Pain Trajectories and Predictors: A 7-Year Longitudinal Study of Women With Vulvodynia

IntroductionA significant proportion of women report a reduction of symptoms over time—even without treatment—yet the natural progression of vulvodynia and which factors may explain decrease vs persistence of pain remain unclear.AimTo identify subgroups of pain trajectories in women with vulvodynia and to predict these different trajectories by treatments undertaken, pain characteristics, and psychosocial factors.MethodsData on pain intensity, treatments undertaken, pain characteristics, and psychosocial factors were collected 3 times over a 7-year period from 173 women who screened positive for vulvodynia. Latent class growth analysis was conducted to identify homogeneous subgroups with distinct pain trajectories. A multivariate binomial logistic regression was used to examine whether treatments, pain characteristics, and psychosocial factors predicted these trajectories.Main Outcome MeasureThe main outcome was pain intensity (0–10), measured at 3 time points with the numerical rating scale.Results2 pain trajectories were identified: 1 where pain persisted (28.9%), and 1 where pain decreased over time (71.1%). Whether a treatment had been undertaken was not predictive of the course of pain over time. Women who were older at first pain onset, had pain at another location than the entrance of the vagina, and reported more anxiety were more likely to have a persistent pain trajectory relative to the decreased pain trajectory.Clinical ImplicationsFindings suggest that the evolution of pain differs among women with vulvodynia depending on pain characteristics and anxiety.Strengths & LimitationsStrengths of the study include the 7-year longitudinal design to examine the natural history of provoked vestibulodynia and the inclusion of biopsychosocial factors as predictors of pain trajectories. However, women with major medical and psychiatric illnesses or deep dyspareunia were not included, and, thus, these factors could not be examined as predictors.ConclusionAssessing baseline characteristics associated with different pain trajectories during medical visits could have positive implications for the management of vulvodynia.Pâquet M, Vaillancourt-Morel M-P, Jodouin J-F, et al. Pain Trajectories and Predictors: A 7-Year Longitudinal Study of Women With Vulvodynia. J Sex Med 2019;16:1606–1614.     

Toxicity of ZnO nanoparticles (NPs) to THP-1 macrophages: interactions with saturated or unsaturated free fatty acids

In a biological microenvironment, free fatty acids (FFA) as ubiquitous biological molecules might interact with nanoparticles (NPs) and consequently change the toxicological responses. However, whether the chemical structures of FFA could influence their interactions with NPs remain unknown. This study investigated the interactions between ZnO NPs and saturated or unsaturated FFA (complexed to BSA), namely stearic acid (SA, C18:0), oleic acid (OA, C18:1), and α-linolenic acid (ALA, C18:3). It was shown that BSA, SA, OA, and ALA increased the atomic force microscope (AFM) heights as well the polydispersity index (PDI) of ZnO NPs. BSA modestly protected THP-1 macrophages from ZnO NP exposure, whereas OA and ALA led to relatively less cyto-protective effects of BSA. Moreover, only co-exposure to ZnO NPs and SA significantly promoted the release of interleukin-8. BSA, SA, OA, and ALA equally changed intracellular ROS and Zn ions associated with ZnO exposure, but co-exposure to ZnO NPs and OA/ALA particularly activated the expression of endoplasmic reticulum stress-apoptosis genes. In combination, these results showed that FFA could influence the colloidal aspects and toxicological signaling pathway of ZnO NPs, which is dependent on the number of unsaturated bonds of FFA.     

Qualitative evidence for Resilience,Stress, and Ethnicity (RiSE): A program to address race-based stress among Black women at risk for cardiovascular disease

ObjectiveGrowing evidence demonstrates that perceived discrimination and racism are significant contributing factors to psychological distress, low-grade chronic inflammation, and cardiovascular health disparities among minorities, particularly among Black women. Despite this evidence, there are no evidence-based complementary therapy interventions available to ameliorate chronic stress associated with racism and discrimination. The purpose of this study was to examine the feasibility and effectiveness of a novel, 8-week, group-based stress reduction program, Resilience, Stress and Ethnicity (RiSE), designed to help Black women at risk for cardiovascular disease (CVD) develop effective coping skills for dealing with chronic stress uniquely associated with being a minority.MethodsWe conducted two semi-structured focus groups with Black women (N = 22) following their participation in the 8-week RiSE program. We analyzed the data using constant comparative qualitative methods.ResultsAttrition rate was low (13%) with all participants attending at least 6 of the 8 classes. Participants reported high levels of satisfaction with the program and the majority (81%) reported practicing the skills that they learned in real-life stressful situations. In describing the participants’ response to the program, four key categories emerged from the data: (1) Increasing awareness of stressors associated with perceived discrimination and racism; (2) Coping with race-based stressors; (3) Coping with other sources of stress; and (4) Increasing sense of empowerment and emotion regulation.ConclusionsFindings suggest that RiSE is feasible and effective in helping Black women at risk for CVD cope with chronic stress associated with being a minority. Given evidence that perceived discrimination and racism are underlying factors in many inflammatory-based chronic diseases, this research may have broader implications for reducing health disparities across a wide-spectrum of chronic illnesses in which women minorities are disproportionately affected.     

Therapeutic cooperation between auranofin,a thioredoxin reductase inhibitor and anti-PD-L1 antibody for treatment of triple-negative breast cancer

Triple-negative breast cancer (TNBCs) is a very aggressive and lethal form of breast cancer with no effective targeted therapy. Neoadjuvant chemotherapies and radiotherapy remains a mainstay of treatment with only 25–30% of TNBC patients responding. Thus, there is an unmet clinical need to develop novel therapeutic strategies for TNBCs. TNBC cells have increased intracellular oxidative stress and suppressed glutathione, a major antioxidant system, but still, are protected against higher oxidative stress. We screened a panel of antioxidant genes using the TCGA and METABRIC databases and found that expression of the thioredoxin pathway genes is significantly upregulated in TNBC patients compared to non-TNBC patients and is correlated with adverse survival outcomes. Treatment with auranofin (AF), an FDA-approved thioredoxin reductase inhibitor caused specific cell death and impaired the growth of TNBC cells grown as spheroids. Furthermore, AF treatment exerted a significant in vivo antitumor activity in multiple TNBC models including the syngeneic 4T1.2 model, MDA-MB-231 xenograft and patient-derived tumor xenograft by inhibiting thioredoxin redox activity. We, for the first time, showed that AF increased CD8^+Ve T-cell tumor infiltration in vivo and upregulated immune checkpoint PD-L1 expression in an ERK1/2-MYC-dependent manner. Moreover, combination of AF with anti-PD-L1 antibody synergistically impaired the growth of 4T1.2 primary tumors. Our data provide a novel therapeutic strategy using AF in combination with anti-PD-L1 antibody that warrants further clinical investigation for TNBC patients.     

The Second Victim Phenomenon: How Are Midwives Affected?

Perinatal care providers are likely to encounter adverse events such as intrapartum emergencies, traumatic births, or maternal or fetal deaths. As a result of being directly or indirectly involved in an adverse event, health care providers can be considered second victims. The experience of the second victim phenomenon can lead to significant physical, psychological, and psychosocial sequelae that can negatively impact the provider's personal and professional life for either a short or long duration of time. When health care providers experience an adverse event, they may manifest symptoms of guilt, shame, blame, flashbacks, nightmares, insomnia, isolation, helplessness, and hopelessness, thereby becoming the second victim. Following an adverse event, health care providers who experience second victim phenomenon experience stages of recovery that influence subsequent professional and personal well‐being. Persons who experience the second victim phenomenon can incorporate self‐care behaviors to assist with recovery. Health care organizations have a responsibility to implement efficacious support programs that promote the provider's recovery and a return to safe and full function in the workplace.     

Damage-associated molecular pattern (DAMP) activation in melanoma: investigation of the immunogenic activity of 15-deoxy, Δ12,14 prostamide J2

Metastatic melanoma is the most deadly skin neoplasm in the United States. Outcomes for this lethal disease have improved dramatically due to the use of both targeted and immunostimulatory drugs. Immunogenic cell death (ICD) has emerged as another approach for initiating antitumor immunity. ICD is triggered by tumor cells that display damage-associated molecular patterns (DAMPs). These DAMP molecules recruit and activate dendritic cells (DCs) that present tumor-specific antigens to T cells which eliminate neoplastic cells. Interestingly, the expression of DAMP molecules occurs in an endoplasmic reticulum (ER) stress-dependent manner. We have previously shown that ER stress was required for the cytotoxic activity of the endocannabinoid metabolite, 15-deoxy, Δ^12,14 prostamide J₂ (15dPMJ₂). As such, the current study investigates whether 15dPMJ₂ induces DAMP signaling in melanoma. In B16F10 cells, 15dPMJ₂ caused a significant increase in the cell surface expression of calreticulin (CRT), the release of ATP and the secretion of high-mobility group box 1 (HMGB1), three molecules that serve as surrogate markers of ICD. 15dPMJ₂ also stimulated the cell surface expression of the DAMP molecules, heat shock protein 70 (Hsp70) and Hsp90. In addition, the display of CRT and ATP was increased by 15dPMJ₂ to a greater extent in tumorigenic compared to non-tumorigenic melanocytes. Consistent with this finding, the activation of bone marrow-derived DCs was upregulated in co-cultures with 15dPMJ₂-treated tumor compared to non-tumor melanocytes. Moreover, 15dPMJ₂-mediated DAMP exposure and DC activation required the electrophilic cyclopentenone double bond within the structure of 15dPMJ₂ and the ER stress pathway. These results demonstrate that 15dPMJ₂ is a tumor-selective inducer of DAMP signaling in melanoma.