Correction: Bayesian space-time SIR modeling of Covid-19 in two US states during the 2020-2021 pandemic.

[This corrects the article DOI: 10.1371/journal.pone.0278515.].

The impact of reproductive hormones on T cell immunity; normal and assisted reproductive cycles.

During pregnancy, a unique immune milieu is established systemically and locally at the maternal-fetal interface. While preparing for embryonic implantation, endometrial effectors significantly change their proportions and function, which are synchronized with hormonal changes. During assisted reproductive technology cycles, various cytokines, chemokines, and immune factors dynamically change with the altered receptor expressions on the immune effectors. Thus, the hormonal regulation of immune effectors is critical to maintaining the immune milieu. In this review, hormonal effects on T cell subsets are reviewed. Sex hormones affect T cell ontogeny and development, consequently affecting their functions. Like other T cell subsets, CD4+ T helper (Th) cells are modulated by estrogen, where low estrogen concentration promotes Th1-driven cell-mediated immunity in the uterus and in vitro by enhancing IFN-γ production, while a high estrogen level decreases it. The abundance and differentiation of T regulatory (Treg) cells are controlled by estrogen, inducing Treg expansion. Conversely, progesterone maintains immune homeostasis by balancing Th1/Th2 and Th17/Treg immunity, leading to maternal-fetal tolerance. Therefore, the understanding of the hormonal impact on various T cell subsets during the reproductive cycles is critical to improving reproductive outcomes in women with recurrent pregnancy losses, repeated implantation failures, and undergoing assisted reproductive cycles.

Geospatial disparities in survival of patients with breast cancer in sub-Saharan Africa from the African Breast Cancer-Disparities in Outcomes cohort (ABC-DO): a prospective cohort study.

BACKGROUND: There is an urgent need to improve breast cancer survival in sub-Saharan Africa. Geospatial barriers delay diagnosis and treatment, but their effect on survival in these settings is not well understood. We examined geospatial disparities in 4-year survival in the African Breast Cancer-Disparities in Outcomes cohort. METHODS: In this prospective cohort study, women (aged ≥18 years) newly diagnosed with breast cancer were recruited from eight hospitals in Namibia, Nigeria, South Africa, Uganda, and Zambia. They reported sociodemographic information in interviewer-administered questionnaires, and their clinical and treatment data were collected from medical records. Vital status was ascertained by contacting participants or their next of kin every 3 months. The primary outcome was all-cause mortality in relation to rural versus urban residence, straight-line distance, and modelled travel time to hospital, analysed using restricted mean survival time, Cox proportional hazards, and flexible parametric survival models. FINDINGS: 2228 women with breast cancer were recruited between Sept 8, 2014, and Dec 31, 2017. 127 were excluded from analysis (58 had potentially recurrent cancer, had previously received treatment, or had no follow-up; 14 from minority ethnic groups with small sample sizes; and 55 with missing geocoded home addresses). Among the 2101 women included in analysis, 928 (44%) lived in a rural area. 1042 patients had died within 4 years of diagnosis; 4-year survival was 39% (95% CI 36-42) in women in rural areas versus 49% (46-52) in urban areas (unadjusted hazard ratio [HR] 1·24 [95% CI 1·09-1·40]). Among the 734 women living more than 1 h from the hospital, the crude 4-year survival was 37% (95% CI 32-42) in women in rural areas versus 54% (46-62) in women in urban areas (HR 1·35 [95% CI 1·07-1·71] after adjustment for age, stage, and treatment status). Among women in rural areas, mortality rates increased with distance (adjusted HR per 50 km 1·04, 1·01-1·07) and travel time (adjusted HR per h 1·06, 1·02-1·10). Among women with early-stage breast cancer receiving treatment, women in rural areas had a strong survival disadvantage (overall HR 1·54, 1·14-2·07 adjusted for age and stage; >1 h distance adjusted HR 2·14, 1·21-3·78). INTERPRETATION: Geospatial barriers reduce survival of patients with breast cancer in sub-Saharan Africa. Specific attention is needed to support patients with early-stage breast cancer living in rural areas far from cancer treatment facilities. FUNDING: US National Institutes of Health (National Cancer Institute), Susan G Komen for the Cure, and the International Agency for Research on Cancer.

Characteristics and functions of memory regulatory T cells in normal pregnancy cycle and pregnancy complications.

Regulatory T cells (Tregs) are activated and expanded after exposure to fetal-specific (paternal) antigens. A proportion of Tregs differentiate into memory Tregs (mTregs), exhibiting immune memory function and exerting more potent immunosuppression than naive Tregs (nTregs). However, it is unclear how mTregs are regulated during normal and pathological pregnancies (e.g., gestational diabetes mellitus (GDM) and preeclampsia (PE)). In this study, PD-1, HLA-G, and HLA-DR expressions on memory CD4+ T cells, naive CD4+ T cells, Tregs, mTregs, and nTregs in healthy non-pregnant women (n=20), healthy first (n=20), second (n=20), and third-trimester women (n=20), postpartum women (n=20), GDM (n=20), and PE patients (n=20) were analyzed. The proportion of mTregs out of Tregs was increased (P<0.05) in the first trimester compared with that in non-pregnancy and reduced in the second and third trimesters. The proportions of PD-1+ Tregs and mTregs were significantly increased during the first trimester compared to those of non-pregnancy (P<0.01), reached their maximum in the second trimester. Moreover, the proportions of HLA-G+ memory CD4+ T cells, Tregs, and mTregs were increased in the first and second trimesters (P<0.01), reached their maximum in the third trimester. GDM patients were characterized by significantly lower percentages of PD-1+ and HLA-G+ mTregs (P<0.01), while PE patients were characterized by significantly lower percentages of HLA-G+ mTregs (P<0.01), compared with the healthy third-trimester women. In general, as demonstrated by this study, mTregs increase in number and enhance maternal-fetal immunoregulation during pregnancy, and their dysfunction can result in pregnancy complications such as GMD or PE.

Maternal exposure to pyrethroid insecticides during pregnancy and respiratory allergy symptoms among children participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE).

BACKGROUND: Pyrethroid insecticides use for indoor residual spraying (IRS) in malaria-endemic areas results in high levels of exposure to local populations. Pyrethroids may cause asthma and respiratory allergies but no prior study has investigated this question in an IRS area. METHODS: We measured maternal urinary concentrations of pyrethroid metabolites (cis-DBCA, cis-DCCA, trans-DCCA, 3-PBA) in samples collected at delivery from 751 mothers participating in the Venda Health Examination of Mothers, Babies, and their Environment (VHEMBE), a birth cohort study based in Limpopo, South Africa. At 3.5-year and 5-year follow-up visits, caregivers of 647 and 620 children, respectively, were queried about children's respiratory allergy symptoms based on validated instruments. We applied marginal structural models for repeated outcomes to estimate associations between biomarker concentrations and asthma diagnosis as well as respiratory allergy symptoms at ages 3.5 and 5 years. RESULTS: We found that a10-fold increase in maternal urinary cis-DCCA, trans-DCCA and 3-PBA concentrations were associated with more than a doubling in the risk of doctor-diagnosed asthma (cis-DCCA: RR = 2.1, 95% CI = 1.3, 3.3; trans-DCCA: RR = 2.1, 95% CI = 1.1, 3.9; 3-PBA: RR = 2.4, 95% CI = 1.0, 5.8) and an about 80% increase in the risk of wheezing or whistling in the chest (cis-DCCA: RR = 1.8, 95% CI = 1.1, 3.0; trans-DCCA: RR = 1.7, 95% CI = 1.1, 2.6; 3-PBA: RR = 1.8, 95% CI = 1.0, 3.3) and suspected asthma (cis-DCCA: RR = 1.8, 95% CI = 1.1, 3.1; trans-DCCA: RR = 1.8, 95% CI = 1.1, 2.8). We also observed that higher concentrations of cis-DBCA and 3-PBA were related to increases in the risks of dry cough at night (RR = 3.5, 95% CI = 1.3, 9.5) and seasonal rhinoconjunctivitis (RR = 2.0, 95% CI = 1.1, 3.9), respectively. CONCLUSION: Maternal exposure to pyrethroids may increase the risk of asthma and other respiratory allergy symptoms among preschool children from an IRS area.

Memory regulatory T cells in pregnancy.

Pregnancy requires the process of maternal immune tolerance to semi-allogeneic embryos. In contrast, an overreactive maternal immune system to embryo-specific antigens is likely to result in the rejection of embryos while damaging the invading placenta, such that the likelihood of adverse pregnancy outcomes can be increased. Regulatory T cells (Tregs) are capable of suppressing excessive immune responses and regulating immune homeostasis. When stimulating Tregs, specific antigens will differentiate into memory Tregs with long-term survival and rapid and powerful immune regulatory ability. Immunomodulatory effects mediated by memory Tregs at the maternal-fetal interface take on critical significance in a successful pregnancy. The impaired function of memory Tregs shows a correlation with various pregnancy complications (e.g., preeclampsia, gestational diabetes mellitus, and recurrent pregnancy losses). However, the differentiation process and characteristics of memory Tregs, especially their role in pregnancy, remain unclear. In this study, a review is presented in terms of memory Tregs differentiation and activation, the characteristics of memory Tregs and their role in pregnancy, and the correlation between memory Tregs and pregnancy complications. Furthermore, several potential therapeutic methods are investigated to restore the function of memory Tregs in accordance with immunopathologies arising from memory Tregs abnormalities and provide novel targets for diagnosing and treating pregnancy-associated diseases.

Poor ovarian response in assisted reproductive technology cycles is associated with anti-ovarian antibody and pro-inflammatory immune responses.

Anti-ovarian antibody (AOA) could be considered an independent marker for autoimmune ovarian disease and predicting future premature ovarian failure (POF). This study aims to investigate if AOA is associated with poor ovarian response (POR) and pro-inflammatory immune responses in women undergoing assisted reproductive technology (ART) cycles. Two hundred forty-eight women undergoing ART cycles were divided into four groups based on AOA test results and the presence of POR: POR(-)/AOA(-) group (N = 148), POR(+)/AOA(-) group (N = 34), POR (-)/AOA(+) group (N = 44), POR(+)/AOA(+) group (N = 22). The POR patients have a significantly higher prevalence of AOA than non-POR patients (P < 0.05). Peripheral blood CD56 + natural killer (NK) cell level (%), NK cytotoxicity, CD19 +CD5 + B-1 cell level (%), and IFN-γ/IL-10 producing T helper (Th) 1/Th2 cell ratios were significantly higher in POR(+)/AOA(+) group than those of other groups (P < 0.001, P < 0.005, P < 0.01, P < 0.05, respectively). TNF-α/IL-10 producing Th1/Th2 cell ratio of POR(+)/AOA(+) group was significantly higher than those of POR(+)/AOA(-) and POR(-)/AOA(-) groups (P < 0.05, respectively). Homocysteine and vitamin D levels of the POR(+)/AOA(+) group were significantly lower than those of other groups (P < 0.005, respectively). Plasminogen activator inhibiter-1 (PAI-1) level of POR(+)/AOA(+) group was significantly higher than that of POR(-)/AOA(-) group (P < 0.05). In the POR(+)/AOA(+) group, the prevalence of antiphospholipid antibodies was significantly higher than that of the POR(+)/AOA(-) group (P = 0.005). Women with autoimmune POR (POR(+)/AOA(+)) have dysregulated pro-inflammatory immune responses and metabolic factors. The diagnostic and therapeutic approaches for autoimmune POR should be differentiated from those for non-autoimmune POR.

The Association between Mediated Deprivation and Ovarian Cancer Survival among African American Women.

BACKGROUND: Deprivation indices are often used to adjust for socio-economic disparities in health studies. Their role has been partially evaluated for certain population-level cancer outcomes, but examination of their role in ovarian cancer is limited. In this study, we evaluated a range of well-recognized deprivation indices in relation to cancer survival in a cohort of self-identified Black women diagnosed with ovarian cancer. This study aimed to determine if clinical or diagnostic characteristics lie on a mediating pathway between socioeconomic status (SES) and deprivation and ovarian cancer survival in a minority population that experiences worse survival from ovarian cancer. METHODS: We used mediation analysis to look at the direct and indirect causal effects of deprivation indices with main mediators of the SEER stage at diagnosis and residual disease. The analysis employed Bayesian structural equation models with variable selection. We applied a joint Bayesian structural model for the mediator, including a Weibull mixed model for the vital outcome with deprivation as exposure. We selected modifiers via a Monte Carlo model selection procedure. RESULTS: The results suggest that high SES-related indices, such as Yost, Kolak urbanicity (URB), mobility (MOB) and SES dimensions, and concentrated disadvantage index (CDI), all have a significant impact on improved survival. In contrast, area deprivation index (ADI)/Singh, and area level poverty (POV) did not have a major impact. In some cases, the indirect effects have very wide credible intervals, so the total effect is not well estimated despite the estimation of the direct effect. CONCLUSIONS: First, it is clear that commonly used indices such as Yost, or CDI both significantly impact the survival experience of Black women diagnosed with epithelial ovarian cancer. In addition, the Kolak dimension indices (URB, MOB, mixed immigrant: MICA and SES) also demonstrate a significant association, depending on the mediator. Mediation effects differ according to the mediator chosen.

Evaluation of Bayesian spatiotemporal infectious disease models for prospective surveillance analysis.

BACKGROUND: COVID-19 brought enormous challenges to public health surveillance and underscored the importance of developing and maintaining robust systems for accurate surveillance. As public health data collection efforts expand, there is a critical need for infectious disease modeling researchers to continue to develop prospective surveillance metrics and statistical models to accommodate the modeling of large disease counts and variability. This paper evaluated different likelihoods for the disease count model and various spatiotemporal mean models for prospective surveillance. METHODS: We evaluated Bayesian spatiotemporal models, which are the foundation for model-based infectious disease surveillance metrics. Bayesian spatiotemporal mean models based on the Poisson and the negative binomial likelihoods were evaluated with the different lengths of past data usage. We compared their goodness of fit and short-term prediction performance with both simulated epidemic data and real data from the COVID-19 pandemic. RESULTS: The simulation results show that the negative binomial likelihood-based models show better goodness of fit results than Poisson likelihood-based models as deemed by smaller deviance information criteria (DIC) values. However, Poisson models yield smaller mean square error (MSE) and mean absolute one-step prediction error (MAOSPE) results when we use a shorter length of the past data such as 7 and 3 time periods. Real COVID-19 data analysis of New Jersey and South Carolina shows similar results for the goodness of fit and short-term prediction results. Negative binomial-based mean models showed better performance when we used the past data of 52 time periods. Poisson-based mean models showed comparable goodness of fit performance and smaller MSE and MAOSPE results when we used the past data of 7 and 3 time periods. CONCLUSION: We evaluate these models and provide future infectious disease outbreak modeling guidelines for Bayesian spatiotemporal analysis. Our choice of the likelihood and spatiotemporal mean models was influenced by both historical data length and variability. With a longer length of past data usage and more over-dispersed data, the negative binomial likelihood shows a better model fit than the Poisson likelihood. However, as we use a shorter length of the past data for our surveillance analysis, the difference between the Poisson and the negative binomial models becomes smaller. In this case, the Poisson likelihood shows robust posterior mean estimate and short-term prediction results.

Deprivation and segregation in ovarian cancer survival among African American women: a mediation analysis.

PURPOSE: Deprivation and segregation indices are often examined as possible explanations for observed health disparities in population-based studies. In this study, we assessed the role of recognized deprivation and segregation indices specifically as they affect survival in a cohort of self-identified Black women diagnosed with ovarian cancer who enrolled in the African American Cancer Epidemiology Study. METHODS: Mediation analysis was used to examine the direct and indirect effects between deprivation or segregation and overall survival via a Bayesian structural equation model with Gibbs variable selection. RESULTS: The results suggest that high socioeconomic status-related indices have an association with increased survival, ranging from 25% to 56%. In contrast, index of concentration at the extremes-race does not have a significant impact on overall survival. In many cases, the indirect effects have very wide credible intervals; consequently, the total effect is not well estimated despite the estimation of the direct effect. CONCLUSIONS: Our results show that Black women living in higher socioeconomic status neighborhoods are associated with increased survival with ovarian cancer using area-level economic indices such as Yost or index of concentration at the extremes-income. In addition, the Kolak urbanization index has a similar impact and highlights the importance of area-level deprivation and segregation as potentially modifiable social factors in ovarian cancer survival.

Increased serum IL-12 levels are associated with adverse IVF outcomes.

Interleukin-12 (IL-12) is involved in the occurrence and development of many diseases, such as preeclampsia, intrauterine growth restriction, preterm labor, and recurrent pregnancy losses. This study aimed to determine whether a high serum level of IL-12 was associated with adverse in vitro fertilization (IVF) outcomes. Included infertile women with high serum IL-12 levels who underwent IVF cycles and infertile controls with pure tubal etiology. The impact of serum IL-12 on baseline and clinical characteristics, immune-related indicators, IVF laboratory, and pregnancy outcomes were compared. In addition, the correlation of follicular fluid IL-12 and serum IL-12 level and the role of IL-12 in apoptosis of granulosa cells (GCs) was investigated. Women with high serum IL-12 levels had lower numbers of retrieved oocytes, embryos, perfect and available embryos, lower rates of perfect and available embryos, and blastocyst formation. Additionally, significantly higher levels of serum Th1, Th2, and Th17-related cytokines were observed in women with high serum IL-12 levels than in the controls. Meanwhile, the follicular fluid IL-12 levels were positively correlated with serum IL-12 levels, and IL-12 promoted apoptosis of GCs in vitro. We concluded that women with serum high IL-12 levels may have adverse IVF outcomes, partly by promoting apoptosis of GCs. Therefore, early screening for cytokines, especially IL-12, and appropriate consultation for couples receiving IVF-ET should be considered. In addition, specific immune and inflammatory mechanisms associated with high serum IL-12 levels should be further explored.

Exposure to pesticides and risk of Hodgkin lymphoma in an international consortium of agricultural cohorts (AGRICOH).

PURPOSE: Some pesticides may increase the risk of certain lymphoid malignancies, but few studies have examined Hodgkin lymphoma (HL). In this exploratory study, we examined associations between agricultural use of 22 individual active ingredients and 13 chemical groups and HL incidence. METHODS: We used data from three agricultural cohorts participating in the AGRICOH consortium: the French Agriculture and Cancer Cohort (2005-2009), Cancer in the Norwegian Agricultural Population (1993-2011), and the US Agricultural Health Study (1993-2011). Lifetime pesticide use was estimated from crop-exposure matrices or self-report. Cohort-specific covariate-adjusted overall and age-specific (< 40 or ≥ 40 years) hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression and combined using random effects meta-analysis. RESULTS: Among 316 270 farmers (75% male) accumulating 3 574 815 person-years at risk, 91 incident cases of HL occurred. We did not observe statistically significant associations for any of the active ingredients or chemical groups studied. The highest risks of HL overall were observed for the pyrethroids deltamethrin (meta-HR = 1.86, 95% CI 0.76-4.52) and esfenvalerate (1.86, 0.78-4.43), and inverse associations of similar magnitude were observed for parathion and glyphosate. Risk of HL at ≥ 40 years of age was highest for ever-use of dicamba (2.04, 0.93-4.50) and lowest for glyphosate (0.46, 0.20-1.07). CONCLUSION: We report the largest prospective investigation of these associations. Nonetheless, low statistical power, a mixture of histological subtypes and a lack of information on tumour EBV status complicate the interpretability of the results. Most HL cases occurred at older ages, thus we could not explore associations with adolescent or young adult HL. Furthermore, estimates may be attenuated due to non-differential exposure misclassification. Future work should aim to extend follow-up and refine both exposure and outcome classification.

Peripheral blood natural killer cell cytotoxicity in recurrent miscarriage: a systematic review and meta-analysis.

Dysregulated natural killer (NK) cells have been associated with recurrent miscarriages (RM). Studies have suggested that high peripheral blood NK cell cytotoxicities (pNKCs) are associated with an increased risk of RM. The aim of this systematic review (SR) and meta-analysis (MAs) is to investigate the difference in pNKC between nonpregnant and pregnant women with RM and controls and determine whether pNKC is reduced by immunotherapy. We searched the PubMed/Medline, Embase, and Web of Science databases. The MAs were conducted to compare pNKCs between women with and without RM before and during pregnancy as well as pre- and post-immunotherapy. Risk of bias in nonrandomized studies was assessed by the Newcastle-Ottawa Scale. Statistical analysis was performed using the Review Manager software. A total of 19 studies were included in the SR and 14 studies in the MAs. The MAs revealed higher pNKCs among nonpregnant women with RM compared to controls (MD, 7.99 95 %CI 6.40-9.58; p < 0.00001). pNKCs were also higher in pregnant women with RM than in pregnant controls (MD, 8.21 95 %CI 6.08-10.34; p < 0.00001). Women with RM showed significantly decreased pNKCs after the immunotherapy compared to before (MD, -8.20 95 %CI -10.20 - -6.19; p < 0, 00001). Additionally, there is an association between high pNKCs and the risk of pregnancy loss in women with RM. However, included studies showed substantial heterogeneities regarding the inclusion criteria of patients, techniques measuring pNKC, and types of immunotherapies. More studies are needed to evaluate the clinical efficiency of pNKCs in managing RM.

Immune checkpoint inhibitors and reproductive failures.

The human conceptus is a semi-allograft, which is antigenically foreign to the mother. Hence, the implantation process needs mechanisms to prevent allograft rejection during successful pregnancy. Immune checkpoints are a group of inhibitory pathways expressed on the surface of various immune cells in the form of ligand receptors. Immune cells possess these pathways to regulate the magnitude of immune responses and induce maternal-fetal tolerance. Briefly, 1) CTLA-4 can weaken T cell receptor (TCR) signals and inhibit T cell response; 2) The PD-1/PD-L1 pathway can reduce T cell proliferation, enhance T cell anergy and fatigue, reduce cytokine production, and increase T regulatory cell activity to complete the immunosuppression; 3) TIM3 interacts with T cells by binding Gal-9, weakening Th1 cell-mediated immunity and T cell apoptosis; 4) The LAG-3 binding to MHC II can inhibit T cell activation by interfering with the binding of CD4 to MHC II, and; 5) TIGIT can release inhibitory signals to NK and T cells through the ITIM structure of its cytoplasmic tail. Therefore, dysregulated immune checkpoints or the application of immune checkpoint inhibitors may impair human reproduction. This review intends to deliver a comprehensive overview of immune checkpoints in pregnancy, including CTLA-4, PD-1/PD-L1, TIM-3, LAG-3, TIGIT, and their inhibitors, reviewing their roles in normal and pathological human pregnancies.

Subjective and objective sleep quality does not predict behavioural episodic foresight in younger or older adults.

Episodic foresight refers to one's capacity to use imagined scenarios to guide future-directed behaviors. It is important in facilitating complex activities of daily living, such as managing finances. Broader literature shows that older adults perform more poorly on tests of episodic foresight relative to their younger counterparts. At the same time, age-related changes in sleep often contribute to age-related decline in other cognitive abilities known to support episodic foresight, such as memory. No study to date has tested whether sleep quality is associated with episodic foresight when it is measured behaviorally; or whether this relationship is moderated by age. To address this, in the present study healthy younger (n = 39) and older (n = 41) adults were asked to wear an actigraphy watch and self-report their sleep quality for seven nights. Participants then completed the virtual-week foresight task-a behavioral assessment of episodic foresight. Neither objective or subjective sleep quality predicted episodic foresight outcomes, and this was not moderated by age group. Bayesian analyses provided evidence in favour of the null hypotheses. These results suggest that sleep quality (at least in healthy adult populations) may not be linked to episodic foresight.

Unexplained recurrent pregnancy loss: Novel causes and advanced treatment.

In this study, recent research focusing on recurrent pregnancy loss (RPL) are reviewed. Recurrent pregnancy loss is a devastating reproductive health burden that affects about 5% of couples trying to conceive globally. Currently, there are few evidence-based diagnostic and treatment strategies for RPL. More so, the number of unexplained etiology cases in patients with RPL arrives at 50%. Here, we discuss the progress in diagnosis and treatment of unexplained RPL, as well as recommended treatment strategies and controversial etiologies.

Bayesian space-time SIR modeling of Covid-19 in two US states during the 2020-2021 pandemic.

This paper describes the Bayesian SIR modeling of the 3 waves of Covid-19 in two contrasting US states during 2020-2021. A variety of models are evaluated at the county level for goodness-of-fit and an assessment of confounding predictors is also made. It is found that models with three deprivation predictors and neighborhood effects are important. In addition, the work index from Google mobility was also found to provide an increased explanation of the transmission dynamics.

Anticardiolipin and/or anti-ß2-glycoprotein-I antibodies are associated with adverse IVF outcomes.

Objective: The purpose of the study is to evaluate the effects of anticardiolipin (aCL) and/or anti-ß2-glycoprotein-I (aß2GPI) antibodies, namely antiphospholipid antibodies (aPL), on in vitro fertilization (IVF) outcomes. Materials and methods: The study group comprised infertile women with aPL undergoing IVF-ET cycles. Controls were infertile women with tubal etiology without aPL. The impact of aPL on reproductive outcomes, such as oocyte quality, embryo quality, and implantation capacity, was compared between the study group and controls. Additionally, peripheral blood T cell subsets, such as T helper (Th)1, Th2, Th17, and T regulatory (Treg) cells and cytokines, were analyzed by the flow cytometry. Differences between the study group and controls were analyzed. Results: A total of 132 infertile women, including 44 women with aPL, and 88 controls were sequentially recruited for this study. Women with aPL had lower numbers of total and perfect/available embryos and lower rates of MII oocytes, blastocyst formation, perfect and available embryos, implantation, clinical pregnancy, and take-home baby. Additionally, imbalanced Th1/Th2 and Th17/Treg ratios, significantly higher levels of serum IL-2, TNF-α, IFN-γ, and IL-17A, and a significantly lower serum IL-4 were noticed in women with aPL compared to controls. Conclusion: Women with aPL such as aCL and/or aß2GPI antibodies were associated with adverse IVF outcomes. Early screening for aPL and appropriate consultation for couples undergoing IVF should be considered. In addition, underlying immunopathology and inflammatory immune mechanisms associated with aPL should be further explored.

Developmental and Momentary Dynamics in the Onset and Maintenance of Nonsuicidal Self-Injurious Behavior and Borderline Personality Disorder.

PURPOSE OF REVIEW: Traditional conceptualizations of both nonsuicidal self-injury (NSSI) and borderline personality disorder (BPD) typically rely on static and unidirectional, linear associations between key biopsychosocial vulnerabilities. Instead, we argue that utilizing a complex dynamic systems view of NSSI and BPD will advance the field, as such conceptual models allow for analysis of bottom-up effects for key vulnerabilities on disorder and behavior emergence, as well as top-down effects of the emergent disorder on underlying vulnerabilities. RECENT FINDINGS: Following the presentation of a novel framework highlighting momentary and developmental dynamics, we explore several advances in the field that exhibit key dynamic qualities or inform dynamic conceptualizations of NSSI and BPD. At the momentary dynamic level, several advances are being made with multimethod and repeated assessment approaches, as well as advanced bidirectional and complex modeling procedures. Additional progress is being made at the developmental dynamic level, although several questions have arisen regarding the problem of onset and subsequent trajectory, particularly with issues such as pain perception and the interplay between interpersonal, emotional, and behavioral symptoms before and after treatment. Self-injury and BPD both exhibit substantial momentary and developmental dynamics in underlying vulnerabilities, including potential variance in momentary dynamics as a function of psychopathological developmental stage (e.g., onset versus maintenance versus recovery). Recent work has highlighted the necessity of utilizing multimodal research to encapsulate a holistic view of the interplay of several vulnerability factors, the developmental importance of assessment timing, and the need to examine the dynamic interplay between affect, behavior, and interpersonal experiences in BPD and/or NSSI. Research also indicated substantial variation in key vulnerability factors at both between- and within-person levels, highlighting the utility of harnessing statistical models that allow for the simultaneous incorporation of numerous variables at both levels and across several time points. As such, by using a complex dynamic systems conceptualization, we can begin to better understand integrated connections between key vulnerabilities, how they collectively interact in the short term, and how changes in the dynamic interplay between vulnerabilities may arise over the long term and with successful treatment.