Inclusion and perception of hand therapy content in occupational therapy programs: A mixed-method study.

STUDY DESIGN: Mixed-methods with cross-sectional survey and interviews. INTRODUCTION: Hand therapy is a specialty area of practice for occupational (OT) and physical therapists (PT), requiring experience and certification beyond entry-level generalist education. Perspectives and inclusion of content related to hand therapy differs among entry-level OT programs and faculty. PURPOSE: Perception and inclusion of hand therapy content in OT programs was examined in this mixed-method study to better understand the trends in academia regarding integration of content related to hand therapy. METHODS: A survey was developed, peer-reviewed, and emailed to all accredited entry-level masters and doctorate OT programs via Survey Monkey (SurveyMonkey, Inc., San Mateo, CA). Respondents were also given the opportunity to participate in an interview (n = 2; 5%). RESULTS: A total of 43 participants responded to the survey, representing a 23% response rate. Quantitative results revealed that 65% of OT programs report including 41+ hours of hand therapy content and 54% report integration of hand therapy content in 2-3 courses. Qualitative trends included the perception of hand content as necessary and beneficial to other areas of practice as well as the perspective that it is too specialized and advanced for generalist curriculum. DISCUSSION: Educators have a largely positive opinion regarding inclusion and generalizability of hand therapy content within OT curricula with varied content inclusion. While hand therapy related content is valued, increased emphasis on occupation during didactic instruction is recommended for more holistic understanding and occupation-based practice. CONCLUSION: While trends of hand therapy content inclusion were revealed in the survey, perceptions of hand therapy within the broad spectrum of OT curricula were diverse, indicating a possible lack of unity within the profession regarding this specialty area of practice.

Degradation of MAC13243 and studies of the interaction of resulting thiourea compounds with the lipoprotein targeting chaperone LolA.

The discovery of novel small molecules that function as antibacterial agents or cellular probes of biology is hindered by our limited understanding of bacterial physiology and our ability to assign mechanism of action. We previously employed a chemical genomic strategy to identify a novel small molecule, MAC13243, as a likely inhibitor of the bacterial lipoprotein targeting chaperone, LolA. Here, we report on the degradation of MAC13243 into the active species, S-(4-chlorobenzyl)isothiourea. Analogs of this compound (e.g., A22) have previously been characterized as inhibitors of the bacterial actin-like protein, MreB. Herein, we demonstrate that the antibacterial activity of MAC13243 and the thiourea compounds are similar; these activities are suppressed or sensitized in response to increases or decreases of LolA copy number, respectively. We provide STD NMR data which confirms a physical interaction between LolA and the thiourea degradation product of MAC13243, with a Kd of ~150 µM. Taken together, we conclude that the thiourea series of compounds share a similar cellular mechanism that includes interaction with LolA in addition to the well-characterized target MreB.

Chemical genomics in Escherichia coli identifies an inhibitor of bacterial lipoprotein targeting.

One of the most significant hurdles to developing new chemical probes of biological systems and new drugs to treat disease is that of understanding the mechanism of action of small molecules discovered with cell-based small-molecule screening. Here we have assembled an ordered, high-expression clone set of all of the essential genes from Escherichia coli and used it to systematically screen for suppressors of growth inhibitory compounds. Using this chemical genomic approach, we demonstrate that the targets of well-known antibiotics can be identified as high copy suppressors of chemical lethality. This approach led to the discovery of MAC13243, a molecule that belongs to a new chemical class and that has a unique mechanism and promising activity against multidrug-resistant Pseudomonas aeruginosa. We show that MAC13243 inhibits the function of the LolA protein and represents a new chemical probe of lipoprotein targeting in bacteria with promise as an antibacterial lead with Gram-negative selectivity.

Chemical genomic approaches to study model microbes.

Recent genome-scale analyses of genetic interactions in model microbes have revealed the inherent functional organization of the cell as a dense network of highly interconnected pathways. While classical one gene at a time paradigms offer limited insight into cellular systems, genome-scale approaches are making considerable headway. Indeed, where small organic compounds are ideal probes of biological complexity, systematic chemical genomic methods are emerging as requisite and powerful approaches to describing both the small molecule probe and network with which it interacts. Here, we highlight various chemical genomic approaches that are being pioneered in model microbes.