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Dozens of new antiviral systems have been recently characterized in bacteria. Some of these systems are present in eukaryotes and appear to have originated in prokaryotes, but little is known about these defense mechanisms in archaea. Here, we explore the diversity and distribution of defense systems in archaea and identify 2610 complete systems in Asgardarchaeota, a group of archaea related to eukaryotes. The Asgard defense systems comprise 89 unique systems, including argonaute, NLR, Mokosh, viperin, Lassamu, and CBASS. Asgard viperin and argonaute proteins have structural homology to eukaryotic proteins, and phylogenetic analyses suggest that eukaryotic viperin proteins were derived from Asgard viperins. We show that Asgard viperins display anti-phage activity when heterologously expressed in bacteria. Eukaryotic and bacterial argonaute proteins appear to have originated in Asgardarchaeota, and Asgard argonaute proteins have argonaute-PIWI domains, key components of eukaryotic RNA interference systems. Our results support that Asgardarchaeota played important roles in the origin of antiviral defense systems in eukaryotes., (© 2024. The Author(s).)

Context: Treatment for transmasculine youth (TMY) can involve testosterone treatment and is sometimes preceded by gonadotropin-releasing hormone agonist (GnRHa) treatment for puberty blockade. GnRHas can increase final height in birth-assigned females with central precocious puberty. Maximizing final adult height (FAH) is an important outcome for many TMY., Objective: Our objective was to determine how GnRHa treatment before testosterone impacts FAH., Methods: Retrospective cohort study at 5 US transgender health clinics. Participants were 32 TMY treated with GnRHas in early to midpuberty before testosterone (GnRHa + T group) and 62 late/postpubertal TMY treated with testosterone only (T-only group)., Results: The difference between FAH minus midparental target height (MPTH) was +2.3 ± 5.7 cm and -2.2 ± 5.6 cm in the GnRHa + T and T-only groups, respectively ( P < .01). In the GnRHa + T group, FAH was 1.8 ± 3.4 cm greater than predicted adult height (PAH) ( P < .05) and FAH vs initial height (IH) z-score was 0.5 ± 1.2 vs 0.16 ± 1.0 ( P < .05). After adjusting for patient characteristics, each additional month of GnRHa monotherapy increased FAH by 0.59 cm (95% CI 0.31, 0.9 cm), stage 3 breast development at start of GnRHa was associated with 6.5 cm lower FAH compared with stage 2 (95% CI -10.43, -2.55), and FAH was 7.95 cm greater in the GnRHa + T group than in T-only group (95% CI -10.85, -5.06)., Conclusion: Treatment with GnRHa in TMY in early puberty before testosterone increases FAH compared with MPTH, PAH, IH, and TMY who only received testosterone in late/postpuberty. TMY considering GnRHas should be counseled that GnRHas may mildly increase their FAH if started early., (Published by Oxford University Press on behalf of the Endocrine Society 2024.)

Human immunodeficiency virus (HIV) prevention and treatment remain critically important to outpatient care among transgender and gender-nonbinary individuals. Epidemiologically, trans men and trans women are significantly more likely to have HIV compared with all adults of reproductive age. Here, we provide an overview of unique primary care considerations affecting transgender and gender-nonbinary individuals, including screening and treatment of HIV and other sexually transmitted infections as well as cancer screening and fertility preservation options. We also seek to review current literature and clinical practice guidelines related to drug-drug interactions between antiretroviral therapy (ART) and gender-affirming hormonal therapy (GAHT). In short, integrase strand transfer inhibitor-based therapy is not expected to have significant drug interactions with most GAHT and is preferred in most transgender individuals, including those on GAHT. Clinicians should also remain aware of current GAHT regimens and consider tailoring ART and GAHT to reduce cardiovascular and other risk factors., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: As the healthcare needs of transgender patients become increasingly recognized and supported, gender-affirming surgery services are in increasing demand. However, establishing a gender-affirming surgery service is unlike many other surgical specialties and requires unique expertise and administrative support. The aim of this article is to outline the considerations for starting a gender-affirming surgery service and identify pearls for success., Methods: In this article, we describe the critical components of building and maintaining a successful gender-affirming surgery service. We intersperse findings from our own experiences developing a gender-affirming surgery service., Results: A successful gender-affirming surgery service starts by developing a clear vision of the patient population within your hospital system's area, as well as the design of your center. Establishing a center relies on early engagement of hospital administration and its continued support. A multidisciplinary team with intensive interpersonal and operative training offers the best patient experience and surgical outcomes. By following these steps, our service has been able to provide gender-affirming surgery to more than 200 patients since its inception. Future goals entail partnerships with other institutions and continued outcomes evaluation to ensure sustained success of all gender-affirming surgery services., Conclusion: Although there are unique challenges and considerations for establishing a gender-affirming surgery service, careful planning and stakeholder engagement allow providers to deliver high-quality care. We hope that our experience can serve as a model for future much needed gender-affirming surgery services., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective : A series of studies report elevated rates of autism and autistic characteristics among gender-diverse youth seeking gender services. Although youth with the co-occurrence present with complex care needs, existing studies have focused on co-occurrence rates. Further, clinical commentaries have emphasized provider-centered interpretations of clinical needs rather than key stakeholder-driven clinical approaches. This study aimed to employ community-based participatory research methodologies to develop a key stakeholder-driven clinical group program. Method : Autistic/neurodiverse gender-diverse (A/ND-GD) youth ( N = 31), parents of A/ND-GD youth ( N = 46), A/ND-GD self-advocates ( N = 10), and expert clinical providers ( N = 10) participated in a multi-stage community-based participatory procedure. Needs assessment data were collected repeatedly over time from A/ND-GD youth and their parents as the youth interacted with one another through ongoing clinical groups, the curriculum of which was developed progressively through the iterative needs assessments. Results : Separate adolescent and parent needs assessments revealed key priorities for youth (e.g., the importance of connecting with other A/ND-GD youth and the benefit of experiencing a range of gender-diverse role models to make gender exploration and/or gender affirmation more concrete) and parents (e.g., the need for A/ND-related supports for their children as well as provision of an A/ND-friendly environment that fosters exploration of a range of gender expressions/options). Integration and translation of youth and parent priorities resulted in 11 novel clinical techniques for this population. Conclusions : With generally high acceptability ratings for each component of the group program, this study presents a community-driven clinical model to support broad care needs and preferences of A/ND-GD adolescents.

Summary: This review discusses the current evidence regarding perioperative hormone therapy for transgender individuals, with an emphasis on strategies to reduce the risk of perioperative venous thromboembolism. Historically, surgeons routinely discontinued estrogen therapy in the perioperative period with the goal of reducing the risk of venous thromboembolism. However, abrupt estrogen cessation may also lead to adverse emotional and physiologic effects, including an exacerbation of one's gender dysphoria. The data on the relationship of feminizing hormones and venous thromboembolism in the perioperative setting are largely based on extrapolation of hormone regimens that are no longer in use and may not accurately reflect the actual risk of venous thromboembolism. Future studies will allow surgeons to engage in evidence-based, patient-centered, informed consent while also minimizing the risk of complications, such as venous thromboembolism., (Copyright © 2021 by the American Society of Plastic Surgeons.)

Objectives: Mindfulness is effective for reducing anxiety and depression and increasing chronic disease self-management. An accessible, insurance-reimbursable model for implementation in patient-centered medical homes within US healthcare systems has promise for patients with multi-morbid conditions. Clarifying both the dose needed to impact anxiety, depression and self-management, and the design requirements for accessible primary care implementation, is essential., Methods: We tested feasibility, acceptability, and effectiveness of Mindfulness Training for Primary Care (MTPC), an 8-week, referral-based, insurance-reimbursable mindfulness program integrated within primary care, compared with a Low-Dose Comparator (LDC), consisting of a 60-minute mindfulness introduction plus referral to community and digital resources. Outcome measures were assessed at baseline and 8 weeks. MTPC is trauma-informed, incorporates mindfulness-oriented behavior change skills, and is designed to target anxiety, depression, stress, and chronic illness selfmanagement. Participants schedule a PCP visit to co-create a self-management action plan during week 6., Results: Primary care providers (PCP) referred 344 patients over 14 months. Eighty-one participants with DSM-V anxiety disorders, depressive disorders, trauma- and stress-related disorders participated in this pilot randomized-controlled comparative effectiveness trial [MTPC (n=54); LDC (n=27)]. These data suggest that MTPC was more effective than LDC for reducing anxiety ( p =0.01), enhancing mindfulness ( p =0.02) and self-compassion ( p =0.001), and for catalyzing selfmanagement behavior change through action plan initiation (OR=4.34, p =0.03)., Conclusions: MTPC was successfully integrated into a health system, was billed to insurance, and was acceptable to a diverse primary care population. Replication with a larger study and further accessibility adaptations are needed to confirm and expand these pilot results., Competing Interests: Conflict of Interest: The authors declare no conflict of interest.

Background: Self-management of health is important for improving health outcomes among primary care patients with chronic disease. Anxiety and depressive disorders are common and interfere with self-regulation, which is required for disease self-management. An insurance-reimbursable mindfulness intervention integrated within primary care may be effective for enhancing chronic disease self-management behaviors among primary care patients with anxiety, depression, trauma, and stress-related and adjustment disorders compared with the increasingly standard practice of referring patients to outside mindfulness resources., Objective: Mindfulness Training for Primary Care (MTPC) is an 8-week, referral-based, insurance-reimbursable program integrated into safety-net health system patient-centered medical homes. We hypothesized that MTPC would be more effective for catalyzing chronic disease self-management action plan initiation within 2 weeks, versus a low-dose comparator (LDC) consisting of a 60-min mindfulness introduction, referral to community and digital resources, and addition to a 6-month waitlist for MTPC., Participants: Primary care providers (PCPs) and mental health clinicians referred 465 patients over 12 months. All participants had a DSM-V diagnosis., Design and Interventions: Participants (N = 136) were randomized in a 2:1 allocation to MTPC (n = 92) or LDC (n = 44) in a randomized controlled comparative effectiveness trial. MTPC incorporates mindfulness, self-compassion, and mindfulness-oriented behavior change skills and is delivered as insurance-reimbursable visits within primary care. Participants took part in a chronic disease self-management action planning protocol at week 7., Main Measures: Level of self-reported action plan initiation on the action plan initiation survey by week 9., Key Results: Participants randomized to MTPC, relative to LDC, had significantly higher adjusted odds of self-management action plan initiation in an intention-to-treat analysis (OR = 2.28; 95% CI = 1.02 to 5.06, p = 0.025)., Conclusions: An 8-week dose of mindfulness training is more effective than a low-dose mindfulness comparator in facilitating chronic disease self-management behavior change among primary care patients.

Purpose: There is concern among physicians that the rising use of technology in medicine may have a negative impact on compassionate patient-centered care. This study explores medical student attitudes and ideas about technology in medicine in order to consider ways to achieve symbiosis between technology use and the delivery of humanistic, patient-centered care., Methods: This qualitative study uses data from 138 essays written by medical students in the United States and Canada responding to the prompt "Using a real life experience, describe how technology played a role, either negatively or positively, in the delivery of humanistic patient care." Data were analyzed for themes about technology and the impact on humanistic patient care., Results: Seven themes emerged from the medical students' essays: Patient Perspective; Life-Giving versus Life-Prolonging; Boundaries between Human and Technology; Distancing versus Presence; Adapting to Change; Tools to Enhance Care; and Definitions of Technology., Conclusion: Listening to medical students lends insight into ways to integrate technology into the healthcare environment, to ensure that physicians' ability to deliver compassionate care is enhanced, not hindered. Utilizing perceptions of the next generation of physicians, educational and developmental strategies are proposed to ensure the successful integration of technology with humanistic patient-centered care.

Graduates of Harvard Medical School's Cambridge Integrated Clerkship (CIC) describe several core processes that may underlie professional identity formation (PIF): encouragement to integrate pre-professional and professional identities; support for learner autonomy in discovering meaningful roles and responsibilities; learning through caring relationships; and a curriculum and an institutional culture that make values explicit. The authors suggest that the benefits of educational integrity accrue when idealistic learners inhabit an educational model that aligns with their own core values, and when professional development occurs in the context of an institutional home that upholds these values. Medical educators should clarify and animate principles within curricula and learning environments explicitly in order to support the professional identity formation of their learners.

Given a growing emphasis on early intervention for children with autism, valid quantitative tools for measuring treatment response are needed. The Social Responsiveness Scale (SRS) is a brief (15-20 minute) quantitative measure of autistic traits in 4-to 18-year-olds, for which a version for 3-year-olds was recently developed. We obtained serial SRS measurements on 73 preschool children with (n = 51) and without (n = 22) autism spectrum conditions. Inter-rater reliability (mothers and teachers) and test-retest reliability were of the order of 0.75 (Pearson's r). There was substantial agreement between SRS scores and (1) the Vineland Adaptive Behavior Composite (Pearson's r = -0.86) and (2) scores for social impairment on the Autism Diagnostic Interview-Revised (r = 0.63). Overall, quantitative autistic trait scores tended to improve over time in preschoolers, irrespective of treatment conditions. We conclude that it is possible to obtain reliable quantitative measurements of autistic social impairment in preschoolers, suitable for assessing treatment response.

Sarcodes sanguinea is a nonphotosynthetic mycoheterotrophic plant that obtains all of its fixed carbon from neighboring trees through a shared ectomycorrhizal fungus. We studied the spatial structuring of this tripartite symbiosis in a forest where Sarcodes is abundant, and its only fungal and photosynthetic plant associates are Rhizopogon ellenae and Abies magnifica, respectively. We found disproportionately high concentrations of Abies roots adjacent to Sarcodes roots compared to the surrounding soil. Rhizopogon ellenae colonizes the vast majority of those Abies roots (86-98%), and its abundance tends to decrease with increasing distance from Sarcodes plants. At 500 cm from Sarcodes plants we did not detect R. ellenae, and the ectomycorrhizal community instead was dominated by members of the Russulaceae and Thelephoraceae, which are commonly dominant in other California pinaceous forests. The highly clumped distribution of Abies-R. ellenae ectomycorrhizas indicates that Sarcodes plants either establish within pre-existing clumps, or they stimulate clump formation. Several lines of evidence favor the latter interpretation, suggesting an unexpected mutualistic aspect to the symbiosis. However, the mechanism involved remains unknown.

Homobasidiomycete fungi display many complex fruiting body morphologies, including mushrooms and puffballs, but their anatomical simplicity has confounded efforts to understand the evolution of these forms. We performed a comprehensive phylogenetic analysis of homobasidiomycetes, using sequences from nuclear and mitochondrial ribosomal DNA, with an emphasis on understanding evolutionary relationships of gilled mushrooms and puffballs. Parsimony-based optimization of character states on our phylogenetic trees suggested that strikingly similar gilled mushrooms evolved at least six times, from morphologically diverse precursors. Approximately 87% of gilled mushrooms are in a single lineage, which we call the "euagarics." Recently discovered 90 million-year-old fossil mushrooms are probably euagarics, suggesting that (i) the origin of this clade must have occurred no later than the mid-Cretaceous and (ii) the gilled mushroom morphology has been maintained in certain lineages for tens of millions of years. Puffballs and other forms with enclosed spore-bearing structures (Gasteromycetes) evolved at least four times. Derivation of Gasteromycetes from forms with exposed spore-bearing structures (Hymenomycetes) is correlated with repeated loss of forcible spore discharge (ballistospory). Diverse fruiting body forms and spore dispersal mechanisms have evolved among Gasteromycetes. Nevertheless, it appears that Hymenomycetes have never been secondarily derived from Gasteromycetes, which suggests that the loss of ballistospory has constrained evolution in these lineages.