Quantifying the Regional Load-Bearing Ability of Trans-Tibial Stumps

This paper reports findings of experiments aiming to (1) compare the load tolerant ability over different regions of stumps of lower limb amputees, (2) study the effect of walking on the load tolerant ability, and (3) examine the distal-end weight-bearing ability supported by different interface materials. The method was to apply increasing load to the stump up to the pain level through a force transducer or a digital scale, considering the effect of regional difference, walking, and interface materials. The results show that the patellar tendon and the distal end of the fibula were the best and worst load-tolerant region, respectively. Walking with prostheses tended to increase the load-tolerant ability, which is thought to be due to the massage-like effect of the socket. Different interface materials did not significantly alter the distal-end weight-bearing ability. However, there was a great difference in the distal-end weight-bearing ability among different subjects

Reversible Signal Binding by the Pseudomonas aeruginosa Quorum-Sensing Signal Receptor LasR

Many members of the LuxR family of acyl-homoserine lactone (acyl-HSL)-dependent quorum-sensing transcriptional activators are thought to have the unusual characteristics of requiring the signal ligand during polypeptide synthesis to fold into an active conformation and of binding signal extraordinarily tightly. This is the case for the N-3-oxo-dodecanoyl-HSL-dependent Pseudomonas aeruginosa virulence regulator LasR. We present evidence that LasR can fold into an active conformation in vivo in the absence of the acyl-HSL ligand. We also present evidence indicating that in the cellular environment, LasR and N-3-oxo-dodecanoyl-HSL readily dissociate. After dissociation, LasR can remain in a properly folded conformation capable of reassociating with signal. We present a new model for the folding and signal binding of LasR and other members of the family of transcription factors to which LasR belongs. Our findings have important implications concerning the cellular responses to decreased environmental concentrations of signals and have implications about potential quorum-sensing inhibition strategies

Septal projections to the nucleus incertus in the rat: Bidirectional pathways for modulation of hippocampal function

Projections from the nucleus incertus (NI) to the septum have been implicated in the modulation of hippocampal theta rhythm. In this study we describe a previously uncharacterized projection from the septum to the NI, which may provide feedback modulation of the ascending circuitry. Fluorogold injections into the NI resulted in retrograde labeling in the septum that was concentrated in the horizontal diagonal band and areas of the posterior septum including the septofimbrial and triangular septal nuclei. Double-immunofluorescent staining indicated that the majority of NI-projecting septal neurons were calretinin-positive and some were parvalbumin-, calbindin-, or glutamic acid decarboxylase (GAD)−67-positive. Choline acetyltransferase-positive neurons were Fluorogold-negative. Injection of anterograde tracers into medial septum, or triangular septal and septofimbrial nuclei, revealed fibers descending to the supramammillary nucleus, median raphe, and the NI. These anterogradely labeled varicosities displayed synaptophysin immunoreactivity, indicating septal inputs form synapses on NI neurons. Anterograde tracer also colocalized with GAD-67-positive puncta in labeled fibers, which in some cases made close synaptic contact with GAD-67-labeled NI neurons. These data provide evidence for the existence of an inhibitory descending projection from medial and posterior septum to the NI that provides a "feedback loop" to modulate the comparatively more dense ascending NI projections to medial septum and hippocampus. Neural processes and associated behaviors activated or modulated by changes in hippocampal theta rhythm may depend on reciprocal connections between ascending and descending pathways rather than on unidirectional regulation via the medial septum.Grant sponsors: Fundación Alicia Koplowitz Fellowship (to A.M.S.P.), CAPES-Brasil Bex - 4494/09-1 (to F.N.S.) and 4496/09-4 (to C.W.P.) and Fapitec edital #01/08 (to F.N.S.), FIS-isciiiPI10/01399 (to J.S.), National Health and Medical Research Council of Australia - 520299 (to S.M.), 509246, 1005985, and 1005988 (to A.L.G.), the Florey Foundation (to S.M., A.L.G.), Besen Family Foundation (to A.L.G.) and a NEUREN project, FP7-PEOPLE-IRSES PIRSES-GA-2012-318997 (to A.L.G., F.E.O.-B.)

Early Alterations in Hippocampal Circuitry and Theta Rhythm Generation in a Mouse Model of Prenatal Infection: Implications for Schizophrenia

Post-mortem studies suggest that GABAergic neurotransmission is impaired in schizophrenia. However, it remains unclear if these changes occur early during development and how they impact overall network activity. To investigate this, we used a mouse model of prenatal infection with the viral mimic, polyriboinosinic–polyribocytidilic acid (poly I∶C), a model based on epidemiological evidence that an immune challenge during pregnancy increases the prevalence of schizophrenia in the offspring. We found that prenatal infection reduced the density of parvalbumin- but not somatostatin-positive interneurons in the CA1 area of the hippocampus and strongly reduced the strength of inhibition early during postnatal development. Furthermore, using an intact hippocampal preparation in vitro, we found reduced theta oscillation generated in the CA1 area. Taken together, these results suggest that redistribution in excitatory and inhibitory transmission locally in the CA1 is associated with a significant alteration in network function. Furthermore, given the role of theta rhythm in memory, our results demonstrate how a risk factor for schizophrenia can affect network function early in development that could contribute to cognitive deficits observed later in the disease

Comparison of Therapeutic Effects between Pulsed and Continuous Wave 810-nm Wavelength Laser Irradiation for Traumatic Brain Injury in Mice

Background and Objective Transcranial low-level laser therapy (LLLT) using near-infrared light can efficiently penetrate through the scalp and skull and could allow non-invasive treatment for traumatic brain injury (TBI). In the present study, we compared the therapeutic effect using 810-nm wavelength laser light in continuous and pulsed wave modes in a mouse model of TBI. Study Design/Materials and Methods TBI was induced by a controlled cortical-impact device and 4-hours post-TBI 1-group received a sham treatment and 3-groups received a single exposure to transcranial LLLT, either continuous wave or pulsed at 10-Hz or 100-Hz with a 50% duty cycle. An 810-nm Ga-Al-As diode laser delivered a spot with diameter of 1-cm onto the injured head with a power density of 50-mW/cm2 for 12-minutes giving a fluence of 36-J/cm2. Neurological severity score (NSS) and body weight were measured up to 4 weeks. Mice were sacrificed at 2, 15 and 28 days post-TBI and the lesion size was histologically analyzed. The quantity of ATP production in the brain tissue was determined immediately after laser irradiation. We examined the role of LLLT on the psychological state of the mice at 1 day and 4 weeks after TBI using tail suspension test and forced swim test. Results The 810-nm laser pulsed at 10-Hz was the most effective judged by improvement in NSS and body weight although the other laser regimens were also effective. The brain lesion volume of mice treated with 10-Hz pulsed-laser irradiation was significantly lower than control group at 15-days and 4-weeks post-TBI. Moreover, we found an antidepressant effect of LLLT at 4-weeks as shown by forced swim and tail suspension tests. Conclusion The therapeutic effect of LLLT for TBI with an 810-nm laser was more effective at 10-Hz pulse frequency than at CW and 100-Hz. This finding may provide a new insight into biological mechanisms of LLLT.National Institutes of Health (U.S.) (NIH grant R01AI050875)Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006)United States. Dept. of Defense. Congressionally Directed Medical Research Programs (W81XWH-09-1-0514)United States. Air Force Office of Scientific Research (Military Photomedicine Program (FA9950-04-1-0079))Japan. Ministry of Education, Culture, Sports, Science and TechnologyJapan Society for the Promotion of Scienc

Noninvasive biophotonic imaging for studies of infectious disease

According to World Health Organization estimates, infectious organisms are responsible for approximately one in four deaths worldwide. Animal models play an essential role in the development of vaccines and therapeutic agents but large numbers of animals are required to obtain quantitative microbiological data by tissue sampling. Biophotonic imaging (BPI) is a highly sensitive, nontoxic technique based on the detection of visible light, produced by luciferase-catalysed reactions (bioluminescence) or by excitation of fluorescent molecules, using sensitive photon detectors. The development of bioluminescent/fluorescent microorganisms therefore allows the real-time noninvasive detection of microorganisms within intact living animals. Multiple imaging of the same animal throughout an experiment allows disease progression to be followed with extreme accuracy, reducing the number of animals required to yield statistically meaningful data. In the study of infectious disease, the use of BPI is becoming widespread due to the novel insights it can provide into established models, as well as the impact of the technique on two of the guiding principles of using animals in research, namely reduction and refinement. Here, we review the technology of BPI, from the instrumentation through to the generation of a photonic signal, and illustrate how the technique is shedding light on infection dynamics in vivo

Towards the optimization of design parameters for monolimb using taguchi method and finite element analysis

Monolimb refers to a trans-tibial prosthesis having the socket and the shank molded into one piece of thermoplastics. It has a characteristic that the shank could deflect during walking stimulating motions at ankle joints. Positive feedbacks were gained including improved gait efficiency and comfort from patients using prostheses with deformable shanks. Comfort and gait could be further improved by properly raising the shank flexibility. However, structural integrity should be remained which resists buckling of the prosthesis. Till now there is no guideline for the shank design of monolimb. Currently, the structural test specifications of lower limb prostheses are specified in ISO10328. To optimize the design of the shank, monolimbs with different shank designs have to be subjected to tests according to the ISO standards. Performing such test experimentally is expensive and time demanding. Two approaches help ease the problem. A statistical approach developed by Taguchi using orthogonal arrays allows the design of an experiment involved a few well chosen tests but contains all main factor effects. Finite element (FE) analysis allows parametric analyses to be done efficiently. In this work, FE analysis and Taguchi method were used to predict possible failure under structural test and identify which parameter is most sensitive to the overall performance. This promotes further optimization of the shank design of monolimbs