Mifepristone Antagonization With Progesterone to Prevent Medical Abortion: A Randomized Controlled Trial.

ObjectiveTo estimate the efficacy and safety of mifepristone antagonization with high-dose oral progesterone.MethodsWe planned to enroll 40 patients in a double-blind, placebo-controlled, randomized trial. We enrolled patients at 44-63 days of gestation with ultrasound-confirmed gestational cardiac activity who were planning surgical abortion. Participants ingested mifepristone 200 mg and initiated oral progesterone 400 mg or placebo 24 hours later twice daily for 3 days, then once daily until their planned surgical abortion 14-16 days after enrollment. Follow-up visits were scheduled 3±1, 7±1, and 15±1 days after mifepristone intake with ultrasonography and blood testing for human chorionic gonadotropin and progesterone. Participants exited from the study when they had their surgical abortion or earlier for gestational cardiac activity absence, gestational sac expulsion, or medically indicated suction aspiration. We assessed the primary outcome of continued gestational cardiac activity at approximately 2 weeks (15±1 day), side effects after drug ingestion, and safety outcomes including hemorrhage and emergent treatment.ResultsWe enrolled participants from February to July 2019 and stopped enrollment after 12 patients for safety concerns. Mean gestational age was 52.5 days. Two (one per group) voluntarily discontinued 3 days after mifepristone ingestion for subjective symptoms (nausea and vomiting, bleeding). Among the remaining 10 patients (five per group), gestational cardiac activity continued for 2 weeks in four in the progesterone group and two in the placebo group. One patient in the placebo group had no gestational cardiac activity 3 days after mifepristone use. Severe hemorrhage requiring ambulance transport to hospital occurred in three patients; one received progesterone (complete expulsion, no aspiration) and two received placebo (aspiration for both, one required transfusion). We halted enrollment after the third hemorrhage. No other significant side effects were reported.ConclusionWe could not estimate the efficacy of progesterone for mifepristone antagonization due to safety concerns when mifepristone is administered without subsequent prostaglandin analogue treatment. Patients in early pregnancy who use only mifepristone may be at high risk of significant hemorrhage.Clinical trial registrationClinicalTrials.gov, NCT03774745

The Persistent Maladaptation of \u3cem\u3ePieris macdunnoughii\u3c/em\u3e: Constraints on Adaptation to an Evolutionary Trap

Evolutionary traps arise when organisms use novel, low-quality or even lethal resources based on previously reliable cues. Persistence of such maladaptive interactions depends not only on how individuals locate important resources, such as host plants, but also the mechanisms underlying poor performance. Pieris macdunnoughii (Remington) (Lepidoptera: Pieridae) lays eggs on a non-native mustard, Thlaspi arvense (L.) (Brassicaceae), which is lethal to its larvae. However, in the 150 years since T. arvense invaded this butterfly continues to recognize and oviposit on the invasive mustard. I evaluated two possible constraints on the evolution of decreased preference within an invaded population. First, an evolutionary response to selection may be constrained by low heritable genetic variation for preference. Second, evolutionary traps are expected to persist when overlapping cue sets (cue similarity) link decreased preference for the novel, unsuitable plant with decreased preference for the historical, high-quality resources. I determined that while preference for the nonnative host over the native host is heritable, sex-linked, and varies considerably in the population, it is unlikely that this preference is correlated with preference for native hosts with similar defensive chemical profiles. Thus, neither a lack of heritable genetic variation nor an increased risk of excluding good host plants when avoiding T. arvense are likely to be constraining escape from this evolutionary trap. Instead, our results suggest behavioral plasticity may buffer populations from innate preference for the lethal host. Finally, I tested the mechanisms underlying poor performance of neonate larvae on the novel host. Larvae were less likely to start eating T. arvense and starvation was a primary cause of mortality, indicating a pre-ingestive feeding deterrent. A primary oviposition stimulant, the glucosinolate sinigrin, increased this deterrent effect and mortality when added to T. arvense and native host plant leaves. Pre-ingestive deterrents, even those familiar to herbivorous insects, may significantly contribute to the persistence of evolutionary traps

A systematic review and qualitative meta-synthesis of first-hand conceptualisations of nonsuicidal self-injury (NSSI)

Nonsuicidal self-injury (NSSI) is a growing phenomenon that correlates with significantly negative outcomes including psychopathology, hospitalisation and suicide; however, there exists little consensus on how to best understand it. This lack of conceptual consensus risks inconsistent clinical practice in a population that often reports poor experiences of professional support, therefore an understanding of how individuals conceptualise their own NSSI without attempting to fit it into existing causal and functionalist models is needed. This review sought to examine and synthesise first-hand conceptualisations of NSSI in existing qualitative literature using interpretive phenomenological synthesis. A systematic database search of qualitative literature was conducted, including interviews with individuals with experience of NSSI across all ages and settings, published in English from 1950 to 2022. Twenty-three studies were included in the final meta-synthesis. Three superordinate themes were generated via the synthesis: (1) NSSI is embedded in the social world; (2) NSSI is symbolic and communicative; and (3) NSSI represents taking back agency. This synthesis, comprised of both reported data and the themes identified by the researchers in the papers, highlighted that NSSI is a diverse behaviour that is inextricably linked with sociocultural context and that, paradoxically, it can be simultaneously communicative and private. This research urges an introspective examination of how clinicians and researchers in the field conceptualise NSSI and how this juxtaposes with how individuals who engage in the behaviour conceptualise it

Long-term outcomes after elective sterilization procedures — a comparative retrospective cohort study of Medicaid patients

Objectives: The objectives were to compare the long-termoutcomes, including hysterectomy, chronic pelvic pain (CPP) and abnormal uterine bleeding (AUB), in women post hysteroscopic sterilization (HS) and laparoscopic tubal ligation (TL) in the Medicaid population. Study design: This was a retrospective observational cohort analysis using data from the US Medicaid Analytic Extracts Encounters database.Women aged 18 to 49 years with at least one claimfor HS (n=3929) or TL (n=10,875) between July 1, 2009, through December 31, 2010, were included. Main outcome measures were hysterectomy, CPP or AUB in the 24 months poststerilization. Propensity score matching was used to control for patient demographics and baseline characteristics. Logistic regression analysis investigated the variables associated with a 24-month rate of each outcome in the HS versus laparoscopic TL cohorts. Results: Postmatching analyses were performed at 6, 12 and 24 months post index procedure. At 24 months, hysterectomy was more common in the laparoscopic TL than the HS group (3.5% vs. 2.1%; p=.0023), as was diagnosis of CPP (26.8% vs. 23.5%; p=.0050). No significant differences in AUB diagnoseswere observed. Logistic regression identified HS as being associated with lower risk of hysterectomy ( odds ratio [OR] 0.77 [95% confidence interval {CI} 0.60–0.97]; p=.0274) and lower risk of CPP diagnosis (OR 0.91 [95% CI 0.83–0.99]; p= .0336) at 24 months poststerilization. Conclusion: In Medicaid patients,HS is associated with a significantly lower risk of hysterectomyor CPP diagnosis 24 months poststerilization versus laparoscopic TL. Incidence of AUB poststerilization is not significantly different.While some differences in outcomes were statistically significant, the effect sizes were small, and the conclusion is one of equivalence and not clinical superiority. Implications statement: This propensity score matching analysis confirms that pelvic pain andAUBarecommon in women before and after sterilization regardless of whether the procedure is performed hysteroscopically or laparoscopically. Moreover, HS is associated with a significantly lower risk of hysterectomy or a CPP diagnosis in the 24 months poststerilization when compared to TL

Chromosome Level Assembly of the Comma Butterfly (Polygonia c-album)

The comma butterfly (Polygonia c-album, Nymphalidae, Lepidoptera) is a model insect species, most notably in the study of phenotypic plasticity and plant-insect coevolutionary interactions. In order to facilitate the integration of genomic tools with a diverse body of ecological and evolutionary research, we assembled the genome of a Swedish comma using 10X sequencing, scaffolding with matepair data, genome polishing, and assignment to linkage groups using a high-density linkage map. The resulting genome is 373 Mb in size, with a scaffold N50 of 11.7 Mb and contig N50 of 11,2Mb. The genome contained 90.1% of single-copy Lepidopteran orthologs in a BUSCO analysis of 5,286 genes. A total of 21,004 gene-models were annotated on the genome using RNA-Seq data from larval and adult tissue in combination with proteins from the Arthropoda database, resulting in a high-quality annotation for which functional annotations were generated. We further documented the quality of the chromosomal assembly via synteny assessment with Melitaea cinxia. The resulting annotated, chromosome-level genome will provide an important resource for investigating coevolutionary dynamics and comparative analyses in Lepidoptera.Peer reviewe

Hyporheic invertebrates as bioindicators of ecological health in temporary rivers: a meta-analysis

Worldwide, many rivers cease flow and dry either naturally or owing to human activities such as water extraction. However, even when surface water is absent, diverse assemblages of aquatic invertebrates inhabit the saturated sediments below the river bed (hyporheic zone). In the absence of surface water or flow, biota of this zone may be sampled as an alternative to surface water-based ecological assessments. The potential of hyporheic invertebrates as ecological indicators of river health, however, is largely unexplored. We analysed hyporheic taxa lists from the international literature on temporary rivers to assess compositional similarity among broad-scale regions and sampling conditions, including the presence or absence of surface waters and flow, and the regional effect of hydrological phase (dry channel, non-flowing waters, surface flow) on richness. We hypothesised that if consistent patterns were found, then effects of human disturbances in temporary rivers may be assessable using hyporheic bioindicators. Assemblages differed geographically and by climate, but hydrological phase did not have a strong effect at the global scale. However, hyporheic assemblage composition within regions varied along a gradient of higher richness during wetter phases

Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults.

UNLABELLED: Excess reactive oxygen species production by mitochondria is a key mechanism of age-related vascular dysfunction. Our laboratory has shown that supplementation with the mitochondrial-targeted antioxidant MitoQ improves vascular endothelial function by reducing mitochondrial reactive oxygen species and ameliorates arterial stiffening in old mice, but the effects in humans are unknown. Here, we sought to translate our preclinical findings to humans and determine the safety and efficacy of MitoQ. Twenty healthy older adults (60-79 years) with impaired endothelial function (brachial artery flow-mediated dilation 7.60 m/s; n=11). Plasma oxidized LDL (low-density lipoprotein), a marker of oxidative stress, also was lower after MitoQ versus placebo (P0.1). These findings in humans extend earlier preclinical observations and suggest that MitoQ and other therapeutic strategies targeting mitochondrial reactive oxygen species may hold promise for treating age-related vascular dysfunction. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02597023.This work was supported by National Institutes of Health (NIH) awards AG049451, AG000279, AG053009, Colorado CTSA UL1 TR001082, and an industry contract with MitoQ Limited (MitoQ Limited provided MitoQ and some financial support). M.P. Murphy is supported by UK MRC MC_U105663142 and as a Wellcome Trust Investigator (110159/Z/15/Z)

Intergenerational programming during the pandemic: Transformation during (constantly) changing times

Intergenerational programs have long been employed to reduce ageism and optimize youth and older adult development. Most involve in-person meetings, which COVID-19 arrested. Needs for safety and social contact were amplified during COVID-19, leading to modified programming that engaged generations remotely rather than eliminating it. Our collective case study incorporates four intergenerational programs in five US states prior to and during COVID-19. Each aims to reduce ageism, incorporating nutrition education, technology skills, or photography programming. Authors present case goals, participants, implementation methods, including responses to COVID-19, outcomes, and lessons learned. Technology afforded opportunities for intergenerational connections; non-technological methods also were employed. Across cases, programmatic foci were maintained through adaptive programming. Community partners’ awareness of immediate needs facilitated responsive programming with universities, who leveraged unique resources. While new methods and partnerships will continue post-pandemic, authors concurred that virtual contact cannot fully substitute for in-person relationship-building. Remote programming maintained ties between groups ready to resume shared in-person programming as soon as possible; they now have tested means for responding to routine or novel cancellations of in-person programming. Able to implement in-person and remote intergenerational programming, communities can fight ageism and pursue diverse goals regardless of health, transportation, weather, or other restrictions

Lesion detection in epilepsy surgery: Lessons from a prospective evaluation of a machine learning algorithm

AIM: To evaluate a lesion detection algorithm designed to detect focal cortical dysplasia (FCD) in children undergoing stereoelectroencephalography (SEEG) as part of their presurgical evaluation for drug-resistant epilepsy. METHOD: This was a prospective, single-arm, interventional study (Idea, Development, Exploration, Assessment, and Long-Term Follow-Up phase 1/2a). After routine SEEG planning, structural magnetic resonance imaging sequences were run through an FCD lesion detection algorithm to identify putative clusters. If the top three clusters were not already sampled, up to three additional SEEG electrodes were added. The primary outcome measure was the proportion of patients who had additional electrode contacts in the SEEG-defined seizure-onset zone (SOZ). RESULTS: Twenty patients (median age 12 years, range 4-18 years) were enrolled, one of whom did not undergo SEEG. Additional electrode contacts were part of the SOZ in 1 out of 19 patients while 3 out of 19 patients had clusters that were part of the SOZ but they were already implanted. A total of 16 additional electrodes were implanted in nine patients and there were no adverse events from the additional electrodes. INTERPRETATION: We demonstrate early-stage prospective clinical validation of a machine learning lesion detection algorithm used to aid the identification of the SOZ in children undergoing SEEG. We share key lessons learnt from this evaluation and emphasize the importance of robust prospective evaluation before routine clinical adoption of such algorithms

Outil de sensibilisation des proches à la conduite automobile des aînés

Cette étude visait à explorer les effets d’un outil de sensibilisation chez les proches de conducteurs âgés (OSCARPA) sur i) leur intérêt, ouverture et connaissances, ii) les changements des habiletés requises pour une conduite automobile sécuritaire, et iii) l’utilisation de stratégies compensatoires. Un dispositif pré-expérimental avec prétest (T0) et post-test (T1) huit à dix semaines après la remise de l’OSCARPA a été réalisé auprès de 45 proches côtoyant un conducteur âgé d’au moins 65 ans et conduisant au minimum 1 fois par semaine. Globalement, les résultats démontrent que l’OSCARPA augmente i) l’intérêt, l’ouverture et les connaissances des proches (p<0,001), ainsi que leur perception ii) des changements de capacités du conducteur âgé (p=0,02) et iii) de son utilisation de stratégies compensatoires (p=0,001). Afin de poursuivre l’évaluation et d’accroître l’efficacité de l’OSCARPA, de futures études seraient pertinentes.Abstract : This study aimed to explore the impact of an awareness tool for relatives of older drivers (OSCARPA) on i) their interest, openness and knowledge, ii) changes of abilities required for safe driving, and iii) utilization of compensatory strategies. A pre-experimental design with pretest (T0) and post-test (T1) eight to ten weeks after the intervention was realized with 45 relatives in contact with an older driver of 65 years old or older and who was driving at least once a week. Overall, the results demonstrated that OSCARPA increased i) interest, openness and knowledge of relatives (p<0.001), as well as their perceptions of ii) changes of abilities of older drivers (p=0.02), and iii) their utilization of compensatory strategies (p=0.001). Future studies would be relevant to further evaluate and increase the effectiveness of OSCARPA