Indigenous knowledge and the shackles of wilderness.

The environmental crises currently gripping the Earth have been codified in a new proposed geological epoch: the Anthropocene. This epoch, according to the Anthropocene Working Group, began in the mid-20th century and reflects the "great acceleration" that began with industrialization in Europe [J. Zalasiewicz et al., Anthropocene 19, 55-60 (2017)]. Ironically, European ideals of protecting a pristine "wilderness," free from the damaging role of humans, is still often heralded as the antidote to this human-induced crisis [J. E. M. Watson et al., Nature, 563, 27-30 (2018)]. Despite decades of critical engagement by Indigenous and non-Indigenous observers, large international nongovernmental organizations, philanthropists, global institutions, and nation-states continue to uphold the notion of pristine landscapes as wilderness in conservation ideals and practices. In doing so, dominant global conservation policy and public perceptions still fail to recognize that Indigenous and local peoples have long valued, used, and shaped "high-value" biodiverse landscapes. Moreover, the exclusion of people from many of these places under the guise of wilderness protection has degraded their ecological condition and is hastening the demise of a number of highly valued systems. Rather than denying Indigenous and local peoples' agency, access rights, and knowledge in conserving their territories, we draw upon a series of case studies to argue that wilderness is an inappropriate and dehumanizing construct, and that Indigenous and community conservation areas must be legally recognized and supported to enable socially just, empowering, and sustainable conservation across scale.

Updated clinical practice recommendations for managing adults with 22q11.2 deletion syndrome.

This review aimed to update the clinical practice guidelines for managing adults with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society recruited expert clinicians worldwide to revise the original clinical practice guidelines for adults in a stepwise process according to best practices: (1) a systematic literature search (1992-2021), (2) study selection and synthesis by clinical experts from 8 countries, covering 24 subspecialties, and (3) formulation of consensus recommendations based on the literature and further shaped by patient advocate survey results. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text review, with 2318 meeting inclusion criteria (clinical care relevance to 22q11.2DS) including 894 with potential relevance to adults. The evidence base remains limited. Thus multidisciplinary recommendations represent statements of current best practice for this evolving field, informed by the available literature. These recommendations provide guidance for the recognition, evaluation, surveillance, and management of the many emerging and chronic 22q11.2DS-associated multisystem morbidities relevant to adults. The recommendations also address key genetic counseling and psychosocial considerations for the increasing numbers of adults with this complex condition.

The Medical Institutional Repositories in Libraries (MIRL) Symposium: a blueprint designed in response to a community of practice need.

Background: Health sciences libraries in medical schools, academic health centers, health care networks, and hospitals have established institutional repositories (IRs) to showcase their research achievements, increase visibility, expand the reach of institutional scholarship, and disseminate unique content. Newer roles for IRs include publishing open access journals, tracking researcher productivity, and serving as repositories for data sharing. Many repository managers oversee their IR with limited assistance from others at their institution. Therefore, IR practitioners find it valuable to network and learn from colleagues at other institutions. Case Presentation: This case report describes the genesis and implementation of a new initiative specifically designed for a health sciences audience: the Medical Institutional Repositories in Libraries (MIRL) Symposium. Six medical librarians from hospitals and academic institutions in the U.S. organized the inaugural symposium held virtually in November 2021. The goal was to fill a perceived gap in conference programming for IR practitioners in health settings. Themes of the 2021 and subsequent 2022 symposium included IR management, increasing readership and engagement, and platform migration. Post-symposium surveys were completed by 73/238 attendees (31%) in 2021 and by 62/180 (34%) in 2022. Feedback was overwhelmingly positive. Discussion: Participant responses in post-symposium surveys rated MIRL highly. The MIRL planning group intends to continue the symposium and hopes MIRL will steadily evolve, build community among IR practitioners in the health sciences, and expand the conversation around best practices for digital archiving of institutional content. The implementation design of MIRL serves as a blueprint for collaboratively bringing together a professional community of practice.

Sexual knowledge and behaviour in 22q11.2 deletion syndrome, a complex care condition.

BACKGROUND: There is limited information about sexual knowledge and behaviours in adults with complex care needs, including those with 22q11.2 deletion syndrome (22q) which represents a group predisposed to intellectual disabilities. METHODS: We conducted sexual health assessments with 67 adults with 22q, examining whether those with knowledge deficits and a history of engaging in sexual activities with others would be more likely to engage in high-risk behaviours. RESULTS: The majority (65.7%) of adults with 22q were sexually active with others; most (70.1%) had sexual knowledge deficits. Those with intellectual disabilities were more likely (p = .0012) to have deficits in certain topics. In the sexually active subgroup, most (81.8%) engaged in high-risk sexual behaviours, regardless of intellectual disability or knowledge deficits. CONCLUSION: The results suggest a need for increased dialogue, repeated education, genetic counselling and preventive healthcare measures related to sexuality in 22q and potentially in other complex care conditions.

Age-Related Parkinsonian Signs in Microdeletion 22q11.2.

BACKGROUND: The recurrent hemizygous 22q11.2 deletion associated with 22q11.2 deletion syndrome has been identified as a genetic risk factor for early-onset PD. However, little is known about early motor signs in this condition. OBJECTIVES: We examined the presence, severity and possible factors associated with parkinsonism in adults with 22q11.2 deletion syndrome and without PD. METHODS: We compared motor signs between 82 adults with 22q11.2 deletion syndrome and 25 healthy controls, using the MDS-UPDRS part III, and three-dimensional motion-tracker technology to quantify components of bradykinesia. RESULTS: Median MDS-UPDRS part III total and bradykinesia subscores were significantly higher in 22q11.2 deletion syndrome (median age: 26 years; range, 17-65) than in controls (P = 0.000; P = 0.000, respectively). Age was a significant contributor to bradykinesia subscore (B = 0.06; P = 0.01) and to the electronic bradykinesia component, velocity (B = -0.02; P = 0.000); psychotic illness did not significantly impact these analyses. In 22q11.2 deletion syndrome, MDS-UPDRS-defined bradykinesia was present in 18.3%, rigidity in 14.6%, and rest tremor in 12.2%. CONCLUSIONS: Parkinsonian motor signs appear to be common and age related in 22q11.2 deletion syndrome. Longitudinal studies are needed to investigate possible symptom progression to PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Service user and family participation in mental health policy making in Timor-Leste: a qualitative study with multiple stakeholders.

BACKGROUND: Participation in mental health system strengthening by people with mental health problems and their families is a cornerstone of people-centred mental health care, yet there is a dearth of research about participation from low- and middle-income countries (LMICs), particularly from the Asia Pacific region. Hence, this study aimed to assess the current situation, challenges, enabling factors and future actions for service user and family participation in mental health policy making in Timor-Leste. METHODS: In-depth interviews were conducted with 85 adults (≥18 years) who were: (1) mental health service users (n = 20) and their families (n = 10); (2) government decision makers (n = 10); (3) mental health and social service providers (n = 23); (4) civil society (n = 9); and (5) other groups (n = 13). Interview data was analysed using framework analysis. RESULTS: There was limited service user, family and community participation in mental health policy making in Timor-Leste. Perceptions that policy making is a technical exercise and that people with mental health problems lack cognitive capacity, and a lack of supportive mechanisms challenged participation. Enabling factors were a strong focus on human rights within the social sector, and existing mechanisms for advocacy and representation of people with disabilities in social policy making. Participants suggested bolstering civil society representation of people with mental health problems, and increasing mental health awareness and literacy, including government competencies to facilitate service user participation. CONCLUSION: The findings highlight the need for theoretical and practical focus on the role of family within mental health system development in LMICs. Global mental health research and practice should adopt a critical approach to mental health service user and family participation to ensure that the concept and strategies to achieve this are embedded in LMIC knowledge.

Low prevalence of substance use in people with 22q11.2 deletion syndrome.

BACKGROUND: 22q11.2 deletion syndrome (22q11DS), one of the most common recurrent copy number variant disorders, is associated with dopaminergic abnormalities and increased risk for psychotic disorders. AIMS: Given the elevated prevalence of substance use and dopaminergic abnormalities in non-deleted patients with psychosis, we investigated the prevalence of substance use in 22q11DS, compared with that in non-deleted patients with psychosis and matched healthy controls. METHOD: This cross-sectional study involved 434 patients with 22q11DS, 265 non-deleted patients with psychosis and 134 healthy controls. Psychiatric diagnosis, full-scale IQ and COMT Val158Met genotype were determined in the 22q11DS group. Substance use data were collected according to the Composite International Diagnostic Interview. RESULTS: The prevalence of total substance use (36.9%) and substance use disorders (1.2%), and weekly amounts of alcohol and nicotine use, in patients with 22q11DS was significantly lower than in non-deleted patients with psychosis or controls. Compared with patients with 22q11DS, healthy controls were 20 times more likely to use substances in general (P < 0.001); results were also significant for alcohol and nicotine use separately. Within the 22q11DS group, there was no relationship between the prevalence of substance use and psychosis or COMT genotype. Male patients with 22q11DS were more likely to use substances than female patients with 22q11DS. CONCLUSIONS: The results suggest that patients with 22q11DS are at decreased risk for substance use and substance use disorders despite the increased risk of psychotic disorders. Further research into neurobiological and environmental factors involved in substance use in 22q11DS is necessary to elucidate the mechanisms involved. DECLARATION OF INTEREST: None.

Social inclusion and exclusion of people with mental illness in Timor-Leste: a qualitative investigation with multiple stakeholders.

BACKGROUND: Social inclusion is a human right for all people, including people with mental illness. It is also an important part of recovery from mental illness. In Timor-Leste, no research has investigated the social experiences of people with mental illness and their families. To fill this knowledge gap and inform ongoing mental health system strengthening, we investigated the experiences of social inclusion and exclusion of people with mental illness and their families in Timor-Leste. METHODS: Eighty-five participants from the following stakeholder groups across multiple locations in Timor-Leste were interviewed: (1) people with mental illness and their families; (2) mental health and social service providers; (3) government decision makers; (4) civil society members; and (5) other community members. Framework analysis was used to analyse interview transcripts. RESULTS: People with mental illness in Timor-Leste were found to face widespread, multi-faceted sociocultural, economic and political exclusion. People with mental illness were stigmatised as a consequence of beliefs that they were dangerous and lacked capacity, and experienced instances of bullying, physical and sexual violence, and confinement. Several barriers to formal employment, educational, social protection and legal systems were identified. Experiences of social inclusion for people with mental illness were also described at family and community levels. People with mental illness were included through family and community structures that promoted unity and acceptance. They also had opportunities to participate in activities surrounding family life and livelihoods that contributed to intergenerational well-being. Some, but not all, Timorese people with mental illness benefited from disability-inclusive programming and policies, including the disability pension, training programs and peer support. CONCLUSIONS: These findings highlight the need to combat social exclusion of people with mental illness and their families by harnessing local Timorese sociocultural strengths. Such an approach could centre around people with mental illness and their families to: increase population mental health awareness; bolster rights-based and culturally-grounded mental health services; and promote inclusive and accessible services and systems across sectors.

The institutional repository landscape in medical schools and academic health centers: a 2018 snapshot view and analysis.

OBJECTIVE: This study uses survey research methods to gain a deeper understanding of the institutional repository (IR) landscape in medical schools and academic health centers. METHODS: Members of the Association of Academic Health Sciences Libraries (AAHSL) were surveyed about their IRs. The authors used a mixed-methods approach of a survey and qualitative content analysis to identify common themes. RESULTS: Survey results indicate that a large majority of responding medical schools and academic health centers have or are implementing an IR (35 out of 50, 70%). Of these, 60% (21 institutions) participate in an institution-wide IR rather than administer their own repositories. Much of the archived content is grey literature that has not already been published, but the percentage of original content varies greatly among institutions. The majority (57.1%) of respondent institutions are not considering an open access policy or mandate. Most institutions (71.4%) reported that repository staff are depositing materials on behalf of users. DSpace and bepress Digital Commons are the most popular repository platforms in this community. The planned enhancements that were most frequently reported were implementing a discovery layer and ORCID integration. The majority of respondents (54.3%) do not plan to migrate to a different platform in the foreseeable future. Analysis of respondent comments identified the following themes: integration, redundancy, and reporting; alternatives and exploration; uniqueness; participation; and funding and operations. CONCLUSIONS: The study results capture a view of the IR landscape in medical schools and academic health centers and help readers understand what services their peers have in place as well as their plans for future developments.

Elucidating the diagnostic odyssey of 22q11.2 deletion syndrome.

Clinical molecular testing has been available for 22q11.2 deletion syndrome (22q11.2DS) for over two decades yet under-recognition and diagnostic delays are common. To characterize the "diagnostic odyssey" in 22q11.2DS we studied 202 well-characterized unrelated adults, none ascertained through an affected relative. We used a regression model to identify clinical and demographic factors associated with length of time to molecular diagnosis. Kaplan-Meier analysis compared time to diagnosis for the molecular testing era (since 1994) and earlier birth cohorts. The results showed that the median time to molecular diagnosis of the 22q11.2 deletion was 4.7 (range 0-20.7) years. Palatal and cardiac anomalies, but not developmental delay/intellectual disability, were associated with a shorter time to molecular diagnosis. Non-European ethnicity was associated with longer time to diagnosis. Inclusion of a cohort from another 22q11.2DS center increased power to observe a significantly earlier diagnosis for patients born in the molecular testing era. Nonetheless, only a minority were diagnosed in the first year of life. On average, patients were seen in seven (range 2-15) different clinical specialty areas prior to molecular diagnosis. The findings indicate that even for those born in the molecular testing era, individuals with 22q11.2DS and their families face a diagnostic odyssey that is often prolonged, particularly in the absence of typical physical congenital features or for those of non-European ancestry. The results support educational efforts to improve clinical recognition and testing, and ultimately newborn screening as a means of maximizing early detection that would provide the best opportunity to optimize outcomes.

Research evaluation support services in biomedical libraries.

Objective: The paper provides a review of current practices related to evaluation support services reported by seven biomedical and research libraries. Methods: A group of seven libraries from the United States and Canada described their experiences with establishing evaluation support services at their libraries. A questionnaire was distributed among the libraries to elicit information as to program development, service and staffing models, campus partnerships, training, products such as tools and reports, and resources used for evaluation support services. The libraries also reported interesting projects, lessons learned, and future plans. Results: The seven libraries profiled in this paper report a variety of service models in providing evaluation support services to meet the needs of campus stakeholders. The service models range from research center cores, partnerships with research groups, and library programs with staff dedicated to evaluation support services. A variety of products and services were described such as an automated tool to develop rank-based metrics, consultation on appropriate metrics to use for evaluation, customized publication and citation reports, resource guides, classes and training, and others. Implementing these services has allowed the libraries to expand their roles on campus and to contribute more directly to the research missions of their institutions. Conclusions: Libraries can leverage a variety of evaluation support services as an opportunity to successfully meet an array of challenges confronting the biomedical research community, including robust efforts to report and demonstrate tangible and meaningful outcomes of biomedical research and clinical care. These services represent a transformative direction that can be emulated by other biomedical and research libraries.

Augmentation of CFTR maturation by S-nitrosoglutathione reductase.

S-nitrosoglutathione (GSNO) reductase regulates novel endogenous S-nitrosothiol signaling pathways, and mice deficient in GSNO reductase are protected from airways hyperreactivity. S-nitrosothiols are present in the airway, and patients with cystic fibrosis (CF) tend to have low S-nitrosothiol levels that may be attributed to upregulation of GSNO reductase activity. The present study demonstrates that 1) GSNO reductase activity is increased in the cystic fibrosis bronchial epithelial (CFBE41o(-)) cells expressing mutant F508del-cystic fibrosis transmembrane regulator (CFTR) compared with the wild-type CFBE41o(-) cells, 2) GSNO reductase expression level is increased in the primary human bronchial epithelial cells expressing mutant F508del-CFTR compared with the wild-type cells, 3) GSNO reductase colocalizes with cochaperone Hsp70/Hsp90 organizing protein (Hop; Stip1) in human airway epithelial cells, 4) GSNO reductase knockdown with siRNA increases the expression and maturation of CFTR and decreases Stip1 expression in human airway epithelial cells, 5) increased levels of GSNO reductase cause a decrease in maturation of CFTR, and 6) a GSNO reductase inhibitor effectively reverses the effects of GSNO reductase on CFTR maturation. These studies provide a novel approach to define the subcellular location of the interactions between Stip1 and GSNO reductase and the role of S-nitrosothiols in these interactions.

Hypoxia-induced changes in protein s-nitrosylation in female mouse brainstem.

Exposure to hypoxia elicits an increase in minute ventilation that diminishes during continued exposure (roll-off). Brainstem N-methyl-D-aspartate receptors (NMDARs) and neuronal nitric oxide synthase (nNOS) contribute to the initial hypoxia-induced increases in minute ventilation. Roll-off is regulated by platelet-derived growth factor receptor-ß (PDGFR-ß) and S-nitrosoglutathione (GSNO) reductase (GSNOR). S-nitrosylation inhibits activities of NMDAR and nNOS, but enhances GSNOR activity. The importance of S-nitrosylation in the hypoxic ventilatory response is unknown. This study confirms that ventilatory roll-off is virtually absent in female GSNOR(+/-) and GSNO(-/-) mice, and evaluated the location of GSNOR in female mouse brainstem, and temporal changes in GSNOR activity, protein expression, and S-nitrosylation status of GSNOR, NMDAR (1, 2A, 2B), nNOS, and PDGFR-ß during hypoxic challenge. GSNOR-positive neurons were present throughout the brainstem, including the nucleus tractus solitarius. Protein abundances for GSNOR, nNOS, all NMDAR subunits and PDGFR-ß were not altered by hypoxia. GSNOR activity and S-nitrosylation status temporally increased with hypoxia. In addition, nNOS S-nitrosylation increased with 3 and 15 minutes of hypoxia. Changes in NMDAR S-nitrosylation were detected in NMDAR 2B at 15 minutes of hypoxia. No hypoxia-induced changes in PDGFR-ß S-nitrosylation were detected. However, PDGFR-ß phosphorylation increased in the brainstems of wild-type mice during hypoxic exposure (consistent with roll-off), whereas it did not rise in GSNOR(+/-) mice (consistent with lack of roll-off). These data suggest that: (1) S-nitrosylation events regulate hypoxic ventilatory response; (2) increases in S-nitrosylation of NMDAR 2B, nNOS, and GSNOR may contribute to ventilatory roll-off; and (3) GSNOR regulates PDGFR-ß phosphorylation.

Phenotype of asthmatics with increased airway S-nitrosoglutathione reductase activity.

S-Nitrosoglutathione is an endogenous airway smooth muscle relaxant. Increased airway S-nitrosoglutathione breakdown occurs in some asthma patients. We asked whether patients with increased airway catabolism of this molecule had clinical features that distinguished them from other asthma patients. We measured S-nitrosoglutathione reductase expression and activity in bronchoscopy samples taken from 66 subjects in the Severe Asthma Research Program. We also analysed phenotype and genotype data taken from the program as a whole. Airway S-nitrosoglutathione reductase activity was increased in asthma patients (p=0.032). However, only a subpopulation was affected and this subpopulation was not defined by a "severe asthma" diagnosis. Subjects with increased activity were younger, had higher IgE and an earlier onset of symptoms. Consistent with a link between S-nitrosoglutathione biochemistry and atopy: 1) interleukin 13 increased S-nitrosoglutathione reductase expression and 2) subjects with an S-nitrosoglutathione reductase single nucleotide polymorphism previously associated with asthma had higher IgE than those without this single nucleotide polymorphism. Expression was higher in airway epithelium than in smooth muscle and was increased in regions of the asthmatic lung with decreased airflow. An early-onset, allergic phenotype characterises the asthma population with increased S-nitrosoglutathione reductase activity.

Hemoglobin α/eNOS coupling at myoendothelial junctions is required for nitric oxide scavenging during vasoconstriction.

OBJECTIVE: Hemoglobin α (Hb α) and endothelial nitric oxide synthase (eNOS) form a macromolecular complex at myoendothelial junctions; the functional role of this interaction remains undefined. To test if coupling of eNOS and Hb α regulates nitric oxide signaling, vascular reactivity, and blood pressure using a mimetic peptide of Hb α to disrupt this interaction. APPROACH AND RESULTS: In silico modeling of Hb α and eNOS identified a conserved sequence of interaction. By mutating portions of Hb α, we identified a specific sequence that binds eNOS. A mimetic peptide of the Hb α sequence (Hb α X) was generated to disrupt this complex. Using in vitro binding assays with purified Hb α and eNOS and ex vivo proximity ligation assays on resistance arteries, we have demonstrated that Hb α X significantly decreased interaction between eNOS and Hb α. Fluorescein isothiocyanate labeling of Hb α X revealed localization to holes in the internal elastic lamina (ie, myoendothelial junctions). To test the functional effects of Hb α X, we measured cyclic guanosine monophosphate and vascular reactivity. Our results reveal augmented cyclic guanosine monophosphate production and altered vasoconstriction with Hb α X. To test the in vivo effects of these peptides on blood pressure, normotensive and hypertensive mice were injected with Hb α X, which caused a significant decrease in blood pressure; injection of Hb α X into eNOS(-/-) mice had no effect. CONCLUSIONS: These results identify a novel sequence on Hb α that is important for Hb α/eNOS complex formation and is critical for nitric oxide signaling at myoendothelial junctions.

Loss of collectrin, an angiotensin-converting enzyme 2 homolog, uncouples endothelial nitric oxide synthase and causes hypertension and vascular dysfunction.

BACKGROUND: Collectrin is an orphan member of the renin-angiotensin system and is a homolog of angiotensin-converting enzyme 2, sharing ≈50% sequence identity. Unlike angiotensin-converting enzyme 2, collectrin lacks any catalytic domain. Collectrin has been shown to function as a chaperone of amino acid transporters. In rodents, the renal expression of collectrin is increased after subtotal nephrectomy and during high-salt feeding, raising the question of whether collectrin has any direct role in blood pressure regulation. METHODS AND RESULTS: Using a susceptible genetic background, we demonstrate that deletion of collectrin results in hypertension, exaggerated salt sensitivity, and impaired pressure natriuresis. Collectrin knockout mice display impaired endothelium-dependent vasorelaxation that is associated with vascular remodeling, endothelial nitric oxide synthase uncoupling, decreased nitric oxide production, and increased superoxide generation. Treatment with Tempol, a superoxide scavenger, attenuates the augmented sodium sensitivity in collectrin knockout mice. We report for the first time that collectrin is expressed in endothelial cells. Furthermore, collectrin directly regulates l-arginine uptake and plasma membrane levels of CAT1 and y(+)LAT1 amino acid transporters in endothelial cells. Treatment with l-arginine modestly lowers blood pressure of collectrin knockout mice. CONCLUSIONS: Collectrin is a consequential link between the transport of l-arginine and endothelial nitric oxide synthase uncoupling in hypertension.

The role of regulatory proteins and S-nitrosylation of endothelial nitric oxide synthase in the human clitoris: implications for female sexual function.

INTRODUCTION: During female sexual arousal, clitoral blood flow is controlled by endothelial nitric oxide synthase (eNOS) and its product, nitric oxide (NO). The mechanisms regulating eNOS activity and NO bioavailability in the clitoris are largely unknown. AIM: To identify proteins involved in regulation of eNOS activity within the clitoris and to evaluate the effects of S-nitrosoglutathione reductase (GSNO-R) and eNOS nitrosylation/denitrosylation on clitoral blood flow. METHODS: Immunohistochemistry for eNOS, caveolin-1 (Cav1), heat shock protein-90 (Hsp90), phosphodiesterase type 5 (PDE5), GSNO-R, and soluble guanylate cyclase (sGC) was performed on human and murine clitoral tissue. Western blot analysis was performed for eNOS, phosphorylated eNOS (phospho-eNOS, Ser1177), Cav1, Hsp90, sGC, PDE5, phosphoinositide 3-kinase (PI3K), Akt (protein kinase B), and GSNO-R on protein from human clitoral tissue. A biotin switch assay was used to analyze the S-nitrosylation of eNOS, nNOS, and GSNO-R. Clitoral blood flow was measured in wild-type and GSNO-R(-/-) mice at baseline and during cavernous nerve electrical stimulation (CNES). MAIN OUTCOME MEASURES: Localization of eNOS regulatory proteins and clitoral blood flow. RESULTS: eNOS and GSNO-R co-localized to the vascular endothelium and sinusoids of human clitoral tissue. Immunohistochemistry also localized Cav1 and Hsp90 to the endothelium and PDE5 and sGC to the trabecular smooth muscle. Expression of S-nitrosylated (SNO)-eNOS and SNO-GSNO-R was detected by biotin switch assays. Wild-type control mice exhibited increased clitoral blood flow with CNES whereas GSNO-R(-/-) animals failed to show an increase in blood flow. CONCLUSIONS: Several key eNOS regulatory proteins are present in the clitoral tissue in a cellular specific pattern. S-nitrosylation of eNOS may also represent a key regulatory mechanism governing eNOS activation/deactivation since mice deficient in GSNO-R failed to increase clitoral blood flow. Additional studies are necessary to define the role of S-nitrosylation in the genital vascular response and its subsequent impact on female sexual function.

The mental health and traumatic experiences of mothers of children with 22q11DS.

Background: 22q11 Deletion Syndrome (22q11DS) is the most common microdeletion syndrome with broad phenotypic variability, leading to significant morbidity and some mortality. The varied health problems associated with 22q11DS and the evolving phenotype (both medical and developmental/behavioural) across the lifespan can strongly impact the mental health of patients as well as their caregivers. Like caregivers of children with other chronic diseases, caregivers of children with 22q11DS may experience an increased risk of traumatisation and mental health symptoms.Objective: The study's primary objective was to assess the frequency of traumatic experiences and mental health symptoms among mothers of children with 22q11DS. The secondary objective was to compare their traumatic experiences to those of mothers of children with other neurodevelopmental disorders (NDDs).Method: A total of 71 mothers of children diagnosed with 22q11DS completed an online survey about their mental health symptoms and traumatic experiences. Descriptive statistics were used to summarise the prevalence of their mental health symptoms and traumatic experiences. Logistic regression models were run to compare the traumatic experiences of mothers of children with 22q11DS to those of 335 mothers of children with other neurodevelopmental disorders (NDDs).Results: Many mothers of children with 22q11DS experienced clinically significant mental health symptoms, including depression (39%), anxiety (25%), and post-traumatic stress disorder (PTSD) symptoms (30%). The types of traumatic events experienced by mothers of children with 22q11DS differed from those of mothers of children with other NDDs as they were more likely to observe their child undergoing a medical procedure, a life-threatening surgery, or have been with their child in the intensive care unit.Conclusion: 22q11DS caregivers are likely to require mental health support and trauma-informed care, tailored to the specific needs of this population as they experience different kinds of traumatic events compared to caregivers of children with other NDDS.

Mothers of children with 22q11DS experience clinically significant levels of depression, anxiety, and PTSD.Mothers of children with 22q11DS experience many and diverse trauma particularly related to medical interventions of their child.The types of traumatic events experienced by mothers of children with 22q11DS are different from those of the mothers of children with other neurodevelopmental disorders.