Research-practice partnership: supporting rural cancer survivors in Montana.

The objective of this Research-Practice Partnership was to disseminate and implement strategies to assist Community Health Centers in improving the care of rural cancer survivors in Montana. Funded by the National Cancer Institute's Community Outreach and Engagement mechanism, this project utilized the MAP-IT (Mobilize, Assess, Plan, Implement, Track) program planning framework from Healthy People 2020. Partners included Montana's Department of Public Health and Human Services' Cancer Control Program, Montana Primary Care Association, One Health Community Health Center, and Huntsman Cancer Institute at the University of Utah. Project activities focused on (1) Planning, creating, implementing, and evaluating provider/care team education sessions through the Project ECHO tele-mentoring platform and through short webinars and (2) Building processes for identifying, documenting, and connecting with survivors using electronic health records (EHRs) and other resources. Lessons learned from this project include the value of aligning partner goals from the outset to foster sustained commitment, the importance of adapting implementation plans to address challenges and leverage opportunities, and the need for accurate EHR data and formal processes for identifying and engaging with cancer survivors.

Aerosol Particle Size Influences the Infectious Dose and Disease Severity in a Golden Syrian Hamster Model of Inhalational COVID-19.

Background: Significant evidence suggests that SARS-CoV-2 can be transmitted via respiratory aerosols, which are known to vary as a function of respiratory activity. Most animal models examine disease presentation following inhalation of small-particle aerosols similar to those generated during quiet breathing or speaking. However, despite evidence that particle size can influence dose-infectivity relationships and disease presentation for other microorganisms, no studies have examined the infectivity of SARS-CoV-2 contained in larger particle aerosols similar to those produced during coughing, singing, or talking. Therefore, the aim of the present study was to assess the influence of aerodynamic diameter on the infectivity and virulence of aerosols containing SARS-CoV-2 in a hamster model of inhalational COVID-19. Methods: Dose-response relationships were assessed for two different aerosol particle size distributions, with mass median aerodynamic diameters (MMADs) of 1.3 and 5.2 µm in groups of Syrian hamsters exposed to aerosols containing SARS-CoV-2. Results: Disease was characterized by viral shedding in oropharyngeal swabs, increased respiratory rate, decreased activity, and decreased weight gain. Aerosol particle size significantly influenced the median doses to induce seroconversion and viral shedding, with both increasing ∼30-fold when the MMAD was increased. In addition, disease presentation was dose-dependent, with seroconversion and viral shedding occurring at lower doses than symptomatic disease characterized by increased respiratory rate and decreased activity. Conclusions: These results suggest that aerosol particle size may be an important factor influencing the risk of COVID-19 transmission and needs to be considered when developing animal models of disease. This result agrees with numerous previous studies with other microorganisms and animal species, suggesting that it would be generally translatable across different species. However, it should be noted that the absolute magnitude of the observed shifts in the median doses obtained with the specific particle sizes utilized herein may not be directly applicable to other species.

Pancreatic cancer survival trends in the US from 2001 to 2014: a CONCORD-3 study.

BACKGROUND: Survival from pancreatic cancer is low worldwide. In the US, the 5-year relative survival has been slightly higher for women, whites and younger patients than for their counterparts, and differences in age and stage at diagnosis [Corrections added Nov 16, 2022, after first online publication: a new affiliation is added to Maja Niksic] may contribute to this pattern. We aimed to examine trends in survival by race, stage, age and sex for adults (15-99 years) diagnosed with pancreatic cancer in the US. METHODS: This population-based study included 399,427 adults registered with pancreatic cancer in 41 US state cancer registries during 2001-2014, with follow-up to December 31, 2014. We estimated age-specific and age-standardized net survival at 1 and 5 years. RESULTS: Overall, 12.3% of patients were blacks, and 84.2% were whites. About 9.5% of patients were diagnosed with localized disease, but 50.5% were diagnosed at an advanced stage; slightly more among blacks, mainly among men. No substantial changes were seen over time (2001-2003, 2004-2008, 2009-2014). In general, 1-year net survival was higher in whites than in blacks (26.1% vs. 22.1% during 2001-2003, 35.1% vs. 31.4% during 2009-2014). This difference was particularly evident among patients with localized disease (49.6% in whites vs. 44.6% in blacks during 2001-2003, 60.1% vs. 55.3% during 2009-2014). The survival gap between blacks and whites with localized disease was persistent at 5 years after diagnosis, and it widened over time (from 24.0% vs. 21.3% during 2001-2003 to 39.7% vs. 31.0% during 2009-2014). The survival gap was wider among men than among women. CONCLUSIONS: Gaps in 1- and 5-year survival between blacks and whites were persistent throughout 2001-2014, especially for patients diagnosed with a localized tumor, for which surgery is currently the only treatment modality with the potential for cure.

Comparison of Dose-Response Relationships for Two Isolates of SARS-CoV-2 in a Nonhuman Primate Model of Inhalational COVID-19.

Background: As the COVID-19 pandemic has progressed, numerous variants of SARS-CoV-2 have arisen, with several displaying increased transmissibility. Methods: The present study compared dose-response relationships and disease presentation in nonhuman primates infected with aerosols containing an isolate of the Gamma variant of SARS-CoV-2 to the results of our previous study with the earlier WA-1 isolate of SARS-CoV-2. Results: Disease in Gamma-infected animals was mild, characterized by dose-dependent fever and oronasal shedding of virus. Differences were observed in shedding in the upper respiratory tract between Gamma- and WA-1-infected animals that have the potential to influence disease transmission. Specifically, the estimated median doses for shedding of viral RNA or infectious virus in nasal swabs were approximately 10-fold lower for the Gamma variant than the WA-1 isolate. Given that the median doses for fever were similar, this suggests that there is a greater difference between the median doses for viral shedding and fever for Gamma than for WA-1 and potentially an increased range of doses for Gamma over which asymptomatic shedding and disease transmission are possible. Conclusions: These results complement those of previous studies, which suggested that differences in exposure dose may help to explain the range of clinical disease presentations observed in individuals with COVID-19, highlighting the importance of public health measures designed to limit exposure dose, such as masking and social distancing. The dose-response data provided by this study are important to inform disease transmission and hazard modeling, as well as to inform dose selection in future studies examining the efficacy of therapeutics and vaccines in animal models of inhalational COVID-19.

Prostate Cancer Trends in Montana.

Prostate cancer is the most common cancer among men in Montana and the second-most-common cause of cancer deaths. In 2014, prostate cancer incidence in Montana started increasing significantly, even as incidence in the United States overall stayed about the same. The increased incidence was not accompanied by an increase in prostate cancer mortality. Trends in local stage incidence and incidence among men aged 65 to 79 years mirrored the trends in overall prostate cancer incidence and suggest that changes are due to screening behavior. However, it is difficult to determine what may have caused increased screening among Montana men since 2014. Monitoring prostate cancer incidence and mortality is an important tool in determining if there is a change in prostate cancer disease burden or in overdiagnosis, and informs planning for possible public health intervention.

Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19.

While evidence exists supporting the potential for aerosol transmission of SARS-CoV-2, the infectious dose by inhalation remains unknown. In the present study, the probability of infection following inhalation of SARS-CoV-2 was dose-dependent in a nonhuman primate model of inhalational COVID-19. The median infectious dose, assessed by seroconversion, was 52 TCID50 (95% CI: 23-363 TCID50), and was significantly lower than the median dose for fever (256 TCID50, 95% CI: 102-603 TCID50), resulting in a group of animals that developed an immune response post-exposure but did not develop fever or other clinical signs of infection. In a subset of these animals, virus was detected in nasopharyngeal and/or oropharyngeal swabs, suggesting that infected animals without signs of disease are able to shed virus and may be infectious, which is consistent with reports of asymptomatic spread in human cases of COVID-19. These results suggest that differences in exposure dose may be a factor influencing disease presentation in humans, and reinforce the importance of public health measures that limit exposure dose, such as social distancing, masking, and increased ventilation. The dose-response data provided by this study are important to inform disease transmission and hazard modeling, and, ultimately, mitigation strategies. Additionally, these data will be useful to inform dose selection in future studies examining the efficacy of therapeutics and vaccines against inhalational COVID-19, and as a baseline in healthy, young adult animals for assessment of the importance of other factors, such as age, comorbidities, and viral variant, on the infectious dose and disease presentation.

Interfrontal Bone Among Inbred Strains of Mice and QTL Mapping.

The interfrontal bone (IF) is a minor skeletal trait residing between the frontal bones. IF is considered a quasi-continuous trait. Genetic and environmental factors appear to play roles in its development. The mechanism(s) underlying IF bone development are poorly understood. We sought to survey inbred strains of mice for the prevalence of IF and to perform QTL mapping studies. Archived mouse skulls from a mouse phenome project (MPP) were available for this study. 27 inbred strains were investigated with 6-20 mice examined for each strain. Skulls were viewed dorsally and the IF measured using a zoom stereomicroscope equipped with a calibrated reticle. A two generation cross between C3H/HeJ and C57BL/6J mice was performed to generate a panel of 468 F2 mice. F2 mice were phenotyped for presence or absence of IF bone and among mice with the IF bone maximum widths and lengths were measured. F2 mice were genotyped for 573 SNP markers informative between the two strains and subjected to linkage map construction and interval QTL mapping. Results: Strain dependent differences in the prevalence of IF bones were observed. Overall, 77.8% or 21/27, of the inbred strains examined had IF bones. Six strains (C3H/HeJ, MOLF/EiJ, NZW/LacJ, SPRET/EiJ, SWR/J, and WSB/EiJ) lack IF bones. Among the strains with IF bones, the prevalence ranged from 100% for C57BL/6J, C57/LJ, CBA/J, and NZB/B1NJ and down to 5% for strains such as CAST/Ei. QTL mapping for IF bone length and widths identifies for each trait one strong QTL detected on chromosome 14 along with several other significant QTLs on chromosomes 3, 4, 7, and 11. Strain dependent differences in IF will facilitate investigation of genetic factors contributing to IF development. IF bone formation may be a model to understand intrasutural bone formation.

Attacks on healthcare in conflict: generating attention in the modern information landscape.

Attacks on healthcare in conflict (AHCC) is receiving increased attention as a pressing global concern from humanitarian organisations, the media, policymakers, academics, and the public. This study examines the extent to which this increased attention leads to mainstream reporting and understanding of AHCC that is representative of reality by investigating the ways that information and knowledge about the issue is produced. Based on a rapid review of documentation on AHCC since 2011, this is one of the first studies to assess the rigour, validity, and representativeness of mainstream data on AHCC. Findings indicate that information and knowledge about AHCC is molded by a particular representation of the issue created by international media and humanitarian organisations seeking to capture public and political attention. This dominant understanding is not representative of the complex reality of AHCC, but is instead driven by organisational objectives and advocacy agendas. These findings hold important implications for the above-mentioned stakeholders by exploring the complexity and impacts of documenting AHCC. Most notably, the research investigates the relationship between information and understanding about the issue and the action that it encourages.

Use of Microcomputed Tomography to Measure the Relaxin-induced Expansion of Intrapubic Ligaments in Mice.

Relaxin is a 6-kDa peptide in the insulin superfamily of hormones. In addition to its effects on reproductive and musculoskeletal ligaments, relaxin has demonstrated beneficial effects on cardiac, renal, and vascular systems in preclinical models. The mouse intrapubic ligament ex vivo bioassay is the current standard for measuring in vivo relaxin bioactivity. However, this bioassay necessitates euthanasia and dissection of large cohorts to measure the intrapubic ligament at specified time points. We hypothesized that µCT imaging could be used to reduce the number of animals necessary for the intrapubic ligament bioassay by enabling a single animal to be followed longitudinally throughout the study rather than euthanizing different cohorts at established time points. Female CD1 mice were used to compare µCT imaging with the current standard. Both protocols revealed significant differences in intrapubic ligament length, with the µCT data having greater power when corrected for baseline imaging. From these data, we concluded that using µCT to measure the intrapubic ligament in mice primed with estrogen and dosed with relaxin is a viable refinement and will allow the use of fewer animals in longitudinal studies and provide more robust data, because animals can serve as their own controls.

Reach of the Montana Cancer Control Program to Women with Disabilities.

Women with disabilities have lower screening rates for breast and cervical cancer with some evidence suggesting that people with disabilities experience higher cancer mortality and may receive a different course of treatment. This study examined whether women with and without disabilities using Montana Cancer Control Program (MCCP) differ in use of breast (BCS) and cervical (CCS) screening services, receipt of and follow up for inconclusive or abnormal results, and compliance with BCS and CCS US Preventive Services Task Force recommendations. Study participants were women eligible for MCCP screening services between November 2012 and October 2014, with eligibility based on insurance status (underinsured/no insurance), income requirements (<200 % poverty based on income/household size), and age. The data derive from participant self-report (demographic, disability, and health history including previous mammogram or Papanicolaou test) and MCCP records of screening tests (clinical breast exam, mammogram, or Pap test), results, and follow up visits. About 11.5 % of MCCP participants reported having a disability. MCCP recipients with a disability were significantly older, more likely to be non-Hispanic White, and more likely to have poor health profiles. Disability status did not affect use of MCCP screening services, screening outcome, or follow up for inconclusive or abnormal results. However, women with disability had significantly lower BCS and CCS compliance (based on US Preventive Task Force guidelines) than women without disability, which persisted in adjusted analyses controlling for other significant factors. The MCCP is reaching un/underinsured Montana women with disabilities. While disability status in this sample was not related to use of MCCP services or screening outcome, MCCP recipients with disabilities have significantly lower BCS and CCS compliance. Efforts to increase compliance for un/underinsured Montana women with a disability are warranted.

Chemical Differentiation of Osseous, Dental, and Non-skeletal Materials in Forensic Anthropology using Elemental Analysis.

Forensic anthropologists are generally able to identify skeletal materials (bone and tooth) using gross anatomical features; however, highly fragmented or taphonomically altered materials may be problematic to identify. Several chemical analysis techniques have been shown to be reliable laboratory methods that can be used to determine if questionable fragments are osseous, dental, or non-skeletal in nature. The purpose of this review is to provide a detailed background of chemical analysis techniques focusing on elemental compositions that have been assessed for use in differentiating osseous, dental, and non-skeletal materials. More recently, chemical analysis studies have also focused on using the elemental composition of osseous/dental materials to evaluate species and provide individual discrimination, but have generally been successful only in small, closed groups, limiting their use forensically. Despite significant advances incorporating a variety of instruments, including handheld devices, further research is necessary to address issues in standardization, error rates, and sample size/diversity.

Preliminary validation of handheld X-ray fluorescence spectrometry: distinguishing osseous and dental tissue from nonbone material of similar chemical composition.

One of the tasks of a forensic anthropologist is to sort human bone fragments from other materials, which can be difficult when dealing with highly fragmented and taphonomically modified material. The purpose of this research is to develop a method using handheld X-ray fluorescence (HHXRF) spectrometry to distinguish human and nonhuman bone/teeth from nonbone materials of similar chemical composition using multivariate statistical analyses. The sample materials were derived primarily from previous studies: human bone and teeth, nonhuman bone, nonbiological materials, nonbone biological materials, and taphonomically modified materials. The testing included two phases, testing both the reliability of the instrument and the accuracy of the technique. The results indicate that osseous and dental tissue can be distinguished from nonbone material of similar chemical composition with a high degree of accuracy (94%). While it was not possible to discriminate rock apatite and synthetic hydroxyapatite from bone/teeth, this technique successfully discriminated ivory and octocoral.

High incidence of spontaneous cataracts in aging laboratory rabbits of an inbred strain.

OBJECTIVE: To investigate the occurrence of spontaneous cataracts in a breeding colony of the inbred EIII/JC strain of New Zealand White rabbits (Oryctolagus cuniculi) and the congenic strain of EIII/JC-HLA-A2.1transgenic rabbits. PROCEDURE: A retrospective study was conducted by collecting and analyzing data from clinical records for individual rabbits filed between January 2011 and October 2013. RESULTS: Thirteen cases (eight females and five males) of cataract were identified in a group of 51 EIII/JC inbred rabbits with a morbidity of 25.5%. The median age of the rabbits identified with unilateral or bilateral cataracts was 43 months in contrast to the median age of 23 months of the entire group of 51 rabbits. Additionally, seven cases (five females and two males) of cataracts were identified in a group of 21 EIII/JC-HLA-A2.1 transgenic rabbits. The EIII/JC-HLA-A2.1 transgenic rabbits showed similar morbidity (33.3%) and median age (41 months) for the development of cataracts as the EIII/JC rabbits. In both groups, none of the rabbits younger than 37 months developed cataracts while 13 (93%) of 14 EIII/JC rabbits aged 37-49 months and seven (63.6%) of 11 EIII/JC-HLA-A2.1 transgenic rabbits aged 37-43 months developed cataracts. In contrast, none of 78 outbred rabbits with a median age of 26 months (10-67 months) developed cataracts. CONCLUSION: Results of this study indicate that the occurrence and high incidence of spontaneous cataracts in this inbred strain (EIII/JC) of rabbits were strictly age related and consistently transmitted through inbreeding.

Adipose transplant for inborn errors of branched chain amino acid metabolism in mice.

Liver transplantation appears to be quite beneficial for treatment of maple syrup urine disease (MSUD, an inherited disorder of branched chain amino acid metabolism); however, there is a limited availability of donor livers worldwide and the first year costs of liver transplants are quite high. Recent studies have suggested that intact adipose tissue, already widely used in reconstructive surgery, may have an underappreciated high capacity for branched chain amino acid (BCAA) metabolism. Here we examined the potential for adipose tissue transplant to lower circulating BCAAs in two models of defective BCAA metabolism, BCATm and PP2Cm [branched chain keto acid dehydrogenase complex (BCKDC) phosphatase] knockout (KO) mice. After 1-2g fat transplant, BCATm and PP2Cm KO mice gained or maintained body weight 3weeks after surgery and consumed similar or more food/BCAAs the week before phlebotomy. Transplant of fat into the abdominal cavity led to a sterile inflammatory response and nonviable transplanted tissue. However when 1-2g of fat was transplanted subcutaneously into the back, either as small (0.1-0.3g) or finely minced pieces introduced with an 18-ga. needle, plasma BCAAs decreased compared to Sham operated mice. In two studies on BCATm KO mice and one study on PP2Cm KO mice, fat transplant led to 52-81% reductions in plasma BCAAs compared to baseline plasma BCAA concentrations of untreated WT type siblings. In PP2Cm KO mice, individual BCAAs in plasma were also significantly reduced by fat transplant, as were the alloisoleucine/Phe ratios. Therefore, subcutaneous fat transplantation may have merit as an adjunct to dietary treatment of MSUD. Additional studies are needed to further refine this approach.

Prevalence of asthma among adults in metropolitan versus nonmetropolitan areas in Montana, 2008.

INTRODUCTION: Most US studies on asthma prevalence have been conducted in urban areas, and few have assessed the prevalence of asthma among residents of rural areas versus urban areas. The objective of this study was to compare the prevalence of asthma among adults living in metropolitan versus nonmetropolitan counties in Montana. METHODS: We analyzed data from 6,846 adult Montanans who completed the Behavioral Risk Factor Surveillance System survey in 2008. We used Rural-Urban Continuum Codes to categorize respondents' county of residence as metropolitan (Metro), nonmetropolitan and adjacent to a metropolitan county (NMA), and nonmetropolitan and nonadjacent to a metropolitan county (NMNA). We compared the prevalence of current self-reported asthma among respondents in the 3 areas, overall and by selected characteristics, and conducted multivariable logistic regression analyses to identify factors independently associated with current self-reported asthma. RESULTS: No differences in the prevalence of self-reported asthma were found between residents of Metro and NMA or NMNA counties, overall or by age, sex, race, years of education, health insurance status, annual household income, or body mass index. Respondents aged 65 years or older (adjusted odds ratio [AOR], 0.7; 95% confidence interval [CI], 0.5-0.9) and men (AOR, 0.6; 95% CI, 0.5-0.8) were less likely to report current asthma than younger respondents and women, respectively. Obese respondents were more likely (AOR, 1.9; 95% CI, 1.4-2.7) to report asthma than were respondents who were not obese. Metropolitan county of residence was not independently associated with self-reported current asthma. CONCLUSION: The prevalence of self-reported current asthma is similar in metropolitan and nonmetropolitan counties in Montana, but other sociodemographic differences exist. Our findings highlight the need to conduct regional and state surveillance of asthma to understand the demographic risk factors associated with it and to determine the potential geographic variation of asthma prevalence in the United States.

A crossover intervention trial evaluating the efficacy of a chlorhexidine-impregnated sponge in reducing catheter-related bloodstream infections among patients undergoing hemodialysis.

BACKGROUND: Catheter-related bloodstream infections (CRBSIs) account for the majority of hemodialysis-related infections. There are no published data on the efficacy of the chlorhexidine-impregnated foam dressing at reducing the rate of CRBSI among patients undergoing hemodialysis. DESIGN: A prospective, nonblinded, crossover intervention trial to determine the efficacy of a chlorhexidine-impregnated foam dressing to reduce the rate of CRBSI among patients undergoing hemodialysis. SETTING: Two outpatient dialysis centers. PATIENTS: A total of 121 patients who underwent dialysis through tunneled central venous catheters received the intervention during the trial. METHODS: The primary outcome of interest was the incidence of CRBSI. A nested cohort study of all patients who received the chlorhexidine-impregnated foam dressing was also conducted. Backward stepwise logistic regression analysis was used to determine independent risk factors for development of CRBSI. RESULTS: Thirty-seven CRBSIs occurred in the intervention group, for an incidence of 6.3 CRBSIs per 1,000 dialysis sessions, and 30 CRBSIs occurred in the control group, an incidence of 5.2 CRBSIs per 1,000 dialysis sessions (risk ratio, 1.22 [95% confidence interval {CI}, 0.75-1.97]; P = .46). The chlorhexidine-impregnated foam dressing was well tolerated, with only 2 patients (<2%) experiencing dermatitis that led to its discontinuation. The only independent risk factor for development of CRBSI was dialysis treatment at one dialysis center (adjusted odds ratio, 4.4 [95% CI, 1.77-13.65]; P = .002). Age of at least 60 years (adjusted odds ratio, 0.28 [95% CI, 0.09-0.82]; P = .02) was associated with lower risk of CRBSI. CONCLUSIONS: The use of a chlorhexidine-impregnated foam dressing did not decrease the incidence of CRBSI among patients with tunneled central venous catheters who were undergoing hemodialysis.