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The article discusses the broader implications of overturning Roe v Wade in June 2022, highlighting concerns beyond abortion statistics, such as maternal and infant mortality. Topics include the potential mental health repercussions of restrictive abortion policies, a study's findings on increased anxiety and depression symptoms in trigger-ban states post-Dobbs, and the importance of clinicians' awareness in states with abortion restrictions.

A long standing challenge in biological and artificial intelligence is to understand how new knowledge can be constructed from known building blocks in a way that is amenable for computation by neuronal circuits. Here we focus on the task of storage and recall of structured knowledge in long-term memory. Specifically, we ask how recurrent neuronal networks can store and retrieve multiple knowledge structures. We model each structure as a set of binary relations between events and attributes (attributes may represent e.g., temporal order, spatial location, role in semantic structure), and map each structure to a distributed neuronal activity pattern using a vector symbolic architecture scheme.We then use associative memory plasticity rules to store the binarized patterns as fixed points in a recurrent network. By a combination of signal-to-noise analysis and numerical simulations, we demonstrate that our model allows for efficient storage of these knowledge structures, such that the memorized structures as well as their individual building blocks (e.g., events and attributes) can be subsequently retrieved from partial retrieving cues. We show that long-term memory of structured knowledge relies on a new principle of computation beyond the memory basins. Finally, we show that our model can be extended to store sequences of memories as single attractors. [ABSTRACT FROM AUTHOR]

Recognition of RNA by receptors of the innate immune system is regulated by various posttranslational modifications. Different single 2′-O-ribose (2′-O-) methylations have been shown to convert TLR7/TLR8 ligands into specific TLR8 ligands, so we investigated whether the position of 2′-O-methylation is crucial for its function. To this end, we designed different 2′-O-methylated RNA oligoribonucleotides (ORN), investigating their immune activity in various cell systems and analyzing degradation under RNase T2 treatment. We found that the 18S rRNA-derived TLR7/8 ligand, RNA63, was differentially digested as a result of 2′-O-methylation, leading to variations in TLR8 and TLR7 inhibition. The suitability of certain 2′-O-methylated RNA63 derivatives as TLR8 agonists was further demonstrated by the fact that other RNA sequences were only weak TLR8 agonists. We were thus able to identify specific 2′-O-methylated RNA derivatives as optimal TLR8 ligands. [ABSTRACT FROM AUTHOR]

Background: To inform effective genomic medicine strategies, it is important to examine current approaches and gaps in well-established applications. Lynch syndrome (LS) causes 3–5% of colorectal cancers (CRCs). While guidelines commonly recommend LS tumour testing of all CRC patients, implementation in health systems is known to be highly variable. To provide insights on the heterogeneity in practice and current bottlenecks in a high-income country with universal healthcare, we characterise the approaches and gaps in LS testing and referral in seven Australian hospitals across three states. Methods: We obtained surgery, pathology, and genetics services data for 1,624 patients who underwent CRC resections from 01/01/2017 to 31/12/2018 in the included hospitals. Results: Tumour testing approaches differed between hospitals, with 0–19% of patients missing mismatch repair deficiency test results (total 211/1,624 patients). Tumour tests to exclude somatic MLH1 loss were incomplete at five hospitals (42/187 patients). Of 74 patients with tumour tests completed appropriately and indicating high risk of LS, 36 (49%) were missing a record of referral to genetics services for diagnostic testing, with higher missingness for older patients (0% of patients aged ≤ 40 years, 76% of patients aged > 70 years). Of 38 patients with high-risk tumour test results and genetics services referral, diagnostic testing was carried out for 25 (89%) and identified a LS pathogenic/likely pathogenic variant for 11 patients (44% of 25; 0.7% of 1,624 patients). Conclusions: Given the LS testing and referral gaps, further work is needed to identify strategies for successful integration of LS testing into clinical care, and provide a model for hereditary cancers and broader genomic medicine. Standardised reporting may help clinicians interpret tumour test results and initiate further actions. [ABSTRACT FROM AUTHOR]

Summary: Background: Previous studies suggest that polygenic risk scores (PRSs) may improve melanoma risk stratification. However, there has been limited independent validation of PRS‐based risk prediction, particularly assessment of calibration (comparing predicted to observed risks). Objectives: To evaluate PRS‐based melanoma risk prediction in prospective UK and Australian cohorts with European ancestry. Methods: We analysed invasive melanoma incidence in the UK Biobank (UKB; n = 395 647, 1651 cases) and a case‐cohort nested within the Melbourne Collaborative Cohort Study (MCCS, Australia; n = 4765, 303 cases). Three PRSs were evaluated: 68 single‐nucleotide polymorphisms (SNPs) at 54 loci from a 2020 meta‐analysis (PRS68), 50 SNPs significant in the 2020 meta‐analysis excluding UKB (PRS50) and 45 SNPs at 21 loci known in 2018 (PRS45). Ten‐year melanoma risks were calculated from population‐level cancer registry data by age group and sex, with and without PRS adjustment. Results: Predicted absolute melanoma risks based on age and sex alone underestimated melanoma incidence in the UKB [ratio of expected/observed cases: E/O = 0·65, 95% confidence interval (CI) 0·62–0·68] and MCCS (E/O = 0·63, 95% CI 0·56–0·72). For UKB, calibration was improved by PRS adjustment, with PRS50‐adjusted risks E/O = 0·91, 95% CI 0·87–0·95. The discriminative ability for PRS68‐ and PRS50‐adjusted absolute risks was higher than for risks based on age and sex alone (Δ area under the curve 0·07–0·10, P < 0·0001), and higher than for PRS45‐adjusted risks (Δ area under the curve 0·02–0·04, P < 0·001). Conclusions: A PRS derived from a larger, more diverse meta‐analysis improves risk prediction compared with an earlier PRS, and might help tailor melanoma prevention and early detection strategies to different risk levels. Recalibration of absolute risks may be necessary for application to specific populations. [ABSTRACT FROM AUTHOR]

Objective: We examined whether contraceptive method type, satisfaction with use, and confidence in correct use were independently associated with switching intentions, a precursor of switching behaviors.Study Design: Data were from a probability-based sample survey carried out in Delaware and Maryland in 2016 and 2017 among women ages 18 to 44. Women's current contraceptive methods were classified into 5 categories: coitally-dependent methods (barrier methods, withdrawal, and natural family planning); oral contraceptive pills, patches, and rings; injections; implants; and intrauterine contraception (IUC). Satisfaction, confidence, and switching intentions were dichotomized into being very versus less satisfied, being completely versus less confident, and having very low versus not very low switching intentions. We conducted binomial logistic regression to examine whether method type, satisfaction, and confidence were independently associated with having very low switching intentions, adjusting for a range of covariates including sociodemographics, perceived health, religious attendance frequency, sexual, contraceptive, and reproductive experiences, and state of residence (Maryland or Delaware).Results: Among 1,077 women using reversible contraception, those using IUC relative to implants, pills, patches, or rings, and coitally-dependent methods were more likely to have very low switching intentions. Among all survey respondents, those who were very satisfied and those who were completely confident in correct use were also more likely to report very low switching intentions.Conclusions: Using IUC, being very satisfied, and being very confident in correct use were independently associated with having very low switching intentions.Implications: These results suggest that those using IUC have very low intentions to switch for reasons in addition to satisfaction-level with their method. Other aspects of using IUC such as ease of use, perceived barriers to switching, or having very low switching intentions before beginning IUC may be such reasons. [ABSTRACT FROM AUTHOR]

Exposures to cancer risk factors such as smoking and alcohol are not mutually independent. We aimed to identify risk factor exposure patterns and their associations with sociodemographic characteristics and cancer incidence. We considered 120,771 female and, separately, 100,891 male participants of the Australian prospective cohort 45 and Up Study. Factor analysis grouped 36 self-reported variables into 8 combined factors each for females (largely representing 'smoking', 'alcohol', 'vigorous exercise', 'age at childbirth', 'Menopausal Hormone Therapy', 'parity and breastfeeding', 'standing/sitting', 'fruit and vegetables') and males (largely representing 'smoking', 'alcohol', 'vigorous exercise', 'urology and health', 'moderate exercise', 'standing/sitting', 'fruit and vegetables', 'meat and BMI'). Associations with cancer incidence were investigated using multivariable logistic regression (4–8 years follow-up: 6193 females, 8749 males diagnosed with cancer). After multiple-testing correction, we identified 10 associations between combined factors and cancer incidence for females and 6 for males, of which 14 represent well-known relationships (e.g. bowel cancer: females 'smoking' factor Odds Ratio (OR) 1.16 (95% Confidence Interval (CI) 1.08–1.25), males 'smoking' factor OR 1.15 (95% CI 1.07–1.23)), providing evidence for the validity of this approach. The catalogue of associations between exposure patterns, sociodemographic characteristics, and cancer incidence can help inform design of future studies and targeted prevention programmes. [ABSTRACT FROM AUTHOR]

Objective: A previous Australian study compared the observed numbers of cancer cases and deaths in 2007 with the expected numbers based on 1987 rates. This study examines the impact of cancer rate changes over the 20-year period 1996–2015, for people aged under 75 years. Results: The overall age-standardised cancer incidence rate increased from 350.7 in 1995 to 364.4 per 100,000 in 2015. Over the period 1996–2015, there were 29,226 (2.0%) more cases (males: 5940, 0.7%; females: 23,286, 3.7%) than expected numbers based on 1995 rates. Smaller numbers of cases were observed compared to those expected for cancers of the lung for males and colorectum, and cancers with unknown primary. Larger numbers of cases were observed compared to those expected for cancers of the prostate, thyroid and female breast. The overall age-standardised cancer mortality rate decreased from 125.6 in 1995 to 84.3 per 100,000 in 2015. During 1996 to 2015 there were 106,903 (− 20.6%) fewer cancer deaths (males: − 69,007, − 22.6%; females: − 37,896, − 17.9%) than expected based on the 1995 mortality rates. Smaller numbers of deaths were observed compared to those expected for cancers of the lung, colorectum and female breast, and more cancer deaths were observed for liver cancer. [ABSTRACT FROM AUTHOR]

Objective: To examine whether depression, intimate partner violence, and other psychosocial stressors were independently associated with effectiveness level of postpartum contraception among women who recently had an unintended birth.Methods: We analyzed cross-sectional data from PRAMS (the Pregnancy Risk Assessment Monitoring System) to identify women who had an unintended birth between 2012 and 2015. The effectiveness level of the contraceptive method was coded into one of five categories based on the postpartum contraceptive method that women were using: none, less effective (withdrawal, rhythm, condoms, or other barrier), moderately effective (pill, patch, ring, or shot), long-acting reversible contraception (LARC; intrauterine devices or implants), and sterilization (female or male sterilization). Multinomial logistic regression was used to examine whether prepregnancy depression or elevated postpartum depressive symptoms, intimate partner violence before or during pregnancy, and number of psychosocial stressors before birth were associated with effectiveness level of method (compared with no method), in models adjusted for sociodemographics, pregnancy context, and postpartum context.Results: Complete data were available for 56,445 (88.2%) of the 64,030 eligible women: 24.2% experienced depression; 5.3% experienced intimate partner violence; and 16.8% experienced five or more psychosocial stressors around the time of pregnancy or birth. In adjusted models, experiencing intimate partner violence and more stressors lowered women's relative risk of using sterilization, LARC, moderately effective methods, and less-effective contraceptive methods relative to no method use. Only prepregnancy depression was associated with using sterilization compared with no method use.Conclusions: Experiencing intimate partner violence and having more psychosocial stressors were each independently associated with not using a postpartum contraceptive method. Standardized screening for psychosocial factors during prenatal and postpartum care should be integrated, and practices that encourage the discussion of patients' psychosocial experiences and postpartum contraception use together are warranted. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Large‐scale studies investigating health‐related quality of life (HRQL) in cancer survivors are limited. This study aims to investigate HRQL and its relation to optimism and social support among Australian women following a cancer diagnosis.Data were from the Australian Longitudinal Study on Women's Health, a large cohort study (n = 14,715; born 1946–51), with 1428 incident cancer cases ascertained 1996–2017 via linkage to the Australian Cancer Database. HRQL was measured using the Short Form‐36 (median 1.7 years post‐cancer‐diagnosis). Multivariable linear regression was performed on each HRQL domain, separately for all cancers combined, major cancer sites, and cancer‐free peers.Higher optimism and social support were significantly associated with better HRQL across various domains in women with and without a cancer diagnosis (p < 0.05). Mean HRQL scores across all domains for all cancer sites were significantly higher among optimistic versus not optimistic women with cancer (p < 0.05). Adjusting for sociodemographic and other health conditions, lower optimism was associated with reduced scores across all domains, with greater reductions in mental health (adjusted mean difference (AMD) = −11.54, p < 0.01) followed by general health (AMD = −11.08, p < 0.01). Social support was less consistently related to HRQL scores, and following adjustment was only significantly associated with social functioning (AMD = −7.22, p < 0.01) and mental health (AMD = −6.34, p < 0.01).Our findings highlight a strong connection between optimism, social support, and HRQL among cancer survivors. Providing psychosocial support and addressing behavioral and socioeconomic factors and other health conditions associated with optimism and social support may improve HRQL. [ABSTRACT FROM AUTHOR]

Highlights • Quantified the number of lung cancer deaths averted in Australia through tobacco control. • Almost 2 million lung cancer deaths have already been prevented over the period 1956–2100. • Lung cancer will continue to be a significant public health concern in Australia. • Achieving zero smoking by 2025 would result in 360,000 more lung cancer deaths being averted by 2100. • Highlighted the urgent need for more effective and targeted tobacco control strategies to be implemented. Abstract Objectives To estimate the number of past and future lung cancer deaths that have already been averted by tobacco control initiatives in Australia, and to estimate the number of additional deaths averted under various smoking scenarios. Methods We predicted lung cancer mortality rates and case numbers to 2100 using a previously validated generalized linear model based on age, birth cohort and population cigarette smoking exposure. We estimated the impact of various tobacco control scenarios: 'actual tobacco control' (incorporating the aggregate effect of past and current taxation, plain packaging, mass media campaigns and other initiatives) and scenarios where 10%, 5% and 0% smoking prevalence was achieved by 2025, all of which were compared to a counterfactual scenario with the highest historical smoking consumption level continuing into the future as if no tobacco control initiatives had been implemented. Results Without tobacco control, there would have been an estimated 392,116 lung cancer deaths over the period 1956–2015; of these 20% (78,925 deaths; 75,839 males, 3086 females) have been averted due to tobacco control. However, if past and current measures continue to have the expected effect, an estimated 1.9 million deaths (1,579,515 males, 320,856 females; 67% of future lung cancer deaths) will be averted in 2016–2100. If smoking prevalence is reduced to 10%, 5% or 0% by 2025, an additional 97,432, 208,714 or 360,557 deaths could be averted from 2016 to 2100, respectively. Conclusion Tobacco control in Australia has had a dramatic impact on the number of people dying from lung cancer. Several hundred thousand more lung cancer deaths could be averted over the course of the century if close-to-zero smoking prevalence could be achieved in the next decade. [ABSTRACT FROM AUTHOR]

Background: Cervical screening and human papillomavirus (HPV) vaccination have been implemented in most high-income countries; however, coverage is low in low-income and middle-income countries (LMICs). In 2018, the Director-General of WHO announced a call to action for the elimination of cervical cancer as a public health problem. WHO has called for global action to scale-up vaccination, screening, and treatment of precancer, early detection and prompt treatment of early invasive cancers, and palliative care. An elimination threshold in terms of cervical cancer incidence has not yet been defined, but an absolute rate of cervical cancer incidence could be chosen for such a threshold. In this study, we aimed to quantify the potential cumulative effect of scaled up global vaccination and screening coverage on the number of cervical cancer cases averted over the 50 years from 2020 to 2069, and to predict outcomes beyond 2070 to identify the earliest years by which cervical cancer rates could drop below two absolute levels that could be considered as possible elimination thresholds-the rare cancer threshold (six new cases per 100 000 women per year, which has been observed in only a few countries), and a lower threshold of four new cases per 100 000 women per year.Methods: In this statistical trends analysis and modelling study, we did a statistical analysis of existing trends in cervical cancer worldwide using high-quality cancer registry data included in the Cancer Incidence in Five Continents series published by the International Agency for Research on Cancer. We then used a comprehensive and extensively validated simulation platform, Policy1-Cervix, to do a dynamic multicohort modelled analysis of the impact of potential scale-up scenarios for cervical cancer prevention, in order to predict the future incidence rates and burden of cervical cancer. Data are presented globally, by Human Development Index (HDI) category, and at the individual country level.Findings: In the absence of further intervention, there would be 44·4 million cervical cancer cases diagnosed globally over the period 2020-69, with almost two-thirds of cases occurring in low-HDI or medium-HDI countries. Rapid vaccination scale-up to 80-100% coverage globally by 2020 with a broad-spectrum HPV vaccine could avert 6·7-7·7 million cases in this period, but more than half of these cases will be averted after 2060. Implementation of HPV-based screening twice per lifetime at age 35 years and 45 years in all LMICs with 70% coverage globally will bring forward the effects of prevention and avert a total of 12·5-13·4 million cases in the next 50 years. Rapid scale-up of combined high-coverage screening and vaccination from 2020 onwards would result in average annual cervical cancer incidence declining to less than six new cases per 100 000 individuals by 2045-49 for very-high-HDI countries, 2055-59 for high-HDI countries, 2065-69 for medium-HDI countries, and 2085-89 for low-HDI countries, and to less than four cases per 100 000 by 2055-59 for very-high-HDI countries, 2065-69 for high-HDI countries, 2070-79 for medium-HDI countries, and 2090-2100 or beyond for low-HDI countries. However, rates of less than four new cases per 100 000 would not be achieved in all individual low-HDI countries by the end of the century. If delivery of vaccination and screening is more gradually scaled up over the period 2020-50 (eg, 20-45% vaccination coverage and 25-70% once-per-lifetime screening coverage by 2030, increasing to 40-90% vaccination coverage and 90% once-per-lifetime screening coverage by 2050, when considered as average coverage rates across HDI categories), end of the century incidence rates will be reduced by a lesser amount. In this scenario, average cervical cancer incidence rates will decline to 0·8 cases per 100 000 for very-high-HDI countries, 1·3 per 100 000 for high-HDI countries, 4·4 per 100 000 for medium-HDI countries, and 14 per 100 000 for low-HDI countries, by the end of the century.Interpretation: More than 44 million women will be diagnosed with cervical cancer in the next 50 years if primary and secondary prevention programmes are not implemented in LMICs. If high coverage vaccination can be implemented quickly, a substantial effect on the burden of disease will be seen after three to four decades, but nearer-term impact will require delivery of cervical screening to older cohorts who will not benefit from HPV vaccination. Widespread coverage of both HPV vaccination and cervical screening from 2020 onwards has the potential to avert up to 12·5-13·4 million cervical cancer cases by 2069, and could achieve average cervical cancer incidence of around four per 100 000 women per year or less, for all country HDI categories, by the end of the century. A draft global strategy to accelerate cervical cancer elimination, with goals and targets for the period 2020-30, will be considered at the World Health Assembly in 2020. The findings presented here have helped inform initial discussions of elimination targets, and ongoing comparative modelling with other groups is supporting the development of the final goals and targets for cervical cancer elimination.Funding: National Health and Medical Research Council (NHMRC) Australia, part-funded via the NHMRC Centre of Excellence for Cervical Cancer Control (C4; APP1135172). [ABSTRACT FROM AUTHOR]

Abstract Rationale More thoroughly understanding the association between elevated depressive symptoms and effectiveness level of contraceptive method selected at a reproductive health visit could help women prevent unintended pregnancy. Objective This study examined how the association between both current and past depressive symptoms and effectiveness level of contraceptive method selected at a clinic visit varies by type of reproductive health visit. Methods Current and past depressive symptoms and contraceptive method selected were assessed among 1215 women aged 18–25 years seeking general reproductive health or abortion services at 40 community clinics throughout the United States. Using standard categories of effectiveness based on pregnancy rates during typical use, women's contraceptive method selected was coded as a low (e.g., no method, withdrawal, condoms), moderately (pill, patch, ring, or shot), or highly effective method (IUD, sterilization, implant). Depression status was divided into four categories: 1) no elevated depressive symptoms ever, 2) current elevated depressive symptoms only, 3) past elevated depressive symptoms only, and 4) past and current elevated depressive symptoms. Visit type, general reproductive health versus abortion care, was a moderator. The interaction effect between depressive symptoms and visit type on contraceptive method effectiveness level chosen was estimated with multinomial logistic regression analyses. Results In general reproductive health visits, having both elevated current and past depressive symptoms increased women's likelihood of choosing low versus moderately effective methods (RRR = 5.63, 95% CI = 2.31 to 13.71, p <.0005). In contrast, among abortion patients, only current elevated depressive symptoms were associated with choosing high versus moderate effectiveness methods (RRR = 1.74, 95% CI = 1.06 to 2.86, p =.029). Conclusion Results suggest that considering both women's current and past elevated depressive symptoms and the type of reproductive health visit may assist providers in helping women prevent unintended pregnancy. Highlights • Elevated depressive symptoms predicted contraceptive effectiveness method chosen. • Current depressive symptoms predicted choosing highly effective methods. • Current and past depressive symptoms predicted choosing low effective methods. [ABSTRACT FROM AUTHOR]

Objectives To identify molecular differences between chondrocytes from osteophytic and articular cartilage tissue from OA patients. Methods We investigated genes and pathways by combining genome-wide DNA methylation, RNA sequencing and quantitative proteomics in isolated primary chondrocytes from the cartilaginous layer of osteophytes and matched areas of low- and high-grade articular cartilage across nine patients with OA undergoing hip replacement surgery. Results Chondrocytes from osteophytic cartilage showed widespread differences to low-grade articular cartilage chondrocytes. These differences were similar to, but more pronounced than, differences between chondrocytes from osteophytic and high-grade articular cartilage, and more pronounced than differences between high- and low-grade articular cartilage. We identified 56 genes with significant differences between osteophytic chondrocytes and low-grade articular cartilage chondrocytes on all three omics levels. Several of these genes have known roles in OA, including ALDH1A2 and cartilage oligomeric matrix protein, which have functional genetic variants associated with OA from genome-wide association studies. An integrative gene ontology enrichment analysis showed that differences between osteophytic and low-grade articular cartilage chondrocytes are associated with extracellular matrix organization, skeletal system development, platelet aggregation and regulation of ERK1 and ERK2 cascade. Conclusion We present a first comprehensive view of the molecular landscape of chondrocytes from osteophytic cartilage as compared with articular cartilage chondrocytes from the same joints in OA. We found robust changes at genes relevant to chondrocyte function, providing insight into biological processes involved in osteophyte development and thus OA progression. [ABSTRACT FROM AUTHOR]

Objective: We examined whether preabortion depressive symptoms were associated with contraceptive method effectiveness level chosen among women seeking abortions.Study Design: Three-hundred and forty-seven young, low-income women 18 years or older who were seeking abortions at 3 community reproductive health clinics in Northern California were recruited to participate in a study on contraceptive decision making. We classified women into choosing low-, moderate- or high-effectiveness contraceptive methods based on typical-use failure rates. We used the Center for Epidemiologic Studies Depression scale to assess depressive symptoms as a continuous and dichotomous variable. Using the standard cutoff of 20, women who scored at or above this were considered depressed for the dichotomous measure. We used multinomial logistic regression to examine the association between preabortion depressive symptoms and contraceptive effectiveness level chosen to use after an abortion, adjusting for sociodemographics, abortion characteristics, pregnancy history, future pregnancy desires, relationship characteristics and adverse experiences.Results: After adjusting for covariates, we found that a one-unit increase in depressive symptoms was associated with a higher likelihood of choosing low- versus moderate- [adjusted odd ratio (aOR)=1.05, 95% confidence interval (CI): 1.01-1.10, p<.02] and high-effectiveness methods (aOR=1.05, 95% CI: 1.002-1.10, p<.05). Furthermore, women scoring above the cutoff for depression were more likely to choose low- versus moderate-effectiveness methods (aOR=4.56, 95% CI: 1.27-16.32, p=.02).Conclusions: More preabortion depressive symptoms were independently associated with choosing low- versus moderate- and high-effectiveness contraceptives.Implications: These findings together with other findings show that preabortion depressive symptoms do not uniformly influence effectiveness level of contraceptive method selected to use after an abortion. Reproductive health care providers should consider the impact of women's psychological symptoms on their contraceptive decision making. [ABSTRACT FROM AUTHOR]

ABSTRACT Metal-on-metal (MOM) hip resurfacing has recently been a popular prosthesis choice for the treatment of symptomatic arthritis, but results in the release of cobalt and chromium ions into the circulation that can be associated with adverse clinical effects. The mechanism underlying these effects remains unclear. While chromosomal aneuploidy and translocations are associated with this exposure, the presence of subtle structural epigenetic modifications in patients with MOM joint replacements remains unexplored. Consequently, we analyzed whole blood DNA methylation in 34 OA patients with MOM hip resurfacing (MOM HR) compared to 34 OA patients with non-MOM total hip replacements (non-MOM THR), using the genome-wide Illumina HumanMethylation 450k BeadChip. No probes showed differential methylation significant at 5% false-discovery rate (FDR). We also tested association of probe methylation levels with blood chromium and cobalt levels directly; there were no significant associations at 5% FDR. Finally, we used the 'epigenetic clock' to compare estimated to actual age at sample for all individuals. We found no significant difference between MOM HR and non-MOM THR, and no correlation of age acceleration with blood metal levels. Our results suggest the absence of large methylation differences systemically following metal exposure, however, larger sample sizes will be required to identify potential small effects. Any DNA methylation changes that may occur in the local periprosthetic tissues remain to be elucidated. © 2017 The Authors. Orthopaedic Research Society. Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:2323-2328, 2017. [ABSTRACT FROM AUTHOR]

Policymakers need to know the abortion attitudes of those they represent. In addition, inaccurate knowledge of or negative attitudes toward abortion may lead to more abortion stigma, which may adversely affect abortion access and women's health. The first objective was to examine whether individual's abortion knowledge and attitudes changed during 2016–2020 in Delaware and Maryland. The second was to explore whether personally knowing someone who had an abortion in 2020 was associated with knowledge, attitudes, and changes in them from 2016 to 2020. Data were from the Delaware [Maryland] Survey of Women, a probability sample that was self-administered via web and mail (N = 1106). Women aged 18–44 from Delaware and Maryland were followed from 2016/2017 to 2019/2020. Outcomes were each two facets of abortion knowledge (perceived safety and perceived access) and abortion attitudes (acceptability and advocacy self-identification), and changes in these outcomes. The main predictor was whether women personally knew someone who had an abortion. Covariates included state, religiosity, pregnancy history, and sociodemographic factors. We used logistic models with inverse probability weights. The percentage of respondents who changed between the first and third waves varied: 46% changed their views on safety and accessibility; 21% changed their views on acceptability; and 25% changed their advocacy self-identification. Knowing someone personally who had an abortion was associated with changing toward viewing abortion as very safe and towards pro-choice, and with not changing towards viewing abortion as wrong or identifying as pro-life. These findings suggest abortion knowledge and attitudes are not fixed but change over time, and knowing someone who had an abortion or having an abortion oneself was associated with changing toward positive attitudes and accurate knowledge. Sharing one's abortion experience with others one knows may reduce negative attitudes and inaccurate knowledge regarding abortion. • More women changed toward viewing abortion as very safe than very dangerous. • More women changed toward viewing abortion as acceptable than wrong. • More women changed toward pro-choice than pro-life. • Knowing someone who had an abortion was associated with abortion knowledge changes. • Knowing someone who had an abortion was associated with abortion attitude changes. [ABSTRACT FROM AUTHOR]

Understanding whether postpartum depressive (PPD) symptoms vary by pregnancy intention and use of fertility treatments has implications for reproductive health policies and practices. The first aim of this study was to determine whether PPD symptoms differ between women who had unintended pregnancies, women who conceived spontaneously and were unsure about their pregnancy intention, women who used fertility treatments to conceive, and women who conceived spontaneously and intentionally. The second aim was to determine whether PPD symptoms differed based on the fertility treatment used to conceive (fertility drugs only, medicated insemination, or assisted reproductive technology [ART]). Data from the Pregnancy Risk Assessment Monitoring System (2012–2019), a cross-sectional survey administered to women throughout the U.S. who have recently given birth, was used to carry out our aims. For the first aim (unweighted N = 243,677), compared to women who had spontaneous, intended pregnancies, women who had unintended pregnancies (OR: 1.32, 95% CI: 1.26–1.39, p < 0.01) and those with spontaneous pregnancies who were unsure about their intention (OR: 1.30, 95% CI: 1.23–1.38, p < 0.01) had higher odds of elevated PPD symptoms, adjusting for a range of covariates. Women who conceived with fertility treatments did not have higher odds of elevated PPD symptoms (OR: 0.97, 95% CI: 0.84–1.10, p = 0.61). For the second aim (unweighted N = 2,210), compared to those in the ART group, those who conceived using only fertility enhancing drugs had greater odds of developing elevated PPD symptoms (OR: 2.00, 95% CI: 1.24–3.24, p < 0.01). These findings suggest that giving birth to an unintended pregnancy in the U.S. increases risk of elevated PPD symptoms. While overall women who conceive with the use of fertility treatments are not at increased risk of experiencing elevated PPD symptoms, there may be variability in risk based on the specific fertility treatments used. • Postpartum depression (PPD) is a serious problem. • Unintended and unsure pregnancies had the highest risk of PPD. • Pregnancies conceived intentionally and spontaneously had moderate risk of PPD. • Pregnancies conceived with fertility treatments had the lowest risk of PPD. • Risk of PPD varied by type of fertility treatment used to conceive. [ABSTRACT FROM AUTHOR]

ABSTRACT Osteoarthritis (OA) is a common complex disease of high public health burden. OA is characterized by the degeneration of affected joints leading to pain and reduced mobility. Over the last few years, several studies have focused on the genomic changes underpinning OA. Here, we provide a comprehensive overview of genome-wide, non-hypothesis-driven functional genomics (methylation, gene, and protein expression) studies of knee and hip OA in humans. Individual studies have generally been limited in sample size and hence power, and have differed in their approaches; nonetheless, some common themes have started to emerge, notably the role played by biological processes related to the extracellular matrix, immune response, the WNT pathway, angiogenesis, and skeletal development. Larger-scale studies and streamlined, robust methodologies will be needed to further elucidate the biological etiology of OA going forward. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1105-1110, 2016. [ABSTRACT FROM AUTHOR]

Rationale Most research in mental health and abortion has examined factors associated with post-abortion psychological health. However, research that follows women from before to after their abortion consistently finds that depressive, anxiety, and stress symptoms are highest just before an abortion compared to any time afterwards. Objective This finding suggests that studies investigating psychosocial factors related to pre-abortion mental health are warranted. Methods The current study uses data from 353 women seeking abortions at three community reproductive health clinics to examine predictors of pre-abortion psychological health. Drawing from three perspectives in the abortion and mental health literature, common risks, stress and coping, and sociocultural context, we conducted multivariable analyses to examine the contribution of important factors on depressive, anxiety, and stress symptoms just before an abortion, including sociodemographics, abortion characteristics, childhood adversities, recent adversities with an intimate partner, relationship context, future pregnancy desires, and perceived abortion stigma. Results Childhood and partner adversities, including reproductive coercion, were associated with negative mental health symptoms, as was perceived abortion stigma. Before perceived abortion stigma was entered into the model, 18.6%, 20.7%, and 16.8% of the variance in depressive, anxiety, and stress symptoms respectively, was explained. Perceived abortion stigma explained an additional 13.2%, 9.7%, and 10.7% of the variance in depressive, anxiety, and stress symptoms pre-abortion. Conclusion This study, one of the first to focus on pre-abortion mental health as an outcome, suggests that addressing stigma among women seeking abortions may significantly lower their psychological distress. [ABSTRACT FROM AUTHOR]

Maternal postpartum depression has been shown to be one of the main predictors of externalizing and internalizing behaviors in toddlers and adolescents. Research suggests that presence of such behaviors can be observed as early as infancy. The current study uses longitudinal data from 247 mothers to examine the relationship between postpartum depressive symptoms at 8 weeks and the infant's externalizing and internalizing behaviors at 12 months. In unadjusted linear regression models, there were associations between postpartum depressive symptoms and infant externalizing behaviors (β=0.082, SE=0.032, p=0.012) and internalizing behaviors (β=0.111, SE=0.037, p=0.003). After controlling for potential confounding factors, including maternal age, race, education, home ownership, smoking status in the postpartum period, marital status, parenting stress, and happiness from becoming a parent, the associations between postpartum depressive symptoms and infant externalizing (β=0.051, SE=0.034, p=0.138) and internalizing behaviors (β=0.077, SE=0.040, p=0.057) were reduced and became non-significant. Furthermore, in these models the total amount of variance explained was 17.2% (p<0.0001) for externalizing behaviors and 10.5% (p<0.01) for internalizing behaviors; the only significant predictor of externalizing behaviors was maternal age (β=-0.074, SE=0.030, p=0.014), and of internalizing behaviors was white non-Hispanic ethnicity (β=-1.33, SE=0.378, p=0.0005). A combined effect of the confounding factors seems to explain the finding of no significant independent association between postpartum depressive symptoms and infant externalizing and internalizing behaviors. [ABSTRACT FROM AUTHOR]

Background/aims To analyse appearance, development over 2 years and characteristic patterns of reticular drusen (RDR) in eyes with high-risk characteristics for progression to late-stage age-related macular degeneration (AMD) (age-related eye disease study stages 3 and 4). Methods 98 eyes of 98 patients (median age 73.4 years, IQR [69-78]) participating in the Molecular Diagnostic of Age-related Macular Degeneration study were included. Simultaneous combined confocal scanning laser ophthalmoscopy (cSLO) and spectraldomain optical coherence tomography (SD-OCT) imaging as well as colour-fundus imaging was performed at baseline and at 24 months. Two independent graders determined the presence of different RDR phenotypes (cSLO modalities: 'dot', 'target', 'ribbon'; SD-OCT: 'spike' and 'wave') at both visits. Results At baseline, RDR were detected in 44% (κ 0.96). They were always visible in near-infrared reflectance images. Detection rate was 42% using fundus autofluorescence (FAF), 39% on SD-OCT (waves: 100%; spikes: 90%) and 26% on blue reflectance (BR). 'Dots' were more frequently detected in all imaging compared with 'targets'. The 'ribbon' pattern was most frequently observed in colour images, BR images and FAF images. In 8 of the 48 eyes with no signs of RDR in any imaging modality at baseline, the development of RDR lesions was observed at 24 months (16.6%, κ 0.42). Conclusions Careful and meticulous analysis using three-dimensional in vivo imaging reveals distinct characteristic RDR patterns underlying detectable dynamic changes over a period of 2 years. RDR in eyes with early or intermediate AMD are a common observation but appear to be overall less common compared with eyes with geographic atrophy. [ABSTRACT FROM AUTHOR]

Fundus autofluorescence (FAF) imaging allows for topographic mapping of intrisnic fluorophores in the retinal pigment epithelial cell monolayer, as well as mapping of other fluorophores that may occur with disease in the outer retina and the sub-neurosensory space. FAF imaging provides information not obtainable with other imaging modalities. Near-infrared fundus autofluorescence images can also be obtained in vivo, and may be largely melanin-derived. FAF imaging has been shown to be useful in a wide spectrum of macular and retinal diseases. The scope of applications now includes identification of diseased RPE in macular/retinal diseases, elucidating pathophysiological mechanisms, identification of early disease stages, refined phenotyping, identification of prognostic markers for disease progression, monitoring disease progression in the context of both natural history and interventional therapeutic studies, and objective assessment of luteal pigment distribution and density as well as RPE melanin distribution. Here, we review the use of FAF imaging in various phenotypic manifestations of dry AMD. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate longitudinal variations of reticular drusen (RDR) in age-related macular degeneration using confocal scanning laser ophthalmoscopy (cSLO), near-infrared reflectance (NIR) and spectral-domain optical coherence tomography (SD-OCT) imaging. Methods: Eighteen eyes of 12 patients with RDR (median observational time 5 months, range 3-10) were included. Changes over time in the en face cSLO NIR images, the identical SD-OCT B scan (simple approach) and the dense SD-OCT volume scans (11 µm between B scans, detailed approach) for 5 preselected RDR lesions were analysed, respectively. Results: Nineteen of 90 (21%) lesions were no longer detectable at the follow-up examination with the simple SD-OCT approach (increase 7/decrease 48/unchanged 15/not gradable 1). By contrast, no disappearance of single lesions was noted for both cSLO (3/8/61/18) and detailed SD-OCT image analysis (67/22/1/0). Within the dense SD-OCT volume scan, a median change of individual lesion height of 10 µm/year was determined. Conclusions: The findings indicate a recordable progression of RDR lesions in lateral and vertical dimensions. Using dense SD-OCT volume scans, individual RDR lesion progression can be quantified and may be applied in future longitudinal studies. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To examine whether a first abortion increases risk of mental health disorders compared with a first childbirth with and without considering prepregnancy mental health and adverse exposures, childhood economic status, miscarriage history, age at first abortion or childbirth, and race or ethnicity.Methods: A cohort study compared rates of mental disorders (anxiety, mood, impulse-control, substance use, eating disorders, and suicidal ideation) among 259 women postabortion and 677 women postchildbirth aged 18-42 years at the time of interview from The National Comorbidity Survey-Replication.Results: The percentage of women with no, one, two, and three or more mental health disorders before their first abortion was 37.8%, 19.7%, 15.2%, and 27.3% and before their first childbirth was 57.9%, 19.6%, 9.2%, and 13.3%, respectively, indicating that women in the abortion group had more prior mental health disorders than women in the childbirth group (P<.001). Although in unadjusted Cox proportional hazard models, abortion compared with childbirth was associated with statistically significant higher hazards of postpregnancy mental health disorders, associations were reduced and became nonstatistically significant for five disorders after adjusting for the aforementioned factors. Hazard ratios and associated 95% confidence intervals dropped from 1.52 (1.08-2.15) to 1.12 (0.87-1.46) for anxiety disorders; from 1.56 (1.23-1.98) to 1.18 (0.88-1.56) for mood disorders; from 1.62 (1.02-2.57) to 1.10 (0.75-1.62) for impulse-control disorders; from 2.53 (1.09-5.86) to 1.82 (0.63-5.25) for eating disorders; and from 1.62 (1.09-2.40) to 1.25 (0.88-1.78) for suicidal ideation. Only the relationship between abortion and substance use disorders remained statistically significant, although the hazard ratio dropped from 3.05 (1.94-4.79) to 2.30 (1.35-3.92).Conclusions: After accounting for confounding factors, abortion was not a statistically significant predictor of subsequent anxiety, mood, impulse-control, and eating disorders or suicidal ideation. LEVEL OF EVEDIENCE: II. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine whether a first abortion increases risk of mental health disorders compared with a first childbirth with and without considering prepregnancy mental health and adverse exposures, childhood economic status, miscarriage history, age at first abortion or childbirth, and race or ethnicity. METHODS: A cohort study compared rates of mental disorders (anxiety, mood, impulse-control, substance use, eating disorders, and suicidal ideation) among 259 women postabortion and 677 women postchild birth aged 18-42 years at the time of interview from The National Comorbidity Survey-Replication. RESULTS: The percentage of women with no, one, two, and three or more mental health disorders before their first abortion was 37.8%, 19.7%, 15.2%, and 27.3% and before their first childbirth was 57.9%, 19.6%, 9.2%, and 13.3%, respectively, indicating that women in the abortion group had more prior mental health disorders than women in the childbirth group (P<.001). Although in unadjusted Cox proportional hazard models, abortion compared with childbirth was associated with statistically significant higher hazards of postpregnancy mental health disorders, associations were reduced and became nonstatistically significant for five disorders after adjusting for the aforementioned factors. Hazard ratios and associated 95% confidence intervals dropped from 1.52 (1.08-2.15) to 1.12 (0.87-1.46) for anxiety disorders; from 1.56 (1.23-1.98) to 1.18 (0.88-1.56) for mood disorders; from 1.62 (1.02-2.57) to 1.10 (0.75-1.62) for impulse-control disorders; from 2.53 (1.09-5.86) to 1.82 (0.63-5.25) for eating disorders; and from 1.62 (1.09-2.40) to 1.25 (0.88-1.78) for suicidal ideation. Only the relationship between abortion and sub-stance use disorders remained statistically significant, although the hazard ratio dropped from 3.05 (1.94-4.79) to 2.30 (1.35-3.92). CONCLUSIONS: After accounting for confounding factors, abortion was not a statistically significant predictor of subsequent anxiety, mood, impulse-control, and eating disorders or suicidal ideation. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We investigated whether more psychological distress before an abortion is associated with the effectiveness of contraception selected (low, moderate, or high effectiveness) at an abortion clinic visit. Method: Using data from 253 women attending an urban abortion clinic that primarily serves low-income women, we tested the association between pre-abortion psychological distress and the effectiveness level of post-abortion contraceptive choice. Based on typical use failure rates, we classified effectiveness of contraceptive choice into three levels—low, moderate, and high effectiveness. We measured psychological distress with four validated measures of depressive, anxious, and stress symptoms, and negative affect, as well as with a global measure comprising these four measures. We used multivariable ordinal logistic regression to measure the association of each psychological distress measure with post-abortion contraceptive method effectiveness level, adjusting for sociodemographic factors, pregnancy history, trimester of abortion, and importance of avoiding pregnancy in the next year. Results: We found that compared to women experiencing less stress symptoms, negative affect and global psychological distress, women experiencing more stress symptoms [AOR=1.028, 95% CI: 1.001–1.050], negative affect [AOR=1.05, 95% CI: 1.01–1.09] and global psychological distress [AOR=1.46, 95% CI: 1.09–1.95] were more likely to choose more effective versus less effective methods, p<.05, in adjusted models. Using dichotomous psychological measures we found similar results. Conclusions: Women experiencing more psychological distress before an abortion selected more effective contraceptive methods after their abortion. Future research should examine whether this distress is associated with subsequent contraceptive use or continuation. Implications: The current study suggests that contraceptive providers should not assume that women experiencing more psychological distress prefer to use less effective contraceptive methods. [Copyright &y& Elsevier]

Autism spectrum disorder (ASD) is a highly heritable complex neurodevelopmental condition characterized by impairments in social interaction and communication and restricted and repetitive behaviors. Although roles for both de novo and familial genetic variation have been documented, the underlying disease mechanisms remain poorly elucidated. In this study, we defined and explored distinct etiologies of genetic variants that affect genes regulated by Fragile-X mental retardation protein (FMRP), thought to play a key role in neuroplasticity and neuronal translation, in ASD-affected individuals. In particular, we developed the Trend test, a pathway-association test that is able to robustly detect multiple-hit etiologies and is more powerful than existing approaches. Exploiting detailed spatiotemporal maps of gene expression within the human brain, we identified four discrete FMRP-target subpopulations that exhibit distinct functional biases and contribute to ASD via different types of genetic variation. We also demonstrated that FMRP target genes are more likely than other genes with similar expression patterns to contribute to disease. We developed the hypothesis that FMRP targets contribute to ASD via two distinct etiologies: (1) ultra-rare and highly penetrant single disruptions of embryonically upregulated FMRP targets (“single-hit etiology”) or (2) the combination of multiple less penetrant disruptions of nonembryonic, synaptic FMRP targets (“multiple-hit etiology”). The Trend test provides rigorous support for a multiple-hit genetic etiology in a subset of autism cases and is easily extendible to combining information from multiple types of genetic variation (i.e., copy-number and exome variants), increasing its value to next-generation sequencing approaches. [Copyright &y& Elsevier]

The author comments on a study about the relationship between abortion and mental health published in this issue of the journal. She points out the inadequacy of the study's design which questioned whether abortion reduces mental health risks in women. She argues that women having unwanted or unintended pregnancies who choose not to seek abortions are very different from those seeking abortions for mental health reasons.

Abstract: Although many studies have found an association between childhood adversities and mental health disorders, few have examined whether childhood adversities are linked to having abortions. This research investigates the association between a range of childhood adversities and risk of abortion in part to identify which adversities should be considered when examining the association between abortion and subsequent mental health. Using the U.S. National Comorbidity Survey-Replication (NCS-R), we tested the association between 10 childhood adversities and risk of 0, 1, or multiple abortions among 1511 women ages 18–41. We employed multinomial logistic regression to examine the independent association between each childhood adversity and number of subsequent abortions, controlling for sociodemographic factors, total number of pregnancies, and each adversity. Women who had experienced two or more personal safety threats, one parental mental illness, or two or more parental mental illnesses while growing up were more likely subsequently to have multiple versus no abortions [Relative Risk Ratio (RRR) = 9.87, 95% CI: 2.45–39.72; OR = 2.81, 95% CI: 1.27–6.21; RRR = 5.28, 95% CI: 1.60–17.38, respectively], and multiple versus one abortion [RRR = 13.33, 95% CI: 2.48–71.68; RRR = 2.17, 95% CI: 1.03–4.56; RRR = 3.67, 95% CI: 1.15–11.76, respectively]. Women who had experienced childhood physical abuse were more likely to have one compared to no abortions [RRR = 2.00; 1.19–3.34]. These results suggest that some childhood adversities may partially explain the association between abortion and mental health. Accordingly, they should be considered in future research examining the link between abortion and mental health. [Copyright &y& Elsevier]

Abstract: Similar to other reviews within the last 4 years, a thorough review by the Royal College of Psychiatrists, published in December 2011, found that compared to delivery of an unintended pregnancy, abortion does not increase women''s risk of mental health problems. In contrast, a meta-analysis published in September 2011 concluded that abortion increases women''s risk of mental health problems by 81% and that 10% of mental health problems are attributable to abortions. Like others, we strongly question the quality of this meta-analysis and its conclusions. Here we detail seven errors of this meta-analysis and three significant shortcomings of the included studies because policy, practice and the public have been misinformed. These errors and shortcomings render the meta-analysis'' conclusions invalid. [Copyright &y& Elsevier]

Objectification theory contends that women are socialized to view their body as an object to be evaluated by others (Fredickson and Roberts ). In contrast, pregnancy may be a time that women are more attuned to their body's functionality. Extending objectification theory, we investigate relationships among body surveillance, awareness and appreciation of body functionality, depressive symptoms, and prenatal health behaviors among an on-line sample of 156 predominantly White, middle-class pregnant women from throughout the U.S recruited through maternity stores, message boards, listservs, and snowballing techniques. We examine whether higher levels of awareness and appreciation of body functionality may attenuate, and thereby possibly protect women from the negative effects of high body surveillance. We found that higher body surveillance was associated with depressive symptoms and, although not significant, tended to be associated with engagement in unhealthy prenatal behaviors. Awareness and appreciation of body functionality were each associated with fewer depressive symptoms and less engagement in unhealthy prenatal behaviors. Supporting our hypotheses, we found that at higher levels of appreciation of body functionality, the relationship between body surveillance and engagement in unhealthy behaviors was attenuated. However, in contrast to our hypotheses, the relationship between body surveillance and depression was stronger at higher levels of awareness of body functionality, and attenuated at lower levels. These findings suggest appreciation of body functionality may buffer negative effects of body surveillance. Future research examining these relationships over the course of pregnancy, and among ethnically and socioeconomically diverse women, is needed. [ABSTRACT FROM AUTHOR]

This study examines the risk of depression, suicidal ideation, and lower self-esteem following an abortion versus a delivery, with and without adjusting for important correlates. Using the National Comorbidity Survey, we tested how first pregnancy outcome (abortion vs. delivery) related to subsequent major depression, suicidal ideation, and self-esteem. Models controlling for risk factors, such as background and economic factors, prepregnancy violence experience, and prepregnancy mental health, as well as a model with all risk factors, were examined. When no risk factors were entered in the model, women who had abortions were more likely to have subsequent depression, OR = 1.53, 95% CI [1.05-2.22], and suicidal ideation, OR = 2.02, 95% CI [1.40-2.92], but they were not more likely to have lower self-esteem, B = −.02. When all risk factors were entered, pregnancy outcome was not significantly related to later depression, OR = 0.87, 95% CI [0.54-1.37], and suicidal ideation, OR = 1.19, 95% CI [0.70-2.02]. Predictors of mental health following abortion and delivery included prepregnancy depression, suicidal ideation, and sexual violence. Policies and practices implemented in response to the claim that abortion hurts women are not supported by our findings. Efforts to support women's mental health should focus on known risk factors, such as gender-based violence and prior mental health problems, rather than abortion history. [ABSTRACT FROM AUTHOR]

Abstract: Using the US National Comorbidity Survey (NCS), published an analysis indicating that compared to women who had never had an abortion, women who had reported an abortion were at an increased risk of several anxiety, mood, and substance use disorders. Here, we show that those results are not replicable. That is, using the same data, sample, and codes as indicated by those authors, it is not possible to replicate the simple bivariate statistics testing the relationship of ever having had an abortion to each mental health disorder when no factors were controlled for in analyses ( in ). Furthermore, among women with prior pregnancies in the NCS, we investigated whether having zero, one, or multiple abortions (abortion history) was associated with having a mood, anxiety, or substance use disorder at the time of the interview. In doing this, we tested two competing frameworks: the abortion-as-trauma versus the common-risk-factors approach. Our results support the latter framework. In the bivariate context when no other factors were included in models, abortion history was not related to having a mood disorder, but it was related to having an anxiety or substance use disorder. When prior mental health and violence experience were controlled in our models, no significant relation was found between abortion history and anxiety disorders. When these same risk factors and other background factors were controlled, women who had multiple abortions remained at an increased risk of having a substance use disorder compared to women who had no abortions, likely because we were unable to control for other risk factors associated with having an abortion and substance use. Policy, practice, and research should focus on assisting women at greatest risk of having unintended pregnancies and having poor mental health—those with violence in their lives and prior mental health problems. [Copyright &y& Elsevier]

Purpose: To determine microstructural retinal alterations associated with reticular drusen in patients with age-related macular degeneration (AMD) using high-resolution in vivo imaging techniques. Design: Retrospective case series. Participants: A total of 116 eyes of 78 AMD patients with reticular drusen were examined. Methods: Simultaneous spectral-domain optical coherence tomography (SD OCT; 870 nm, 40 000 A-scans/sec) and near-infrared confocal scanning laser ophthalmoscopy (cSLO; 830 nm) were performed using a combined imaging instrument (Spectralis HRA+OCT, Heidelberg Engineering, Heidelberg, Germany). Individual anatomic layers in SD OCT were evaluated and correlated to en face cSLO fundus imaging. Main Outcome Measures: Description of corresponding structural changes in areas of reticular drusen. Results: Reticular drusen appeared as an interlacing network of round or oval irregularities by near-infrared cSLO reflectance imaging. On SD OCT, reticular drusen corresponded to marked changes at a level anterior to the retinal pigment epithelium (RPE) and Bruch''s membrane complex to the interface of inner and outer photoreceptor segment layer (IPRL). Individual reticular drusen correlated to focal elevations of the IPRL, accumulation of highly reflective material below the IPRL, and an increased distance between the IPRL and RPE. Conclusions: The findings indicate that the morphologic substrate of reticular drusen is the accumulation of highly reflective material within outer retinal layers anterior to the RPE. This is in contrast to previous assumptions pointing toward a localization of abnormal material at the level of the inner choroid. Although the origin of the material is unknown, the results may indicate a role for primary abnormalities in the neurosensory retina. Because reticular drusen represent high-risk markers for the progression of AMD, their ready identification is relevant both for natural history studies as well as for interventional trials. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Using data from the United States National Survey of Family Growth (NSFG) and the National Comorbidity Survey (NCS), we conducted secondary data analyses to examine the relationship of abortion, including multiple abortions, to anxiety after first pregnancy outcome in two studies. First, when analyzing the NSFG, we found that pre-pregnancy anxiety symptoms, rape history, age at first pregnancy outcome (abortion vs. delivery), race, marital status, income, education, subsequent abortions, and subsequent deliveries accounted for a significant association initially found between first pregnancy outcome and experiencing subsequent anxiety symptoms. We then tested the relationship of abortion to clinically diagnosed generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), and social anxiety disorder, using NCS data. Contrary to findings from our analyses of the NSFG, in the NCS analyses we did not find a significant relationship between first pregnancy outcome and subsequent rates of GAD, social anxiety, or PTSD. However, multiple abortions were found to be associated with much higher rates of PTSD and social anxiety; this relationship was largely explained by pre-pregnancy mental health disorders and their association with higher rates of violence. Researchers and clinicians need to learn more about the relations of violence exposure, mental health, and pregnancy outcome to avoid attributing poor mental health solely to pregnancy outcomes. [Copyright &y& Elsevier]

Background To improve melanoma early detection, tools to predict personal risk based on genetic information (polygenic risk scores, PRS) have been developed, but require external validation. Methods We analysed invasive melanoma incidence in UK Biobank (UKB; n = 395,647; 1,651 cases) and the Melbourne Collaborative Cohort Study (MCCS, Australia; n = 4,765; 303 cases). Three PRS were evaluated: 68 genetic variants (SNPs) at 54 loci from a 2020 meta-analysis (PRS68); 50 SNPs significant in the 2020 meta-analysis excluding UKB (PRS50); 45 SNPs at 21 loci known pre-2020 (PRS45). 10-year melanoma risks were calculated from population-level cancer registry data by age group and sex, with and without PRS adjustment. Results All PRS were strongly associated with melanoma incidence, including after adjustment for age, sex, ethnicity, and ease of tanning. Predicted absolute melanoma risks based on age and sex alone underestimated melanoma incidence in UKB (ratio expected/observed cases E/O=0.65, 95% confidence interval 0.62-0.68) and MCCS (E/O=0.65, 0.57-0.73). For UKB, this was reduced by PRS-adjustment, e.g. PRS50-adjusted risks E/O=0.91 (0.87-0.95). Discriminative ability for PRS68- and PRS50-adjusted absolute risks was higher than for risks based on age and sex alone (deltaAUC 0.07-0.1, p < 0.0001), and higher than for PRS45-adjusted risks (deltaAUC 0.02-0.04, p < 0.001). Conclusions A PRS derived from a larger, more diverse meta-analysis improves melanoma risk prediction compared to an earlier PRS. Re-calibration of absolute risks may be necessary for application to specific populations. Key messages A genetic score can improve prediction of melanoma risk and might help tailor melanoma prevention and early detection strategies to different risk levels. [ABSTRACT FROM AUTHOR]

As a result of a viral infection, viral genomes are not only recognized by RIG-I, but also lead to the activation of RNase L, which cleaves cellular RNA to generate the endogenous RIG-I ligand (eRL). The eRL was previously identified as a specific sequence derived from the internal transcribed spacer region 2, which bears a 2′3′ cyclic phosphate instead of the common 5′ triphosphate. By now, the generation of the eRL and its immunostimulatory effect were shown both in vitro and in reporter systems. In this work, we aimed to elucidate whether the eRL is also generated in Influenza A (IAV) and vesicular stomatitis virus (VSV) infected cells. RNA was extracted from virus-infected cells and used for immunostimulations as well as specific PCR-strategies to detect eRL cleavage. We show that the eRL is generated in IAV infected HEK293 cells, but we could not detect specific eRL fragments in VSV infected cells. Further, RIG-I mediated IFN-response depends not only on viral genomes but also on the eRL, as immunostimulatory properties remain present under 5′triphosphate degrading conditions. In summary, we prove the IAV infection induced eRL generation in HEK293 cells, amplifying the innate immune response. [ABSTRACT FROM AUTHOR]

We present GeneNet Toolbox for MATLAB (also available as a set of standalone applications for Linux). The toolbox, available as command-line or with a graphical user interface, enables biologists to assess connectivity among a set of genes of interest (‘seed-genes’) within a biological network of their choosing. Two methods are implemented for calculating the significance of connectivity among seed-genes: ‘seed randomization’ and ‘network permutation’. Options include restricting analyses to a specified subnetwork of the primary biological network, and calculating connectivity from the seed-genes to a second set of interesting genes. Pre-analysis tools help the user choose the best connectivity-analysis algorithm for their network. The toolbox also enables visualization of the connections among seed-genes. GeneNet Toolbox functions execute in reasonable time for very large networks (~10 million edges) on a desktop computer. [ABSTRACT FROM AUTHOR]

Purpose: Lung cancer (LC) in never-smoking individuals would rank as Australia's eighth most deadly cancer, yet risk factors remain uncertain. We investigated demographic, lifestyle and health-related exposures for LC among never-smoking Australians. Methods: Using the prospective 45 and Up Study with 267,153 New South Wales (NSW) residents aged ≥ 45 years at recruitment (2006–2009), we quantified the relationship of 20 potential exposures with LC among cancer-free participants at baseline who self-reported never smoking. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for incident LC were estimated using Cox regression. The NSW Cancer, Lifestyle and Evaluation of Risk (CLEAR) Study, a case–control study including 10,781 NSW residents aged ≥ 18 years (2006–2014), was used to examine 16 potential LC exposures among cancer-free never-smoking participants. Adjusted odds ratios (OR) and 95% CI of LC were estimated using logistic regression. Results: There were 226 LC cases among 132,354 cancer-free 45 and Up Study participants who reported never smoking, with a median follow-up of 5.41 years. The CLEAR Study had 58 LC cases and 1316 cancer-free controls who had never smoked. Analyses of both datasets showed that Asian-born participants had a higher risk of LC than those born elsewhere: cohort, adjusted HR = 2.83 (95% CI 1.64–4.89) and case–control, adjusted OR = 3.78 (1.19–12.05). No significant association with LC was found for other exposures. Conclusion: Our findings support the growing evidence that never-smoking, Asian-born individuals are at higher risk of developing LC than those born elsewhere. Ethnicity could be considered when assessing potential LC risk among never-smoking individuals. [ABSTRACT FROM AUTHOR]

A recent analysis from the Turnaway study focused on women who were just under the gestational limit of a clinic and received an abortion and those who had first trimester abortions to examine trends in decisional rightness and negative and positive emotions over 5 years after the abortion. Specifically, Rocca et al. (in press) analyzed these data and found that women were overwhemingly sure of their decision: 95% felt their decision was the right one at each assessment after their abortion, and the predicted probability of abortion being the right decision was 99% at 5 years afterwards. Relief was the most common emotion felt by women, and negative emotions or decision regret did not emerge over time. These results and others from studies conducted globally counter assertions by abortion opponents that women are not certain of their decisions, or that women regret or have mainly negative emotions about their abortions if not in the short run then after a long period of time. This commentary addresses not only these findings but also relevant U.S. abortion policies based on these unsubstantiated claims. Policies should not be based on the notions that women are unsure of their decision, come to regret, it or have negative emotions because there is no evidence to support these claims. [ABSTRACT FROM AUTHOR]

[Display omitted] • EV sources tested for their applicability for EV bulk production. • sequential protocol for the mass purification of EVs from urine developed. • protocol is time-saving and cost-effective. • new methodology enables new therapeutic, diagnostic and technical developments. Research on extracellular vesicles (EVs), both in general laboratory methods and in novel therapeutic approaches, is limited by the difficulty of obtaining large quantities of EVs. This is due to the fact that EVs are only present at low concentrations in most starting samples and common methods for concentrating EVs from large volumes have decisive disadvantages. In particular, ultracentrifugation (UC) and tangential flow filtration (TFF) are used in EV bulk production. However, while UC leads to low EV-yield with high levels of impurities and damaged EVs, TFF is suitable for enriching EVs from large volumes, but requires expensive equipment. In addition, both methods require pre-purification of the EV material and downstream EV isolation steps. To circumvent all these obstacles, we evaluated various methods for their applicability to EV mass purification, optimized both their implementation and the workflow, and thus developed the following sequential protocol for EV bulk production: First, a preclearing step is performed by 1 µm filtration, followed by PEG precipitation to reduce total volume. Larger debris and apoptotic bodies are removed by centrifugation and filtration prior to enrichment and pre-purification of EVs by ultrafiltration or using the ExoEasyMaxi kit. Finally, EVs are purified by size exclusion chromatography. Since the availability of suitable starting material to obtain pure EVs is also a challenge, we compared different biological fluids, with urine proving to be the most suitable source. We determined the purity and quantity of the EV samples using nanotracking analysis, dynamic light scattering, phospholipid-, RNA- and protein-concentration measurement, electron microscopy and western blot. In summary, we have developed procedures to obtain about 1012 pure EVs in less than a day, with a handling time under 2 h, and at a cost of approximately €24. This method should facilitate further scientific and technical developments in the field of EV biology. [ABSTRACT FROM AUTHOR]

Previously published sub-site Australian projections for colon and rectal cancers to 2035 using the World Health Organization's mortality database sourced from the Australian Bureau of Statistics (ABS) predicted mortality rate decreases for colon cancer and increases for rectal cancer. There are complexities related to the interpretation of ABS's Australian colon and rectal cancer mortality rates, which could lead to possible inaccuracies in mortality rates for these sub-sites. The largest Australian population-wide registry, New South Wales Cancer Registry (NSWCR), compares routinely-reported causes of death with the recorded medical history from multiple data sources. Therefore, this study used the NSWCR data to project mortality rates for colon and rectal cancers separately to 2040 in Australia. The mortality rates for colon cancer are projected to continuously decline over the period 2015–2040, from 7.0 to 4.7 per 100,000 males, and from 5.3 to 3.2 per 100,000 females. Similar decreasing trends in mortality rates for rectal cancer were projected over the period 2015–2040, from 4.9 to 3.7 per 100,000 males, and from 2.6 to 2.3 per 100,000 females. These projections provide benchmark estimates for the colorectal cancer burden in Australia against which the effectiveness of cancer control interventions can be measured. [ABSTRACT FROM AUTHOR]

Background: Symptoms of mental distress increased sharply during the COVID-19 pandemic, especially among older adolescents and young adults. Mental health distress may make it more challenging for young people to seek other needed health care, including contraception. This study explored the association of symptoms of depression, anxiety, and stress with delays in getting a contraceptive method or prescription. Materials and Methods: Data from a supplementary study (May 15, 2020–March 20, 2023) to a cluster randomized trial in 29 sites in Texas and California were used. The diverse study sample included community college students assigned female at birth of ages 18–29 years (n = 1,665 with 7,023 observations over time). We measured the association of depression (CES-D [Center for Epidemiologic Studies Depression Scale]) or anxiety and stress (DASS-21 [Depression Anxiety Stress Scales]) symptoms with delayed contraceptive care-seeking with mixed-effects multivariable regression with random effects for individual and site. We controlled for age and sociodemographic factors important for access to care. Results: Over one-third of participants (35%) reported they delayed getting the contraceptive method they needed. Multivariable regression results showed increased odds of delayed contraceptive care among participants with symptoms of depression (adjusted odds ratio [aOR] 1.58, 95% confidence interval [CI] 1.27–1.96). Likewise, delays were associated with anxiety and stress symptoms (aOR 1.46, 95% CI 1.17–1.82). Adolescents were more likely to delay seeking contraception than young adults (aOR 1.32, 95% CI 1.07–1.63). Conclusions: Results showed a strong association between mental distress and delayed contraception. Interventions are needed to increase contraceptive access for young people delaying care, along with supportive mental health care services, including for adolescents who face elevated odds of delay. ClinicalTrials.gov Identifier:NCT03519685. [ABSTRACT FROM AUTHOR]

Background: Intimate partner violence and differential power dynamics are associated with contraceptive behaviors. This study examines the role of reproductive coercion (RC) by an intimate partner in women's decisions about contraceptive use. Materials and Methods: A self-report survey was administered to a probability sample of a diverse group of women of reproductive age in Delaware's Title X health care facilities. Currently used contraceptive methods were categorized into three effectiveness levels based on typical use failure rates: no method or low effectiveness (>10% failure), moderate effectiveness (>1% and <10% failure), and high effectiveness (<1% failure). The short-form RC scale was used to categorize RC experiences: no RC, verbal only, or behavioral. We conducted multinomial logistic regression to examine the association between types of RC and effectiveness level of current contraceptive method, taking our sampling design into account and adjusting for covariates. Results: Among 240 women (weighted n = 6529) included in the sample, 13.9% reported experiencing only verbal RC, and 16.1% reported behavioral RC. Women who reported behavioral RC were more likely to currently be using highly versus moderately (adjusted relative risk ratio [aRRR]: 26.71, 95% confidence interval [CI]: 4.59–156.0) and low effective methods (aRRR: 3.08, 95% CI: 0.97–9.82), but less likely to be using moderately (aRRR: 0.12, 95% CI: 0.02–0.77) than low effective methods. Conclusions: Using highly and low effective methods may indicate two opposing ways of managing behavioral RC experiences: controlling fertility by choosing less detectable but highly effective methods or feeling disempowered and using no or low effective partner-dependent methods. [ABSTRACT FROM AUTHOR]