Association of early menarche with breast tumor molecular features and recurrence.

BACKGROUND: Early menarche is an established risk factor for breast cancer but its molecular contribution to tumor biology and prognosis remains unclear. METHODS: We profiled transcriptome-wide gene expression in breast tumors (N = 846) and tumor-adjacent normal tissues (N = 666) from women in the Nurses' Health Studies (NHS) to investigate whether early menarche (age < 12) is associated with tumor molecular and prognostic features in women with breast cancer. Multivariable linear regression and pathway analyses using competitive gene set enrichment analysis were conducted in both tumor and adjacent-normal tissue and externally validated in TCGA (N = 116). Subgroup analyses stratified on ER-status based on the tumor were also performed. PAM50 signatures were used for tumor molecular subtyping and to generate proliferation and risk of recurrence scores. We created a gene expression score using LASSO regression to capture early menarche based on 28 genes from FDR-significant pathways in breast tumor tissue in NHS and tested its association with 10-year disease-free survival in both NHS (N = 836) and METABRIC (N = 952). RESULTS: Early menarche was significantly associated with 369 individual genes in adjacent-normal tissues implicated in extracellular matrix, cell adhesion, and invasion (FDR ≤ 0.1). Early menarche was associated with upregulation of cancer hallmark pathways (18 significant pathways in tumor, 23 in tumor-adjacent normal, FDR ≤ 0.1) related to proliferation (e.g. Myc, PI3K/AKT/mTOR, cell cycle), oxidative stress (e.g. oxidative phosphorylation, unfolded protein response), and inflammation (e.g. pro-inflammatory cytokines IFN α and IFN γ ). Replication in TCGA confirmed these trends. Early menarche was associated with significantly higher PAM50 proliferation scores (ß = 0.082 [0.02-0.14]), odds of aggressive molecular tumor subtypes (basal-like, OR = 1.84 [1.18-2.85] and HER2-enriched, OR = 2.32 [1.46-3.69]), and PAM50 risk of recurrence score (ß = 4.81 [1.71-7.92]). Our NHS-derived early menarche gene expression signature was significantly associated with worse 10-year disease-free survival in METABRIC (N = 952, HR = 1.58 [1.10-2.25]). CONCLUSIONS: Early menarche is associated with more aggressive molecular tumor characteristics and its gene expression signature within tumors is associated with worse 10-year disease-free survival among women with breast cancer. As the age of onset of menarche continues to decline, understanding its relationship to breast tumor characteristics and prognosis may lead to novel secondary prevention strategies.

Evaluation of community-based screening tools for the early screening of osteoporosis in postmenopausal Vietnamese women.

BACKGROUND: Osteoporosis affects people worldwide. However, there are few validated tools for the early screening of osteoporosis in Vietnam. We set out to evaluate the performance of the osteoporosis self-assessment tool for Asians (OSTA) and the osteoporosis screening tool for Chinese (OSTC) for the early screening of osteoporosis in postmenopausal Vietnamese women. METHODS: We analyzed retrospective data from 797 postmenopausal Vietnamese women. The bone mineral density (BMD) in the lumbar vertebrae (L1-L4) and the left and right femoral necks of all participants were measured using dual-energy X-ray absorptiometry (DXA). Osteoporosis was defined as the BMD (T-score) < -2.5. The OSTA and OSTC scores were calculated from the age and weight of participants. Receiver operating characteristic analysis was conducted to compare the performance of the two tools with the BMD measurements by DXA at different anatomical sites. RESULTS: The rates of osteoporosis determined by BMD varied between anatomical sites, and ranged from 43.4% to 54.7% in the lumbar vertebrae and 29.2% and 8.9% in the left and right femoral necks, respectively. For the vertebrae, the area under the curve (AUC) for OSTA ranged from 70.9% to 73.9% and for OSTC ranged from 68.7% to 71.6%. The predictive value of both tools was higher for femoral necks, with the AUC of OSTA for the left and right femoral necks being 80.0% and 85.8%, respectively. The corresponding figures for OSTC were 80.5% and 86.4%, respectively. The highest sensitivity and specificity of OSTA were 74.6% and 81.4%, while these figures for OSTC were 73.9% and 82.6%, respectively. CONCLUSION: OSTA and OSTC were shown to be useful self-assessment tools for osteoporosis detection in Vietnam postmenopausal women. Further research is encouraged to determine the applicability of tools for other populations and settings.

Violence and non-fatal injuries among Vietnamese in-school adolescents: national prevalence estimates and associated factors.

School violence and injury are major public health problems worldwide. The data of this study were from the Viet Nam Global School-based Student Health Survey (GSHS) - a nationally representative survey conducted in 2019, with a sample size of 7690 students aged 13-17 years old. We found the prevalence of violence and non-fatal injury to be 14.5% and 21.4%, respectively. Factors related to higher odds of violence and non-fatal injuries in both sexes included smoking cigarettes, drinking alcohol, having mental health problems (loneliness, worrying and suicidal thinking), and truancy. In contrast, parental monitoring was associated with lower odds of violence, and parental respect was a protective factor of both violence and non-fatal injuries. Students who experienced violence had a higher likelihood of having non-fatal injuries in both sexes. Future policies should consider individual factors and parent-child bonding, to mitigate the burden of violence and injury among in-school adolescents in Viet Nam.

Cost of postoperative sepsis in Vietnam.

Despite improvements in medical care, the burden of sepsis remains high. In this study, we evaluated the incremental cost associated with postoperative sepsis and the impact of postoperative sepsis on clinical outcomes among surgical patients in Vietnam. We used the national database that contained 1,241,893 surgical patients undergoing seven types of surgery. We controlled the balance between the groups of patients using propensity score matching method. Generalized gamma regression and logistic regression were utilized to estimate incremental cost, readmission, and reexamination associated with postoperative sepsis. The average incremental cost associated with postoperative sepsis was 724.1 USD (95% CI 553.7-891.7) for the 30 days after surgery, which is equivalent to 28.2% of the per capita GDP in Vietnam in 2018. The highest incremental cost was found in patients undergoing cardiothoracic surgery, at 2,897 USD (95% CI 530.7-5263.2). Postoperative sepsis increased patient odds of readmission (OR = 6.40; 95% CI 6.06-6.76), reexamination (OR = 1.67; 95% CI 1.58-1.76), and also associated with 4.9 days longer of hospital length of stay among surgical patients. Creating appropriate prevention strategies for postoperative sepsis is extremely important, not only to improve the quality of health care but also to save health financial resources each year.

Effect of Nanoparticles on the Bulk Shear Viscosity of a Lung Surfactant Fluid.

Inhaled nanoparticles (<100 nm) reaching the deep lung region first interact with the pulmonary surfactant, a thin lipid film lining the alveolar epithelium. To date, most biophysical studies have focused on particle-induced modifications of the film interfacial properties. In comparison, there is less work on the surfactant bulk properties and on their changes upon particle exposure. Here we study the viscoelastic properties of a biomimetic pulmonary surfactant in the presence of various engineered nanoparticles. The microrheology technique used is based on the remote actuation of micron-sized wires via the application of a rotating magnetic field and on time-lapse optical microscopy. It is found that particles strongly interacting with lipid vesicles, such as cationic silica (SiO2, 42 nm) and alumina (Al2O3, 40 nm) induce profound modifications of the surfactant flow properties, even at low concentrations. In particular, we find that silica causes fluidification, while alumina induces a liquid-to-soft solid transition. Both phenomena are described quantitatively and accounted for in the context of colloidal physics models. It is finally suggested that the structure and viscosity changes could impair the fluid reorganization and recirculation occurring during breathing.