Pseudo Pelger-Huët anomalies as potential biomarkers for acute exposure radiation dose in rhesus macaques (Macaca mulatta).

PURPOSE: The potential for malicious use of radiation, or radiation accidents could potentially lead to acute, high radiation doses to the public. Following acute accidental exposure to high doses of radiation, medical intervention is pivotal to the survivability of the patient, and the sooner the appropriate measures are taken the better the odds for survival. Early estimates of acute accidental radiation doses can be determined via biomarkers such as dicentric chromosome analysis or scenario reconstruction using computer software. However, both take valuable time and can be expensive. Increased frequencies of abnormal neutrophils in peripheral blood, referred to as pseudo Pelger-Huët anomalies (PPHAs), have been shown to be potential biomarkers of radiation exposure in several scenarios, including the 1958 Y-12 criticality accident and the radium dial painters. PPHAs are potentially a faster and cheaper quantitative biomarker for radiation exposure, and here they were evaluated in acutely exposed rhesus macaques. METHODS AND MATERIALS: Peripheral blood smears from acutely exposed rhesus macaques were evaluated for the percentage of neutrophils that displayed the PPHA morphology using light microscopy. Irradiated animals received 0 to 8.5 Gy total body radiation using one of two strategies: (1) linear accelerator-produced 6 MV photons delivered at 80 cGy/minute; or (2) Cobalt 60-produced gamma irradiation delivered at 60 cGy/min. Zero dose animals were used to determine a baseline percentage of PPHAs, and blood smears taken periodically throughout the lifetime of exposed animals post-irradiation were used to determine the persistence and biokinetics of PPHAs. RESULTS: The baseline prevalence of the PPHA in rhesus macaques was determined to be 0.58 ± 0.46%. The dose-response curve with doses ranging from 0 Gy to 8.5 Gy (LD90/30) displayed a strong positive correlation between PPHA percentage and acute radiation dose (R2 of 0.88 p = 3.62 × 10-22). Statistically significant differences were found when animals were separated into dose cohorts of 0, 4, 6.4-6.5, and 8-8.5 Gy. The biokinetics model utilized only 4 Gy exposures and blood smears taken periodically over 3.1 years post-irradiation. PPHA morphology increases quickly following irradiation and appears stable over 3.1 years post-irradiation. CONCLUSION: PPHA morphology was confirmed to be present in rhesus macaques, a dose-response relationship was constructed, and it is stable over 3 years post-irradiation. This study demonstrates that PPHA analysis can be a fast and cheap method of biodosimetry. Future studies will work to determine the accuracy of dose determination and lower limits of detection.

Proteomic Biomarker Analysis of Serum from Japanese Field Mice (Apodemus Speciosus) Collected within the Fukushima Difficult-to-return Zone.

ABSTRACT: The environmental impact of the Fukushima Daiichi nuclear power plant accident is a source of ongoing concern as there is uncertainty regarding the effects of chronic radiation exposure on local plant and animal life from Fukushima-derived radionuclides. In the current study, changes in proteomic biomarker expression due to chronic environmentally-derived radiation exposures was examined in wild field mice. Serum from 10 wild field mice (Apodemus speciosus) native to the Fukushima difficult-to-return zone and from eight wild field mice native to the Soma area (control) were collected. External dose estimations were completed using measurements of ambient radiation levels and calculating 137Cs concentrations in soil. Internal dose was estimated by counting whole mice using an HPGe detector. Age of the mice was estimated using molar wear. Serum was screened using the aptamer-based SOMAscan proteomic assay technology for changes in expression of 1,310 protein analytes. A subset panel of protein biomarkers that demonstrated significant changes in expression between control and exposed mice was determined and analyzed using Ingenuity Pathway Analysis (IPA). Control animals had a calculated lifetime dose range from 0.001 to 0.007 Gy, and exposed animals had a calculated lifetime dose range from 0.01 to 0.64 Gy. No discernable effect of dose rate was seen as relative dose rate correlated with dose for all samples. Detectable values were obtained for all 1,310 proteins included in the SOMAscan assay. Subset panels of proteins demonstrating significant (p < 0.05) changes in expression with either an upregulated or downregulated 1.5-fold change over control were identified for both the sample cohort inclusive of all exposed samples and the sample cohort restricted to samples from animals receiving "low" dose exposures. These panels of proteins from exposed animals were analyzed using IPA, which highlighted changes in key biological pathways related to injury, respiratory, renal, urological, and gastrointestinal disease, and cancer. Significant changes in expression of proteomic biomarkers were seen in the serum of wild field mice that received environmental exposure to Fukushima-derived radionuclides. Our findings demonstrate novel biomarkers of radiation exposure in wildlife within the Fukushima difficult-to-return zone.

Comparison of a dual-surgeon versus single-surgeon approach for scoliosis surgery: a systematic review and meta-analysis.

PURPOSE: Corrective surgery for scoliosis is a complex and challenging prospect for experienced spine surgeons due to the prolonged duration of surgery and the significant level of technical skill and expertise required. Traditionally, shorter operative time and lower blood loss have correlated well with improved outcomes and as such, efforts have been made to affect these metrics including the use of two attending surgeons for major cases in preference to one. This systematic review and meta-analysis assessed the available literature to further clarify the potential benefit that adopting a dual-surgeon approach offers over single-surgeon operations. METHODS: A systematic review and meta-analysis assessed the effect of dual-surgeon operating compared to single-surgeon with respect to a number of indicators including blood loss, operative duration and length of hospital stay. In addition, we evaluated whether blood transfusion or complication rates differed between the two groups. RESULT: Seven studies met our inclusion criteria. Mean difference indicated shorter duration of surgery (- 90.5 min, 95% CI [- 103.3, - 77.6]) and a lower blood loss (- 379.1, 95% CI [- 572.2, - 230.9]) in the dual-surgeon group compared to the single-surgeon group. Six studies reported mean length of stay and also favoured the dual-surgeon group. CONCLUSION: This review observed that there are no randomised control trials evaluating dual-surgeon versus single-surgeon operating for scoliosis. We provide aggregated data and analysis of available literature, suggesting that outcomes in complex scoliosis surgery may be improved by adopting a dual-surgeon approach. LEVEL OF EVIDENCE: III.

Effects of chronic low-dose radiation on cataract prevalence and characterization in wild boar (Sus scrofa) from Fukushima, Japan.

This study evaluated cataracts in wild boar exposed to chronic low-dose radiation. We examined wild boar from within and outside the Fukushima Exclusion Zone for nuclear, cortical, and posterior subcapsular (PSC) cataracts in vivo and photographically. Plausible upper-bound, lifetime radiation dose for each boar was estimated from radioactivity levels in each animal's home range combined with tissue concentrations of 134+137Cesium. Fifteen exposed and twenty control boar were evaluated. There were no significant differences in overall prevalence or score for cortical or PSC cataracts between exposed and control animals. Nuclear (centrally located) cataracts were significantly more prevalent in exposed boar (p < 0.05) and had statistically higher median scores. Plausible upper-bound, lifetime radiation dose ranged from 1 to 1,600 mGy in exposed animals, with no correlation between dose and cortical or PSC score. While radiation dose and nuclear score were positively associated, the impact of age could not be completely separated from the relationship. Additionally, the clinical significance of even the highest scoring nuclear cataract was negligible. Based on the population sampled, wild boar in the Fukushima Exclusion Zone do not have a significantly higher prevalence or risk of cortical or PSC cataracts compared to control animals.

Two-hole versus four-hole plate dynamic hip screw: a systematic review of current evidence.

BACKGROUND: The dynamic hip screw (DHS) is a common device used in the fixation of hip fractures. Traditionally, this involves the use of a four-hole side plate. Reducing the length of the side plate would theoretically reduce the amount of surgical exposure required, decrease surgery duration, and decrease perioperative morbidity and mortality. Our study aims to review the current evidence regarding the use of two-hole side plates, their use and potential complications. METHODS: Using PRISMA guidelines, two independent reviewers performed a search to collate the available literature from medical databases PubMed, EMBASE, Web of Science, and the Cochrane library. Only clinical and biochemical studies were included. The reference lists of articles included for full text review were searched for any additional primary or review publications. RESULTS: Four online libraries were searched, with a combined total of 5344 titles reviewed. Following title, abstract, and full text review, 8 articles were considered suitable for inclusion in qualitative analysis. There was a trend towards equal efficiency between two- and four-hole plates when used in stable fractures in terms of blood loss, failure/revision rates, operative and hospital stay durations, collapse loading testing, maximum stress, and fragment migration. CONCLUSION: The results of this study show that DHS constructs with two- or four-hole side plates have comparable outcomes when used in patients with stable fracture patterns. However, the majority of the clinical data regarding the use of two-hole DHS plates come from retrospective case series; further prospective, randomised control trials would be of significant benefit. LEVEL OF EVIDENCE: Level II; systematic review of all levels of evidence.

Scaphoid fractures: has magnetic resonance imaging become a cost-effective alternative to definitive diagnosis?

BACKGROUND: A clinical examination finding of anatomical snuffbox tenderness (AST) with plain film radiographs alone yields low sensitivity and specificity in diagnosing scaphoid fractures. International guidelines suggest immediate referral for magnetic resonance imaging (MRI) following one non-diagnostic radiograph in such patients. Perceived cost, high demand and limited capacity of MRI scanners have resulted in few suspected fractures following this pathway in our institution. AIMS: Our study aimed to audit cost-effectiveness of immediate MRI referral following one non-diagnostic radiograph in the patient with AST versus current local practice. METHODS: Retrospective analysis of all patients with suspected scaphoid fractures referred from the ED to the orthopaedic service over a six-month period was performed. Mean pricing per radiograph, casting, MRI and fracture clinic presentation was obtained from our hospital's Finance department. RESULTS: Ninety-seven patients were identified; 26 had scaphoid fractures (26.8%). Seventy-one patients with no fractures cost a mean €82,111.50 (IQR: €55,025, €98,335) having a mean of 3.1 clinic visits, 4.6 radiographs and 4.7 weeks casted, versus €40,115 for early MRI referral as per guidelines (p > 0.05). CONCLUSIONS: In conclusion, when compared with current local practice, immediate referral of the patient with AST for MRI following one non-diagnostic ED radiograph is potentially cost-effective in establishing efficient diagnosis of scaphoid fractures. We recommend the implementation of published international guidelines in the investigation of query scaphoid fractures as a pragmatic and cost-effective practice.

Effective Half-life of 134Cs and 137Cs in Fukushima Prefecture When Compared to Theoretical Decay Models.

On 11 March 2011, a 9.0 magnitude earthquake struck the Tohoku region of Japan. The earthquake caused a 15 m tsunami that bombarded the east coast of the island nation. Among the losses was the damage to the Fukushima Daiichi nuclear reactor that lost onsite power and was unable to cool the reactor cores. The reactors melted down and released a plume of radionuclides into the environment. Radiocesiums (Cs and Cs) are the long-lived radionuclides of concern that were deposited along the plume and were distributed on the soil. Radiological decay models are typically used to determine the reduction in external radiation dose over time. However, these radiological decay models do not take into account physical removal by wind and water erosion, or sedimentation in soil outside expected depths. Thirty-five fixed dose-rate monitors were used to record dose rates at 1 mo intervals from the time of installation in Fukushima Prefecture in April 2012 until December 2018 and were used to estimate the effective half-life for radiocesium contamination based on external radiation dose rates. The effective half-life of cesium in the environment was calculated to be 3.2 ± 0.5 y, compared to a theoretical half-life of 7.8 y.

The prevalence of venous thromboembolism in rectal surgery: a systematic review and meta-analysis.

PURPOSE: Venous thromboembolism (VTE) following rectal surgery is a significant and preventable cause of morbidity and mortality, yet the true prevalence is not well established. This systematic review and meta-analysis assessed the available literature and determined its prevalence following rectal surgery. METHODS: A systematic review assessed the prevalence of VTE following rectal surgery. In addition, we evaluated whether subgroups (open vs. minimally invasive or benign vs. malignant resections) impacted on its prevalence or rate of deep venous thrombosis (DVT) or pulmonary embolism (PE). RESULT: Thirty-eight studies met the predefined inclusion criteria. The aggregate prevalence of VTE following rectal surgery was 1.25% (95% CI 0.86-1.63), with DVT and PE occurring in 0.68% (95% CI 0.48-0.89) and 0.57% (95% CI 0.47-0.68) of patients. VTE following cancer and benign resection was 1.59% (95% CI 0.60-1.23 and 1.5% (95% CI 0.89-2.12) respectively. The prevalence of VTE in patients having minimally invasive resection was lower than those having open surgery [0.58% (16/2770) vs. 2.22% (250/11278); RR 0.54, 95% CI 0.33-0.86]. CONCLUSION: This review observed that there is sparse evidence on prevalence of VTE following rectal surgery. It provides aggregated data and analysis of available literature, showing overall prevalence is low, especially in those having minimally invasive procedures.

Human-origin probiotic cocktail increases short-chain fatty acid production via modulation of mice and human gut microbiome.

The gut bacteria producing metabolites like short-chain fatty acids (SCFAs; e.g., acetate, propionate and butyrate), are frequently reduced in Patients with diabetes, obesity, autoimmune disorders, and cancers. Hence, microbiome modulators such as probiotics may be helpful in maintaining or even restoring normal gut microbiome composition to benefit host health. Herein, we developed a human-origin probiotic cocktail with the ability to modulate gut microbiota to increase native SCFA production. Following a robust protocol of isolation, characterization and safety validation of infant gut-origin Lactobacillus and Enterococcus strains with probiotic attributes (tolerance to simulated gastric and intestinal conditions, adherence to intestinal epithelial cells, absence of potential virulence genes, cell-surface hydrophobicity, and susceptibility to common antibiotics), we select 10 strains (5 from each genera) out of total 321 isolates. A single dose (oral gavage) as well as 5 consecutive doses of this 10-strain probiotic cocktail in mice modulates gut microbiome and increases SCFA production (particularly propionate and butyrate). Inoculation of these probiotics in human feces also increases SCFA production along with microbiome modulation. Results indicate that human-origin probiotic lactobacilli and enterococci could ameliorate gut microbiome dysbiosis and hence may prove to be a potential therapy for diseases involving reduced SCFAs production in the gut.

The prevalence of dental caries in Missouri and its relation to systemic disease: opportunities for Missouri to improve the health of its citizens.

Recently, it has been recognized that poor oral health conditions, especially periodontitis, have been a contributing factor to several systemic diseases. Evidence shows that Missouri should be concerned about the current state of caries and its prevention. The prevalence of caries and lack of preventative care in Missouri warrants an examination of the current efforts in place to reduce caries and the creation of novel approaches that bridge the gap between oral and medical care. This paper discusses this problem in depth.

Distribution of streptogramin resistance determinants among Enterococcus faecium from a poultry production environment of the USA.

OBJECTIVES: The impact of agricultural use of antimicrobials on the present and future efficacy of therapeutic drugs in human medicine is a growing public concern. Quinupristin/dalfopristin has been approved to treat human disease caused by vancomycin-resistant Enterococcus faecium and is related to virginiamycin, a streptogramin complex that has long been used in USA agriculture poultry production. METHODS: Streptogramin-resistant isolates of E. faecium from poultry production environments on the eastern seaboard were recovered without selection for streptogramin resistance and examined using ribotyping to evaluate clonal bias. Colony PCR screening for the previously described streptogramin resistance determinants erm(A), erm(B), msr(C), vgb(A), vat(D) and vat(E) was performed to determine the prevalence of streptogramin resistance mechanisms from these environments. RESULTS: The collection of E. faecium isolates was unevenly distributed among 28 ribogroups and did not cluster geographically. The most prevalent ribogroups was composed of isolates that possessed diverse antimicrobial resistance profiles. Of the 127 isolates examined, 63% were resistant to quinupristin/dalfopristin. The resistance determinants erm(A) and erm(B) were observed among 6% and 10%, respectively, of streptogramin-resistant isolates. msr(C) was detected in a single isolate that was resistant to macrolide and lincosamide antimicrobials. The streptogramin B hydrolase vgb(A) and the streptogramin A acetyltransferases genes vat(D) and vat(E) were not detected in any of the E. faecium isolates. CONCLUSIONS: These results indicate that there is widespread resistance to streptogramin antimicrobials among E. faecium throughout the poultry production region in this study and that the mechanisms of resistance to streptogramin antimicrobials within this population remain largely uncharacterized.

Multiple-antibiotic resistance of Enterococcus spp. isolated from commercial poultry production environments.

The potential impact of food animals in the production environment on the bacterial population as a result of antimicrobial drug use for growth enhancement continues to be a cause for concern. Enterococci from 82 farms within a poultry production region on the eastern seaboard were isolated to establish a baseline of susceptibility profiles for a number of antimicrobials used in production as well as clinical environments. Of the 541 isolates recovered, Enterococcus faecalis (53%) and E. faecium (31%) were the predominant species, while multiresistant antimicrobial phenotypes were observed among all species. The prevalence of resistance among isolates of E. faecalis was comparatively higher among lincosamide, macrolide, and tetracycline antimicrobials, while isolates of E. faecium were observed to be more frequently resistant to fluoroquinolones and penicillins. Notably, 63% of the E. faecium isolates were resistant to the streptogramin quinupristin-dalfopristin, while high-level gentamicin resistance was observed only among the E. faecalis population, of which 7% of the isolates were resistant. The primary observations are that enterococci can be frequently isolated from the poultry production environment and can be multiresistant to antimicrobials used in human medicine. The high frequency with which resistant enterococci are isolated from this environment suggests that these organisms might be useful as sentinels to monitor the development of resistance resulting from the usage of antimicrobial agents in animal production.

Prevalence and antimicrobial resistance of enterococcus species isolated from retail meats.

From March 2001 to June 2002, a total of 981 samples of retail raw meats (chicken, turkey, pork, and beef) were randomly obtained from 263 grocery stores in Iowa and cultured for the presence of Enterococcus spp. A total of 1,357 enterococcal isolates were recovered from the samples, with contamination rates ranging from 97% of pork samples to 100% of ground beef samples. Enterococcus faecium was the predominant species recovered (61%), followed by E. faecalis (29%), and E. hirae (5.7%). E. faecium was the predominant species recovered from ground turkey (60%), ground beef (65%), and chicken breast (79%), while E. faecalis was the predominant species recovered from pork chops (54%). The incidence of resistance to many production and therapeutic antimicrobials differed among enterococci recovered from retail meat samples. Resistance to quinupristin-dalfopristin, a human analogue of the production drug virginiamycin, was observed in 54, 27, 9, and 18% of E. faecium isolates from turkey, chicken, pork, and beef samples, respectively. No resistance to linezolid or vancomycin was observed, but high-level gentamicin resistance was observed in 4% of enterococci, the majority of which were recovered from poultry retail meats. Results indicate that Enterococcus spp. commonly contaminate retail meats and that dissimilarities in antimicrobial resistance patterns among enterococci recovered from different meat types may reflect the use of approved antimicrobial agents in each food animal production class.

Experimental and theoretical determination of dosimetric characteristics of IsoAid ADVANTAGE 125I brachytherapy source.

125I brachytherapy sources are being used for interstitial implants in tumor sites such as the prostate. Recently, the ADVANTAGE 125I, Model IAI-125, source became commercially available for interstitial brachytherapy treatment. Dosimetric characteristics (dose rate constant, radial dose function, and anisotropy function) of this source were experimentally and theoretically determined, following the AAPM Task Group 43 recommendations. Derivation of the dose rate constant was based on recent NIST WAFAC calibration performed in accordance with their 1999 standard. Measurements were performed in Solid Water phantom using LiF thermoluminescent dosimeters. The theoretical calculations were performed in both Solid Water and water using the PTRAN Monte Carlo code. The results indicated that a dose rate constant of the new source in water was 0.98 +/- 0.03 cGy h(-1) U(-1). The radial dose function of the new source was measured in Solid Water and calculated both in water and Solid Water at distances up to 10.0 cm. The anisotropy function, F(r, theta), of the new source was measured and calculated in Solid Water at distances of 2 cm, 3 cm, 5 cm, and 7 cm and also was calculated in water at distances ranging from 1 cm to 7 cm from the source. From the anisotropy function, the anisotropy factors and anisotropy constant were derived. The anisotropy constant of the ADVANTAGE 125I source in water was found to be 0.97 +/- 0.03. The dosimetric characteristics of this new source compared favorably with those from the Amersham Health Model 6711 source. Complete dosimetric parameters of the new source are presented in this paper.

Experimental determination of the TG-43 dosimetric characteristics of EchoSeed model 6733 I25I brachytherapy source.

Recently an improved design of a 125I brachytherapy source has been introduced for interstitial seed implants, particularly for prostate seed implants. This design improves the in situ ultrasound visualization of the source compared to the conventional seed. In this project, the TG-43 recommended dosimetric characteristics of the new brachytherapy source have been experimentally determined in Solid Water phantom material. The measured dosimetric characteristics of the new source have been compared with data reported in the literature for other source designs. The measured dose rate constant, A, in Solid Water was multiplied by 1.05 to extract the dose rate constant in water. The dose rate constant of the new source in water was found to be 0.99 +/- 8% cGy h(-1) U(-1). The radial dose function was measured at distances between 0.5 and 10 cm using LiF TLDs in Solid Water phantom. The anisotropy function, F(r, theta), was measured at distances of 2, 3, 5, and 7 cm.