Gas Delivery Relevant to Human Health using Porous Materials.

Gases are essential for various applications relevant to human health, including in medicine, biomedical imaging, and pharmaceutical synthesis. However, gases are significantly more challenging to safely handle than liquids and solids. Herein, we review the use of porous materials, such as metal-organic frameworks (MOFs), zeolites, and silicas, to adsorb medicinally relevant gases and facilitate their handling as solids. Specific topics include the use of MOFs and zeolites to deliver H2S for therapeutic applications, 129Xe for magnetic resonance imaging, O2 for the treatment of cancer and hypoxia, and various gases for use in organic synthesis. This Perspective aims to bring together the organic, inorganic, medicinal, and materials chemistry communities to inspire the design of next-generation porous materials for the storage and delivery of medicinally relevant gases.

Unravelling White Phosphorus: Experimental and Computational Studies Reveal the Mechanisms of P4 Hydrostannylation.

The hydrostannylation of white phosphorus (P4) allows this crucial industrial precursor to be easily transformed into useful P1 products via direct, 'one pot' (or even catalytic) procedures. However, a thorough mechanistic understanding of this transformation has remained elusive, hindering attempts to use this rare example of successful, direct P4 functionalization as a model for further reaction development. Here, we provide a deep and generalizable mechanistic picture for P4 hydrostannylation by combining DFT calculations with in situ31P NMR reaction monitoring and kinetic trapping of previously unobservable reaction intermediates using bulky tin hydrides. The results offer important insights into both how this reaction proceeds and why it is successful and provide implicit guidelines for future research in the field of P4 activation.

Early intermediates in bacterial RNA polymerase promoter melting visualized by time-resolved cryo-electron microscopy.

During formation of the transcription-competent open complex (RPo) by bacterial RNA polymerases (RNAPs), transient intermediates pile up before overcoming a rate-limiting step. Structural descriptions of these interconversions in real time are unavailable. To address this gap, here we use time-resolved cryogenic electron microscopy (cryo-EM) to capture four intermediates populated 120 ms or 500 ms after mixing Escherichia coli σ70-RNAP and the λPR promoter. Cryo-EM snapshots revealed that the upstream edge of the transcription bubble unpairs rapidly, followed by stepwise insertion of two conserved nontemplate strand (nt-strand) bases into RNAP pockets. As the nt-strand 'read-out' extends, the RNAP clamp closes, expelling an inhibitory σ70 domain from the active-site cleft. The template strand is fully unpaired by 120 ms but remains dynamic, indicating that yet unknown conformational changes complete RPo formation in subsequent steps. Given that these events likely describe DNA opening at many bacterial promoters, this study provides insights into how DNA sequence regulates steps of RPo formation.

Cancers with epidemiologic signatures of viral oncogenicity among immunocompromised populations in the United States.

BACKGROUND: Immunosuppressed individuals have elevated risk of virus-related cancers. Identifying cancers with elevated risk in people with HIV (PWH) and solid organ transplant recipients (SOTRs), two immunosuppressed populations, may help identify novel etiologic relationships with infectious agents. METHODS: We utilized two linkages of population-based cancer registries with HIV and transplant registries in the United States. Cancer entities were systematically classified based on site and histology codes. Standardized incidence ratios (SIRs) were used to compare risk in PWH and SOTRs with the general population. For selected cancer entities, incidence rate ratios (IRRs) were calculated for indicators of immunosuppression within each population. FINDINGS: We identified 38,047 cancer cases in SOTRs and 53,592 in PWH, yielding overall SIRs of 1.66 (95%CI = 1.65-1.68) and 1.49 (95%CI = 1.47-1.50), respectively. Forty-three cancer entities met selection criteria, including conjunctival squamous cell carcinoma (SCC) (PWH SIR = 7.1, 95%CI = 5.5-9.2; SOTRs SIR = 9.4; 95%CI = 6.8-12.6). Sebaceous adenocarcinoma was elevated in SOTRs (SIR = 16.2; 95%CI = 14.0-18.6) and, among SOTRs, associated with greater risk in lung/heart transplant recipients compared to recipients of other organs (IRR = 2.3; 95%CI = 1.7-3.2). Salivary gland tumors, malignant fibrous histiocytoma (MFH), and intrahepatic cholangiocarcinoma showed elevated risk in SOTRs (SIR = 3.9; SIR = 4.7; and SIR = 3.2, respectively) but not in PWH. However, risks for these cancers were elevated following an AIDS diagnosis among PWH (IRR = 2.4; IRR = 4.3; and IRR = 2.0, respectively). INTERPRETATION: Elevated SIRs among SOTRs and PWH, and associations with immunosuppression within these populations, suggest novel infectious causes for several cancers including conjunctival SCC, sebaceous adenocarcinoma, salivary gland tumors, MFH, and intrahepatic cholangiocarcinoma.

Performance of restorations in primary molars over a seven-year period.

OBJECTIVE: The aim of this study was to evaluate the use and reintervention rate of fillings compared to preformed metal crowns in the everyday clinical practice of German dentists. METHODS: In this retrospective, longitudinal analysis, fee codes from the Kassenzahnärztliche Vereinigung Westfalen-Lippe for restorations placed in primary molars between 2012 and 2015 in children until 7 years of age followed for a 7-year period (latest until December 2022) were filtered and analyzed with the Fine and Gray competing risk regression and Cox proportional hazards regression to calculate the risk of reintervention divided into the main outcomes "Successful", "Minor Failure/Repair" and "Major Failure/Endodontic Treatment/Extraction". 367,139 primary molars (one-surface fillings: n = 117,721; two-surface fillings n = 198,815; three-surface fillings n = 36,695; more than three-surface fillings n = 8,267 and preformed metal crowns n = 5,641 were included in this study. RESULTS: Teeth treated with preformed crowns needed significantly less re-interventions. Subdistribution hazard ratio for minor events was 0.117 (95 %-CI: 0.097 to 0.141) and hazard ratio of major events (HR=0.786; 95 %-CI: 0.695 to 0.890) when compared to one-surface fillings in multivariable adjusted analysis. Within 7-year follow-up preformed crowns required less repairs (80.6 % success rate, minor failure 4.4 %, major failure 16.3 %) than the teeth treated with composite fillings (46.2 %-52.6 % success rate, minor failure 27.0 %-39.5 %, major failure 15.5 %-28.4 %, p < 0.001). CONCLUSION: Within the German healthcare system fillings are the first choice for treating primary molars despite considerably higher reintervention rates. This encourages a discussion on the indication of fillings and the more durable preformed metal crowns to reduce unnecessary reintervention in young children. CLINICAL SIGNIFICANCE: This study gives an unprecedented insight into the German healthcare system regarding the reintervention rates of the most relevant treatment techniques for caries in primary molars.

"Intramuscular Breast Augmentation in Secondary Mastopexy Augmentation."

BACKGROUND: Breast augmentation with implants is one of the most performed aesthetic surgical procedures performed worldwide. We describe this new option for breast implant secondary procedures, the intra pectoralis major pocket, as a feasible and reproducible surgical technique. METHODS: A retrospective chart review was conducted on all patients who underwent revision augmentation or mastopexy augmentation procedure between 2005 and 2022 by the senior author. The intramuscular pocket is dissected between the pectoral muscle fascicles where almost is not bleeding. RESULTS: Patients were followed for an average of 21.5 months. A total of 319 patients underwent revisionary breast augmentation/mastopexies performed by the senior author. Indications for reoperation were based both on specific patient dissatisfaction with their original surgery and surgeon's physical examination and assessment. In 196 cases we performed the intramuscular pocket. None of the intramuscular had capsular contracture or animation deformity in the follow up period. CONCLUSIONS: The intramuscular technique is a valuable and safe technique for secondary breast augmentation.

Insomnia Symptoms Are Associated with Measures of Functional Deterioration and Dementia Status in Adults with Down Syndrome at High Risk for Alzheimer's Disease.

Background: While obstructive sleep apnea (OSA) and insomnia symptoms in neurotypical populations are associated with Alzheimer's disease (AD), their association with dementia in adults with Down syndrome (DS) remains less clear, even though these symptoms are prevalent and treatable in DS. Understanding their associations with AD-related dementia status, cognitive impairment, and functional deterioration may lead to interventions to slow decline or disease progression in adults with DS. Objective: To characterize differences in OSA and insomnia symptom expression by dementia status, and to determine which sleep factors support dementia diagnosis. Methods: Multimodal consensus conference was used to determine dementia status in 52 adults with DS (52.2 ±â€Š6.4 years, 21 women). Cognitive impairment, adaptive behavior skills, and symptoms of OSA and insomnia were quantified using validated assessments for adults with DS and their primary informants. Results: A sex by dementia status interaction demonstrated that older women with DS and dementia had more severe terminal insomnia but not OSA symptoms relative to older women with DS who were cognitively stable (CS). Greater insomnia symptom severity was associated with greater functional impairments in social and self-care domains adjusting for age, sex, premorbid intellectual impairment, and dementia status. Conclusions: Insomnia symptoms are more severe in women with DS with dementia than in women with DS and no dementia, and regardless of dementia status or sex, more severe insomnia symptoms are associated with greater impairment in activities of daily living. These findings underscore the potential importance of early insomnia symptom evaluation and treatment in women with DS at risk of developing AD.

Highly acidic N-triflylphosphoramides as chiral Brønsted acid catalysts: the effect of weak hydrogen bonds and multiple acceptors on complex structures and aggregation.

N-Triflylphosphoramides (NTPAs) represent an important catalyst class in asymmetric catalysis due to their multiple hydrogen bond acceptor sites and acidity, which is increased by several orders of magnitude compared to conventional chiral phosphoric acids (CPAs). Thus, NTPAs allow for several challenging transformations, which are not accessible with CPAs. However, detailed evidence on their hydrogen bonding situation, complex structures and aggregation is still lacking. Therefore, this study covers the hydrogen bonding behavior and structural features of binary NTPA/imine complexes compared to their CPA counterparts. Deviating from the single-well potential hydrogen bonds commonly observed in CPA/imine complexes, the NTPA/imine complexes exhibit a tautomeric equilibrium between two proton positions. Low-temperature NMR at 180 K supported by computer simulations indicates a OHN hydrogen bond between the phosphoramide oxygen and the imine, instead of the mostly proposed NHN H-bond. Furthermore, this study finds no evidence for the existence of dimeric NTPA/NTPA/imine complexes as previously suggested for CPA systems, both synthetically and through NMR studies.

Integrative Review of Sources of Baccalaureate Nursing Students' Clinical Practice Anxiety.

BACKGROUND: Nursing education research and anecdotal literature has revealed that undergraduate nursing students report anxiety related to clinical practice. Most published studies have focused on the effectiveness of interventions to reduce anxiety; only a few identify specific sources of clinical practice anxiety. METHOD: We conducted an integrative literature review to understand the sources of nursing students' practice-related anxiety and how this anxiety has been measured. RESULTS: We classified sources of practice-related anxiety into nine themes grouped into five categories: consequences of making a mistake; fear of the unknown; incivility of staff members or teachers; threat to self-concept, image, or health; and theory-practice gap. Practice-related anxiety was measured quantitatively with various surveys and qualitatively using semistructured individual or group interviews and students' journal entries. CONCLUSION: Different sources of practice-related anxiety likely require distinct interventions. Further research is recommended to identify effective interventions to reduce anxiety related to each of the identified themes. [J Nurs Educ. 2024;63(6):349-355.].

Big data study using health insurance claims to predict multidisciplinary low vision service uptake.

SIGNIFICANCE: There is a lack of research from high-income countries with various health care and funding systems regarding barriers and facilitators in low vision services (LVS) access. Furthermore, very few studies on LVS provision have used claims data. PURPOSE: This study aimed to investigate which patient characteristics predict receiving multidisciplinary LVS (MLVS) in the Netherlands, a high-income country, based on health care claims data. METHODS: Data from a Dutch national health insurance claims database (2015 to 2018) of patients with eye diseases causing potentially severe visual impairment were retrieved. Patients received MLVS (n = 8766) and/or ophthalmic treatment in 2018 (reference, n = 565,496). MLVS is provided by professionals from various clinical backgrounds, including nonprofit low vision optometry. Patient characteristics (sociodemographic, clinical, contextual, general health care utilization) were assessed as potential predictors using a multivariable logistic regression model, which was internally validated with bootstrapping. RESULTS: Predictors for receiving MLVS included prescription of low vision aids (odds ratio [OR], 8.76; 95% confidence interval [CI], 7.99 to 9.61), having multiple ophthalmic diagnoses (OR, 3.49; 95% CI, 3.30 to 3.70), receiving occupational therapy (OR, 2.32; 95% CI, 2.15 to 2.51), mental comorbidity (OR, 1.17; 95% CI, 1.10 to 1.23), comorbid hearing disorder (OR, 1.98; 95% CI, 1.86 to 2.11), and receiving treatment in both a general hospital and a specialized ophthalmic center (OR, 1.23; 95% CI, 1.10 to 1.37), or by a general practitioner (OR, 1.23; 95% CI, 1.18 to 1.29). Characteristics associated with lower odds included older age (OR, 0.30; 95% CI, 0.28 to 0.32), having a low social economic status (OR, 0.91; 95% CI, 0.86 to 0.97), physical comorbidity (OR, 0.87; 95% CI, 0.82 to 0.92), and greater distance to an MLVS (OR, 0.95; 95% CI, 0.92 to 0.98). The area under the curve of the model was 0.75 (95% CI, 0.75 to 0.76; optimism = 0.0008). CONCLUSIONS: Various sociodemographic, clinical, and contextual patient characteristics, as well as factors related to patients' general health care utilization, were found to influence MLVS receipt as barriers or facilitators. Eye care practitioners should have attention for socioeconomically disadvantaged older patients when considering MLVS referral.

A programmable seekRNA guides target selection by IS1111 and IS110 type insertion sequences.

IS1111 and IS110 insertion sequence (IS) family members encode an unusual DEDD transposase type and exhibit specific target site selection. The IS1111 group include identifiable subterminal inverted repeats (sTIR) not found in the IS110 type1. IS in both families include a noncoding region (NCR) of significant length and, as each individual IS or group of closely related IS selects a different site, we had previously proposed that an NCR-derived RNA was involved in target selection2. Here, we find that the NCR is usually downstream of the transposase gene in IS1111 family IS and upstream in the IS110 type. Four IS1111 and one IS110 family members that target different sequences are used to demonstrate that the NCR determines a short seeker RNA (seekRNA) that co-purified with the transposase. The seekRNA is essential for transposition of the IS or a cargo flanked by IS ends from and to the preferred target. Short sequences matching both top and bottom strands of the target are present in the seekRNA but their order in IS1111 and IS110 family IS is reversed. Reprogramming the seekRNA and donor flank to target a different site is demonstrated, indicating future biotechnological potential for these systems.

Protodefluorinated Selectfluor® Aggregatively Activates Selectfluor® for Efficient Radical C(sp3)-H Fluorination Reactions.

Efficient fluorination reactions are key in the late-stage functionalization of complex molecules in medicinal chemistry, in upgrading chemical feedstocks, and in materials science. Radical C(sp3)-H fluorinations using Selectfluor® - one of the most popular fluorination agents - allow to directly engage unactivated precursors under mild photochemical or thermal catalytic conditions. However, H-TEDA(BF4)2 to date is overlooked and discarded as waste, despite comprising 95% of the molecular weight of Selectfluor®. We demonstrate that the addition of H-TEDA(BF4)2 at the start of fluorination reactions markedly promotes their rates and accesses higher overall yields of fluorinated products (~3.3x higher on average across the cases studied) than unpromoted reactions. Several case studies showcase generality of the promotor, for photochemical, photocatalytic and thermal radical fluorination reactions. Detailed mechanistic investigations reveal the key importance of aggregation changes in Selectfluor® and H-TEDA(BF4)2 to fill gaps of understanding in how radical C(sp3)-H fluorination reactions work. This study exemplifies an overlooked reaction waste product being upcycled for a useful application.

Untangling the genetics of beta cell dysfunction and death in type 1 diabetes.

Type 1 diabetes (T1D) is a complex multi-system disease which arises from both environmental and genetic factors, resulting in the destruction of insulin-producing pancreatic beta cells. Over the past two decades, human genetic studies have provided new insight into the etiology of T1D, including an appreciation for the role of beta cells in their own demise. Here, we outline models supported by human genetic data for the role of beta cell dysfunction and death in T1D. We highlight the importance of strong evidence linking T1D genetic associations to bona fide candidate genes for mechanistic and therapeutic consideration. To guide rigorous interpretation of genetic associations, we describe molecular profiling approaches, genomic resources, and disease models that may be used to construct variant-to-gene links and to investigate candidate genes and their role in T1D. We profile advances in understanding the genetic causes of beta cell dysfunction and death at individual T1D risk loci. We introduce genetic risk prediction models and discuss how they can be used to address disease heterogeneity. Finally, we present areas where investment will be critical for future use of genetics to address open questions and to develop new treatment and prevention strategies for T1D.

Evaluation of an ambulatory care pathway for patients with nitrous oxide-induced myeloneuropathy.

Introduction: Cases of nitrous oxide (N2O)-induced myeloneuropathy are increasing at UK hospitals. At our centre, a dedicated ambulatory care pathway, endorsed nationally, was established to treat and monitor patients with N2O-myeloneuropathy in 2021 and refined through three audit cycles. We analysed the outcomes of patients on this pathway to better understand factors associated with non-engagement. Alongside, a novel approach using WhatsApp for questionnaire delivery was trialled in an attempt to improve engagement with treatment. Methods: Patients on the N2O ambulatory care pathway were identified from MDT meeting lists from 9 September 2022 to 25 April 2023. Clinical data were collected via electronic clinical records, including the most recent neurological examination and reason for discharge from the pathway. Patients identified from MDT lists from 27 January 2023 to 14 March 2023 were approached to participate in weekly 12-item surveys, delivered via WhatsApp. This was approved as a service development project with approval for WhatsApp use given by the chief clinical information officer. Results: 35/56 (62.5%) patients were discharged from ambulatory care due to non-attendance and 17/56 (30.4%) completed their treatment course. The median time from initial presentation to discharge was 49 days. 24/40 (60.0%) of patients with a final neurological examination documented had a residual deficit, with objective sensory deficits most common. 12 patients were approached to receive weekly questionnaires via WhatsApp. 5/8 who expressed interest returned a consent form. All participants were withdrawn due to non-response or participant choice. 1/5 returned more than two surveys. Conclusion: Despite poor participation in surveys delivered via WhatsApp, novel approaches are needed to improve engagement with patients on the N2O ambulatory care pathway.

Medical Image sharing: What do the public see when reviewing radiographs? A pilot study.

INTRODUCTION: Policymakers wish to extend access to medical records, including medical imaging. Appreciating how patients might review radiographs could be key to establishing future training needs for healthcare professionals and how image sharing could be integrated into practice. METHOD: A pilot study in the UK using a survey was distributed to adult participants via the online research platform Prolific. All subjects were without prior professional healthcare experience. Participants reviewed ten radiographs (single projection only) and were asked a two-stage question. Firstly, if the radiograph was 'normal' or 'abnormal' and secondly, if they had answered 'abnormal', to identify the abnormality from a pre-determined list featuring generic terms for pathologies. RESULTS: Fifty participants completed the survey. A mean of 65.8 % of participants were able to correctly identify if radiographs were normal or abnormal. Results in relation to the identification of a pathology were not as positive, but still notable with a mean of 46.4 % correctly identifying abnormalities. Qualitative data demonstrated that members of the public are enthralled with reviewing radiographs and intrigued to understand their performance in identifying abnormalities. CONCLUSION: In the pilot, members of the public could identify if a radiograph is normal or abnormal to a reasonable standard. Further detailed interpretation of images requires supportive intervention. This pilot study suggests that patients can participate in image sharing as part of their care. Image sharing may be beneficial to the therapeutic relationship, aiding patient understanding and enhancing consultations between healthcare professional and patient. Further research is indicated.

Microglia-targeted inhibition of miR-17 via mannose-coated lipid nanoparticles improves pathology and behavior in a mouse model of Alzheimer's disease.

Neuroinflammation and accumulation of Amyloid Beta (Aß) accompanied by deterioration of special memory are hallmarks of Alzheimer's disease (AD). Effective preventative and treatment options for AD are still needed. Microglia in AD brains are characterized by elevated levels of microRNA-17 (miR-17), which is accompanied by defective autophagy, Aß accumulation, and increased inflammatory cytokine production. However, the effect of targeting miR-17 on AD pathology and memory loss is not clear. To specifically inhibit miR-17 in microglia, we generated mannose-coated lipid nanoparticles (MLNPs) enclosing miR-17 antagomir (Anti-17 MLNPs), which are targeted to mannose receptors readily expressed on microglia. We used a 5XFAD mouse model (AD) that recapitulates many AD-related phenotypes observed in humans. Our results show that Anti-17 MLNPs, delivered to 5XFAD mice by intra-cisterna magna injection, specifically deliver Anti-17 to microglia. Anti-17 MLNPs downregulated miR-17 expression in microglia but not in neurons, astrocytes, and oligodendrocytes. Anti-17 MLNPs attenuated inflammation, improved autophagy, and reduced Aß burdens in the brains. Additionally, Anti-17 MLNPs reduced the deterioration in spatial memory and decreased anxiety-like behavior in 5XFAD mice. Therefore, targeting miR-17 using MLNPs is a viable strategy to prevent several AD pathologies. This selective targeting strategy delivers specific agents to microglia without the adverse off-target effects on other cell types. Additionally, this approach can be used to deliver other molecules to microglia and other immune cells in other organs.

Older adults at greater risk for Alzheimer's disease show stronger associations between sleep apnea severity in REM sleep and verbal memory.

BACKGROUND: Obstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimer's disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk. METHODS: Eighty-one adults (mean age:61.7 ± 6.0 years, 62% females, 32% apolipoprotein E ε4 allele (APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined. RESULTS: Apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60 + years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning, and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers. CONCLUSION: Greater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low.

Associations of tubal ligation and hysterectomy with serum androgen and estrogen metabolites among postmenopausal women in the Women's Health Initiative Observational Study.

PURPOSE: Hysterectomy is associated with subsequent changes in circulating hormone levels, but the evidence of an association for tubal ligation is unclear. We evaluated whether circulating concentrations of androgens and estrogens differ by tubal ligation or hysterectomy status in postmenopausal women from the Women's Health Initiative (WHI)-Observational Study (OS). METHODS: Serum androgens and estrogens were measured in 920 postmenopausal women who did not use menopausal hormone therapy at the time of blood draw, of whom 139 self-reported a history of tubal ligation and 102 reported hysterectomy (with intact ovaries). Geometric mean hormone concentrations (GMs) and 95% confidence intervals (CIs) associated with a history of tubal ligation or hysterectomy (ever/never), as well as time since procedures, were estimated using adjusted linear regression with inverse probability of sampling weights to account for selection. RESULTS: Circulating levels of 12 androgen/androgen metabolites and 20 estrogen/estrogen metabolites did not differ by tubal ligation status. Among women reporting prior hysterectomy compared to women without hysterectomy, we observed lower levels of several androgens (e.g., testosterone (nmol/L): GMyes 0.46 [95% CI:0.37-0.57] vs. GMno 0.62 [95% CI:0.53-0.72]) and higher levels of estrogen metabolites, for example, 2-hydroxyestrone-3-methyl ether (GMyes 11.1 [95% CI:8.95-13.9] pmol/L vs. GMno 8.70 [95% CI:7.38-10.3]) and 4-methoxyestrone (GMyes 6.50 [95% CI:5.05-8.37] vs. GMno 4.92 [95% CI:4.00-6.05]). CONCLUSION: While we did not observe associations between prior tubal ligation and postmenopausal circulating hormone levels, our findings support that prior hysterectomy was associated with lower circulating testosterone levels and higher levels of some estrogen metabolites, which may have implications for future hormone-related disease risks.