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The relative risk of pregnancy with the levonorgestrel 52 mg IUD is 3 times lower than with optimal combined oral contraceptive use.

ObjectiveTo evaluate menstrual cup use and intrauterine device (IUD) expulsion.Study designWe performed a secondary analysis of a 3-year contraceptive efficacy trial comparing two copper 380 mm2 IUDs. Investigators randomized participants approximately 1:4 to the TCu380A or NTCu380-Mini IUD. Approximately 12 months after enrollment began, we advised participants against menstrual cup use due to observed IUD expulsions in cup users. We evaluated IUD expulsion (including spontaneous partial and complete expulsion and accidental self-removal) at 12 and 36 months. We used multivariable logistic regression to evaluate IUD expulsion by age, baseline menstrual volume, body mass index, IUD type, menstrual cup use, parity, and uterine length.ResultsThis analysis included 1046 participants (203 TCu380A and 843 NTCu380-Mini), with 879 (84.0%) nulliparas. Through 12 and 36 months, expulsion occurred in 74 (7.1%, 95% CI 5.5-8.6%) and 133 (12.7%, 95% CI 10.7-14.7%) participants, respectively. Overall, 250 (23.9%) reported menstrual cup use. More menstrual cup users than non-users experienced expulsion through 12 months (32/203 [15.8%] vs. 42/843 [5.0%]) and 36 months (58/250 [23.2%] vs. 75/796 [9.4%]). Through 36 months, NTCu380-Mini menstrual cup users had higher expulsion odds, while TCu380A cup users did not. Menstrual cup users more frequently experienced accidental self-removal than non-users in participants using the TCu380A (3/53 [5.7%] vs. 0/150 [0.0%]) and the NTCu380-Mini (20/197 [10.2%] vs. 7/646 [1.1%]). In multivariable regression, we found increased odds of expulsion through 36 months in participants using menstrual cups with the NTCu380-Mini (aOR 3.13, 95% CI 1.16-8.46) and

ObjectiveTo evaluate differences based on intrauterine device (IUD) frame geometry in force, and stress, and strain at the stem/arms junction during simulated IUD removal.Study designWe manufactured injection-molded frame models for three Nova-T IUDs (Mirena [model M]; Liletta [model L]; Kyleena [model K]) and a Tatum-T IUD (Paragard [model P]) at two-times scaling. We created a custom fixture to simulate the uterus and used a screw-driven machine to pull models at various displacement rates through the 10 cm fixture cavity to measure force and strain and calculate stress at the IUD stem/arms junction. We tested models at 30 mm/min and higher displacement rates for exploratory analyses. We used Mann-Whitney U test for statistical testing.ResultsWe completed testing at 30 mm/min using five of each Nova-T model and nine model P samples. Resistance against the cavity walls created significantly more force on model P (11.83, interquartile range [IQR] 11.61-12.31) than any Nova-T model samples (p

Abstract: Objective: To assess placement outcomes using a levonorgestrel 52 mg intrauterine device (IUD) inserter designed for single‐handed use. Methods: Investigators enroled participants 18–45 years to have the IUD inserted using a redesigned inserter with removal 5–15 min after placement. Physicians and participants provided feedback on their insertion experience. Results: Successful placement occurred in 48 of 50 (96.0%) enroled participants. Investigators rated insertion device loading “easy” in 49 (98.0%) and placement “easy” in 44 (88.0%) cases. Cramping pain was reported at insertion by 47 (94.0%) participants, mostly mild (32 [64.0%]) or moderate (11 [22.0%]). Conclusion: The single‐handed inserter is easy to use and results in high rates of insertion success.

Simarteriviruses (order Nidovirales, family Arteriviridae, subfamily Simarterivirinae) are genetically diverse viruses that naturally infect cercopithecoid monkeys throughout sub-Saharan Africa. Many divergent simarteriviruses can infect macaques, although severity of disease ranges [...]

We present an in-depth analysis of selected CASP15 targets, focusing on their biological and functional significance. The authors of the structures identify and discuss key protein features and evaluate how effectively these aspects were captured in the submitted predictions. While the overall ability to predict three-dimensional protein structures continues to impress, reproducing uncommon features not previously observed in experimental structures is still a challenge. Furthermore, instances with conformational flexibility and large multimeric complexes highlight the need for novel scoring strategies to better emphasize biologically relevant structural regions. Looking ahead, closer integration of computational and experimental techniques will play a key role in determining the next challenges to be unraveled in the field of structural molecular biology.

ObjectivesThis study aimed to compare contraceptive efficacy and safety of drospirenone 4 mg in a 24/4-day regimen in nonobese and obese users and describe pharmacokinetics according to bodyweight.Study designWe analyzed data from three drospirenone 4 mg trials (2 European and 1 United States) to report outcomes in nonobese (body mass index

BackgroundSome patterns of cannabis use may presage risk for long-term negative effects. We examined associations between a novel adolescent cannabis misuse scale and early-adult life course outcomes.MethodsWe performed a secondary data analysis of a cohort of Los Angeles, CA high school students from grade 9 through age 21. Participants reported baseline individual demographic and family characteristics at grade 9, adolescent cannabis misuse (8-items) and alcohol misuse (12-items) at grade 10, and outcomes at age 21. We used multivariable regression to model the associations of cannabis misuse scale score with problem substance use (defined as any of: 30-day illegal drug use, 30-day use of another's prescription to get high, hazardous drinking) and several secondary outcomes (behavioral, mental health, academic, social determinants of health), adjusting for covariates. Parallel analyses were conducted for alcohol misuse.ResultsThe 1,148 participants (86% retention) were 47% male, 90% Latinx, 87% US born, and 40% native English speakers. Approximately 11.4% and 15.9% of participants reported at least one item on the cannabis and alcohol misuse scales, respectively. At age 21, approximately 6.7% of participants reported problem substance use, which was associated with both Cannabis and Alcohol Misuse Scales (OR 1.31, 95%CI[1.16, 1.49] and OR 1.33, 95%CI[1.18, 1.49], respectively). Both scales were similarly associated with outcomes in all four categories.ConclusionsThe Adolescent Cannabis Misuse Scale is a promising tool for identifying early patterns of substance use that predict future negative outcomes and enabling early intervention at a critical period in youth development.

ObjectivesThis study aimed to review clinical practice outcomes of early pregnancy loss (EPL) medical management using mifepristone and misoprostol outside of a clinical trial setting.Study designIn this retrospective cohort study, we reviewed a deidentified database of patients who received mifepristone-misoprostol for EPL from May 2018 to May 2021 at our academic center-based clinic, which was a study site for a multicenter mifepristone-misoprostol EPL trial completed in March 2018. All patients received mifepristone 200 mg orally and misoprostol 800 mcg vaginally or buccally, with clinic follow-up typically scheduled within 1 week. The primary outcome was successful medical management, defined as management without the need for aspiration, and the secondary outcomes included additional interventions and indications, follow-up ultrasonography findings, and adverse events requiring treatment.ResultsWe treated 90 patients with a median ultrasound-measured gestational size of 49 (range 30-80) days and median time from mifepristone to misoprostol of 24 (range 8-66) hours. Follow-up was completed in clinic by 80 (88.9%), completed remotely by five (5.6%), and not completed by five (5.6%) patients. Overall, 76 (95% CI 82.9%-96.0%) of 85 patients (89.4%) with follow-up were successfully managed without uterine aspiration. Eighty patients had initial follow-up ultrasonography interpreted as gestational sac expulsion; seven (8.8%) of these ultimately underwent aspiration, including one patient who had a previously undiagnosed cesarean scar ectopic pregnancy. Two patients had significant safety outcomes: one pelvic infection and one blood transfusion during aspiration in the patient with a cesarean scar ectopic pregnancy.ConclusionsOutside of a clinical trial setting, medical management of EPL with mifepristone and misoprostol remains effective and safe.ImplicationsMedical management of EPL with mifepristone and misoprostol is effective and safe outside of a clinical trial setting. A standardized protocol based on the best available clinical trial evidence can be used in clinical practice for the medical management of EPL.

The authors regret an error in the text of the manuscript. In the Results section, in reference to adverse events and reactions, urinary tract infection rates were reported but not also present in Table 3. The events listed in the table are those considered potentially related to the intrauterine system. As urinary tract infections are not considered by regulatory agencies (and, thus, are not in the label) as potentially related, urinary tract infections were incorrectly included in the text and correctly do not appear in the table. The text should read “The most commonly reported events over 8 or more years of use among the 1714 participants receiving an IUS were vulvovaginal infections with bacteria (n=315, 18.4%) or yeast (n=304, 17.7%).”

ObjectivesTo describe practice patterns and challenges encountered by Complex Family Planning (CFP) fellowship graduates.Study designWe invited all 110 obstetrics and gynecology physicians who graduated from the CFP fellowship from 2017-2020 via email to complete an anonymous online survey. We inquired about demographics, intended and obtained postfellowship positions, and successes and challenges in obtaining jobs. We used Fisher's exact test to assess if the proportion of graduates who grew up, attended residency, and completed fellowship in a US region (Northeast, Midwest, South, and West) and practiced in that same region differed.ResultsNinety-nine (90.0%) graduates completed the survey. When entering fellowship, most (n = 92 [92.9%]) expected to practice in an academic environment. About half (n = 49 [49.5%]) pursued fellowship with the intent to practice in a location with an unmet need for abortion providers, of which 22 (44.9%) did so. Forty-nine (49.5%) respondents did not practice after fellowship where they initially intended, citing common challenges of job availability, family-related concerns, safety concerns, and relationship status changes. We found associations between regions where graduates completed residency and currently practice (p = 0.004), driven primarily by higher associations in the South (76.9%) and West (70.6%) and a lower association in the Midwest (22.7%). We found no association between current practice region and where graduates grew up (p = 0.15) or completed fellowship (p = 0.23).ConclusionsCFP fellowship graduates from 2017-2020 primarily intended to practice in academic environments with half planning to practice in underserved locations. However, more than half of those who entered fellowship hoping to fill an unmet need for abortion providers did not do so.ImplicationsAbout half of CFP fellowship graduates from 2017-2020 intended to obtain positions in areas they defined as having an unmet need for abortion provision. Personal life and job barriers prevented many from serving in such positions after fellowship. Practice location intentions and outcomes may be different in a post-Dobbs environment.

ObjectivesTo describe treatment and outcomes of patients with confirmed cesarean scar ectopic pregnancy (CSEP) at a tertiary referral center.Study designWe reviewed a deidentified family planning clinical database for patients seen by our subspecialty service for CSEP from January 2017 through December 2021 in this case series. We extracted referral information, final diagnosis, management, and outcome measures including estimated blood loss, secondary procedures, and treatment complications.ResultsOf 57 cases referred for suspected CSEPs, 23 (40%) had confirmed diagnoses; one additional case was diagnosed during clinic evaluation for early pregnancy loss. Most (n = 50 [88%]) referrals occurred in the last 2 years of the 5-year study period. Of 24 confirmed CSEP cases, eight were pregnancy losses at the time of diagnosis. Fourteen cases were ≤50 days gestation or gestational size (7 [50%] pregnancy losses) and 10 >50 days gestation (range 39-66 days). We treated all 14 patients ≤50 days primarily with suction aspiration under ultrasound guidance in an operating room with no complications and estimated blood loss of 14 ± 10 mL. Of the 10 patients>50 days (maximum 66 days), seven were managed with primary aspiration of which five were uncomplicated. We treated one patient (57 days) had primary intrauterine double-catheter balloon with immediate hemorrhage requiring uterine artery embolization followed by an uncomplicated suction aspiration.ConclusionsPatients with confirmed CSEPs at 50 days or less gestation or gestational size can likely be primarily treated with suction aspiration with low risk for significant adverse outcomes. Treatment success and complications are directly related to gestational age at treatment.ImplicationsUltrasound-guided suction aspiration monotherapy should be considered for primary CSEP treatment up to 50 days and, with continued experience, may be reasonable beyond 50 days gestation. Invasive treatments or those that require multiple days and visits, such as methotrexate or balloon catheters, are not necessary for early CSEPs.

States provide substantial support for higher education through appropriations to public colleges and universities that can be used to maintain relatively low tuition levels and funds for financial aid. Higher education often receives disproportionate cuts during recessionary periods, and it faces potentially unprecedented reductions in coming years amid a pandemic that has left some states with revenue shortfalls. How states approach higher education cuts has the potential to exacerbate existing inequities among racially minoritized and low-income students and historically underfunded institution types. In this study, we document trends in higher education funding over time and use latent profile analysis to identify distinct approaches states have taken to higher education funding. We then examine the trajectories of higher education funding within each approach over time, particularly during prior recessions. We conclude by discussing the implications of each approach for equity, particularly in light of states' early responses to the current economic downturn.

Genetically diverse simian arteriviruses (simarteriviruses) naturally infect geographically and phylogenetically diverse monkeys, and cross-species transmission and emergence are of considerable concern. Characterization of most simarteriviruses beyond sequence analysis has not been possible because the viruses fail to propagate in the laboratory. We attempted to isolate 4 simarteriviruses, Kibale red colobus virus 1, Pebjah virus, simian hemorrhagic fever virus, and Southwest baboon virus 1, by inoculating an immortalized grivet cell line (known to replicate simian hemorrhagic fever virus), primary macaque cells, macrophages derived from macaque induced pluripotent stem cells, and mice engrafted with macaque CD34+-enriched hematopoietic stem cells. The combined effort resulted in successful virus isolation; however, no single approach was successful for all 4 simarteriviruses. We describe several approaches that might be used to isolate additional simarteriviruses for phenotypic characterization. Our results will expedite laboratory studies of simarteriviruses to elucidate virus-host interactions, assess zoonotic risk, and develop medical countermeasures.

Using the Wabash National Study on Liberal Arts Education and a latent class analysis of 28 outside-the-classroom activities and behaviors, we developed a typology of outside-the-classroom student engagement during the first year of college. We find ten classes of student involvement: academic artist, party athlete, serious athlete, conventional non-worker, disengaged, maximizer, moderate worker, detached partier, involved partier, and religious. Next, we examine the relationship between latent classes and students' characteristics through a multinomial logistic regression analysis. Students reporting as first-generation or racially minoritized are overrepresented in the disengaged and involved partier classes. We found an overrepresentation of White students across all party classes. Students reporting as female were likelier to be members of the religious, moderate worker, and disengaged classes and not to be members of the party classes. Federal grant recipients were likelier to be in the academic artist and moderate worker classes. We discuss other sociocultural, economic, and academic relationships in the paper. Next, we explore the relationship of latent class to academic and developmental outcomes. We find academic artists as the only class with a significant positive relationship across the seven dependent measures. Involved partier, moderate worker, and religious classes have positive relationships with at least five dependent measures. The detached partier and party athlete classes have the lowest first-year GPAs of all latent classes. Finally, we discuss the relationships of latent classes, related institutional policy implications, and directions for future research.

The fast solar wind that fills the heliosphere originates from deep within regions of open magnetic field on the Sun called 'coronal holes'. The energy source responsible for accelerating the plasma is widely debated; however, there is evidence that it is ultimately magnetic in nature, with candidate mechanisms including wave heating1,2 and interchange reconnection3-5. The coronal magnetic field near the solar surface is structured on scales associated with 'supergranulation' convection cells, whereby descending flows create intense fields. The energy density in these 'network' magnetic field bundles is a candidate energy source for the wind. Here we report measurements of fast solar wind streams from the Parker Solar Probe (PSP) spacecraft6 that provide strong evidence for the interchange reconnection mechanism. We show that the supergranulation structure at the coronal base remains imprinted in the near-Sun solar wind, resulting in asymmetric patches of magnetic 'switchbacks'7,8 and bursty wind streams with power-law-like energetic ion spectra to beyond 100 keV. Computer simulations of interchange reconnection support key features of the observations, including the ion spectra. Important characteristics of interchange reconnection in the low corona are inferred from the data, including that the reconnection is collisionless and that the energy release rate is sufficient to power the fast wind. In this scenario, magnetic reconnection is continuous and the wind is driven by both the resulting plasma pressure and the radial Alfvénic flow bursts.

BackgroundAdolescent behaviors and academic outcomes are thought to be shaped by school climate. We sought to identify longitudinal associations between school climate measures and downstream health and academic outcomes.MethodsData from a longitudinal survey of public high school students in Los Angeles were analyzed. Eleventh-grade health and academic outcomes (dependent variables, eg, substance use, delinquency, risky sex, bullying, standardized exams, college matriculation), were modeled as a function of 10th-grade school climate measures (independent variables: institutional environment, student-teacher relationships, disciplinary style), controlling for baseline outcome measures and student/parental covariates.ResultsThe 1114 student respondents (87.8% retention), were 46% male, 90% Latinx, 87% born in the United States, and 40% native English speakers. Greater school order and teacher respect for students were associated with lower odds of multiple high risk behaviors including 30-day alcohol use (odds ratio [OR] 0.81; 95% confidence interval [CI] [0.72, 0.92] and OR 0.73; [0.62, 0.85]) and 30-day cannabis use (OR 0.74; [0.59, 0.91] and OR 0.76; [0.63, 0.92]). Neglectful disciplinary style was associated with multiple poor health and academic outcomes while permissive disciplinary style was associated with favorable academic outcomes.Implications for school health policy, practice, and equitySchool health practitioners may prospectively leverage school environment, teacher-student relationships, and disciplinary style to promote health and learning.ConclusionsOur findings identify specific modifiable aspects of the school environment with critical implications for life course health.

Funding sourceMedicines360. The Sponsor, Medicines360, designed the study and oversaw its conduct, including funding the trial and providing all study product free of charge to participants.Clinical trial registrationClinicalTrials.gov, NCT00995150.

ObjectiveTo evaluate heavy menstrual bleeding treatment outcomes with levonorgestrel 52-mg intrauterine device (IUD) use in participants without body mass index (BMI) or parity restrictions.MethodsInvestigators included participants aged 18-50 years with no pelvic or systemic pathology causing heavy menstrual bleeding at 29 U.S. centers in a prospective trial. Participants had up to three screening cycles with menstrual product collection for alkaline hematin blood-loss measurements. Investigators enrolled those with two menses with blood loss of 80 mL or more (values averaged for baseline blood loss), placed the IUD, and followed participants for up to six 28-day cycles. Participants collected any menstrual products used during cycles 3 and 6 for blood-loss measurement. We evaluated outcomes in participants with at least one follow-up assessment for the primary outcome of median absolute blood-loss change and, secondarily, treatment success , defined as the proportion with a final measured blood loss less than 80 mL and at least 50% reduction from baseline. We evaluated exploratory outcomes of differences in blood-loss changes by BMI and parity using Wilcoxon rank sum test.ResultsOf 105 enrolled participants, 47 (44.8%) had obesity (BMI 30.0 or higher) and 29 (27.6%) were nulliparous. Baseline mean blood loss ranged from 73 to 520 mL (median 143 mL, interquartile range 112-196 mL). Eighty-nine (84.8%) had at least one evaluable follow-up evaluation. Participants had median (interquartile range) absolute blood-loss decreases at cycles 3 (n=86) and 6 (n=81) of 93.3% (86.1-97.7%) and 97.6% (90.4-100%), respectively. At cycle 6, participants without obesity (n=43) and with obesity (n=38) had similar median [interquartile range] decreases (97.6% [91.8-100%] and 97.5% [90.3-100%], respectively; P =.89), with comparable findings for nulliparous (n=25) and parous (n=56) participants (97.0% [91.7-99.1%] and 98.1% [89.9-100%], respectively; P =.43). Treatment success occurred in 81.8% (95% CI 74.2-89.4%) of 99 participants, excluding those with no outcomes due to lost to follow-up or consent withdrawal, and did not vary by BMI or parity. The most common adverse events leading to discontinuation were bleeding or cramping (n=6 [5.7%]) and expulsion (n=5 [4.8%]).ConclusionThis levonorgestrel 52-mg IUD reduces blood loss by more than 90% over 6 months compared with baseline for most users with heavy menstrual bleeding.Funding sourceMedicines360.Clinical trial registrationClinicalTrials.gov , NCT03642210.

ObjectiveTo assess the relationship of adherence and pregnancy in participants using an estetrol and drospirenone combined oral contraceptive.MethodsWe performed a secondary analysis for which we pooled data from two parallel, multicenter, phase 3 trials (United States and Canada, Europe and Russia) that enrolled participants 16-50 years of age to receive estetrol 15 mg and drospirenone 3 mg in a 24 hormone and four placebo pills regimen for up to 13 cycles. Participants reported pill intake, sexual intercourse, and other contraceptive use on paper diaries. We limited this efficacy analysis to at-risk cycles (one or more reported acts of intercourse and no other contraceptive use) in participants 16-35 years of age at screening. We excluded cycles with other contraceptive use unless pregnancy occurred in that cycle. We assessed primarily the relationship between number of pills not taken per cycle and pregnancies and, secondarily, when pregnancies occurred during product use with a test for trend and χ 2 analyses as appropriate.ResultsAmong 2,837 participants in this analysis, 31 on-treatment pregnancies occurred during 26,455 at-risk cycles. Pregnancies occurred in 0.09%, 0.25%, 0.83%, and 1.6% of cycles in which participants reported they took all hormone pills (n=25,613 cycles) or did not take one (n=405 cycles), two (n=121 cycles), and more than two (n=314 cycles) hormone-containing pills, respectively ( P

The Diels-Alder cycloaddition is one of the most powerful approaches in organic synthesis and is often used in the synthesis of important pharmaceuticals. Yet, strictly controlling the stereoselectivity of the Diels-Alder reactions is challenging, and great efforts are needed to construct complex molecules with desired chirality via organocatalysis or transition-metal strategies. Nature has evolved different types of enzymes to exquisitely control cyclization stereochemistry; however, most of the reported Diels-Alderases have been shown to only facilitate the energetically favourable diastereoselective cycloadditions. Here we report the discovery and characterization of CtdP, a member of a new class of bifunctional oxidoreductase/Diels-Alderase, which was previously annotated as an NmrA-like transcriptional regulator. We demonstrate that CtdP catalyses the inherently disfavoured cycloaddition to form the bicyclo[2.2.2]diazaoctane scaffold with a strict α-anti-selectivity. Guided by computational studies, we reveal a NADP+/NADPH-dependent redox mechanism for the CtdP-catalysed inverse electron demand Diels-Alder cycloaddition, which serves as the first example of a bifunctional Diels-Alderase that utilizes this mechanism.

ObjectivesTo assess if quantitative blood loss (QBL) with dilation and evacuation (D&E) procedures correlated with clinically relevant outcomes or hemorrhage.Study designWe used a de-identified database to review D&E procedures performed at UC Davis Health from April 2019 through March 2020. Surgeons determined QBL during procedures and estimated blood loss, when excessive, during post-procedure recovery. We extracted patient demographic and procedure-related information. We defined clinically relevant bleeding as cases with bleeding-related interventions within 24 hours post-procedure including use of ≥2 uterotonics, tranexamic acid administration, cervical injury requiring repair, uterine balloon tamponade, blood transfusion, uterine artery embolization, hospitalization, or return to operating room; the latter 5 criteria defined hemorrhage. We used χ2 test for trend to evaluate bleeding outcomes.ResultsWe evaluated 431 procedures with a mean gestational age of 19 weeks and 3 days. Clinically relevant bleeding outcomes occurred in 6/319 (2%), 15/97 (15%) and 7/12 (58%) patients with total blood loss 500mL, respectively (p

Aims: Diabetes mellitus (DM) induces increased inflammation of atherosclerotic plaques, resulting in elevated plaque instability. Mesenchymal stem cell (MSC) therapy was shown to decrease plaque size and increase stability in non-DM animal models. We now studied the effect of MSC therapy in a streptozotocin-induced hyperglycaemia mouse model using a clinically relevant dose of adipose tissue-derived MSCs (ASCs). Methods: Hyperglycaemia was induced in male C57BL/6 ApoE−/− mice (n=24) via intraperitoneal streptozotocin (STZ) injection (0.05 mg/g bodyweight) for 5 consecutive days. 16 weeks after the first STZ injection, the mice received either 100,000 ASCs (n=9) or vehicle (n=14) intravenously. The effects of ASC treatment on the size and stability of aortic root atherosclerotic plaques were determined 4 weeks post-treatment via (immuno)histochemical analyses. Furthermore, plasma monocyte subsets within 3 days pre- and 3 days post-treatment, and 4 weeks post-treatment, were studied. Results: ASC treatment did not significantly affect atherosclerotic plaque size or intra-plaque inflammation. Although ASC-treated mice had a higher percentage of intra-plaque fibrosis (42.5±3.3%) compared to vehicle-treated mice (37.6±6.8%, p=0.07), this did not reach significance. Additionally, although differences in the percentages of circulating pro- and anti-inflammatory monocytes were observed after ASC treatment compared to pre-treatment (p=0.005), their levels did not differ significantly at any time point compared to vehicle-treated mice. Conclusions: ASC treatment with a clinically relevant dose did not significantly affect atherosclerotic plaque size or intra-plaque inflammation in a hyperglycaemia mouse model. Despite a borderline significant improvement in intraplaque fibrotic content, the potential of ASC treatment on atherosclerotic plaque stability in a diabetic environment remains to be determined.

A number of post-mortem studies conducted in transplanted Huntington’s disease (HD) patients from various trials have reported the presence of pathological and misfolded proteins, in particular mutant huntingtin (mHtt) and phosphorylated tau neuropil threads, in the healthy grafted tissue. Here, we extended these observations with histological analysis of post-mortem tissue from three additional HD patients who had received similar striatal allografts from the fetal tissue transplantation trial conducted in Los Angeles in 1998. Immunohistochemical staining was performed using anti-mHtt antibodies, EM48 and MW7, as well as anti-hyperphosphorylated tau antibodies, AT8 and CP13. Immunofluorescence was used to assess the colocalization of EM48+ mHtt aggregates with the neuronal marker MAP2 and/or the extracellular matrix protein phosphacan in both the host and grafts. We confirmed the presence of mHtt aggregates within grafts of all three cases as well as tau neuropil threads in the grafts of two of the three transplanted HD patients. Phosphorylated tau was also variably expressed in the host cerebral cortex of all three subjects. While mHtt inclusions were present within neurons (immunofluorescence co-localization of MAP2 and EM48) as well as within the extracellular matrix of the host (immunofluorescence co-localization of phosphacan and EM48), their localization was limited to the extracellular matrix in the grafted tissue. This study corroborates previous findings that both mHtt and tau pathology can be found in the host and grafts of HD patients years post-grafting.

Determining the atomic-level structure of a protein has been a decades-long challenge. However, recent advances in transformers and related neural network architectures have enabled researchers to significantly improve solutions to this problem. These methods use large datasets of sequence information and corresponding known protein template structures, if available. Yet, such methods only focus on sequence information. Other available prior knowledge could also be utilized, such as constructs derived from x-ray crystallography experiments and the known structures of the most common conformations of amino acid residues, which we refer to as partial structures. To the best of our knowledge, we propose the first transformer-based model that directly utilizes experimental protein crystallographic data and partial structure information to calculate electron density maps of proteins. In particular, we use Patterson maps, which can be directly obtained from x-ray crystallography experimental data, thus bypassing the well-known crystallographic phase problem. We demonstrate that our method, CrysFormer, achieves precise predictions on two synthetic datasets of peptide fragments in crystalline forms, one with two residues per unit cell and the other with fifteen. These predictions can then be used to generate accurate atomic models using established crystallographic refinement programs.

ObjectiveTo describe experiences with abortion counseling and access in patients with lethal or life-limiting fetal diagnoses in Texas after enactment of Senate Bill 8 (SB8).MethodsIn this qualitative study, we interviewed patients who obtained abortions after enactment of SB8, using semi-structured interviews to explore how restrictions affected abortion care. Two researchers coded all transcripts using an inductive technique and analyzed themes in an iterative approach.ResultsWe interviewed 16 participants who reported gestational durations from 13 to 29 weeks at the time of abortion. Participants described loss of the therapeutic patient-physician relationship and feelings of isolation while pursuing abortion due to the limitations imposed by SB8. For example, participants felt there was a physician "gag rule" regarding abortion ("the unspoken word of termination"), resulting in the need to find information about pregnancy options outside of the medical community and further highlighting the privilege of financial resources necessary to obtain an abortion on their own. Participants also expressed fears regarding confidentiality with their support systems and clinicians ("I would joke around and say, well don't sue me, but halfway mean it") and personal safety when self-referring for abortion ("…am I making the right choice on where I need to go? Is it safe?").ConclusionAbortion restrictions and bans such as SB8 erode the patient-physician relationship, evoking fear and safety concerns during a vulnerable time for those undergoing abortion for lethal or life-limiting fetal diagnoses. They force patients to shoulder the significant burden of understanding pregnancy options and navigating the process of abortion alone, which is likely to have greater effects on those with fewer resources.

ObjectivesTo estimate the effects on cervical mucus, ovarian activity and theoretical contraceptive protection of a 6-hour delay and of missing one norgestrel 0.075 mg progestogen-only pill.Study designIn a prospective, two-site, randomized, crossover study, healthy women aged 18 to 35 with BMI