.9 to 13.5mm and decreased, on average, by 8.8% (S.D. 2.9%) with MPJ extension. CONCLUSIONS: MPJ extension has a profound effect on increasing forefoot plantar soft tissue stiffness and a consistent but minimal effect on reducing soft tissue thickness. These changes may help transform the foot into a rigid lever at push-off consistent with the theory of the windlass mechanism.

Ventricular epicardial lead placement for resynchronization by determination of paced depolarization intervals: technique and rationale.

BACKGROUND: Cardiac resynchronization therapy has been shown to be an effective treatment to improve functional status and prolong survival among patients with advanced congestive heart failure. However, as many as 30% of patients do not respond. Nonresponse may be due to suboptimal left ventricular lead placement. Studies have indicated that leads placed in the midlateral left ventricle (LV) wall usually result in improved dP/dT and increased pulse pressure, compared with other locations. When the surgeon is placing the leads thoracoscopically, however, in a chest with multiple adhesions, anatomic landmarks can be obscured. It is desirable to have an objective physiologic method to determine optimal lead placement. The optimal LV pacing site may be best determined by locating the site with the latest depolarization. METHODS: A pacing lead attached to a pulse analyzer was introduced through a thoracoscopic port and used as a mapping electrode to electrically map exposed areas of the left ventricle. The right ventricular pacing lead was also attached to the pulse analyzer and the interval between the right ventricular pulse and the LV depolarization (paced depolarization interval) was measured in 19 patients undergoing thoracoscopic LV lead placement. A site with a paced depolarization interval less than 110 ms was not accepted. RESULTS: Electrical mapping was possible in 19 of 29 consecutive patients in whom it was attempted. The most frequent reason for not mapping was the presence of extensive scarring. In 7 of 19 patients (36.8%) mapped, the site that would have been chosen by anatomic landmarks was not the site with the longest paced depolarization interval, and thus the lead placement was altered. CONCLUSIONS: The site with the longest paced depolarization interval is only selected 63.2% of the time when utilizing anatomic landmarks for placement. Nonresponse may be due to suboptimal LV lead placement. Measurement of paced depolarization intervals provides a physiologic method of determining optimal LV lead placement.