Lgr5 promotes cancer stemness and confers chemoresistance through ABCB1 in colorectal cancer

Introduction

Chemotherapy failure is a major problem in patients with advanced colorectal carcinoma (CRC). Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is a well-established target gene of the Wnt pathway and is a bona fide marker of CRC cancer stem cells (CSCs). Our previous study showed that CRC patients with higher Lgr5 level are associated with poor response to 5-fluoracil-based treatment. In this study, we investigated the mechanisms underlying Lgr5-associated chemoresistance in cancer stem cells derived from cultured CRC cells.

Materials and methods

Cancer stem cells were isolated from CRC cell lines by spheroid culture. The effect of Lgr5 on CRC cancer stem cell was investigated using both gain- and loss-of-function approaches. Stemness property was evaluated using sphere formation assay, side population analysis, and stem cell marker expression. Lgr5 and ABCB1 expression in CRC tissues was determined using immunohistochemical staining.

Results

Forced expression of Lgr5 increased the CRC sphere-forming efficiency and spheroid size while depletion of Lgr5 reduced the stem cell property in cultured CRC cells. Over-expression of Lgr5 also reduced the sensitivity of cultured CRC cells, including adherent and spheroids, towards 5-fluoracil and oxalipatin. In addition, Lgr5 positively regulates the expression of ABCB1 in both adherent and spheroid CRC cells. Finally, in human CRC tissues, higher expression levels of Lgr5 were associated with higher ABCB1 expression.

Conclusions

The present study demonstrated that Lgr5 plays an active role in promoting the cancer stem cell property and that Lgr5 confers chemoresistance to CRC cells via ABCB1 induction.     

Influence of the physical and chemical properties of magnetic nanoparticles on their performance in a chemiluminescence immunoassay

Objectives

Magnetic nanoparticles (MNPs) are important carriers in immunoassays. In this study, we investigated the influence of the physical and chemical properties of MNPs on their performance in a detection process.

Design and methods

A comparative study of the properties of two MNPs with sizes of 200 nm and 1 μm (MNP-200 nm and MNP-1 μm, respectively) was conducted using the following four aspects: nonspecific adsorption to proteins (IgG was used as a model protein), influence of magnetic nanoparticles on the chemiluminescence signal, response speed to an external magnetic field, and intensity of the detection signal.

Results

MNP-1 μm exhibited lower nonspecific adsorption to IgG in serum, a weaker interference with the chemiluminescence signal, and a higher response speed to the external magnetic field than the same amount of MNP-200 nm. An automated chemiluminescence immunoassay system based on MNP-1 μm was also established.

Conclusions

MNP-1 μm acts as an excellent carrier in an automated chemiluminescence immunoassay system for the analysis of serum samples from clinical patients.     

A randomized controlled trial comparing a computer-assisted insulin infusion protocol with a strict and a conventional protocol for glucose control in critically ill patients

Purpose

The objective of this study is to evaluate blood glucose (BG) control efficacy and safety of 3 insulin protocols in medical intensive care unit (MICU) patients.

Methods

This was a multicenter randomized controlled trial involving 167 MICU patients with at least one BG measurement ≥150 mg/dL and one or more of the following: mechanical ventilation, systemic inflammatory response syndrome, trauma, or burns. The interventions were computer-assisted insulin protocol (CAIP), with insulin infusion maintaining BG between 100 and 130 mg/dL; Leuven protocol, with insulin maintaining BG between 80 and 110 mg/dL; or conventional treatment—subcutaneous insulin if glucose >150 mg/dL. The main efficacy outcome was the mean of patients' median BG, and the safety outcome was the incidence of hypoglycemia (≤40 mg/dL).

Results

The mean of patients' median BG was 125.0, 127.1, and 158.5 mg/dL for CAIP, Leuven, and conventional treatment, respectively (P = .34, CAIP vs Leuven; P < .001, CAIP vs conventional). In CAIP, 12 patients (21.4%) had at least one episode of hypoglycemia vs 24 (41.4%) in Leuven and 2 (3.8%) in conventional treatment (P = .02, CAIP vs Leuven; P = .006, CAIP vs conventional).

Conclusions

The CAIP is safer than and as effective as the standard strict protocol for controlling glucose in MICU patients. Hypoglycemia was rare under conventional treatment. However, BG levels were higher than with IV insulin protocols.     

The Glucosafe system for tight glycemic control in critical care: A pilot evaluation study

Purpose

“Glucosafe’ is a new model-based decision support system for glycemic control in critical care. Safety and achievement of glycemic goals using the system are tested prospectively.

Methods

Four penalty functions were developed to balance regimens of nutrition and insulin therapy against model-predicted glycemic outcome. The system advises the regimen where the penalty sum is minimal. An interactive interface allows advice alterations. Ten hyperglycemic patients (median Acute Physiology and Chronic Health Evaluation II, 12.5; interquartile range, 7.5-16.3) from a neuro and trauma intensive care unit were included for pilot testing using Glucosafe for 12 to 14 hours. Glycemic outcomes were compared to the 24-hour intervals before and after intervention.

Results

Hypoglycemia (blood glucose [BG] <3.5 mmol/L) was not observed. Mean log-normal BG ± standard deviation was reduced from 8.6 ± 2.4 mmol/L preintervention to 7.0 ± 1.1 mmol/L during the intervention. Nine patients reached the 4.4- to 6.1-mmol/L band after a mean 5 hours. At 5 hours intervention, mean log-normal BG was 6.7 mmol/L, 40% of measurements were in the 4.4- to 6.1-mmol/L band, and 84% were in the 4.4- to 7.75-mmol/L band.

Conclusions

Safety was demonstrated with the developed penalty functions. The low BG variance achieved may permit minor adjustments of the penalty function values to reduce average BG if desired.     

Effect of Interferential Current Stimulation in Management of Hemiplegic Shoulder Pain

Objective

To study the immediate effects of interferential current stimulation (IFC) on shoulder pain and pain-free passive range of motion (PROM) of the shoulder in people with hemiplegic shoulder pain (HSP).

Design

Double-blind, placebo-controlled clinical trial.

Setting

Institutional physical therapy clinic, neurologic rehabilitation center.

Participants

A population-based sample of people with HSP (N=30) was recruited.

Intervention

Participants were divided into 2 groups—an IFC group and a placebo group—by using a match-paired method (age, sex, and Brunnstrom motor recovery stage). In the IFC group, participants received IFC for 20 minutes with an amplitude-modulated frequency at 100Hz in vector mode. The current intensity was increased until the participants felt a strong tingling sensation.

Main Outcome Measures

Pain intensity and pain-free PROM of the shoulder until the onset of pain were measured at baseline and immediately after treatment.

Results

Participants reported a greater reduction in pain during the most painful movement after treatment with IFC than with placebo (P<.05). The IFC group showed a greater improvement in posttreatment pain-free PROM than the placebo group in shoulder flexion (P<.01), abduction (P<.01), internal rotation (P<.01), and external rotation (P<.01).

Conclusions

This study provides evidence that IFC is effective for the relief of pain during movement and also increases the pain-free PROM of the shoulder in people with HSP.     

NSAID,aspirin delays gastric ulcer healing with reduced accumulation of CXCR4VEGFR1 cells to the ulcer granulation tissues

Background

Ulcer healing is a complex process, which involves cell migration, proliferation, angiogenesis and re-epithelialization. Several growth factors have been implicated in this process but the precise mechanism is not well understood. This study examined the involvement of VEGFR1 signaling in the gastric ulcer healing.

Methods

Gastric ulcers were induced by the serosal application of 100% acetic acid, and the areas of the ulcers were measured thereafter.

Results

The healing of acetic acid induced ulcers and the progenitor cells expressing CXCR4⁺VEGFR1⁺ cell were significantly delayed in NSAID treated mice. The areas of the ulcer was significantly suppressed in tyrosine kinase-deficient VEGFR1 mice (VEGFR1TKKO) compared with wild type (WT) mice. The plasma level of SDF-1 and stem cell factor (SCF) and bone marrow level of pro-matrix metallopeptidase 9 (pro-MMP-9) were significantly reduced in VEGFR1TKKO mice. In VEGFR1 TKKOmice, the progenitor cells expressing CXCR4⁺VEGFR1⁺ cell from bone marrow and the recruitment of these cells in healing ulcer were suppressed. Furthermore, VEGFR1 TKKO mice treated with NSAID did not suppress gastric ulcer healing compared to vehicle mice. These results suggested that NSAID suppressed VEGFR1 TK signaling plays a critical role in ulcer healing through mobilization of CXCR4⁺VEGFR1⁺ cells.

Conclusion

VEGFR1 signaling is required for healing of NSAID induced gastric ulcer and angiogenesis with increased recruitment of CXCR4⁺VEGFR1⁺ cells to the ulcerative lesion.     

Symptoms of Depression Over Time in Adults With Pediatric-Onset Spinal Cord Injury

Objective

To investigate the prevalence of depressive symptoms in adults with pediatric-onset spinal cord injury (SCI) and explore potential risk factors that may be associated with elevated symptoms.

Design

Longitudinal, cohort survey over a period of 2 to 9 years. Follow-up occurred approximately every year, a total of 868 interviews were conducted, and most participants contributed to at least 3 waves of data (72%; range, 2–8; mean, 4.34±2.16).

Setting

Community.

Participants

Adults (N=214; 133 men; mean age at first interview, 29.52±5.21y; range, 24–42y) who sustained an SCI prior to age 19 (mean age at injury, 13.93±4.37y; range, 0–18y). Participants tended to have complete injuries (71%) and tetraplegia (58%).

Interventions

Not applicable.

Main Outcome Measures

Participants completed measures assessing psychosocial functioning, physical independence, participation, and depression at each time point. Multilevel growth modeling analyses were used to explore depression symptoms across time.

Results

Depression symptoms at initial status were typically minimal (3.07±.24; 95% confidence interval, 2.6–3.54) but fluctuated significantly over time (P<.01). Several factors emerged as significant predictors of depressive symptoms in the final model, including less community participation (P<.01), incomplete injury (P=.02), hazardous drinking (P=.02), bladder incontinence (P=.01), and pain (P=.03). Within individuals, as bowel accidents (P<.01) and pain increased (P<.01), depression scores increased; however, marriage resulted in decreases in depression scores for individuals (P=.02).

Conclusions

These findings suggest that most patients with pediatric-onset SCI are psychologically resilient, but strategies to minimize secondary health complications and foster community participation and engagement should be considered.     

Slower infusion of metoclopramide decreases the rate of akathisia

Objective

We investigated the difference in incidence of acute akathisia related to the rate of infusion in patients receiving metoclopramide for acute nausea, vomiting, or migraine headache in the emergency department (ED).

Methods

Randomized, prospective, double-blind clinical trial of patients aged 18 years and older who were to receive intravenous metoclopramide for the treatment of nausea, vomiting, or headache were eligible. Patients were excluded if they were taking medications that might mimic or mask akathisia, had a movement disorder, renal insufficiency, or were unable or unwilling to consent. Pregnant women and prisoners were also excluded. Subjects were randomized to receive 1 of 2 accepted metoclopramide administration regimens. The regimens included 10 mg of metoclopramide administered either as a 2-minute bolus (BG) or as a slow infusion for 15 minutes (IG). All patients received a normal saline placebo at the opposite rate to maintain blinding. The main outcome was development of akathisia noted at 60 minutes after drug administration as measured either with The Prince Henry Hospital akathisia rating scale or by sudden unexplained departure from the ED during treatment.

Results

One hundred twenty-seven patients were eligible for the study. Fifty-nine patients met exclusion criteria. Of the remaining 68 patients, 36 were randomized to the BG and 32 were randomized to the IG. In the BG, 11.1% of patients developed akathisia compared with 0% in the IG (P = .026). Four patients developed akathisia based on the scale and 2 departed suddenly from the ED.

Conclusions

Slower infusion of metoclopramide reduces the incidence of akathisia.     

The effect of endostatin and gemcitabine combined with HIFU on the animal xenograft model of human pancreatic cancer

Objective

To investigate the influence of the recombinant human endostatin and gemcitabine combined with HIFU on the mouse xenograft model of pancreatic cancer.

Methods

Use human pancreatic cancer cell line PANC-1 to set up the mouse xenograft model, then randomized into four arms. Each arm was treated with gemcitabine, endostatin, gemcitabine combined with endostatin and normal saline respectively. Observe the volume of the tumor, the serum VEGF level and MVD in the tumor tissue among the different arms. All mice were treated with HIFU, then pathological examination was done.

Results

The tumor volume, serum VEGF level and MVD in the combined-therapy arm are all lower than the monotherapy arms and the control arm. The coagulation necrosis occurred in tumors after HIFU treatment.

Conclusion

Endostatin and gemcitabine has better effect than gemcitabine or endostatin monotherapy on the animal xenograft model of human pancreatic cancer. HIFU combined with chemotherapy and/or targeted therapy may enhance the effect for pancreatic cancer.     

Waist Circumference Provides an Indication of Numerous Cardiometabolic Risk Factors in Adults With Cerebral Palsy

Objective

To report the prevalence of cardiometabolic risk factors in a cohort of adults with cerebral palsy (CP) and to investigate the ability of anthropometric measures to predict these factors.

Design

Cross-sectional study.

Setting

Testing took place in a laboratory setting.

Participants

Adults with CP (N=55; mean age, 37.5±13.3y; Gross Motor Function Classification System levels, I–V) participated in this study.

Interventions

Not applicable.

Main Outcome Measures

Total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, insulin, and C-reactive protein levels were measured from a fasting venous blood sample. Insulin resistance was calculated using the Homeostasis Model Assessment (HOMA-IR) index. Blood pressure, body mass index (BMI), waist circumference (WC), waist-hip ratio, and waist-height ratio were also measured. The metabolic syndrome (MetS) was defined according to the 2009 Joint Interim Statement.

Results

The prevalence of the MetS was 20.5% in ambulatory adults and 28.6% in nonambulatory adults. BMI was associated with HOMA-IR only (β=.451; P<.01). WC was associated with HOMA-IR (β=.480; P<.01), triglycerides (β=.450; P<.01), and systolic blood pressure (β=.352; P<.05). Receiver operating characteristic curve analysis revealed that WC provided the best indication of hypertensive blood pressure, dyslipidemia, HOMA-IR, and the presence of multiple risk factors (area under the curve, .713–.763).

Conclusions

A high prevalence of the MetS was observed in this relatively young sample of adults with CP. WC was a better indicator of a number of risk factors than was BMI and presents as a clinically useful method of screening for cardiometabolic risk among adults with CP.     

High-Level Mobility in Chronic Traumatic Brain Injury and Its Relationship With Clinical Variables and Magnetic Resonance Imaging Findings in the Acute Phase

Objectives

To compare high-level mobility in individuals with chronic moderate-to-severe traumatic brain injury (TBI) with matched healthy controls, and to investigate whether clinical variables and magnetic resonance imaging (MRI) findings in the acute phase can predict high-level motor performance in the chronic phase.

Design

A longitudinal follow-up study.

Setting

A level 1 trauma center.

Participants

Individuals (N=136) with chronic TBI (n=65) and healthy matched peers (n=71).

Interventions

Not applicable.

Main Outcome Measures

High-Level Mobility Assessment Tool (HiMAT) and the revised version of the HiMAT performed at a mean of 2.8 years (range, 1.5–5.4y) after injury.

Results

Participants with chronic TBI had a mean HiMAT score of 42.7 (95% confidence interval [CI], 40.2–45.2) compared with 47.7 (95% CI, 46.1–49.2) in the control group (P<.01). Group differences were also evident using the revised HiMAT (P<.01). Acute-phase clinical variables and MRI findings explained 58.8% of the variance in the HiMAT score (P<.001) and 59.9% in the revised HiMAT score (P<.001). Lower HiMAT scores were associated with female sex (P=.031), higher age at injury (P<.001), motor vehicle collisions (P=.030), and posttraumatic amnesia >7 days (P=.048). There was a tendency toward an association between lower scores and diffuse axonal injury in the brainstem (P=.075).

Conclusions

High-level mobility was reduced in participants with chronic, either moderate or severe TBI compared with matched peers. Clinical variables in the acute phase were significantly associated with high-level mobility performance in participants with TBI, but the role of early MRI findings needs to be further investigated. The findings of this study suggest that the clinical variables in the acute phase may be useful in predicting high-level mobility outcome in the chronic phase.     

Negative Affect and Sleep Disturbance May Be Associated With Response to Epidural Steroid Injections for Spine-Related Pain

Objective

To describe whether negative affect and sleep impairment are associated with the clinical effect of epidural steroid injections (ESIs) for low back pain.

Design

Observational study; patients were evaluated before ESI and 1 and 3 months after ESI.

Setting

Spine center and related treatment sites.

Participants

Participants (N=158) seeking treatment for low back pain with or without radiculopathy.

Intervention

ESI for low back pain with or without radiculopathy.

Main Outcome Measures

We assessed the dependent (global pain severity for back and leg pain, pain behavior, pain interference) and independent variables (depression, sleep disturbance, and covariates of back pain response) with the Patient-Reported Outcome Measurement Information System (PROMIS) and legacy measures. Outcome was assessed cross-sectionally using multiple regression and longitudinally with path analysis.

Results

After 1 month, sleep disturbance was the only predictor for the global ratings of improvement in back pain (R²=16.8%) and leg pain (R²=11.4%). The proportions of variance explained by sleep disturbance and negative affect for all dependent variables were greater at 3 months than 1 month. Mediation analysis was significant for negative affect for the 3-month outcomes on PROMIS pain behavior (β=.87, P<.01) and pain interference (β=.37, P<.01). There was no evidence of mediation by sleep disturbance for any outcome.

Conclusions

Negative affect and sleep disturbance are associated with worse outcomes after ESI. Further research is needed to determine if treatment of negative affect and sleep disturbance prior to or concurrently with ESI will improve outcomes.     

Postural Rehabilitation and Kinesio Taping for Axial Postural Disorders in Parkinson's Disease

Objective

To assess the effects of postural rehabilitation (PR) on trunk asymmetry and balance, with and without Kinesio taping (KT) of the back muscles as additional treatment, in patients with Parkinson's disease (PD) who have postural disorders.

Design

Single-blind, randomized controlled trial with 1-month follow-up.

Setting

Ambulatory care in referral center.

Participants

Patients (N=20) with PD showing postural abnormalities of the trunk, in the sagittal and/or coronal plane.

Interventions

Four weeks of patient-tailored proprioceptive and tactile stimulation, combined with stretching and postural reeducation, was provided to 13 subjects (PR group), while 7 received no treatment (control group). Six of the 13 subjects receiving PR also had KT strips applied to their trunk muscles, according to the features of their postural abnormalities.

Main Outcome Measures

Berg Balance Scale, Timed Up and Go, and degrees of trunk bending in the sagittal and coronal planes were assessed at the enrollment (t0), 1 month later (t1), and 2 months later (t2).

Results

At t1, all treated patients showed a significant improvement in trunk posture in both the sagittal (P=.002) and coronal planes (P=.01), compared with baseline. Moreover, they showed an improvement in measures of gait and balance (P<.01). Benefits persisted at t2 for all measures, except lateral trunk bend. No differences were found when comparing the PR and KT groups.

Conclusions

The combination of active posture correction and trunk movements, muscle stretching, and proprioceptive stimulation may usefully impact PD axial symptoms. Repeated training is advocated to avoid waning of the effect.     

Influence of cement penetration and graft density on stem stability in impaction allografting: A finite element study

Background

Excessive stem migration is often problematic after impaction allografting. The mechanisms responsible for migration are not known, but achieving a dense graft bed has traditionally been believed to be essential for stem stability. When the stem is cemented into the allograft bed, however, the graft becomes infiltrated with bone cement. Extensive cement penetration into the graft has been observed in previous studies, resulting in regions of cement–endosteum contact.

Methods

This study explored the effects of graft density and cement penetration on stem motion using a finite element model that was validated against experimental data.

Findings

Cement penetration has a considerable stabilizing effect on stem motion, whereas graft density is important only when there is no cement–endosteum contact. Stem migration can be attributed primarily to slippage at the endosteum and stem–cement interfaces rather than to shear failure within the graft.

Interpretation

Partial cement penetration to the endosteum increases the likelihood of meeting clinical requirements of early implant stability, particularly when a dense graft bed cannot be achieved.     

Slowed Down: Response Time Deficits in Well-Recovered Subjects With Incomplete Spinal Cord Injury

Objective

To quantify remaining motor deficits in well-recovered subjects with incomplete spinal cord injury.

Design

Case-control study.

Setting

Spinal cord injury center of a university hospital.

Participants

Out of a volunteer sample, we recruited 15 subjects with incomplete paraplegia (mean age, 50y; 67% men; neurologic level from T4 to L4; mean time since injury, 6.3y) and close-to-normal walking pattern. They were compared with 15 age- and sex-matched controls.

Interventions

Not applicable.

Main Outcome Measures

Response time and its 4 subparts, processing time, conduction time, motor time, and movement time. These were assessed with an electromyogram-supported lower-limb response time task and single-pulse transcranial magnetic stimulation to measure the motor-evoked potential latency of the M. tibialis anterior. In addition, participants were tested for lower-extremity muscle strength, gait capacity, visual acuity, and upper-extremity response time.

Results

Well-recovered subjects with incomplete paraplegia still suffered from deficits in conduction and movement time, whereas their processing and motor times were essentially normal. In addition, these patients showed delayed movement times of the upper limb, even if their injury was located in the thoracic or lumbar region.

Conclusions

Well-recovered patients with incomplete paraplegia still experience difficulties with quick and accurate movements. Furthermore, combining transcranial magnetic stimulation, electromyogram, and a response time task proved useful for investigating deficits in executing fast and accurate movements.     

The effect of ghrelin on cell proliferation in small intestinal IEC-6 cells

Background and aims

Recent evidence demonstrates that ghrelin, a short orexigenic peptide from the stomach, has dual effects on cell proliferation in different cell types via autocrine and/or paracrine mechanisms. The aim of this study is to investigate the proliferative role of ghrelin in intestinal epithelial IEC-6 cells and explore underlying mechanism.

Methods

RT-PCR was used for the detection of growth hormone secretagogue receptor 1a. Cell proliferation was measured using Cell Counting Kit-8. Protein expression of ERK 1/2 and Akt was examined using western blotting. Inhibitors of mitogen activated protein kinases kinase and phosphatidylinositol 3-kinase were used to evaluate the role of these signalling pathways in ghrelin-induced proliferation of IEC-6 cells.

Results

Growth hormone secretagogue receptor 1a mRNA was present in IEC-6 cells. Ghrelin and des-acyl ghrelin increased IEC-6 cell proliferation in a dose- and time-dependent manner. Ghrelin and des-acyl ghrelin activated ERK1/2, but not Akt. U0126, a specific inhibitor of mitogen activated protein kinases kinase, blocked ghrelin- and des-acyl ghrelin-induced ERK1/2 phosphorylation and cell proliferation in IEC-6 cells.

Conclusion

Ghrelin and des-acyl ghrelin stimulate the proliferation of IEC-6 cells via the ERK1/2 pathway.     

Improvement of Upper Extremity Motor Control and Function After Home-Based Constraint Induced Therapy in Children With Unilateral Cerebral Palsy: Immediate and Long-Term Effects

Objective

To investigate the long-term effects of home-based constraint induced therapy (CIT) on motor control underlying functional change in children with unilateral cerebral palsy (CP).

Design

Randomized controlled trial.

Setting

Home based.

Participants

Children with unilateral CP (N=45; aged 6–12y) were randomly assigned to receive home-based CIT (n=23) or traditional rehabilitation (TR) (n=22).

Interventions

Both groups received a 4-week therapist-based intervention at home. The home-based CIT involved intensive functional training of the more affected upper extremity during which the less affected one was restrained. The TR involved functional unimanual and bimanual training.

Main Outcome Measures

All children underwent kinematic and clinical assessments at baseline, 4 weeks (posttreatment), and 3 and 6 months (follow-up). The reach-to-grasp kinematics were reaction time (RT), normalized movement time, normalized movement unit, peak velocity (PV), maximum grip aperture (MGA), and percentage of movement where MGA occurs. The clinical measures were the Peabody Developmental Motor Scales, Second Edition (PDMS-2), Bruininks-Oseretsky Test of Motor Proficiency (BOTMP), and Functional Independence Measure for children (WeeFIM).

Results

The home-based CIT group showed a shorter RT (P<.05) and normalized movement time (P<.01), smaller MGA (P=.006), and fewer normalized movement units (P=.014) in the reach-to-grasp movements at posttreatment and follow-up than the TR group. The home-based CIT group improved more on the PDMS-2 (P<.001) and WeeFIM (P<.01) in all posttreatment tests and on the BOTMP (P<.01) at follow-up than the TR group.

Conclusions

The home-based CIT induced better spatial and temporal efficiency (smoother movement, more efficient grasping, better movement preplanning and execution) for functional improvement up to 6 months after treatment than TR.     

Cognitive Processing Speed Is Related to Fall Frequency in Older Adults With Multiple Sclerosis

Objective

To examine mobility, balance, fall risk, and cognition in older adults with multiple sclerosis (MS) as a function of fall frequency.

Design

Retrospective, cross-sectional design.

Setting

University research laboratory.

Participants

Community-dwelling persons with MS (N=27) aged between 50 and 75 years were divided into 2 groups—single-time (n=11) and recurrent (n=16; >2 falls/12 mo) fallers—on the basis of fall history.

Intervention

Not applicable.

Main Outcome Measures

Mobility was assessed using a variety of measures including Multiple Sclerosis Walking Scale-12, walking speed (Timed 25-Foot Walk test), endurance (6-Minute Walk test), and functional mobility (Timed Up and Go test). Balance was assessed with the Berg Balance Scale, posturography, and self-reported balance confidence. Fall risk was assessed with the Physiological Profile Assessment. Cognitive processing speed was quantified with the Symbol Digit Modalities Test and the Paced Auditory Serial Addition Test.

Results

Recurrent fallers had slower cognitive processing speed than single-time fallers (P≤.01). There was no difference in mobility, balance, or fall risk between recurrent and single-time fallers (P>.05).

Conclusions

Results indicated that cognitive processing speed is associated with fall frequency and may have implications for fall prevention strategies targeting recurrent fallers with MS.     

Development of an improved time-resolved fluoroimmunoassay for simultaneous quantification of C-peptide and insulin in human serum

Objectives

Diabetes mellitus is a chronic disease affecting millions of people globally and resulting in significant death rates each year. A fast, inexpensive alternative to traditional testing and monitoring techniques is desirable, since secretion of insulin and C-peptide is impaired in diabetes mellitus.

Design and methods

A highly sensitive immunoassay was developed for the simultaneous measurement of C-peptide and insulin levels in human serum, utilizing dual-label time-resolved fluoroimmunoassay (TRFIA) and magnetic particle technologies. This assay was characteristic for a single-step sandwich-type immunoassay, wherein antibody-coated magnetic particles were used as the solid phase and Eu^3 + and Sm^3 + chelate labels were used for detection.

Results

Antibody-coated magnetic particles in a TRFIA format performed well in addressing a number of quantitative needs.

Conclusions

The results of this assay correlated well with commercial chemiluminescence assays and provided a number a advantages, including reduced sample volume, reduced reagent and personnel costs and reduced assay time, while maintaining the required clinical sensitivity.