Questioning "Questioning" as a Sexual Identity and Label : An Interpretive Phenomenological Analysis

Sexual or gender minorities often experience poorer health and mental outcomes than their heterosexually-identified or cisgender peers. Among those often included as sexual or gender minorities are those who identify as questioning; however, little is known about this population, due in part to a dearth of research. Among researchers and the LGBTQ+ community, Questioning has many definitions that further complicate the current understanding of the populations. This qualitative study explored the meaning and lived experience of emerging adults who self-identified as Questioning.   The researcher used an interpretive phenomenological framework to inform the study design. Participants were ten emerging adults who resided in both rural and metropolitan areas of a southeastern state  Two major themes that emerged from the study were the meaning of Questioning and the role of experience. Data revealed three sub-groups of participants who shared perspectives on the Meaning of Questioning: Those who used Questioning as their sexual identity, those who used the label of Questioning as an alternate sexual orientation label, and those who believed that questioning was part of a non-questioning sexual identity that was bisexual or asexual. The role of experience, a second major theme, involved attraction, sexual, and relational experience and served as a necessary component in understanding participants' sexual identity or use of Questioning as a label. Subthemes that emerged from the data included participants' desire for experience, perspectives of the need for, or use of, information gained from experience, and difficulty attaining experience.   Contextual variables, such as implicit and explicit social messages, biphobia, geographical constraints, and religious values were important in understanding participants' stories and voices. This study enabled the researcher to affirm and expand upon commonly recognized meanings of questioning are both solidified and expanded. The implications of findings those who work with emerging adults who identify as Questioning are to explore actively what Questioning means to them and to provide opportunities to explore sexual identity.  Ph.D

Long-term follow-up of IPEX syndrome patients after different therapeutic strategies : an international multicenter retrospective study

Background: Immunodysregulation polyendocrinopathy enteropathy x-linked(IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. Objective: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. Methods: Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. Results: We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n 5 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. Conclusions: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term.disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

Mentorship during transitions

Mentorship has been repeatedly shown to be a necessary component of successful professional development. However, effective mentorship can be elusive to define insofar as you know it when you have it, but it is hard to match the objective qualities of mentorship with the subjective experience of effective and helpful mentoring. This article explores the Collaborative Family Healthcare Association\u27s mentorship program from the perspective of one mentor and two mentees over the course of a yearlong formal relationship. During the year, both mentees had to navigate significant transitions, including changing jobs and having a baby; these experiences are relevant for many new career professionals

Questioning "Questioning" as a Sexual Identity and Label : An Interpretive Phenomenological Analysis

Sexual or gender minorities often experience poorer health and mental outcomes than their heterosexually-identified or cisgender peers. Among those often included as sexual or gender minorities are those who identify as questioning\; however, little is known about this population, due in part to a dearth of research. Among researchers and the LGBTQ+ community, Questioning has many definitions that further complicate the current understanding of the populations. This qualitative study explored the meaning and lived experience of emerging adults who self-identified as Questioning. The researcher used an interpretive phenomenological framework to inform the study design. Participants were ten emerging adults who resided in both rural and metropolitan areas of a southeastern state Two major themes that emerged from the study were the meaning of Questioning and the role of experience. Data revealed three sub-groups of participants who shared perspectives on the Meaning of Questioning: Those who used Questioning as their sexual identity, those who used the label of Questioning as an alternate sexual orientation label, and those who believed that questioning was part of a non-questioning sexual identity that was bisexual or asexual. The role of experience, a second major theme, involved attraction, sexual, and relational experience and served as a necessary component in understanding participants' sexual identity or use of Questioning as a label. Subthemes that emerged from the data included participants' desire for experience, perspectives of the need for, or use of, information gained from experience, and difficulty attaining experience. Contextual variables, such as implicit and explicit social messages, biphobia, geographical constraints, and religious values were important in understanding participants' stories and voices. This study enabled the researcher to affirm and expand upon commonly recognized meanings of questioning are both solidified and expanded. The implications of findings those who work with emerging adults who identify as Questioning are to explore actively what Questioning means to them and to provide opportunities to explore sexual identity

Hyperglycemia regulates cardiac K+ channels via O-GlcNAc-CaMKII and NOX2-ROS-PKC pathways

Chronic hyperglycemia and diabetes lead to impaired cardiac repolarization, K+ channel remodeling and increased arrhythmia risk. However, the exact signaling mechanism by which diabetic hyperglycemia regulates cardiac K+ channels remains elusive. Here, we show that acute hyperglycemia increases inward rectifier K+ current (IK1), but reduces the amplitude and inactivation recovery time of the transient outward K+ current (Ito) in mouse, rat, and rabbit myocytes. These changes were all critically dependent on intracellular O-GlcNAcylation. Additionally, IK1 amplitude and Ito recovery effects (but not Ito amplitude) were prevented by the Ca2+/calmodulin-dependent kinase II (CaMKII) inhibitor autocamtide-2-related inhibitory peptide, CaMKIIδ-knockout, and O-GlcNAc-resistant CaMKIIδ-S280A knock-in. Ito reduction was prevented by inhibition of protein kinase C (PKC) and NADPH oxidase 2 (NOX2)-derived reactive oxygen species (ROS). In mouse models of chronic diabetes (streptozotocin, db/db, and high-fat diet), heart failure, and CaMKIIδ overexpression, both Ito and IK1 were reduced in line with the downregulated K+ channel expression. However, IK1 downregulation in diabetes was markedly attenuated in CaMKIIδ-S280A. We conclude that acute hyperglycemia enhances IK1 and Ito recovery via CaMKIIδ-S280 O-GlcNAcylation, but reduces Ito amplitude via a NOX2-ROS-PKC pathway. Moreover, chronic hyperglycemia during diabetes and CaMKII activation downregulate K+ channel expression and function, which may further increase arrhythmia susceptibility

How Waterfowl Use of Wetland Habitats Can Inform Wetland Restoration Designs for Multi‐Species Benefits

Extensive global estuarine wetland losses have prompted intensive focus on restoration of these habitats. In California, substantial tracts of freshwater, brackish and tidal wetlands have been lost. Given the anthropogenic footprint of development and urbanization in this region, wetland restoration must rely on conversion of existing habitat types rather than adding new wetlands. These restorations can cause conflicts among stakeholders and species that win or lose depending on identified restoration priorities. Suisun Marsh on the San Francisco Bay Estuary is the largest brackish marsh on the US Pacific coast. To understand how conversion of brackish managed wetlands to tidal marsh would impact waterfowl populations and whether future tidal marsh restorations could provide suitable habitat for dabbling ducks, we examined waterfowl wetland use with a robust GPS-GSM tracking dataset (442,017 locations) from six dabbling duck species (N = 315). Managed wetlands, which comprise 47% of Suisun Marsh, were consistently and strongly selected by waterfowl over tidal marshes, with use ~98% across seasons and species. However, while use of tidal marsh (only 14% of Suisun Marsh) was generally \u3c2%, almost half our ducks (~44%) spent some time in this habitat and exhibited strong utilization of pond-like features. Ponds only comprise ~10% of this habitat but attracted 44% use (~4.5 times greater than availability). Synthesis and applications. Managed wetlands were vital to dabbling ducks, but losses from conversion of these habitats may be partially mitigated by incorporating pond features that are more attractive to waterfowl, and likely to offer multi-species benefits, into tidal marsh restoration designs. While waterfowl are presently a common taxon, previously seen calamitous population declines can be avoided through informed ecosystem-based management that promotes species richness, biodiversity and helps ‘keep common species common’