PINK1 is a mitochondrial kinase proposed to have a role in the pathogenesis of Parkinson's disease through the regulation of mitophagy. Here, we show that the PINK1 main cleavage product, PINK152, ...after being generated inside mitochondria, can exit these organelles and localize to the cytosol, where it is not only destined for degradation by the proteasome but binds to Parkin. The interaction of cytosolic PINK1 with Parkin represses Parkin translocation to the mitochondria and subsequent mitophagy. Our work therefore highlights the existence of two cellular pools of PINK1 that have different effects on Parkin translocation and mitophagy.
Synopsis
The kinase PINK1, mutants of which are associated with Parkinson disease development, is thought to function in mitochondria. Here, PINK1 is shown to participate in maintaining a healthy pool of mitochondria also by functioning in the cytosol, where it interacts with Parkin.
Cleaved PINK152 is retrotranslocated from mitochondria into the cytosol.
PINK152 directly interacts with Parkin in the cytosol and prevents Parkin mitochondrial translocation.
Cytosolic PINK152 attenuates valinomycin‐induced mitophagy.
PINK1, mutants of which are associated with Parkinson, is thought to function in mitochondria. Here, PINK1 is shown to be exported into the cytosol after cleavage, where it binds Parkin, inhibiting its mitochondrial recruitment and preventing mitophagy.
Treatment teams providing affirmative medical transgender care to young people frequently face moral challenges arising from the care they provide. An adolescent’s capacity to consent, for example, ...could raise several issues and challenges. To deal with these challenges more effectively, several Dutch treatment teams started using a relatively well-established form of clinical ethics support (CES) called Moral Case Deliberation (MCD). MCD is a facilitator-led, collective moral inquiry based on a real case. This study’s purpose is to describe the teams’ perceived value and effectiveness of MCD. We conducted a mixed methods evaluation study using MCD session reports, individual interviews, focus groups, and MCD evaluation questionnaires. Our results show that Dutch transgender care providers rated MCD as highly valuable in situations where participants were confronted with moral challenges. The health care providers reported that MCD increased mutual understanding and open communication among team members and strengthened their ability to make decisions and take action when managing ethically difficult circumstances. However, the health care providers also expressed criticisms of MCD: some felt that the amount of time spent discussing individual cases was excessive, that MCD should lead to more practical and concrete results, and that MCD needed better integration and follow-up in the regular work process. We recommend future research on three matters: studying how MCD contributes to the quality of care, involvement of transgender people themselves in MCD, and integration of CES into daily work processes.
When deciding whether to eat inside a restaurant or how many health protection items to purchase, individuals in the coronavirus disease (COVID-19) era tend to consider the infection risk of crowds ...of generalized others. With a field study and four experiments, the present study identifies associations between COVID-19 and friendship (e.g., thinking of a friend while reading COVID-19-related news, perceiving a friend as the source of infection, noting friends' presence during potential COVID-19 exposure) that decrease both infection risk perceptions and protective behaviors. The sense of safety that stems from psychological closeness of friends reduces perceived virus infection risks associated with third-party crowds. The distinction between psychological closeness and safety toward friends versus acquaintances widens with clear in-group/out-group boundaries, such that this friend-shield effect is especially pronounced among people whose group boundaries are well established. Limiting interactions to close friends and family members is a common protective measure to reduce COVID-19 transmission risk, but the study findings demonstrate that this practice also unintentionally creates other issues, in that people tend to perceive reduced health risks and engage in potentially hazardous health behaviors. By identifying this risk and encouraging more holistic responses, this research offers implications for individuals, health officials, and policymakers.
Public Significance Statement
Even in the face of health measures designed to limit interactions to reduce coronavirus disease (COVID-19) transmission, people experience reduced risk perceptions and engage in riskier behaviors when COVID-19 is associated with their friends. Noting this link, this research shows individuals, health practitioners, and policymakers that they need to consider the effects of social distancing measures on psychological risk perceptions and behaviors when designing and implementing complementary health campaigns.
OBJECTIVES:
Puberty suppression (PS) is a cornerstone of treatment in youth experiencing gender dysphoria. In this study, we aim to inform prescribing professionals on the long-term effects of PS ...treatment on the development of sex characteristics and surgical implications.
METHODS:
Participants received PS according to the Endocrine Society guideline at Tanner 2 or higher. Data were collected from adolescents who received PS between 2006 and 2013 and from untreated transgender controls. Data collection pre- and post-PS and before surgery included physical examination and surgical information.
RESULTS:
In total, 300 individuals (184 transgender men and 116 transgender women) were included. Of these, 43 individuals started PS treatment at Tanner 2/3, 157 at Tanner 4/5, and 100 used no PS (controls). Breast development was significantly less in transgender men who started PS at Tanner 2/3 compared with those who started at Tanner 4/5 and controls. Mastectomy was more frequently omitted or less invasive after PS. In transgender women, the mean penile length was significantly shorter in the PS groups compared with controls (by 4.8 cm Tanner 2/3 and 2.1 cm Tanner 4/5). As a result, the likelihood of undergoing intestinal vaginoplasty was increased (odds ratio = 84 Tanner 2/3; odds ratio = 9.8 Tanner 4/5).
CONCLUSIONS:
PS reduces the development of sex characteristics in transgender adolescents. As a result, transgender men may not need to undergo mastectomy, whereas transgender women may require an alternative to penile inversion vaginoplasty. These surgical implications should inform decision-making when initiating PS.
Objective: Disorders/differences of sex development (DSD) refer to congenital conditions with atypical sex development and are associated with psychosexual issues. The aim of this study was to assess ...body image and self-esteem across the DSD spectrum and to study the impact of diagnosis and mediating characteristics. Method: Data collection was part of dsd-LIFE, a cross-sectional study conducted by 14 European expert clinics on wellbeing and health care evaluation of adults diagnosed with DSD. Main outcome measures in the present analyses were the Body Image Scale and Rosenberg Self-Esteem Scale. Additional data were obtained on treatments, openness, body embarrassment, sexual satisfaction, anxiety, and depression. Results: The participating sample (n = 1,040) included 226 classified as Congenital Adrenal Hyperplasia, 225 as Klinefelter Syndrome, 322 as Turner Syndrome, and 267 as conditions with 46,XY karyotype. Many participants had received hormonal and surgical treatments. Participants scored lower on body image and self-esteem compared to control values, whereas each diagnosis showed different areas of concern. Limited openness, body embarrassment, and sexual issues were frequently reported. Overall body satisfaction was associated with BMI, hormone use, openness, body embarrassment, anxiety, and depression; genital satisfaction with age at diagnosis, openness, sexual satisfaction, and body embarrassment. Body embarrassment, anxiety, and depression predicted lower self-esteem. Conclusions: While each DSD showed specific issues related to body image and self-esteem, our findings indicate that the related factors were similar across the conditions. Clinical care on this subject could be improved by giving specific attention to factors like openness, body embarrassment, sexuality, anxiety, and depression.
Early gender-affirmative treatment (GAT) of adolescents may consist of puberty suppression, use of affirming hormones, and gender-affirmative surgeries. This treatment can potentially influence ...sexual development. In the current study, we describe sexual and romantic development during and after treatment.
The participants were 113 transgender adolescents treated with puberty suppression, affirmative hormones, and affirmative surgery who were assessed as young adults (38 transwomen and 75 transmen; mean age 20.79 years, SD 1.36) during and after their GAT. A questionnaire on sexual experiences, romantic experiences, and subjective sexual experiences was administered and compared to the experiences of a same-aged sample from a Dutch general population study (
= 4020).
One year post surgery, young transgender adults reported a significant increase in experiences with all types of sexual activities: masturbation increased from 56.4% to 81.7%, petting while undressed increased from 57.1% to 78.7%, and sexual intercourse increased from 16.2% to 37.6% post surgery compared to presurgery. Young transmen and transwomen were almost equally experienced. In comparison with the general population, young transgender adults were less experienced with all types of sexual activities.
Early GAT (including puberty suppression, affirmative hormones, and surgeries) may provide young transgender adults with the opportunity to increase their romantic and sexual experiences.
Neonatal stroke in premature neonates Steggerda, S.J.; de Vries, L.S.
Seminars in perinatology,
November 2021, 2021-11-00, 20211101, Letnik:
45, Številka:
7
Journal Article
Recenzirano
Odprti dostop
There are many neuro-imaging studies on the presence of brain lesions in the preterm infant, using cranial ultrasound (cUS) and/or term equivalent age MRI (TEA-MRI). These studies however tend to ...focus on germinal matrix-intraventricular hemorrhage (GMH-IVH) and white matter injury. Data about perinatal arterial ischemic stroke (PAIS) or cerebral sinovenous thrombosis (CSVT) in the preterm infant are very limited. In fact, several large cohort studies on neuro-imaging in preterm infants do not even mention neonatal stroke.1-4 Most studies about PAIS exclude preterm infants.5 The aim of this review was to provide an update on neonatal stroke in the preterm infant, with a focus on neuro-imaging findings.
The current literature shows growing evidence of a link between gender dysphoria (GD) and autism spectrum disorder (ASD). This study reviews the available clinical and empirical data. A systematic ...search of the literature was conducted using the following databases: PubMed, Web of Science, PsycINFO and Scopus; utilizing different combinations of the following search terms: autism, autism spectrum disorder (ASD), Asperger's disorder (AD), co-morbidity, gender dysphoria (GD), gender identity disorder (GID), transgenderism and transsexualism. In total, 25 articles and reports were selected and discussed. Information was grouped by found co-occurrence rates, underlying hypotheses and implications for diagnosis and treatment. GD and ASD were found to co-occur frequently - sometimes characterized by atypical presentation of GD, which makes a correct diagnosis and determination of treatment options for GD difficult. Despite these challenges there are several case reports describing gender affirming treatment of co-occurring GD in adolescents and adults with ASD. Various underlying hypotheses for the link between GD and ASD were suggested, but almost all of them lack evidence.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Transgender adolescents may present to gender identity specialty services earlier or later in adolescence. The aim of this study was to examine whether, ‘younger’ and ‘older’ presenters could be ...identified in a large cohort of transgender adolescents and if differences exist between the two groups. The study sample consisted of 1487 adolescents (506 birth-assigned males, 981 birth-assigned females) referred between 2000 and 2018. The distribution of age at intake was evaluated. Demographic, diagnostic, and treatment characteristics, the Recalled Childhood Gender Identity/Gender Role Questionnaire (RCGI) to measure childhood gender nonconformity and the Body Image Scale (BIS) to measure body image were collected. Based on a stem-and-leaf plot and a histogram, two groups were identified: adolescents presenting at ≤ 13.9 years (‘younger presenters’) and adolescents presenting at 14 years or older (‘older presenters’). The sex ratio was more extreme in the group of older presenters favoring birth-assigned females (
Χ
2
(1,
N
= 1487) = 19.69,
p
< 0.001). Furthermore, more adolescents from the younger presenting group lived with both biological parents (
Χ
2
(1,
N
= 1427) = 24.78,
p
< 0.001), were diagnosed with gender dysphoria and started with medical gender-affirming treatment (
Χ
2
(1,
N
= 1404) = 4.60,
p
= 0.032 and
Χ
2
(1,
N
= 1487) = 29.16,
p
< 0.001). Younger presenters showed more gender nonconformity in childhood (
β
0.315,
p
< 0.001, 95% CI 0.224–0.407). Older presenters were more dissatisfied with various aspects of their bodies (
p
< 0.001). The differences between older and younger presenting adolescents suggest that there may be different developmental pathways in adolescents that lead to seeking gender-affirming medical care and argues for more tailored care.
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