Interlimb coordination is critically important during bipedal locomotion and often must be adapted to account for varying environmental circumstances. Here we studied adaptation of human interlimb ...coordination using a split-belt treadmill, where the legs can be made to move at different speeds. Human adults, infants, and spinal cats can alter walking patterns on a split-belt treadmill by prolonging stance and shortening swing on the slower limb and vice versa on the faster limb. It is not known whether other locomotor parameters change or if there is a capacity for storage of a new motor pattern after training. We asked whether adults adapt both intra- and interlimb gait parameters during split-belt walking and show aftereffects from training. Healthy subjects were tested walking with belts tied (baseline), then belts split (adaptation), and again tied (postadaptation). Walking parameters that directly relate to the interlimb relationship changed slowly during adaptation and showed robust aftereffects during postadaptation. These changes paralleled subjective impressions of limping versus no limping. In contrast, parameters calculated from an individual leg changed rapidly to accommodate split-belts and showed no aftereffects. These results suggest some independence of neural control of intra- versus interlimb parameters during walking. They also show that the adult nervous system can adapt and store new interlimb patterns after short bouts of training. The differences in intra- versus interlimb control may be related to the varying complexity of the parameters, task demands, and/or the level of neural control necessary for their adaptation.
Abstract
There is a big need for the development of novel therapies for the safe management of chronic pain associated with OA. Here we reviewed PubMed (2015 onward) and ClinicalTrials.gov for ...ongoing and recently completed trials where pain in OA is the primary outcome measure. Three broad categories were identified: biological therapies, small molecules and cryoneurolysis. The most promising new strategy is blockade of nerve growth factor with antibodies. Two anti-nerve growth factor antibodies, tanuzemab and fasinumab, are in active development after the 2010 hold on trials was lifted in 2015. In addition, several active clinical trials are testing distinct mechanism-based interventions, including cytokine inhibition, selective μ, δ or κ opioid receptor agonists, zoledronate and intra-articular capsaicin. In addition to pharmacological approaches, cryoneurolytic strategies that directly target peripheral nerves may play a role in OA pain management, but efficacy profiles and long-term effects of such treatments need more study. Clearly, the therapeutic landscape for OA pain is rapidly expanding. Since symptomatic OA is a heterogeneous disease, the challenge will be to identify patients that will benefit the most from specific approaches.
The sophistication and success of recently reported microfabricated organs-on-chips and human organ constructs have made it possible to design scaled and interconnected organ systems that may ...significantly augment the current drug development pipeline and lead to advances in systems biology. Physiologically realistic live microHuman (μHu) and milliHuman (mHu) systems operating for weeks to months present exciting and important engineering challenges such as determining the appropriate size for each organ to ensure appropriate relative organ functional activity, achieving appropriate cell density, providing the requisite universal perfusion media, sensing the breadth of physiological responses, and maintaining stable control of the entire system, while maintaining fluid scaling that consists of ~5 mL for the mHu and ~5 μL for the μHu. We believe that successful mHu and μHu systems for drug development and systems biology will require low-volume microdevices that support chemical signaling, microfabricated pumps, valves and microformulators, automated optical microscopy, electrochemical sensors for rapid metabolic assessment, ion mobility-mass spectrometry for real-time molecular analysis, advanced bioinformatics, and machine learning algorithms for automated model inference and integrated electronic control. Toward this goal, we are building functional prototype components and are working toward top-down system integration.
Coronary artery bypass surgery (CABG) has been considered the therapy of choice for patients with unprotected left main (ULMT) coronary stenoses. Selected single-center reports suggest that the ...results of percutaneous intervention may now approach those of CABG.
To assess the results of percutaneous ULMT treatment from a wide variety of experienced interventional centers, we requested data on consecutive patients treated after January 1, 1994, from 25 centers. One hundred seven patients were identified who were treated either electively (n=91) or for acute myocardial infarction (n=16). Of patients treated electively, 25% were considered inoperable, and 27% were considered high risk for bypass surgery. Primary treatment included stents (50%), directional atherectomy (24%), and balloon angioplasty (20%). Follow-up was 98.8% complete at 15+/-8 months. Results varied considerably, depending on presentation and treatment. For patients with acute myocardial infarction, technical success was achieved in 75%, and survival to hospital discharge was 31%. For elective patients, technical success was achieved in 98.9%, and in-hospital survival was strongly correlated with left ventricular ejection fraction (P=.003). Longer-term event (death, infarction, or bypass surgery) -free survival was correlated with ejection fraction (P<.001) and was inversely related to presentation with progressive or rest angina (P<.001). Surgical candidates with ejection fractions > or = 40% had an in-hospital survival of 98% and a 9-month event-free survival of 86+/-5%, whereas patients with ejection fractions < 40% had 67% and 22+/-12% in-hospital and 9-month event-free survivals, respectively. Nine hospital survivors (10.6%) experienced cardiac death within 6 months of hospital discharge.
While results for selected patients appear promising, until early post-hospital discharge cardiac death can be better understood and minimized, percutaneous revascularization of ULMT stenosis should not be considered an alternative to bypass surgery for most patients. When percutaneous revascularization of ULMT is required, directional atherectomy and stenting appear to be the preferred techniques, and follow-up angiography 6 to 8 weeks after treatment is probably advisable.
Acute cardiovascular events exhibit a circadian rhythm in the frequency of occurrence. The mechanisms underlying these phenomena are not yet fully understood, but they may be due to rhythmicity ...inherent in the cardiovascular system. We have begun to characterize rhythmicity of the clock gene mPer1 in the rat cardiovascular system. Luciferase activity driven by the mPer1 gene promoter is rhythmic in vitro in heart tissue explants and a wide variety of veins and arteries cultured from the transgenic Per1-luc rat. The tissues showed between 3 and 12 circadian cycles of gene expression in vitro before damping. Whereas peak per1-driven bioluminescence consistently occurred during the late night in the heart and all arteries sampled, the phases of the rhythms in veins varied significantly by anatomical location. Varying the time of the culture procedure relative to the donor animal's light:dark cycle revealed that, unlike some other rat tissues such as liver, the phases of in vitro rhythms of arteries, veins, and heart explants were affected by culture time. However, phase relationships among tissues were consistent across culture times; this suggests diversity in circadian regulation among components of the cardiovascular system.
Relations of the carotenoids lutein and zeaxanthin in the diet and serum to photographic evidence of early and late age-related maculopathy (ARM) among persons over age 40 years (n = 8,222) were ...examined. Inverse relations of these carotenoids in the diet or serum to any form of ARM were not observed overall. There was a direct relation of dietary levels to one type of early ARM (soft drusen). However, relations differed by age and race. In the youngest age groups who were at risk for developing early (ages 40-59 years) or late (ages 60-79 years) ARM, higher levels of lutein and zeaxanthin in the diet were related to lower odds for pigmentary abnormalities, one sign of early ARM (odds ratio among persons in high vs. low quintiles = 0.1, 95 percent confidence interval: 0.1, 0.3) and of late ARM (odds ratio = 0.1, 95 percent confidence interval: 0.0, 0.9) after adjustment for age, gender, alcohol use, hypertension, smoking, and body mass index. Relations of these carotenoids to ARM may be influenced by age and race and require further evaluation in separate populations and in prospective studies.
Sedative drugs are often used at the end of life for different clinical indications, and sometimes sedation is not interrupted until the patient dies. The aim of this study was to estimate the ...prevalence of patients who died while deeply sedated in Italy in 2007.
Cross-sectional survey which asked physicians about the last death that occurred among their assisted patients during the last year, and about their attitudes towards end-of-life decisions. All general practitioners (N=5,710) and a random sample of hospital physicians (N=8,950) from 14 Italian provinces were invited to participate.
The response rate was 20%. Among 1855 reported deaths, 1466 (79.2%) were classified by physicians as expected or non-sudden; 18.2% of these expected or non-sudden deaths occurred while the patient was deeply sedated. GPs were the least likely to report deep sedation, whereas anesthetists were the most likely. In 8% of cases, sedation occurred along with an abrupt increase in the dosage of opioids during the last day of life, reaching a dosage considered higher than necessary by the doctor. No association with positive attitudes of the physician towards physician assisted death was found, whereas reporting sedation was associated with a positive attitude towards respecting the choice of relatives to forgo life-sustaining treatment in the case of an incompetent patient.
Our study confirms the high prevalence of patients in Italy who die while being deeply sedated and shows that different practices may converge under the same label. Careful descriptive language is needed.
The current study evaluated the composition and relationships of polyunsaturated fatty acid biohydrogenation products (PUFA-BHP) from the perirenal (PRF) and subcutaneous fat (SCF) of yearling steers ...fed a 70 % grass hay diet with concentrates containing either sunflower-seed (SS) or flaxseed (FS). Analysis of variance indicated several groups or families of structurally related FA, and individual FA within these were affected by a number of novel oilseed by fat depot interactions (
P
< 0.05). Feeding diets containing SS increased the proportions of non-conjugated 18:2 BHP (i.e., atypical dienes, AD) and conjugated linoleic acids (CLA) with the first double bond from carbon 7 to 9,
trans
-18:1 isomers with double bonds from carbon 6 to 12, and these PUFA-BHP had greater proportions in SCF compared to PRF (
P
< 0.05). Enrichment of conjugated linolenic acids, AD and CLA isomers with the first double bond in position 11 or 12, and
t
-18:1 isomers with double bonds from carbon 13 to 16 were achieved by feeding diets containing FS, with PRF having greater proportions than SCF (
P
< 0.05). Principal component analysis visually confirmed interaction effects on these groups/families of FA, and further confirmed or suggested a number of relationships between PUFA-BHP. Feeding SS or FS in a grass hay diet and exploiting adipose tissue differences, therefore, present unique opportunities to differentially enrich a number of PUFA-BHP which seem to have positive health potential in humans (i.e.,
t
11-18:1,
c
9,
t
11-18:2 and
c
9,
t
11,
c
15-18:3).
ABSTRACT High school students were offered a monetary incentive for participating in research. They were given a choice between a smaller fee immediately or a larger fee one week later. Compared to ...students who delayed gratification, those who chose the immediate fee showed more self‐regulatory deficits. They showed greater involvement with cigarettes, alcohol, and marijuana, had a poorer self‐concept and underperformed academically. A replication study with middle‐school students and different reward parameters yielded equivalent results. Younger adolescents who chose the immediate monetary incentive showed a similar pattern of problem behaviors as the high school students. The findings indicate that this simple choice‐delay procedure yields an unobtrusive behavioral measure of self‐regulation and offers a developmentally appropriate extension of the delay‐of‐gratification paradigm for use with older children and adolescents.
Peripheral nerves are often vulnerable to damage during surgeries, with risks of significant pain, loss of motor function, and reduced quality of life for the patient. Intraoperative methods for ...monitoring nerve activity are effective, but conventional systems rely on bench-top data acquisition tools with hard-wired connections to electrode leads that must be placed percutaneously inside target muscle tissue. These approaches are time and skill intensive and therefore costly to an extent that precludes their use in many important scenarios. Here we report a soft, skin-mounted monitoring system that measures, stores, and wirelessly transmits electrical signals and physical movement associated with muscle activity, continuously and in real-time during neurosurgical procedures on the peripheral, spinal, and cranial nerves. Surface electromyography and motion measurements can be performed non-invasively in this manner on nearly any muscle location, thereby offering many important advantages in usability and cost, with signal fidelity that matches that of the current clinical standard of care for decision making. These results could significantly improve accessibility of intraoperative monitoring across a broad range of neurosurgical procedures, with associated enhancements in patient outcomes.
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