Immunoscintigraphy with a new indium-111-labeled monoclonal antibody (MAb 1A3) in patients with colorectal cancer

PURPOSE: This study was designed to evaluate a new anticolorectal carcinoma monoclonal antibody (1A3), conjugated with the bifunctional chelating agent N,N′-bis (2-hydroxybenzyl) 1 (4-bromoacetamidobenzyl) 1,2-ethylenediamine-N,N′-diacetic acid and labeled with indium-111, in a Phase I/II study involving 38 patients with localized or advanced colorectal cancer. METHODS: Patients were injected with indium-111-N,N′-bis(2-hydroxybenzyl) 1 (4-bromoacetamidobenzyl) 1,2-ethylenediamine-N, N′-diacetic acid-monoclonal antibody 1A3 (1–50 mg, 1–5 mCi) and imaged at two or three sessions one to five days later. Scintigraphic findings were compared with radiologic, pathologic, surgical, and other clinical findings to assess the accuracy of radioimmunoscintigraphy. RESULTS: At least one known tumor site was clearly defined by planar scintigraphy in 29 (76 percent) patients. Increased radioactivity was seen in 40 of 63 known tumor sites (37/43 abdominal-pelvic, 3/15 hepatic, and 0/5 pulmonary sites) without any apparent dose-related effects. Nineteen previously undetected sites were considered positive by imaging, and, of these, six were biopsy-proven tumor sites, four were probable tumor sites, three were definitely false positive sites, and six were probable false positive sites. Radioimmunoscintigraphy detected proven tumor in 15 of 16 patients with negative or equivocal computed tomography results. Of the 28 patients with rectosigmoid cancer, 25 (89 percent) had positive studies with 34 of 47 tumor sites showing definite uptake on the scintigrams. This included 3 of 9 hepatic metastases. The only adverse reaction occurred in one patient who developed transient hives. Human anti-mouse antibody responses occurred in approximately one-half of the patients injected with doses of 10 or 50 mg. CONCLUSION: This study shows that radioimmunoscintigraphy with this indium-111-labeled monoclonal antibody is safe, it can detect most nonhepatic abdominalpelvic tumors with a positive predictive value of 83 (44/ 53) percent, and it should prove to be useful, particularly in the diagnosis of recurrent rectal carcinoma.     

Membrane adaptation limitations in Enterococcus faecalis underlie sensitivity and the inability to develop significant resistance to conjugated oligoelectrolytes

The growing problem of antibiotic resistant bacteria, along with a dearth of new antibiotics, has redirected attention to the search for alternative antimicrobial agents. Conjugated oligoelectrolytes (COEs) are an emerging class of antimicrobial agents which insert into bacterial cell membranes and are inhibitory against a range of Gram-positive and Gram-negative bacteria. In this study, the extent of COE resistance that Enterococcus faecalis could achieve was studied. Enterococci are able to grow in hostile environments and develop resistance to membrane targeting antibiotics such as daptomycin in clinical settings. Herein we expand our knowledge of the antimicrobial mechanism of action of COEs by developing COE-resistant strains of E. faecalis OG1RF. Evolution studies yielded strains with a moderate 4–16 fold increase in antimicrobial resistance relative to the wild type. The resistant isolates accumulated agent-specific mutations associated with the liaFSR operon, which is a cell envelope-associated stress-response sensing and regulating system. The COE resistant isolates displayed significantly altered membrane fatty acid composition. Subsequent, exogenous supplementation with single fatty acids, which were chosen based on those dominating the fatty acid profiles of the mutants, increased resistance of the wild-type E. faecalis to COEs. In combination, genetic, fatty acid, and uptake studies support the hypothesis that COEs function through insertion into and disruption of membranes and that the mechanism by which this occurs is specific to the disrupting agent. These results were validated by a series of biophysical experiments showing the tendency of COEs to accumulate in and perturb adapted membrane extracts. Collectively, the data support that COEs are promising antimicrobial agents for targeting E. faecalis, and that there is a high barrier to the emergence of severely resistant strains constrained by biological limits of membrane remodeling that can occur in E. faecalis.

COEs are emerging antimicrobials to combat drug resistant infections and to which bacteria develop only limited resistance.     

Full-participation of students with physical disabilities in science and engineering laboratories

Purpose: To conduct a literature review identifying barriers and facilitators students with physical disabilities (SwD-P) may encounter in science and engineering (S&E) laboratories.

Method: Publications were identified from 1991 to 2015 in ERIC, web of science via web of knowledge, CINAHL, SCOPUS, IEEEXplore, engineering village, business source complete and PubMed databases using search terms and synonyms for accommodations, advanced manufacturing, additive manufacturing, assistive technology (AT), barriers, engineering, facilitators, instructor, laboratory, STEM education, science, students with disabilities and technology.

Results: Twenty-two of the 233 publications that met the review’s inclusion criteria were examined. Barriers and facilitators were grouped based on the international classification of functioning, disability and health framework (ICF). None of the studies directly found barriers or facilitators to SwD-P in science or engineering laboratories within postsecondary environments. The literature is not clear on the issues specifically related to SwD-P.

Conclusion: Given these findings, further research (e.g., surveys or interviews) should be conducted to identify more details to obtain more substantial information on the barriers that may prevent SwD-P from fully participating in S&E instructional laboratories.

• Implications for Rehabilitation

• Students with disabilities remain underrepresented going into STEM careers.

• A need exist to help uncover barriers students with disabilities encounter in STEM laboratory.

• Environments.

• Accommodations and strategies that facilitate participation in STEM laboratory environments are promising for students with disabilities

     

Comparing Electrical Stimulation With and Without Ultrasound Guidance for Phenol Neurolysis to the Musculocutaneous Nerve

Background

Ultrasound guidance is increasingly being used for neurolytic procedures that have traditionally been done with electrical stimulation (e-stim) guidance alone. Ultrasound visualization with e-stim?guided neurolysis can potentially allow adjustments in injection protocols that will reduce the volume of neurolytic agent needed to achieve clinical improvement.

Influence of High and Low Autonomy-Supportive Climates on Physical Activity in Children with and without Developmental Disability

The aim of this study was to compare the influence of two different instructional climates on the accumulation of moderate-to-vigorous physical activity (MVPA) during a fully-inclusive adapted recreational physical activity program. A total of 32 children (18 typically-developing (TD), and 14 with developmental disabilities (DD) ranging in ages from 5 to 9 years, participated in six, 60-min adapted recreational sessions. Of those six sessions, three incorporated an autonomy-supportive climate (high autonomy), and three incorporated direct instruction (low autonomy). MVPA was measured using accelerometers. A repeated measures ANOVA was conducted to determine significant differences in MVPA between group (TD/DD), climate (autonomy/direct), and a group x climate interaction. Significant group and climate main effects were observed (p?=?0.002 and 0.014, respectively). However, there was not a significant group x climate interaction (p?=?0.313). These results suggest that although the group of children with disabilities spent less time in MVPA compared to their typically-developing peers, all participants spent more time in MVPA for the autonomy-supportive climate compared to the low-autonomous climate. This study is the first to quantitatively assess the efficacy of a fully-inclusive autonomy-supportive climate on physical activity levels in children with and without developmental disabilities.