A coactivation strategy in anticipatory postural adjustments during voluntary unilateral arm movement while standing in individuals with bilateral spastic cerebral palsy.

Individuals with bilateral spastic cerebral palsy (BSCP) reportedly has problems with anticipatory postural adjustments (APAs) while standing. However, the use of coactivation strategy in APAs in individuals with BSCP has conflicting evidence. Hence, this study aimed to investigate postural muscle activities in BSCP during unilateral arm flexion task in which postural perturbations occur in the sagittal, frontal, and horizontal planes. We included 10 individuals with BSCP with level II on the Gross Motor Function Classification System (BSCP group) and 10 individuals without disability (control group). The participants stood on a force platform and rapidly flexed a shoulder from 0° to 90° at their own timing. Surface electromyograms were recorded from the rectus femoris, medial hamstring, tibialis anterior, and medial gastrocnemius. The control group showed a mixture of anticipatory activation and inhibition of postural muscles, whereas the BSCP group predominantly exhibited anticipatory activation with slight anticipatory inhibition. Compared with the control group, the BSCP group tended to activate the ipsilateral and contralateral postural muscles and the agonist-antagonist muscle pairs. The BSCP group had a larger disturbance in postural equilibrium, quantified by the peak displacement of center of pressure during the unilateral arm flexion, than those without disability. Individuals with BSCP may use coactivation strategy, mainly the anticipatory activation of postural muscle activity, during a task that requires a selective postural muscle activity to maintain stable posture.

A case of adult patent ductus arteriosus-associated infective endarteritis who was successfully treated with only antibiotics.

Patent ductus arteriosus-associated infective endarteritis (PDA-IE) is an extremely rare complication of PDA in recent years. In this report, we describe a case of PDA-IE complicated by septic pulmonary embolism who was successfully treated with only antibiotics.

Small-Molecule Aptamer for Regulating RNA Functions in Mammalian Cells and Animals.

Synthetic riboswitches that can regulate gene expression by a small molecule recognized by an RNA aptamer in mammalian cells have various potential applications in biotechnology and medicine. However, the variety of small molecules and their cognate aptamers that have been demonstrated to function in mammalian cells is limited. The currently available aptamer-ligand pairs also require high small molecule concentrations to enable gene regulation, making them less desirable for industrial and biomedical applications. We conducted in vitro selection of RNA aptamers against a small molecule ASP7967 whose structure is closely related to ASP2905, a known inhibitor of potassium voltage-gated channel sub-family H member 3 (KCNH3). One of the aptamers selected (AC17-4) was found to be functional in HEK293 cells, and it was used to design aptazyme-based riboswitches that can activate gene expression (>10-fold) in the presence of ASP2905 or ASP7967 at as low as 5 µM in the culture medium. An aptazyme-based riboswitch was successfully used to regulate human erythropoietin expression in mice injected with an adeno-associated virus (AAV8) vector using orally administered ASP7967. Furthermore, by combining aptazyme-based and exon-skipping riboswitch mechanisms, an ON/OFF ratio approaching 300 was achieved with a low basal expression level in cultured cells.

Peroneus longus muscle exhibits pre-programmed anticipatory activity before unilateral abduction of the lower limb while standing: a pilot study.

[Purpose] This study aimed to develop a method for assessing anticipatory postural adjustments associated with voluntary movements in individuals with functional ankle instability. We examined whether the peroneus longus muscle exhibits anticipatory activation before unilateral abduction of the lower limb in individuals without disability. [Participants and Methods] Twelve healthy young adults participated in this study. Participants maintained a standing posture with 95 ± 2.5% of their weight on the left side and with the thenar of their right foot in contact with a small wooden board fixed to a force platform. Thereafter, they abducted their right lower limb by approximately 35° at maximum speed; during this time, electromyographic activities of the focal and postural muscles were recorded. [Results] The peroneus longus, external oblique, and erector spinae muscles on the left side of the body were activated before the right gluteus medius muscle, which is a focal muscle of abduction of the right lower limb. The activation timing of the left peroneus longus was the fastest among these postural muscles. [Conclusion] These findings suggest that the peroneus longus muscle plays an important role in anticipatory postural adjustments associated with unilateral abduction of the lower limb and that an ankle strategy is adopted in anticipatory postural adjustments during this task.

Enhancement of walking ability using a custom-made hinged knee brace in patients who experienced ambient stroke and are in the acute phase.

[Purpose] In this study, we investigated the immediate effect on walking using a custom-made hinged knee brace with adjustable knee flexion and extension support (support brace) in patients in the acute phase of stroke. [Participants and Methods] Thirteen patients (56.8 ± 6.8 years) who experienced stroke and who were able to walk independently participated in the study. The walking speed and mean knee extension strength were evaluated under three conditions: no brace, general brace, and support brace. [Results] The walking speed of patients while using the support brace was significantly faster (0.60 ± 0.11 m/s) than that without brace (0.45 ± 0.16 m/s) and with general brace (0.52 ± 0.14 m/s). The fastest walking speed among all 8 patterns (no brace, general brace, and the support brace with six different patterns of support) was with the support brace. The mean knee extension strength while wearing a support brace (1.01 ± 0.24 Nm/kg) was significantly greater than that without wearing a brace (0.82 ± 0.28 Nm/kg). [Conclusion] The support brace, which allows for customizable adjustment of the flexion and extension strength, enhanced the walking ability of patients who experienced ambient stroke and were in the acute phase.

Synthesis and Evaluation of Dolastatin 10 Analogues Containing Heteroatoms on the Amino Acid Side Chains.

Synthetic analogues of the natural occurring dolastatin 10 are of great interest in cancer due to their potent in vitro activity and their uses as payloads in antibody drug conjugates (ADCs). Modification of the dolastatin 10 core scaffold has mainly focused on modifications of the P1, N-terminus, and P5, C-terminus, with minimal attention to the P2 subunit. In this paper we discuss the introduction of heteroatoms to the P2 side chain, which results in potent activity in vitro. The most active compounds contained azides in the P2 unit and required a phenylalanine-derived P5 subunit.

Use of the sit-to-stand task to evaluate motor function of older adults using telemetry.

BACKGROUND: Physical exercises are widely used in community programs, but not all older adults are willing to participate. Information and communication technology may solve this problem by allowing older people to participate in fitness programs at home. Use of remote instruction will facilitate physical exercise classes without requiring that participants gather at one place. The aim of this study was to examine use of a sit-to-stand task in evaluating motor function using conventional video communication in a telemetry system to enable real-time monitoring, and evaluation in physical performance of older adults at home. METHODS: The participants were 59 older individuals and 81 university students. Three physical exercise batteries were used: arm curl, figure-of-eight walk test, and functional reach. The knee extension maximum angular velocity (KEMAV) and the iliac elevation maximum velocity (IEMV) during standing up from a chair and the heel rise frequency were used in the motion-capture measurements. The results were assessed using multi-group structural equation modeling (SEM) for the young and older groups. RESULTS: Young participants consistently performed better than their older counterparts on all items. Analyses with multi-group SEM based on correlations between items yielded a good model-fit for the data. Among all path diagrams for IEMV and KEMAV in the older and young groups, paths from muscular strength to skillfulness showed significant effects. The path from the IEMV to muscular strength was also significant in the older group. CONCLUSIONS: Multi-group SEM suggested that video-based measurements of IEMV during sit-to-stand motion can estimate muscular strength, which suggests that remote monitoring of physical performance can support wellness of community-dwelling older adults.

Effects of a custom-made hinged knee brace with knee flexion support for patients with knee osteoarthritis:a preliminary study.

A knee brace for medial knee osteoarthritis (OA) is required to restrict knee adduction moment (KAM), but must not restrict knee flexion during swing phase. There is no report of a knee brace with both functions. The purpose of this study is to investigate the effect of the custom-made hinged knee brace for patients with knee OA compared to the hinged knee brace generally used, and to assess the KAM and knee flexion angle during swing phase. Fifteen patients (average age: 71.6 ± 7.8 years old) with medial knee OA participated. Gait analysis was performed using a 3-D motion analysis system to measure two conditions: hinged knee brace (KB), and a custom-made hinged knee brace with knee-flexion support- equipped rubber tubes at the posterior of the lateral and medial side poles (KBF). The peak KAM with KBF was significantly smaller than those with the KB (P=0.004, the difference between these conditions of KAM: 0.06 Nm/kg). The peak knee flexion angles during swing phase with KBF were also significantly larger than those with the KB (P=0.004, the difference between these conditions of knee flexion angle: 1.5 degrees). The custom-made brace with one type of tube actuator in the present study could decrease KAM and make for a small increase of knee flexion angle as opposed to the hinged knee brace.

Biomechanical investigation of ambulatory training in patients with acetabular dysplasia.

The purpose of this study was to investigate the effectiveness and safety of ambulatory training in patients with acetabular dysplasia. To achieve this, we studied the hip joint moment in subjects walking with laterally and horizontally elevated arms and changing speeds as a form of training to strengthen hip joint abductor muscles. We studied eight women with pre- or early stage hip disease (center-edge angle of Wieberg 18.5 degrees to -3.0 degrees ) and six healthy women. In exercise task 1 the subjects walked at a rate of 90 steps/min, with abduction of 90 degrees in the shoulder joint ipsilateral or contralateral to the affected hip joint, and either no load or a 1 kg weight in either hand. In exercise task 2, walking speed was changed in three stages from 60 steps/min (s-gait), 90 steps/min (n-gait), and 120 steps/min (f-gait), with both hands swinging freely. Using results from a three-dimensional motion analysis system, the hip joint moments were calculated. In both the healthy and the acetabular dysplasia groups, the abduction moment of the hip joint decreased significantly with ipsilateral elevation and increased significantly with contralateral elevation. There was no significant change in hip flexion moment in either group. The hip extension moment decreased significantly with contralateral elevation, but no significant changes were seen in ipsilateral elevation. In the walking rate variation, the extension hip moment in fast gait was higher than in slow gait. It was concluded that ambulatory training with contralateral horizontal arm elevation may be an effective way of increasing hip joint abductor muscle strength. Ipsilateral arm elevation decreases gluteus medius muscle tension and is an effective way of ambulatory training for people with compensated trendelenburg gait. Variable speed walking is an effective exercise method that can strengthen extensor muscles. Therefore, these ambulatory training methods are useful for acetabular dysplasia patients.

Synthetic study on telomerase inhibitor, D8646-2-6: synthesis of the key intermediate using Sn(OTf)2 or Sc(OTf)3 mediated aldol-type reaction and Stille coupling.

The synthesis of the key intermediate (4) in the proposed route to D8646-2-6 is described. The aldol reaction of the carbohydrate-containing pyrone 7 with the aldehyde 6 was accomplished by using LiHMDS and Sc(OTf)3 or Sn(OTf)2. The stepwise dehydration reaction of the aldol adduct 14, followed by Stille coupling with vinyl stannane 5 which contained phosphonate gave the desired 4.

Synthetic studies directed toward the assembly of the C-glycoside fragment of the telomerase inhibitor D8646-2-6.

[reaction: see text] Construction and characterization of the C-glycosidic moiety of telomerase inhibitor D8646-2-6 (1) are described. This is the first example of the C-glycosylation using electron-poor aromatics, 4-hydroxypyrone, as a glycosyl acceptor. The glycosylation reaction and base-promoted isomerization affords desired beta-C-glycoside in a 61% overall yield.