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At least 1,081 records · Page 60

Symptoms and Systemic Drug Reactions in Persons Receiving Weekly Rifapentine Plus Isoniazid (3HP) Treatment for Latent Tuberculosis Infection

Abstract Background Three months of weekly rifapentine plus isoniazid (3HP) therapy for latent tuberculosis infection (LTBI) is recommended worldwide. The development of symptoms and systemic drug reactions (SDRs) on 3HP have not been fully characterized. We aimed to determine the patterns of symptom development and identify SDRs and associated factors in patients taking 3HP. Methods We analyzed symptoms data in participants receiving 3HP in the Tuberculosis Trials Consortium's iAdhere study (Study 33). We examined the patterns of symptom reporting across participants from baseline and 4 monthly visits. Bivariate analyses and multivariable regression models were used to identify factors associated with SDRs. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. Results Among 1002 participants receiving 3HP, 768 (77%) reported at least 1 symptom; 97% of these symptoms were grade 1 (79%) or grade 2 (18%). Most symptoms developed in the first month and resolved. A total of 111 (11%) participants had symptoms that met criteria for SDRs; however, 53 (48%) of these participants completed therapy. Factors associated with SDRs and discontinuation included female sex (RR: 2.05; 95% CI: 1.19–3.54), age ≥45 years (RR: 1.99; 95% CI: 1.19–3.31), and use of concomitant medications (RR: 2.26; 95% CI: 1.15–4.42). Conclusions Although most patients receiving 3HP reported symptoms, most were mild, occurred early, and resolved without stopping treatment. Among patients experiencing SDRs, nearly half were able to complete therapy. Patient and provider education should focus on differentiating severe reactions where 3HP should be stopped from minor symptoms that will resolve. Clinical Trials Registration. NCT01582711.

Immunology↗

Impact of developmental methylmercury exposure on avian embryonic development, hatchling growth, and survival

Abstract Methylmercury (MeHg) is a globally ubiquitous and persistent environmental toxicant that negatively affects animal behavior, health, and reproduction. In birds, MeHg is transferred from female to egg, contaminating embryos during sensitive stages of early embryonic development and growth. This toxic exposure in the prenatal environment not only induces mortality but also possible lasting impacts on physiology, health, and survival, even once hatched. The purpose of our study was to further elucidate the negative effects of MeHg exposure during avian embryonic development and explore how such exposure can impact offspring development, growth, and survival, both in ovo and posthatch. To assess this, we experimentally dosed fertile mallard and wood duck eggs with MeHg II chloride and reared developing embryos and ducklings to various endpoints. We found that embryos not only readily accumulated MeHg throughout incubation, but they also displayed varying dose-dependent disparities in body mass and morphometrics, with control individuals being larger during early and late embryonic stages of development (p < 0.05). Furthermore, hatched offspring exposed to MeHg exhibited increasingly slower growth rates between 7 to 10 and 10 to 15 days posthatch (p < 0.05), and were found to have lower survival probabilities both under controlled laboratory conditions (p < 0.005), and in the natural environment (p < 0.05). Our findings on the detrimental effects of MeHg on avian embryos and hatchlings emphasize the need for more proactive means of environmental protection and remediation to protect vulnerable avian populations and the ecosystems they inhabit.

Leaphart, James C.↗

Supplemental selenium source on gut health: insights on fecal microbiome and fermentation products of growing puppies

ABSTRACT Selenium is an essential trace element that can modulate the gut microbiome with an impact on host health. The present study aimed to evaluate the effects of organic (selenium-enriched yeast) vs inorganic (sodium selenite) selenium source on fecal end-fermentation products and gut microbiome of puppies from 20 to 52 weeks of age. Alpha and beta diversity of the gut bacterial community were affected by age but not by gender or selenium source. The relative abundance of taxa was differently affected by age, and the DNA concentration of all selected bacterial groups increased with age, although total volatile fatty acids (VFA), acetate, propionate, caproate and lactate concentrations decreased. Organic selenium was associated with a higher concentration of total VFA, propionate and butyrate, a higher number of DNA copies of Lactobacillus, and a trend to lower DNA copies of Escherichia coli. Effects on fecal microbiome during growth differed with selenium source. Females had higher fecal end-fermentation products related to protein degradation, whereas males had higher DNA concentration of Bifidobacterium. Organic selenium might be beneficial over inorganic for dog food supplementation due to the positive modulation of the gut microbiome observed in puppies.

Pereira, Ana Margarida↗

Evaluation of data collection bias of third molar stages of mineralisation for age estimation in the living

Abstract Age assessment of the living is a fundamental procedure in the process of human identification, in order to guarantee fair treatment of individuals, which has ethical, civil, legal, and medical repercussions. The careful selection of the appropriate methods requires evaluation of several parameters: accuracy, precision of the method, as well as its reproducibility. The approach proposed by Mincer et al. adapted from Demirjian et al. exploring third molar mineralisation, is one of the most frequently considered for age estimation of the living. Thus, this work aims to assess potential bias in the data collection when applying the classification stages for dental mineralisation adapted by Mincer et al. A total of 102 orthopantomographs, of clinical origin, belonging to individuals aged between 12 and 25 years ($ \bar{\textit x} $ = 20.12 years, SD = 3.49 years; 65 females, 37 males, all of Portuguese nationality) were included and a retrospective analysis performed by five observers with different levels of experience (high, average, and basic). The performance and agreement between five observers were evaluated using Weighted Cohen’s Kappa and the Intraclass Correlation Coefficient. To access the influence of impaction on third molar classification, variables were tested using ordinal logistic regression Generalised Linear Model. It was observed that there were variations in the number of teeth identified among the observers, but the agreement levels ranged from moderate to substantial (0.4–0.8). Upon closer examination of the results, it was observed that although there were discernible differences between highly experienced observers and those with less experience, the gap was not as significant as initially hypothesised, and a greater disparity between the classifications of the upper (0.24–0.49) and lower third molars (>0.55) was observed. When bone superimposition is present, the classification process is not significantly influenced; however, variation in teeth angulation affects the assessment. The results suggest that with an efficient preparation, the level of experience as a factor can be overcome. Mincer and colleague's classification system can be replicated with ease and consistency, even though the classification of upper and lower third molars presents distinct challenges.

de Oliveira Santos, Inês (ORCID:0000000267324347)↗

Physiological Adaptations to Progressive Endurance Exercise Training in Adult and Aged Rats: Insights from the Molecular Transducers of Physical Activity Consortium (MoTrPAC)

While regular physical activity is a cornerstone of health, wellness, and vitality, the impact of endurance exercise training on molecular signaling within and across tissues remains to be delineated. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to characterize molecular networks underlying the adaptive response to exercise. Here, we describe the endurance exercise training studies undertaken by the Preclinical Animal Sites Studies component of MoTrPAC, in which we sought to develop and implement a standardized endurance exercise protocol in a large cohort of rats. To this end, Adult (6-mo) and Aged (18-mo) female (n = 151) and male (n = 143) Fischer 344 rats were subjected to progressive treadmill training (5 d/wk, ~70%–75% VO 2 max) for 1, 2, 4, or 8 wk; sedentary rats were studied as the control group. A total of 18 solid tissues, as well as blood, plasma, and feces, were collected to establish a publicly accessible biorepository and for extensive omics-based analyses by MoTrPAC. Treadmill training was highly effective, with robust improvements in skeletal muscle citrate synthase activity in as little as 1–2 wk and improvements in maximum run speed and maximal oxygen uptake by 4–8 wk. For body mass and composition, notable age- and sex-dependent responses were observed. This work in mature, treadmill-trained rats represents the most comprehensive and publicly accessible tissue biorepository, to date, and provides an unprecedented resource for studying temporal-, sex-, and age-specific responses to endurance exercise training in a preclinical rat model.

60 APPLIED LIFE SCIENCES↗

Chromoanagenesis in the asy1 meiotic mutant of Arabidopsis

Chromoanagenesis is a catastrophic event that involves localized chromosomal shattering and reorganization. In this study, we report a case of chromoanagenesis resulting from defective meiosis in the MEIOTIC ASYNAPTIC MUTANT 1 (asy1) background in Arabidopsis thaliana. We provide a detailed characterization of the genomic structure of this individual with a severely shattered segment of chromosome 1. We identified 260 novel DNA junctions in the affected region, most of which affect gene sequence on 1 or both sides of the junction. Our results confirm that asy1-related defective meiosis is a potential trigger for chromoanagenesis. This is the first example of chromoanagenesis associated with female meiosis and indicates the potential for genome evolution during oogenesis.

59 BASIC BIOLOGICAL SCIENCES↗

High-resolution mapping reveals hotspots and sex-biased recombination in Populus trichocarpa

Abstract Fine-scale meiotic recombination is fundamental to the outcome of natural and artificial selection. Here, dense genetic mapping and haplotype reconstruction were used to estimate recombination for a full factorial Populus trichocarpa cross of 7 males and 7 females. Genomes of the resulting 49 full-sib families (N = 829 offspring) were resequenced, and high-fidelity biallelic SNP/INDELs and pedigree information were used to ascertain allelic phase and impute progeny genotypes to recover gametic haplotypes. The 14 parental genetic maps contained 1,820 SNP/INDELs on average that covered 376.7 Mb of physical length across 19 chromosomes. Comparison of parental and progeny haplotypes allowed fine-scale demarcation of cross-over regions, where 38,846 cross-over events in 1,658 gametes were observed. Cross-over events were positively associated with gene density and negatively associated with GC content and long-terminal repeats. One of the most striking findings was higher rates of cross-overs in males in 8 out of 19 chromosomes. Regions with elevated male cross-over rates had lower gene density and GC content than windows showing no sex bias. High-resolution analysis identified 67 candidate cross-over hotspots spread throughout the genome. DNA sequence motifs enriched in these regions showed striking similarity to those of maize, Arabidopsis, and wheat. These findings, and recombination estimates, will be useful for ongoing efforts to accelerate domestication of this and other biomass feedstocks, as well as future studies investigating broader questions related to evolutionary history, perennial development, phenology, wood formation, vegetative propagation, and dioecy that cannot be studied using annual plant model systems.

59 BASIC BIOLOGICAL SCIENCES↗

Mob4 is essential for spermatogenesis in Drosophila melanogaster

Abstract Gamete formation is essential for sexual reproduction in metazoans. Meiosis in males gives rise to spermatids that must differentiate and individualize into mature sperm. In Drosophila melanogaster, individualization of interconnected spermatids requires the formation of individualization complexes that synchronously move along the sperm bundles. Here, we show that Mob4, a member of the Mps-one binder family, is essential for male fertility but has no detectable role in female fertility. We show that Mob4 is required for proper axonemal structure and its loss leads to male sterility associated with defective spermatid individualization and absence of mature sperm in the seminal vesicles. Transmission electron micrographs of developing spermatids following mob4RNAi revealed expansion of the outer axonemal microtubules such that the 9 doublets no longer remained linked to each other and defective mitochondrial organization. Mob4 is a STRIPAK component, and male fertility is similarly impaired upon depletion of the STRIPAK components, Strip and Cka. Expression of the human Mob4 gene rescues all phenotypes of Drosophila mob4 downregulation, indicating that the gene is evolutionarily and functionally conserved. Together, this suggests that Mob4 contributes to the regulation of the microtubule- and actin-cytoskeleton during spermatogenesis through the conserved STRIPAK complex. Our study advances the understanding of male infertility by uncovering the requirement for Mob4 in sperm individualization.

Santos, Inês B.↗

Evaluating algorithmic bias on biomarker classification of breast cancer pathology reports

Objectives: This work evaluated algorithmic bias in biomarkers classification using electronic pathology reports from female breast cancer cases. Bias was assessed across 5 subgroups: cancer registry, race, Hispanic ethnicity, age at diagnosis, and socioeconomic status. Materials and Methods: We utilized 594 875 electronic pathology reports from 178 121 tumors diagnosed in Kentucky, Louisiana, New Jersey, New Mexico, Seattle, and Utah to train 2 deep-learning algorithms to classify breast cancer patients using their biomarkers test results. We used balanced error rate (BER), demographic parity (DP), equalized odds (EOD), and equal opportunity (EOP) to assess bias. Results: We found differences in predictive accuracy between registries, with the highest accuracy in the registry that contributed the most data (Seattle Registry, BER ratios for all registries >1.25). BER showed no significant algorithmic bias in extracting biomarkers (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2) for race, Hispanic ethnicity, age at diagnosis, or socioeconomic subgroups (BER ratio <1.25). DP, EOD, and EOP all showed insignificant results. Discussion: We observed significant differences in BER by registry, but no significant bias using the DP, EOD, and EOP metrics for socio-demographic or racial categories. This highlights the importance of employing a diverse set of metrics for a comprehensive evaluation of model fairness. Conclusion: A thorough evaluation of algorithmic biases that may affect equality in clinical care is a critical step before deploying algorithms in the real world. We found little evidence of algorithmic bias in our biomarker classification tool. Artificial intelligence tools to expedite information extraction from clinical records could accelerate clinical trial matching and improve care.

60 APPLIED LIFE SCIENCES↗

Attraction and Longevity of 2- and 3-Component Food Cone Lures for the Caribbean Fruit Fly, Anastrepha suspensa (Diptera: Tephritidae)

Abstract The Caribbean fruit fly, Anastrepha suspensa (Loew) (Diptera: Tephritidae), is a quarantine pest of Citrus spp. and a production pest of guava and other specialty fruits in Florida. Effective monitoring lures and traps are needed for early pest detection and timely initiation of control measures. As part of a continued effort to identify attractive synthetic lures for the Caribbean fruit fly, we conducted field tests in Homestead, Florida to compare the efficacy and longevity of commercial 2- and 3-component cone lures (2C [ammonium acetate and putrescine], 3C [ammonium acetate, putrescine, and trimethylamine]), the current standards used by regulatory agencies, versus the traditional liquid protein bait consisting of hydrolyzed torula yeast and borax as a positive control. Additional lures were also field-aged and periodically brought into the laboratory to quantify residual chemical contents. Traps baited with the torula yeast-borax mixture captured the highest mean number of A. suspensa, and traps baited with the commercial 2C lures captured more flies than the 3C lures. Traps baited with torula yeast-borax also captured the highest number of nontarget Diptera. Captures with all three treatments were significantly biased toward females. Attractiveness of the 2C lure began to drop after 6–8 wk, and the 3C lure after 5–6 wk. Overall, these data suggest that the 2C cone lure is more attractive to A. suspensa than the 3C cone lure under field conditions in south Florida, and that the 2C lures are attractive for up to 8 wk.

Entomology↗

Acquisition of Rickettsia rickettsii (Rickettsiales: Rickettsiaceae) by Haemaphysalis longicornis (Acari: Ixodidae) through co-feeding with infected Dermacentor variabilis (Acari: Ixodidae) in the laboratory

Abstract Haemaphysalis longicornis (Neumann) is an invasive ixodid tick originating from eastern Asia which recently has become established in the United States. In its native range, this tick can transmit several pathogens to animals and humans, but little is known about its ability to acquire and transmit pathogens native to the United States. Geographic overlap with ticks such as Dermacentor variabilis (Say), a known vector of Rickettsia rickettsii, makes investigation into the interactions between H. longicornis and D. variabilis of interest to the public health community. Previous studies have shown that H. longicornis can serve as a competent vector of R. rickettsii under laboratory settings, but there is little information on its ability to acquire this pathogen via other biologically relevant routes, such as co-feeding. Here, we assess the ability of H. longicornis nymphs to acquire R. rickettsii through co-feeding with infected D. variabilis adults on a vertebrate animal model under laboratory conditions. The median infection prevalence in engorged H. longicornis nymphs across 8 cohorts was 0% with an interquartile range (IQR) of 4.13%. Following transstadial transmission, the median infection prevalence in flat females was 0.7% (IQR = 2.4%). Our results show that co-feeding transmission occurs at low levels in the laboratory between these 2 species. However, based on the relatively low transmission rates, this may not be a likely mechanism of R. rickettsii introduction to H. longicornis.

Entomology↗

Benefits of colorectal cancer screening using fecal immunochemical testing with varying positivity thresholds by age and sex

Background Fecal immunochemical test (FIT) performance for colorectal cancer screening varies by age and sex, yet most FIT-based screening programs use uniform positivity thresholds. This study assessed the potential benefits of stratifying FIT thresholds based on age and sex. Methods We conducted a meta-analysis of FIT sensitivity and specificity at various positivity thresholds by age and sex. We then used these estimates in 2 microsimulation models of colorectal cancer and projected lifetime clinical outcomes, incremental costs, and quality-adjusted life-years (QALYs) gained from age- and sex-stratified FIT strategies. FIT thresholds ranged from 10 to 50 µg hemoglobin per gram of feces. Results For current uniform FIT screening (20 µg hemoglobin/gram of feces), models projected 85.67 to 122.15 QALYs gained at incremental costs of ‒$982 to $504 per 1000 individuals compared with no screening. At equivalent costs to current uniform screening, only 1 model found stratified FIT approaches cost-effective, yielding a marginal increase of 1.04 and 1.10 QALYs gained/1000 female and male individuals, respectively. At a willingness-to-pay threshold of $100 000/QALYs gained, both models found stratified FIT cutoffs to be the best strategy, with cutoffs being equal to or higher for males and lowest at older ages (70-75 years). Uniform strategies showed comparable effectiveness, falling within 1 quality-adjusted life-day per person of efficient strategies at up to $112 more per person. Results were sensitive to FIT test performance characteristics and 1-time setup costs. Conclusion Stratifying FIT thresholds by age and sex may be cost-effective compared to current screening. The gain in expected health benefits with stratified FIT screening, however, is likely small.

Harlass, Matthias↗

Mentoring in the USDA Forest Service: A Survey of Aquatic Professionals

Abstract Mentoring is suggested as an important strategy to promote workplace inclusivity and is shown to be positively associated with high employee morale, yet mentee needs and experiences may not be universal. To evaluate mentoring impacts from the perspective of USDA Forest Service employees, we conducted an online survey of 251 aquatic professionals, including managers and scientists. 70% of respondents had mentors, and mentorship status did not vary across demographic characteristics. Previous mentoring relationships were most frequently identified as “informal” rather than “formal”; female employees were more likely to desire formal mentoring. Mentored respondents found their work more challenging, fulfilling, and valuable than unmentored respondents. Mentees looked for mentors who could provide constructive feedback, speak candidly, use active listening skills, and who cared about their careers. Overall, respondents were satisfied with their mentors’ skills. Despite strong demand for mentoring, access to mentors among aquatic professionals appears low across all categories.

Forestry↗

Genotoxicity of charged particles of importance in space flight using murine kidney epithelial cells

Ionizing radiation presents significant challenges for human space flight including an increased cancer risk. High-energy heavy ions in the galactic cosmic radiation can produce qualitative and quantitative differences in biological effects when compared with sparsely ionizing radiations. Mutations are induced by charged particle exposure and are integral to the formation and/or progression of human cancers. Most cancer-associated mutations occur on autosomal chromosomes, and most solid cancers occur in epithelial tissues. Here, a combined in vitro/in vivo approach was used to evaluate cell killing and the induction of mutations at a model autosomal locus, Aprt, in mouse kidney epithelium. For in vitro exposures, Aprt heterozygous kidney cells (clones 1a, 4a or 6a) were used from C57BL/6×DBA/2 mice. Additional experiments were performed using whole body irradiation of mice with the same genotype. Both males and females were irradiated in approximately equal numbers. Irradiations were performed at the NASA Space Radiation Laboratories at Brookhaven National Laboratory. For in vitro studies, cells from primary kidney clones were irradiated and seeded at limiting dilution immediately post-irradiation to determine the toxicity of the treatment. The irradiated kidney cells were also seeded in mutation assays within 1 week post-irradiation to determine the Aprt mutant fraction at the earliest time post-exposure. This work was complemented by studies wherein mice were exposed to the same ions with kidneys harvested several months post-irradiation to determine the residual toxicity and the Aprt mutant fraction. Our previous studies focused on sparsely ionizing 1 GeV protons (LET = 0.24 keV/µm) and densely ionizing 1 GeV/amu Fe ions (LET = 151 keV/µm). Our most recent studies have included work with Si ions (240 MeV/amu for in vitro studies, LET = 78 keV/µm; 263 MeV/amu initial energy for in vivo studies to achieve 78 keV/µm near the midline of the animal) and O ions (250 MeV/amu in vitro studies only, LET = 25 keV/µm). Toxicity for the cultured kidney cells in vitro follows this pattern: Fe > Si > O > protons when the results are expressed per unit dose. D0 values were 92 cGy for Fe ions, 103 cGy for Si ions, 192 cGy for O ions and 340 cGy for protons. With regard to the induction of Aprt mutations, Fe ions were more mutagenic than protons. Si ions were also quite mutagenic with evidence for a linear dose–response for Aprt mutations in kidney cells exposed in vitro or in kidneys harvested from mice irradiated several months earlier. These results are consistent with the linear dose–response data obtained previously for Aprt mutation induction following Fe ion exposure in vitro or in vivo, but the results for Si ions differ from the curvilinear dose–response data we recently published following similar exposures to energetic protons [ 1, 2]. Our most recent studies examined the molecular characteristics of Si ion-induced Aprt mutants following in vitro exposure. A dose of 160 cGy was used to collect 58 Aprt kidney cell mutants. Mutational events were classified as follows based on PCR-based analyses of polymorphic markers along mouse chromosome 8: intragenic events, apparent mitotic recombination, interstitial deletions of Aprt only, multilocus deletions, discontinuous loss of heterozygosity or whole chromosome loss. The results for this group of mutants will be compared against our previous studies on Aprt mutants arising after exposure to sparsely ionizing 1 GeV protons or densely ionizing 1 GeV/amu Fe ions. Additional studies are ongoing to define mutational spectra following Si ion exposure to kidney epithelium in vivo.

59 BASIC BIOLOGICAL SCIENCES↗

Transporters involved in pH and K + homeostasis affect pollen wall formation, male fertility, and embryo development

Flowering plant genomes encode multiple cation/H + exchangers (CHXs) whose functions are largely unknown. AtCHX17, AtCHX18, and AtCHX19 are membrane transporters that modulate K+ and pH homeostasis and are localized in the dynamic endomembrane system. Loss of function reduced seed set, but the particular phase(s) of reproduction affected was not determined. Pollen tube growth and ovule targeting of chx17chx18chx19 mutant pollen appeared normal, but reciprocal cross experiments indicate a largely male defect. Although triple mutant pollen tubes reach ovules of a wild-type pistil and a synergid cell degenerated, half of those ovules were unfertilized or showed fertilization of the egg or central cell, but not both female gametes. Fertility could be partially compromised by impaired pollen tube and/or sperm function as CHX19 and CHX18 are expressed in the pollen tube and sperm cell, respectively. When fertilization was successful in self-pollinated mutants, early embryo formation was retarded compared with embryos from wild-type ovules receiving mutant pollen. Thus CHX17 and CHX18 proteins may promote embryo development possibly through the endosperm where these genes are expressed. The reticulate pattern of the pollen wall was disorganized in triple mutants, indicating perturbation of wall formation during male gametophyte development. Lastly, as pH and cation homeostasis mediated by AtCHX17 affect membrane trafficking and cargo delivery, these results suggest that male fertility, sperm function, and embryo development are dependent on proper cargo sorting and secretion that remodel cell walls, plasma membranes, and extracellular factors.

59 BASIC BIOLOGICAL SCIENCES↗

Comparison of Different Variants of the U.S. Army Occupational Physical Assessment Test

The U.S. Army Occupational Physical Assessment Test (OPAT) is a pre-enlistment physical employment screening assessment developed to place recruits and soldiers into Military Occupational Specialties (MOSs) based on their physical capabilities in order to optimize performance and limit injury. The OPAT consists of the seated power throw (SPT), strength deadlift (SDL), standing long jump, and interval aerobic run. During the scientific validation of the OPAT, two variants of the SPT and two variants of the SDL were used. Although the OPAT was validated using both variants for each test, U.S. Army scientists and policymakers have received queries regarding how these variants compare to each other. Therefore, the purpose of this study was to compare different variants of the SPT and SDL. Thirty-two participants (14 male and 18 female) between the ages of 18 and 42 years visited the laboratory on one occasion and performed two variants of the SPT (seated on the ground [the current OPAT standard] versus seated in a chair with a 35 cm seat height) and two variants of the SDL (using a hex-bar [the current OPAT standard] versus using paired dumbbells). Testing order for the different variants was randomized. The protocol was approved by the U.S. Army Medical Research and Development Command Institutional Review Board. Performing the SPT from a chair significantly (P < .05) increased performance when compared to performing the SPT from the ground (5.4 ± 1.3 m versus 5.0 ± 1.4 m, respectively). Values for the two SPT variants were correlated (tau = 0.90). Performing the SDL using the hex-bar significantly increased the maximal weight lifted when compared to performing the SDL using paired dumbbells (86.9 ± 18.4 kg versus 83.1 ± 18.0 kg, respectively). Values for the two SDL variants were correlated (tau = 0.83). Performing different variants of the SPT and SDL influenced the resulting score. Although these findings do not alter the administration or scoring of the OPAT, they do provide a valuable reference in the event of future inquiries regarding the development of the OPAT.

General & Internal Medicine↗

Low-dose radiation from 18 F-FDG PET does not increase cancer frequency or shorten latency but reduces kidney disease in cancer-prone Trp53+/- mice

There is considerable interest in the health effects associated with low-level radiation exposure from medical imaging procedures. Concerns in the medical community that increased radiation exposure from imaging procedures may increase cancer risk among patients are confounded by research showing that low-dose radiation exposure can extend lifespan by increasing the latency period of some types of cancer. The most commonly used radiopharmaceutical for positron emission tomography (PET) scans is 2-[ 18 F] fluoro-2-deoxy-d-glucose ( 18 F-FDG), which exposes tissue to a low-dose, mixed radiation quality: 634 keV β+ and 511 keV γ-rays. The goal of this research was to investigate how modification of cancer risk associated with exposure to low-dose ionising radiation in cancer-prone Trp53 +/- mice is influenced by radiation quality from PET. At 7-8 weeks of age, Trp53 +/- female mice were exposed to one of five treatments: 0 Gy, 10 mGy γ-rays, 10 mGy 18 F-FDG, 4 Gy γ-rays, 10 mGy 18 F-FDG + 4 Gy γ-rays (n > 185 per group). The large 4-Gy radiation dose significantly reduced the lifespan by shortening the latency period of cancer and significantly increasing the number of mice with malignancies, compared with unirradiated controls. The 10 mGy γ-rays and 10 mGy PET doses did not significantly modify the frequency or latency period of cancer relative to unirradiated mice. Similarly, the PET scan administered prior to a large 4-Gy dose did not significantly modify the latency or frequency of cancer relative to mice receiving a dose of only 4 Gy. The relative biological effectiveness of radiation quality from 18 F-FDG, with respect to malignancy, is approximately 1. Furthermore, when non-cancer endpoints were studied, it was found that the 10-mGy PET group had a significant reduction in kidney lesions (P < 0.021), indicating that a higher absorbed dose (20 ± 0.13 mGy), relative to the whole-body average, which occurs in specific tissues, may not be detrimental.

18F-FDG RBE 1.0↗

The Combined Effect of Cigarette Smoking and Fitness on Injury Risk in Men and Women

Abstract Background Prior studies have identified cigarette smoking and low fitness as independent risk factors for injury; however, no studies have evaluated the combined effect of cigarette smoking and fitness on injury risk. Objective To evaluate the combined effect of cigarette smoking and fitness on injury risk in men and women. Design This is a secondary analysis of data collected from US Army recruits (n = 2000) during basic combat training within the United States in 2007. Physical training and fitness, cigarette smoking, and prior injury data were obtained from questionnaires, whereas demographic and injury data were obtained from medical and basic combat training unit records. Chi-squared tests were used to assess differences in injury risk by fitness level and cigarette smoking. Relative risk values were calculated with 95% confidence intervals. Results The primary findings showed that smokers experienced 20%–30% higher risk of injury than nonsmokers. In addition, higher aerobic and muscular fitness was generally not protective against injury between least fit and more fit smokers. However, higher fitness was protective against injury between least and more fit nonsmokers, with least fit nonsmokers being 30%–50% more likely to experience an injury than fit nonsmokers. Conclusion This study revealed that higher aerobic and muscular fitness was not protective against injury among smokers; however, it was protective against injury among nonsmokers. Further implementation of smoking cessation programs may be beneficial for military and civilian personnel who are required to be physically fit in order to carry out their job responsibilities. Implications Male and female smokers experienced significantly higher risk of injury than nonsmokers. Although higher fitness is protective against injury in nonsmokers, the protective effect of fitness is lost among smokers. In an attempt to reduce injury risk among military and emergency personnel, smoking cessation programs should be further implemented among both more fit and less fit smokers.

Brooks, Raina D.↗