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Actinobacillus pleuropneumoniae is the cause of porcine pleuropneumonia, a severe respiratory tract infection that is responsible for major economic losses to the swine industry. Many host-adapted bacterial pathogens encode systems known as phasevarions (phase-variable regulons). Phasevarions result from variable expression of cytoplasmic DNA methyltransferases. Variable expression results in genome-wide methylation differences within a bacterial population, leading to altered expression of multiple genes via epigenetic mechanisms. Our examination of a diverse population of A. pleuropneumoniae strains determined that Type I and Type III DNA methyltransferases with the hallmarks of phase variation were present in this species. We demonstrate that phase variation is occurring in these methyltransferases, and show associations between particular Type III methyltransferase alleles and serovar. Using Pacific BioSciences Single-Molecule, Real-Time (SMRT) sequencing and Oxford Nanopore sequencing, we demonstrate the presence of the first ever characterised phase-variable, cytosine-specific Type III DNA methyltransferase. Phase variation of distinct Type III DNA methyltransferase in A. pleuropneumoniae results in the regulation of distinct phasevarions, and in multiple phenotypic differences relevant to pathobiology. Our characterisation of these newly described phasevarions in A. pleuropneumoniae will aid in the selection of stably expressed antigens, and direct and inform development of a rationally designed subunit vaccine against this major veterinary pathogen.

This pilot qualitative case study was able to elicit rich data enabling a description of how women went through the journey of achieving pregnancy using fertility awareness-based methods. Findings underscore that women preferred using natural ways to detect ovulation and would recommend other women to do so, but with healthcare providers’ guidance. The findings of this case study can serve as a starting point to provide a framework to understand women's experiences of enduring trial and error with multiple fertility awareness-based methods before discovering their effective method. Findings emphasize the importance for healthcare providers to guide women in using fertility awareness-based methods.

Background: In patients with lymphedema (LE), in addition to hand dominance, between-group comparisons of interlimb soft tissue differences need to account for differences in whole-body adiposity, measured directly by dual energy X-ray absorptiometry (DXA) or indirectly by body mass index. No study has evaluated the effects of hand dominance and whole-body adiposity on limb composition in patients with LE. This study's purpose was to compare soft tissue composition of affected and unaffected limbs of women with breast cancer, who did and did not have LE, controlling for dominance and percent body fat. Methods and Results: Whole-body DXA scans were acquired and included measures of percent body fat, upper limb total mass, upper limb fat mass, and upper limb fat-free mass. Participants were classified into one of three groups: women without LE; women with only subjective LE; and women with objective signs of LE at the time of assessment. Differences among the LE groups were evaluated using analysis of variance (ANOVA) and Chi-square analyses. Analysis of covariance (ANCOVA) was used to control for percent body fat and for the affected limb dominance. Compared to women without LE, women with objective signs of LE have greater total limb mass, fat mass, and fat-free mass in their affected limbs, independent of affected side dominance and percent body fat. In addition, the interlimb differences in total mass, fat mass, and fat-free mass were greater for the women with objective signs of LE, compared to the other two groups. Conclusions: DXA is useful in identifying soft tissue changes in patients with LE. Given that limb circumferences measure only changes in limb volume and that bioimpedance provides estimates of extracellular fluid, DXA has the advantage of being able to estimate the volumes of specific tissues in the limb.

Supplementary Methods

Supplementary Figures S1 - S15. Supplementary Figure S1. Effect of obesity on tumor initiation. Supplementary Figure S2. Adipose tissue - tumor interaction. Supplementary Figure S3. Correlation of collagen-I levels with tumor size, co-expression of collagen-I and hyaluronan in PSCs, and impact of obesity on desmoplasia and tumor hyaluronan levels. Supplementary Figure S4. Additional Western blotting data from PAN02 tumors. Supplementary Figure S5. Additional effects of AT-1 inhibition on obesity-aggravated desmoplasia, perfusion and drug delivery. Supplementary Figure S6. Additional data on the effect of obesity on immune cell infiltration in tumors. Supplementary Figure S7. Effects of TAN depletion on vessel perfusion in obese mice. Supplementary Figure S8. Effect of obesity on cytokine profile in AK4.4 tumors. Supplementary Figure S9. Effects of TAN depletion on tumor cytokine expression in obese mice. Supplementary Figure S10. Additional effects of losartan on the tumor immune microenvironment. Supplementary Figure S11. Distribution of PDAC patients according to their BMI. Supplementary Figure S12. Effect of obesity on the expression of AT1, Ly6g, and AT1/Ly6g double positivity in PAN02 tumors. Supplementary Figure S13. Representative picture of AT1 expression in cancer-associated adipocytes (arrows) in PAN02 tumors. Supplementary Figure S14. Additional effects of AT1 inhibition on obesity-aggravated microenvironment. Supplementary Figure S15. Prevalance of hypertesion in PDAC patients.

Supplementary Tables S1 - S6. Supplementary Table S1. CT values for demosplasia-related genes in PAN02 tumors. Data obtained from PCR array. Supplementary Table S2. CT values for demosplasia-related genes in AK4.4 tumors. Data obtained from PCR array. Supplementary Table S3. Univariate analysis of prognostic factors for resected pancreatic cancer patients with body mass index (BMI) {less than or equal to}25. Supplementary Table S4. Multivariate analysis of prognostic factors for resected pancreatic cancer patients with body mass index (BMI) {less than or equal to}25. Supplementary Table S5. Univariate analysis of prognostic factors for resected pancreatic cancer patients with body mass index (BMI) >25. Supplementary Table S6. Multivariate analysis of prognostic factors for resected pancreatic cancer patients with body mass index (BMI) >25.

Background: Lymphedema (LE) is a significant clinical problem for breast cancer survivors. While the water displacement test and circumferential assessment using a tape measure (TM) are common methods to assess differences in arm volumes, faster and more reliable methods are needed. Study purposes, in breast cancer survivors (n = 294), were to compare the average total arm volumes and interlimb volume ratios for women with and without a history of LE, using a TM and three-dimensional (3D), whole-body surface scanner (3D scan); compare the level of agreement between arm volumes and interlimb volume ratios obtained using the two devices; and evaluate the percent agreement between the two measures in classifying cases of LE using three accepted thresholds. Methods and Results: Measurements were done using a spring-loaded TM and Fit3D ProScanner. Paired t-tests and Bland-Altman analyses were used to achieve the study aims. For circumference and volume comparisons, compared with the 3D scan, values obtained using the TM were consistently smaller. In terms of level of agreement, the Bland-Altman analyses demonstrated large biases and wide limits of agreement for the calculated arm volumes and volume ratios. In terms of the classification of caseness, using the 200-mL interlimb volume difference criterion resulted in 81.6% overall agreement; using the >10% volume difference between the affected and unaffected arms resulted in 78.5% overall agreement; and using the volume ratio ≥1.04 criterion resulted in 62.5% overall agreement. For all three accepted threshold criteria, the percentage of cases was significantly different between the TM and 3D scan techniques. Conclusions: The 3D technology evaluated in this study has the potential to be used for self-initiated surveillance for LE. With improvements in landmark identification and software modifications, it is possible that accurate and reliable total arm volumes can be calculated and used for early detection.

Sex education is important to support healthy sexual development/behaviors among heterosexual and sexual minority youth. Efforts to assess the efficacy of different sex education programs have been complicated by the lack of an established and detailed way to characterize overall sex education content. This study delineates seven different types of sex education and compares the impact of education types on the probability of sexual intercourse and contraceptive method use among a nationally representative sample of females aged 15–19 years. Data were obtained from four National Survey of Family Growth surveys (2011–2019). Multinomial logistic regression was used to examine associations and calculate predicted probability values. Among youth in this analysis (N = 3952), 14.9% identified as a sexual minority and 72% reported sex education including refraining from sex, contraception, and STIs/HIV. Compared to their heterosexual peers, sexual minorities were more likely to report no sex education and less likely to report receipt of abstinence-only education. All types of education, except education solely focused on refraining from sex and contraception methods, had a statistically significant effect on sexual behavioral outcomes (intercourse in the past 12 months and type of contraceptive use) as compared to no sex education. Findings highlight the need for consideration of the specific/total content of sex education, benefits/drawbacks of sex education types, and the needs of sexual minority youth. Research is needed to further explore outcomes associated with specific curricular content. Specific content of sex education should be considered prior to making curricular policies decisions.