The Effect of Electrode Placement and Interphase Interval on Force Production During Stimulation of the Dorsiflexor Muscles

The aims of this study were to investigate whether introducing an interphase interval (IPI) to biphasic pulses during stimulation of the dorsiflexor muscles would affect force production and to determine whether the IPI effect is dependent on electrode position. Twelve healthy volunteers participated in the study. Each subject participated in one session during which electrically induced contraction (EIC) forces of the ankle dorsiflexors were measured with five different IPI settings ranging from 0 to 400 μs. Forces of EICs were assessed with the electrodes placed either with the proximal electrode positioned over the common peroneal nerve and the second electrode over the dorsiflexor muscles or with both electrodes located over the dorsiflexor muscles. The order of electrode placements and of the different IPI settings was randomized across subjects. The results indicated that the introduction of a 100‐μs‐long IPI may enhance force production when one electrode is located over the common peroneal nerve. However, increasing the duration of the IPI beyond 100 μs did not result in further increase in force production. In contrast, the introduction of an IPI did not increase force production when both electrodes were located over the dorsiflexor muscles. These findings may help to optimize stimulation settings during functional electrical stimulation to prevent foot‐drop.     

Tunable Pseudo-Piezoelectric Effect in Doped Calcium Titanate for Bone Tissue Engineering

CaTiO₃ is a promising candidate as a pseudo-piezoelectric scaffold material for bone implantation. In this study, pure and magnesium/iron doped CaTiO₃ are synthesized by sol-gel method and spark plasma sintering. Energy dispersive X-ray mapping confirm the homogenous distribution of doping elements in sintered samples. High-energy X-ray diffraction investigations reveal that doping of nanostructured CaTiO₃ increased the strain and defects in the structure of CaTiO₃ compared to the pure one. This led to a stronger pseudo-piezoelectric effect in the doped samples. The charge produced in magnesium doped CaTiO₃ due to the direct piezoelectric effect is (2.9 ± 0.1) pC which was larger than the one produced in pure CaTiO₃ (2.1 ± 0.3) pC, whereas the maximum charge was generated by iron doped CaTiO₃ with (3.6 ± 0.2) pC. Therefore, the pseudo-piezoelectric behavior can be tuned by doping. This tuning of pseudo-piezoelectric response provides the possibility to systematically study the bone response using different piezoelectric strengths and possibly adjust for bone tissue engineering.     

Site-directed mutagenesis of histidine residues involved in Cu(II) binding and reduction by sperm whale myoglobin.

Sperm whale myoglobin (Mb) reduces Cu(II) through a site-specific mechanism involving complexation by one or more surface histidine residues. Three mutants of Mb, derived from recombinant wild-type Mb, were designed in which surface histidine residues exhibiting strong Cu(II) binding were replaced with amino acids with comparatively poor metal binding characteristics. The kinetics of Cu(II)(Gly)2 reduction by native Mb, recombinant wild-type Mb, and the mutants were compared. Recombinant wild-type Mb reduced Cu(II) at a rate similar to that of native Mb. Two single mutations (His-48----Ala and His-116----Asp) decreased the rate by 31% and 7%, respectively, relative to wild-type Mb and decreased the rate by 38% and 16%, respectively, relative to native Mb. A double mutation (His-113----Ala, His-116----Asp) decreased the rate only slightly more than the single mutation at His-116. Previous NMR studies showed that His-113 exhibits the strongest Cu(II) binding of all surface histidines, but the present experiments suggest that it plays little or no role in the reduction of Cu(II) by Mb. His-48, located 12.7 A from the Fe(II)-heme, participates in one-third of the redox activity of the protein. His-116 appears to play a minor role in the overall redox activity of Mb, but its involvement shows that Mb has the ability to reduce Cu(II) through a histidine residue located more than 20 A from the Fe(II)-heme. These experiments demonstrate that electron transport from the Fe(II)-heme to site-specifically bound Cu(II) can be mediated through multiple pathways in sperm whale Mb.     

Experimental support for a β-propeller domain in integrin α-subunits and a calcium binding site on its lower surface

Integrins are large, heterodimeric surface molecules of wide importance in cell adhesion. The N-terminal half of all integrin α-subunits contains seven weak sequence repeats of ≈60 amino acids that are important in ligand binding and have been predicted to fold cooperatively into a single β-propeller domain with seven β-sheets. We provide evidence supporting this model with a mouse mAb to human Mac-1 (αMβ2, CD11b/CD18). This antibody, CBRM1/20, binds to amino acid residues that are in different repeats and are 94 residues apart in the primary structure in the loop between strands 1 and 2 of β-sheet 5 and in the loop between strands 3 and 4 of β-sheet 6. The 1–2 loops of β-sheets 5–7 in integrins have EF hand-like Ca²⁺-binding motifs. CBRM1/20 binds to Mac-1 in the presence of Ca²⁺ or Sr²⁺ with an EC₅₀ of 0.2 mM. Mg²⁺ or Mn²⁺ cannot substitute. Antibodies to other epitopes on the Mac-1 β-propeller domain bind in the absence of calcium. mAb CBRM1/20 does not block ligand binding. Thus, the region on the lower surface of the β-propeller domain to which mAb CBRM1/20 binds does not bind ligand and, furthermore, cannot bind other integrin domains, such as those of the β-subunit.     

The association of total cholesterol with processing speed is moderated by age in mid- to late-age healthy adults

Objectives: To investigate the nature of the association of normal levels of total cholesterol with cognitive function and the contribution of age to this association.

Methods: A sample of 61 senior executives, who were summoned for an annual medical examination with approximately four measurements of total cholesterol during 4 years, were examined with a computerized cognitive battery assessing mental processing speed as a sensitive measure of cognitive decline. We examined the association of total cholesterol with processing speed and the moderating effect of age on this association.

Results: A multiple regression analysis yielded a significant interaction between cholesterol and age for processing speed (p = .045). In order to examine the source of the interaction, simple slope analysis was performed. A significant negative high correlation was found for young subjects (p = .021), while no significant correlation was observed at middle (p = .286) or older (p = .584) age. The difference in slopes was robust to adjustment for potential confounding factors, including body mass index, and fasting glucose.

Conclusions: Within the normal range, higher total cholesterol levels were associated with better processing speed in younger ages and this association diminished with increasing age. Our findings highlight the important role of brain cholesterol in good cognitive functioning.     

The Influence of Community Violence and Protective Factors on Asthma Morbidity and Healthcare Utilization in High-Risk Children

We examined the longitudinal effects of community risk and protective factors on asthma morbidity and healthcare utilization. Three hundred urban caregivers of children with poorly controlled asthma were enrolled in a randomized controlled trial testing the effectiveness of a behavioral/educational intervention and completed measures of exposure to community violence (ECV), social cohesion (SC), informal social control (ISC), child asthma control, child asthma symptom days/nights, and healthcare utilization. Latent growth curve modeling examined the direct and interaction effects of ECV, SC, and ISC on the asthma outcomes over 12 months. Caregivers were primarily the biological mother (92 %), single (70 %), and poor (50 % earned less than $10,000). Children were African American (96 %) and young (mean age = 5.5 years, SD = 2.2). ECV at baseline was high, with 24.7 % of caregivers reporting more than two exposures to violence in the previous 6 months (M = 1.45, SD = 1.61). Caregiver ECV-predicted asthma-related healthcare utilization at baseline (b = 0.19, SE = 0.07, p = 0.003) and 2 months (b = 0.12, s.e. = 0.05, p = 0.04). ISC and SC moderated the effect of ECV on healthcare utilization. Our findings suggest that multifaceted interventions that include strategies to curb violence and foster feelings of cohesion among low-income urban residents may be needed to reduce asthma-related emergency services.     

Management and outcomes of small bowel obstruction in older adult patients: a prospective cohort study

Background

The purpose of this research was to examine the morbidity, mortality and rate of recurrent bowel obstruction associated with the treatment of small bowel obstruction (SBO) in older adults.

Methods

We prospectively enrolled all patients 70 years or older with an SBO who were admitted to a tertiary care teaching centre between Jul. 1, 2011, and Sept. 30, 2012. Data regarding presentation, investigations, treatment and outcomes were collected.

Results

Of the 104 patients admitted with an SBO, 49% were managed nonoperatively and 51% underwent surgery. Patients who underwent surgery experienced more complications (64% v. 27%, p = 0.002) and stayed in hospital longer (10 v. 3 d, p < 0.001) than patients managed nonoperatively. Nonoperative management was associated with a high rate of recurrent SBO: 31% after a median follow-up of 17 months. Of the patients managed operatively, 60% underwent immediate surgery and 40% underwent surgery after attempted nonoperative management. Patients in whom nonoperative management failed underwent surgery after a median of 2 days, and 89% underwent surgery within 5 days. The rate of bowel resection was high (29%) among those who underwent delayed surgery. Surgery after failed nonoperative management was associated with a mortality of 14% versus 3% for those who underwent immediate surgery; however, this difference was not significant.

Conclusion

These data suggest that some elderly patients with SBO may be waiting too long for surgery.