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1.  Does nuclear tissue infected with bacteria following disc herniations lead to Modic changes in the adjacent vertebrae? 
European Spine Journal  2013;22(4):690-696.
To investigate the prevalence of infected herniated nucleus material in lumbar disc herniations and to determine if patients with an anaerobic infected disc are more likely to develop Modic change (MC) (bone oedema) in the adjacent vertebrae after the disc herniation. MCs (bone oedema) in vertebrae are observed in 6 % of the general population and in 35–40 % of people with low back pain. These changes are strongly associated with low back pain. There are probably a mechanical cause and an infective cause that causes MC. Several studies on nuclear tissue from herniated discs have demonstrated the presence of low virulent anaerobic microorganisms, predominantly Propionibacterium acnes, in 7–53 % of patients. At the time of a herniation these low virulent anaerobic bacteria may enter the disc and give rise to an insidious infection. Local inflammation in the adjacent bone may be a secondary effect due to cytokine and propionic acid production.
Patients undergoing primary surgery at a single spinal level for lumbar disc herniation with an MRI-confirmed lumbar disc herniation, where the annular fibres were penetrated by visible nuclear tissue, had the nucleus material removed. Stringent antiseptic sterile protocols were followed.
Sixty-one patients were included, mean age 46.4 years (SD 9.7), 27 % female. All patients were immunocompetent. No patient had received a previous epidural steroid injection or undergone previous back surgery. In total, microbiological cultures were positive in 28 (46 %) patients. Anaerobic cultures were positive in 26 (43 %) patients, and of these 4 (7 %) had dual microbial infections, containing both one aerobic and one anaerobic culture. No tissue specimens had more than two types of bacteria identified. Two (3 %) cultures only had aerobic bacteria isolated.
In the discs with a nucleus with anaerobic bacteria, 80 % developed new MC in the vertebrae adjacent to the previous disc herniation. In contrast, none of those with aerobic bacteria and only 44 % of patients with negative cultures developed new MC. The association between an anaerobic culture and new MCs is highly statistically significant (P = 0.0038), with an odds ratio of 5.60 (95 % CI 1.51–21.95).
These findings support the theory that the occurrence of MCs Type 1 in the vertebrae adjacent to a previously herniated disc may be due to oedema surrounding an infected disc. The discs infected with anaerobic bacteria were more likely (P < 0.0038) to develop MCs in the adjacent vertebrae than those in which no bacteria were found or those in which aerobic bacteria were found.
PMCID: PMC3631023  PMID: 23397187
Bacterial infection; Modic changes; Endplate changes; Propionibacterium acnes; Lumbar disc herniation
2.  Genotypic and Antimicrobial Characterisation of Propionibacterium acnes Isolates from Surgically Excised Lumbar Disc Herniations 
BioMed Research International  2013;2013:530382.
The anaerobic skin commensal Propionibacterium acnes is an underestimated cause of human infections and clinical conditions. Previous studies have suggested a role for the bacterium in lumbar disc herniation and infection. To further investigate this, five biopsy samples were surgically excised from each of 64 patients with lumbar disc herniation. P. acnes and other bacteria were detected by anaerobic culture, followed by biochemical and PCR-based identification. In total, 24/64 (38%) patients had evidence of P. acnes in their excised herniated disc tissue. Using recA and mAb typing methods, 52% of the isolates were type II (50% of culture-positive patients), while type IA strains accounted for 28% of isolates (42% patients). Type III (11% isolates; 21% patients) and type IB strains (9% isolates; 17% patients) were detected less frequently. The MIC values for all isolates were lowest for amoxicillin, ciprofloxacin, erythromycin, rifampicin, tetracycline, and vancomycin (≤1mg/L). The MIC for fusidic acid was 1-2 mg/L. The MIC for trimethoprim and gentamicin was 2 to ≥4 mg/L. The demonstration that type II and III strains, which are not frequently recovered from skin, predominated within our isolate collection (63%) suggests that the role of P. acnes in lumbar disc herniation should not be readily dismissed.
PMCID: PMC3771251  PMID: 24066290
3.  Measured Occupational Solar UVR Exposures of Lifeguards in Pool Settings 
The aim of this study was to measure ultraviolet radiation (UVR) exposures of lifeguards in pool settings and evaluate their personal UVR protective practices.
Lifeguards (n = 168) wore UVR sensitive polysulfone (PS) film badges in wrist bracelets on 2 days and completed a survey and diary covering sun protection use. Analyses were used to describe sun exposure and sun protection practices, to compare UVR exposure across locations, and to compare findings with recommended threshold limits for occupational exposure.
The measured UVR exposures varied with location, ranging from high median UVR exposures of 6.2 standard erythemal doses (SEDs) to the lowest median of 1.7 SEDs. More than 74% of the lifeguards’ PS badges showed UVR above recommended threshold limits for occupational exposure. Thirty-nine percent received more than four times the limit and 65% of cases were sufficient to induce sunburn. The most common protective behaviors were wearing sunglasses and using sunscreen, but sun protection was often inadequate.
At-risk individuals were exposed to high levels of UVR in excess of occupational limits and though appropriate types of sun protection were used, it was not used consistently and more than 50% of lifeguards reported being sunburnt at least twice during the previous year.
PMCID: PMC3728671  PMID: 19572325
lifeguards; occupational UVR exposure; sun protection behaviors
4.  A Controlled Trial of Objective Measures of Sunscreen and Moisturizing Lotion 
Taking an alcohol swab of a person’s forearm and analyzing it using a spectrophotometer has been shown to be a reliable method for detecting the presence of sunscreen. The aims of this study were to determine if moisturizing lotions or other non-sun-screen products influence the absorbance readings from skin swabs in a controlled setting, and to establish the cutoff point in determining the presence or absence of sunscreen using a crystal cuvette instead of a plastic one. In a controlled trial of 30 volunteer office workers, absorbance readings from two popular brands of sunscreen with sun-protection factors (SPF) of 30 and 45 were compared with absorbance readings from two different moisturizing lotions, one with an SPF of 15 and another with no stated SPF. Moisturizers with SPF 15 tested positive for sunscreen, with absorbance readings (mean, 3.77; min, 3.30) comparable to sunblock with SPF 30 or 45 (mean, 3.51; min, 2.02). Moisturizers with no stated SPF factor tested negative for the presence of sunscreen, with extremely low absorbance readings (mean, 0.06; max, 0.19) similar to control readings. The skin swabbing technique remains a valid and useful method for detecting the presence of sunscreen and does not result in false positives when moisturizers with no stated SPF are present. Using a conservative cutoff point of 0.30 with a crystal cuvette reduces any chance of false-positive readings and remains robust when sunscreen of SPF 15 or higher is present.
PMCID: PMC3725572  PMID: 19423519
5.  Linking Agents’ Activities and Communication Patterns in a Study of the Dissemination of an Effective Skin Cancer Prevention Program 
Linking agents connect program developers with end users, enhancing implementation and sustainability of health promotion programs. However, little is known about how linkage systems work in practice and research settings.
This article describes the activities and communication patterns of field coordinators in a 4-year, national study of the dissemination of an effective skin cancer prevention program.
Descriptive and content analyses were completed for all e-mails between field coordinators and program staff and for field coordinator activity logs.
A total of 5 215 e-mails were sent to or from 62 field coordinators from 2003 to 2006. E-mails most often concerned program administration, data collection, and management of program materials. The most common activities recorded in activity logs were communication with program staff and study sites, management of surveys, and delivery and management of program materials.
Field coordinators carried out activities related to program administration and data collection across a large number of study sites. The high volume of e-mails and their emphasis on program administration issues demonstrate the importance of communication between program staff and field coordinators. It is recommended that public health researchers and practitioners implement similar linkage systems when taking effective programs to scale.
PMCID: PMC3725579  PMID: 19704309
diffusion of innovation; public health; qualitative research
6.  A Pilot Study of the Validity of Self-reported Ultraviolet Radiation Exposure and Sun Protection Practices Among Lifeguards, Parents and Children 
Photochemistry and photobiology  2008;84(3):774-778.
Outdoor recreation settings, such as swimming pools, provide a promising venue to assess UVR exposure and sun protection practices among individuals who are minimally clothed and exposed to potentially high levels of UVR. Most studies assessing sun exposure/protection practices rely on self-reported data, which are subject to bias. The aim of this study was to establish the feasibility of conducting a multimethod study to examine the validity of self-reported measures within a swimming pool setting. Data were collected from 27 lifeguards, children and parents in Hawaii. Each participant filled out a survey and a 4 day sun habits diary. On two occasions, researchers assessed observable sun protection behaviors (wearing hats, shirts, sunglasses), swabbed the skin to detect the presence of sunscreen, and subjects wore polysulphone dosimeters to measure UVR exposure. Overall, observed sun protection behaviors were more highly correlated with diary reports than with survey reports. While lifeguards and children reported spending comparable amounts of time in the sun, dosimeter measures showed that lifeguards received twice as much UVR exposure. This study demonstrated the feasibility of implementing a multimethod validity study within a broader population of swimming pools.
PMCID: PMC3725580  PMID: 18179624
7.  Characteristics of swimming pools with high rates of objectively measured sunscreen use 
A combination of verbal reports, observations, and physical assessments can improve understanding of prevention programs.
Skin swabbing techniques were used to detect the presence of sunscreen as part of a sun protection measurement study at 16 swimming pools. Three pools demonstrated much higher sunscreen use (>95%) than the others (47.1%). This paper compares these three pools to the other 13 to examine whether they have common features and if different sources of data can help interpret the findings.
Data were collected from skin swabs detecting the presence of sunscreen; observations of participants; observations of pool environments; and surveys.
Pool observations showed a higher use of shade structures, sun safety signs, and other supporting items at the three high–sunscreen use pools. These three pools had significantly more year-round and long-term employees than did the other 13 pools.
Sunscreen characteristics could not be determined using the swabbing technique. Publicity about the study, or the weather, may have influenced behaviors at the pools.
Supportive environments were associated with consistent high levels of sunscreen use. This study also confirms the importance of using multiple data sources to interpret findings.
PMCID: PMC3724408  PMID: 19293015
8.  Impact of catheter antimicrobial coating on species-specific risk of catheter colonization: a meta-analysis 
Antimicrobial catheters have been utilized to reduce risk of catheter colonization and infection. We aimed to determine if there is a greater than expected risk of microorganism-specific colonization associated with the use of antimicrobial central venous catheters (CVCs).
We performed a meta-analysis of 21 randomized, controlled trials comparing the incidence of specific bacterial and fungal species colonizing antimicrobial CVCs and standard CVCs in hospitalized patients.
The proportion of all colonized minocycline-rifampin CVCs found to harbor Candida species was greater than the proportion of all colonized standard CVCs found to have Candida. In comparison, the proportion of colonized chlorhexidine-silver sulfadiazine CVCs specifically colonized with Acinetobacter species or diphtheroids was less than the proportion of similarly colonized standard CVCs. No such differences were found with CVCs colonized with staphylococci.
Commercially-available antimicrobial CVCs in clinical use may become colonized with distinct microbial flora probably related to their antimicrobial spectrum of activity. Some of these antimicrobial CVCs may therefore have limited additional benefit or more obvious advantages compared to standard CVCs for specific microbial pathogens. The choice of an antimicrobial CVC may be influenced by a number of clinical factors, including a previous history of colonization or infection with Acinetobacter, diphtheroids, or Candida species.
PMCID: PMC3562262  PMID: 23206897
Central venous catheter; Catheter colonization; Catheter-related bloodstream infection; Central line-associated bloodstream infection; Bacteremia; Antimicrobial catheter
9.  CPSF6 Defines a Conserved Capsid Interface that Modulates HIV-1 Replication 
PLoS Pathogens  2012;8(8):e1002896.
The HIV-1 genome enters cells inside a shell comprised of capsid (CA) protein. Variation in CA sequence alters HIV-1 infectivity and escape from host restriction factors. However, apart from the Cyclophilin A-binding loop, CA has no known interfaces with which to interact with cellular cofactors. Here we describe a novel protein-protein interface in the N-terminal domain of HIV-1 CA, determined by X-ray crystallography, which mediates both viral restriction and host cofactor dependence. The interface is highly conserved across lentiviruses and is accessible in the context of a hexameric lattice. Mutation of the interface prevents binding to and restriction by CPSF6-358, a truncated cytosolic form of the RNA processing factor, cleavage and polyadenylation specific factor 6 (CPSF6). Furthermore, mutations that prevent CPSF6 binding also relieve dependence on nuclear entry cofactors TNPO3 and RanBP2. These results suggest that the HIV-1 capsid mediates direct host cofactor interactions to facilitate viral infection.
Author Summary
In order to infect a host cell, HIV-1 must interact with and exploit cellular cofactors. Mutations within capsid, the protein shell that surrounds the virus, have been shown to affect virus usage of these cofactors and susceptibility to host antiviral proteins. However, with the exception of the Cyclophilin A-binding loop, there is no defined protein interface on the capsid that mediates interactions with cellular proteins. Here, we describe the identification of a conserved interface on HIV-1 capsid that binds the host protein CPSF6 and determines viral dependence on nuclear transport cofactors. This data illustrates how host-virus interactions allow HIV-1 to hitch a ride into the nucleus and reveals a potential new target for antiviral drugs.
PMCID: PMC3431306  PMID: 22956906
10.  Validity of Self-Reported Solar UVR Exposure Compared to Objectively Measured UVR Exposure 
Reliance on verbal self-report of solar exposure in skin cancer prevention and epidemiologic studies may be problematic if self-report data are not valid due to systematic errors in recall, social desirability bias, or other reasons.
This study examines the validity of self-reports of exposure to ultraviolet radiation (UVR) compared to objectively measured exposure among children and adults in outdoor recreation settings in four regions of the United States. Objective UVR exposures of 515 participants were measured using polysulfone film badge UVR dosimeters on two days. The same subjects provided self-reported UVR exposure data on surveys and 4-day sun exposure diaries, for comparison to their objectively measured exposure.
Dosimeter data showed that lifeguards had the greatest UVR exposure (24.5% of weekday ambient UVR), children the next highest exposures (10.3% ambient weekday UVR) and parents had the lowest (6.6% ambient weekday UVR). Similar patterns were observed in self-report data. Correlations between diary reports and dosimeter findings were fair to good and were highest for lifeguards (r = 0.38 – 0.57), followed by parents (r = 0.28 – 0.29) and children (r = 0.18 – 0.34). Correlations between survey and diary measures were moderate to good for lifeguards (r = 0.20 – 0.54) and children (r = 0.35 – 0.53).
This is the largest study of its kind to date, and supports the utility of self-report measures of solar UVR exposure.
Overall, self-reports of sun exposure produce valid measures of UVR exposure among parents, children, and lifeguards who work outdoors.
PMCID: PMC3005549  PMID: 20940277
skin cancer; sun exposure; UVR; dosimeters; validation; biomarkers
11.  Enhanced chlorhexidine skin penetration with eucalyptus oil 
BMC Infectious Diseases  2010;10:278.
Chlorhexidine digluconate (CHG) is a widely used skin antiseptic, however it poorly penetrates the skin, limiting its efficacy against microorganisms residing beneath the surface layers of skin. The aim of the current study was to improve the delivery of chlorhexidine digluconate (CHG) when used as a skin antiseptic.
Chlorhexidine was applied to the surface of donor skin and its penetration and retention under different conditions was evaluated. Skin penetration studies were performed on full-thickness donor human skin using a Franz diffusion cell system. Skin was exposed to 2% (w/v) CHG in various concentrations of eucalyptus oil (EO) and 70% (v/v) isopropyl alcohol (IPA). The concentration of CHG (μg/mg of skin) was determined to a skin depth of 1500 μm by high performance liquid chromatography (HPLC).
The 2% (w/v) CHG penetration into the lower layers of skin was significantly enhanced in the presence of EO. Ten percent (v/v) EO in combination with 2% (w/v) CHG in 70% (v/v) IPA significantly increased the amount of CHG which penetrated into the skin within 2 min.
The delivery of CHG into the epidermis and dermis can be enhanced by combination with EO, which in turn may improve biocide contact with additional microorganisms present in the skin, thereby enhancing antisepsis.
PMCID: PMC2955684  PMID: 20860796
12.  Lifeguards’ Sun Protection Habits and Sunburns 
Archives of dermatology  2009;145(2):139-144.
To examine associations among outdoor pool environments, social norms, pool policies, and participation in a sun safety program with lifeguards’ sun protection habits and sunburn.
Cross-sectional survey.
Outdoor swimming pools across the United States.
Lifeguards and aquatic instructors at pools participating in the Pool Cool skin cancer prevention program in 2001 (N=699) and 2002 (N=987).
Main Outcome Measures
Sun protection habits and number of sunburns.
Social norms supporting sun safety were associated with more sun protection habits (95% confidence intervals [CIs], 0.18–0.28 in 2001 and 0.17–0.26 in 2002), as were pool policies supporting sun safety (95% CI, 0.02–0.07 in 2001 and 0.002–0.04 in 2002). There was a trend toward fewer sunburns as social norms, pool policies, and participation in the Pool Cool program increased, but results differed across the 2 years. In 2001, lower social norms scores and pool policy scores were associated with more reported sunburns. In 2002, teaching Pool Cool sun safety lessons was associated with fewer sunburns.
The pool environment is related to sun safety behaviors of outdoor pool staff, with social norms showing the strongest association.
PMCID: PMC2928139  PMID: 19221258
13.  Individual and setting level predictors of the implementation of a skin cancer prevention program: a multilevel analysis 
To achieve widespread cancer control, a better understanding is needed of the factors that contribute to successful implementation of effective skin cancer prevention interventions. This study assessed the relative contributions of individual- and setting-level characteristics to implementation of a widely disseminated skin cancer prevention program.
A multilevel analysis was conducted using data from the Pool Cool Diffusion Trial from 2004 and replicated with data from 2005. Implementation of Pool Cool by lifeguards was measured using a composite score (implementation variable, range 0 to 10) that assessed whether the lifeguard performed different components of the intervention. Predictors included lifeguard background characteristics, lifeguard sun protection-related attitudes and behaviors, pool characteristics, and enhanced (i.e., more technical assistance, tailored materials, and incentives are provided) versus basic treatment group.
The mean value of the implementation variable was 4 in both years (2004 and 2005; SD = 2 in 2004 and SD = 3 in 2005) indicating a moderate implementation for most lifeguards. Several individual-level (lifeguard characteristics) and setting-level (pool characteristics and treatment group) factors were found to be significantly associated with implementation of Pool Cool by lifeguards. All three lifeguard-level domains (lifeguard background characteristics, lifeguard sun protection-related attitudes and behaviors) and six pool-level predictors (number of weekly pool visitors, intervention intensity, geographic latitude, pool location, sun safety and/or skin cancer prevention programs, and sun safety programs and policies) were included in the final model. The most important predictors of implementation were the number of weekly pool visitors (inverse association) and enhanced treatment group (positive association). That is, pools with fewer weekly visitors and pools in the enhanced treatment group had significantly higher program implementation in both 2004 and 2005.
More intense, theory-driven dissemination strategies led to higher levels of implementation of this effective skin cancer prevention program. Issues to be considered by practitioners seeking to implement evidence-based programs in community settings, include taking into account both individual-level and setting-level factors, using active implementation approaches, and assessing local needs to adapt intervention materials.
PMCID: PMC2901365  PMID: 20513242
14.  A Multi-Method Process Evaluation for a Skin Cancer Prevention Diffusion Trial 
This article describes process evaluation methods for the Pool Cool Diffusion Trial across four years. Pool Cool is a skin cancer prevention program that was found to improve behaviors and environments for sun protection at swimming pools in a randomized efficacy trial, which was followed by a national Diffusion Trial. The process evaluation focus shifted from measuring program satisfaction to assessing widespread program implementation, barriers and facilitators to implementation, and program maintenance and sustainability. Data collection methods include training surveys, database tracking, field coordinator activity logs, emails, surveys of parents, lifeguards and pool managers, and process evaluation interviews and site visits. The data revealed high levels of implementation of major program components when disseminated in the diffusion trial, including sun safety lessons, sun safety signs, and sunscreen use. This paper describes program features and participant factors that facilitated local implementation, maintenance and sustainability across dispersed pools such as linkage agents, a packaged program, and adaptations of program elements.
PMCID: PMC2824082  PMID: 19448162
process evaluation; skin cancer prevention; sun protection; child health; organizational adoption
15.  Candida Infective Endocarditis 
Candida infective endocarditis (IE) is uncommon but often fatal. Most epidemiologic data are derived from small case series or case reports. This study was conducted to explore epidemiology, treatment patterns, and outcomes of patients with Candida IE.
We compared 33 Candida IE cases to 2716 patients with non-fungal IE in the International Collaboration on Endocarditis - Prospective Cohort Study. Patients were enrolled and data collected from June 2000 until August 2005.
Patients with Candida IE were more likely to have prosthetic valves (p<0.001), short term indwelling catheters (p<0.0001), and have healthcare-associated infection (p<0.001). Reasons for surgery differed between the two groups: myocardial abscess (46.7% vs. 22.2% p=0.026) and persistent positive blood cultures (33.3% vs. 9.9%, p=0.003) were more common among those with Candida IE. Mortality at discharge was higher in patients with Candida IE (30.3%) when compared to non-fungal cases (17%, p=0.046). Among Candida patients, mortality was similar in patients who received combination surgical and antifungal therapy versus antifungal therapy alone (33.3% vs. 27.8%, p=0.26). New antifungal drugs, particularly echinocandins, were used frequently.
These multi-center data suggest distinct epidemiologic features of Candida IE when compared to non-fungal cases. Indications for surgical intervention are different and mortality is increased. Newer antifungal treatment options are increasingly used. Large, multi-center studies are needed to help better define Candida IE.
PMCID: PMC2757733  PMID: 18283504
16.  Process evaluation of the Pool Cool Diffusion Trial for skin cancer prevention across 2 years 
Health Education Research  2007;23(4):732-743.
Though process evaluation of health programs has received growing attention, few interventions have reported process evaluation over multiple years. This article describes 2 years of process evaluation (2003–04) for the Pool Cool Diffusion Trial. Pool Cool is a skin cancer prevention program designed to increase sun protection habits among children and improve organizational and environmental supports for sun protection at swimming pools. Each year, 80 telephone interviews and 40 site visits at pools across the United States were completed, to examine how fully the program was implemented and the extent of use of program components between the two study conditions. Major components of the Pool Cool program, including sun safety lessons, sun safety signs and sunscreen use, had high implementation. Between the 2 years, most of the core elements were either maintained or increased in use. There were no significant differences between the basic and enhanced conditions on implementation. Reasons given for successful implementation were the provision of a toolkit, ease of implementing the program, pool staff and children enjoying the program and the field coordinators' support. These data provide information on programmatic factors that contribute to successful program diffusion.
PMCID: PMC2733800  PMID: 17956884

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