The longitudinal relation of inflammation to incidence of vasomotor symptoms.

OBJECTIVE: Vasomotor symptoms (VMS), the most frequently reported symptoms during the menopausal transition, have been associated with inflammation. Whether inflammation is a risk factor for or a consequence of VMS remains unclear. The objectives of these analyses were to determine if elevated proinflammatory marker levels were associated with increased incident VMS in women without VMS at baseline and whether these associations varied by menopause transition stage or race/ethnicity. METHODS: We used longitudinal data on incident VMS, high-sensitivity C-reactive protein (hs-CRP; n = 1,922) and interleukin-6 (IL-6; n = 203) from 13 follow-up visits in the Study of Women's Health Across the Nation, which included five racial/ethnic groups of midlife women. We performed multivariable discrete-time survival analyses to determine adjusted hazard ratios (aHRs) for the association of these proinflammatory markers with incident VMS in women without VMS at baseline. RESULTS: We found no significant associations of incident VMS with dichotomized hs-CRP (>3 vs ≤3 mg/L) at baseline, concurrent or prior visit (aHRs, 1.04-2.03) or IL-6 (>1.44 vs ≤1.44 pg/mL) at visit 1, concurrent or prior visit (aHRs, 0.67-1.62), or continuous hs-CRP or IL-6 values over 13 follow-up visits (with nonsignificant adjusted increased hazards ranging from 0% to 2%). CONCLUSIONS: Our results showed no significant association of the proinflammatory biomarkers, hs-CRP or IL-6, either concurrently or with subsequent incident VMS, indicating that inflammation was unlikely to be a risk factor for VMS. Thus, clinical treatments directed at reducing inflammation would be unlikely to reduce the occurrence of VMS.

Circulating integrin α4 ß7+ CD4 T cells are enriched for proliferative transcriptional programs in HIV infection.

HIV preferentially infects α4 ß7+ CD4 T cells, forming latent reservoirs that contribute to HIV persistence during antiretroviral therapy. However, the properties of α4 ß7+ CD4 T cells in blood and mucosal compartments remain understudied. Employing two distinct models of HIV infection, HIV-infected humans and simian-human immunodeficiency virus (SHIV)-infected rhesus macaques, we show that α4 ß7+ CD4 T cells in blood are enriched for genes regulating cell cycle progression and cellular metabolism. Unlike their circulating counterparts, rectal α4 ß7+ CD4 T cells exhibited a core tissue-residency gene expression program. These features were conserved across primate species, indicating that the environment influences memory T-cell transcriptional networks. Our findings provide an important molecular foundation for understanding the role of α4 ß7 in HIV infection.

Misdiagnosis of Leiomyosarcoma after Radiofrequency Ablation of Uterine Myomas.

Minimally invasive therapies to treat symptoms of uterine myomas can be effective alternatives to major surgery. Such modalities include pharmacologic agents, uterine artery embolization, magnetic resonance-guided focused ultrasound, and laparoscopic radiofrequency ablation, known as the Acessa procedure. Acessa is used to treat women with symptomatic myomas and was approved by the US Food and Drug Administration in 2012. This case describes a patient who underwent Acessa and subsequently required hysterectomy for refractory symptoms. Pathology of her tumor was initially classified as epithelioid leiomyosarcoma but on subsequent review was classified as benign. This report highlights the challenges of accurate histologic diagnosis in the setting of using new therapeutic modalities. Clinicians should report such interventions to pathologists at the time of surgery to allow for accurate diagnosis.

Bayesian Nonparametric Longitudinal Data Analysis.

Practical Bayesian nonparametric methods have been developed across a wide variety of contexts. Here, we develop a novel statistical model that generalizes standard mixed models for longitudinal data that include flexible mean functions as well as combined compound symmetry (CS) and autoregressive (AR) covariance structures. AR structure is often specified through the use of a Gaussian process (GP) with covariance functions that allow longitudinal data to be more correlated if they are observed closer in time than if they are observed farther apart. We allow for AR structure by considering a broader class of models that incorporates a Dirichlet Process Mixture (DPM) over the covariance parameters of the GP. We are able to take advantage of modern Bayesian statistical methods in making full predictive inferences and about characteristics of longitudinal profiles and their differences across covariate combinations. We also take advantage of the generality of our model, which provides for estimation of a variety of covariance structures. We observe that models that fail to incorporate CS or AR structure can result in very poor estimation of a covariance or correlation matrix. In our illustration using hormone data observed on women through the menopausal transition, biology dictates the use of a generalized family of sigmoid functions as a model for time trends across subpopulation categories.

Dietary phytoestrogen intakes and cognitive function during the menopausal transition: results from the Study of Women's Health Across the Nation Phytoestrogen Study.

OBJECTIVE: Phytoestrogens, which consist mainly of isoflavones, lignans, and coumestans have estrogenic and anti-inflammatory properties. Previous research suggests that higher dietary or supplemental intakes of isoflavones and lignans are related to better cognitive performance in middle-aged and older women. METHODS: We conducted longitudinal analysis of dietary phytoestrogens and cognitive performance in a cohort of African American, white, Chinese, and Japanese women undergoing the menopausal transition. The tests were Symbol Digit Modalities, East Boston Memory, and Digits Span Backward. Phytoestrogens were assessed using the Food Frequency Questionnaire. We modeled each cognitive score as a function of concurrent value of the primary predictors (highest tertile of isoflavones, lignans, or coumestrol) and covariates including the menopausal transition stage. RESULTS: Coumestrol and isoflavone intakes were 10 and 25 times greater, respectively, in Asian than in non-Asian participants. During late perimenopause and postmenopause, Asian women with high isoflavone intakes did better on processing speed, but during early perimenopause and postmenopause, high-isoflavone Asian consumers performed worse on verbal memory. The highest isoflavone consumers among non-Asians likewise posted lower verbal memory scores during early perimenopause. A verbal memory benefit of higher dietary lignan consumption was apparent only during late perimenopause, when women from all ethnic/racial groups who were in the highest tertile of intake demonstrated a small advantage. Coumestrol was unrelated to cognitive performance. CONCLUSIONS: The cognitive effects of dietary phytoestrogens are small, seem to be class-specific, vary by menopause stage and cognitive domain, and differ among ethnic/racial groups (but whether this is related to dose or to host factors cannot be discerned).