Cynthia M. Gonzalez

Analysis of the RpoS regulon in Borrelia burgdorferi in response to mammalian host signals provides insight into RpoS function during the enzootic cycle

Borrelia burgdorferi (Bb) adapts to its arthropod and mammalian hosts by altering its transcriptional and antigenic profiles in response to environmental signals associated with each of these milieus. In studies presented here, we provide evidence to suggest that mammalian host signals are important for modulating and maintaining both the positive and negative aspects of mammalian host adaptation mediated by the alternative sigma factor RpoS in Bb. Although considerable overlap was observed between genes induced by RpoS during growth within the mammalian host and following temperature‐shift, comparative microarray analyses demonstrated unequivocally that RpoS‐mediated repression requires mammalian host‐specific signals. A substantial portion of the in vivo RpoS regulon was uniquely upregulated within dialysis membrane chambers, further underscoring the importance of host‐derived environmental stimuli for differential gene expression in Bb. Expression profiling of genes within the RpoS regulon by quantitative reverse transcription polymerase chain reaction (qRT‐PCR) revealed a level of complexity to RpoS‐dependent gene regulation beyond that observed by microarray, including a broad range of expression levels and the presence of genes whose expression is only partially dependent on RpoS. Analysis of Bb‐infected ticks by qRT‐PCR established that expression of rpoS is induced during the nymphal blood meal but not within unfed nymphs or engorged larvae. Together, these data have led us to postulate that RpoS acts as a gatekeeper for the reciprocal regulation of genes involved in the establishment of infection within the mammalian host and the maintenance of spirochetes within the arthropod vector.

Recommended weight limits for lifting and holding limbs in the orthopaedic practice setting.

Nurses and other caregivers face high risk for developing work-related musculoskeletal disorders while lifting and holding limbs in the orthopaedic practice setting. A task force including representatives from the National Association of Orthopaedic Nurses, American Nurses Association, National Institute for Occupational Safety and Health, Patient Safety Center of Inquiry at the James A. Haley Veterans Administration Medical Center in Tampa, Diligent Services, and Guldmann, Inc., developed an orthopaedic clinical tool for determining maximum recommended weight limits for lifting and holding arms and legs for treatment of the orthopaedic patient. Scientific evidence, concepts of ergonomic safety, and safe patient-handling equipment were incorporated into this clinical tool.

Recommendations for turning patients with orthopaedic impairments.

Nurses and other caregivers face high risk for developing work-related musculoskeletal disorders associated with turning (logrolling) patients with orthopaedic conditions. The task is considered high risk on the basis of weight limits and awkward positioning. A task force including representatives from the National Association of Orthopaedic Nurses the American Nurses Association, the National Institute for Occupational Safety and Health, the Patient Safety Center of Inquiry at the James A. Haley Veterans Administration Medical Center in Tampa, Diligent Services, and Guldmann, Inc., developed an ergonomic tool for determining best practices for safe patient turning. Scientific evidence, concepts of ergonomic safety, and safe patient handling equipment were incorporated into this ergonomic tool.

Recommendations for vertical transfer of a postoperative total hip replacement patient (bed to chair, chair to toilet, chair to chair, or car to chair).

Vertical transfers of postoperative orthopaedic patients pose a high risk to healthcare workers for developing work-related musculoskeletal disorders. The task is considered high risk based on weight limits and awkward positioning. A task force including representatives from the National Association of Orthopaedic Nurses, the American Nurses Association, the National Institute for Occupational Safety and Health, the Patient Safety Center of Inquiry at the James A. Haley Veterans Administration Medical Center in Tampa, Diligent Services, and Guldmann, Inc., developed an ergonomic tool for determining best practices for safe vertical transfers. Current concepts of ergonomic safety, scientific evidence, and safe patient-handling equipment and devices were incorporated into this ergonomic tool.

Safe ambulation of an orthopaedic patient.

Nurses and other caregivers face high risk for developing work-related musculoskeletal disorders associated with manual ambulation of patients with orthopaedic conditions. In addition to the physical demands needed to support the patients weight during ambulation, injury risk increases if the patient falls. A task force including representatives from the National Association of Orthopaedic Nurses, American Nurses Association, National Institute for Occupational Safety and Health, and Patient Safety Center of Inquiry at the James A. Haley Veterans Administration Medical Center in Tampa developed an ergonomic tool for determining best practices for safe ambulation of orthopaedic patients (C. A. Sedlak, M. O. Doheny, A. Nelson, & T. R. Waters, 2009). Scientific evidence, concepts of ergonomic safety, and safe patient-handling equipment were incorporated into an ergonomic tool designed to increase safety and reduce unnecessary variation in practice associated with this high-risk patient-handling task (National Institute for Occupational Safety Health, 1997; National Research Council/Institute of Medicine, 2001; A. Nelson, 2006; T. Waters, 2007).

Induction of direct repeat recombination by psoralen-DNA adducts in Saccharomyces cerevisiae: defects in DNA repair increase gene copy number variation.

Psoralen photoreaction produces covalent monoadducts and interstrand crosslinks in DNA. The interstrand DNA crosslinks are complex double strand lesions that require the involvement of multiple pathways for repair. Homologous recombination, which can carry out error-free repair, is a major pathway for crosslink repair; however, some recombination pathways can also produce DNA rearrangements. Psoralen photoreaction-induced recombination in yeast was measured using direct repeat substrates that can detect gene conversions, a form of conservative recombination, as well as deletions and triplications, which generate gene copy number changes. In repair-proficient cells the major products of recombination were gene conversions, along with substantial fractions of deletions. Deficiencies in DNA repair pathways increased non-conservative recombination products. Homologous recombination-deficient rad51, rad54, and rad57 strains had low levels of crosslink-induced recombination, and most products were deletions produced by single strand annealing. Nucleotide excision repair-deficient rad1 and rad2 yeast had increased levels of triplications, and rad1 cells had lower crosslink-induced recombination. Deficiencies in post-replication repair increased crosslink-induced recombination and gene copy number changes. Loss of REV3 function, in the error-prone branch, and of RAD5 and UBC13, in the error-free branch, produced moderate increases in deletions and triplications; rad18 cells, deficient in both post-replication repair sub-pathways, exhibited hyperrecombination, with primarily non-conservative products. Proper functioning of all the DNA repair pathways tested was required to maintain genomic stability and avoid gene copy number variation in response to interstrand crosslinks.

Protecting pregnant health care workers from occupational hazards.

The safety of pregnant health care workers and their infants is paramount. The scope and variety of hazards within the health care field is profound and diverse. The occupational health nurse can identify early risks and correct them, as well as provide ongoing surveillance, counseling, and prudent policy recommendations for the multitude of hazards to which pregnant health care workers are exposed. Policy must reflect the real risks taken by these workers every day they go to work, and how those risks will affect them, their immediate families, and future generations.