Parkinson's disease gene, Synaptojanin1, dysregulates the surface maintenance of the dopamine transporter.

Missense mutations of PARK20/SYNJ1 (synaptojanin1/Synj1) were found in complex forms of familial Parkinsonism. However, the Synj1-regulated molecular and cellular changes associated with dopaminergic dysfunction remain unknown. We now report a fast depletion of evoked dopamine and impaired maintenance of the axonal dopamine transporter (DAT) in the Synj1 haploinsufficient (Synj1+/-) neurons. While Synj1 has been traditionally known to facilitate the endocytosis of synaptic vesicles, we provide in vitro and in vivo evidence demonstrating that Synj1 haploinsufficiency results in an increase of total DAT but a reduction of the surface DAT. Synj1+/- neurons exhibit maladaptive DAT trafficking, which could contribute to the altered DA release. We showed that the loss of surface DAT is associated with the impaired 5'-phosphatase activity and the hyperactive PI(4,5)P2-PKCß pathway downstream of Synj1 deficiency. Thus, our findings provided important mechanistic insight for Synj1-regulated DAT trafficking integral to dysfunctional DA signaling, which might be relevant to early Parkinsonism.

Parkinson's disease gene, Synaptojanin1, dysregulates the surface maintenance of the dopamine transporter.

Missense mutations of PARK20/SYNJ1 (synaptojanin1/Synj1) have been linked to complex forms of familial parkinsonism, however, the molecular and cellular changes associated with dopaminergic dysfunction remains unknown. We now report fast depletion of evoked dopamine (DA) and altered maintenance of the axonal dopamine transporter (DAT) in the Synj1+/- neurons. While Synj1 has been traditionally known to facilitate the endocytosis of synaptic vesicles, we demonstrated that axons of cultured Synj1+/- neurons exhibit an increase of total DAT but a reduction of the surface DAT, which could be exacerbated by neuronal activity. We revealed that the loss of surface DAT is specifically associated with the impaired 5'-phosphatase activity of Synj1 and the hyperactive downstream PI(4,5)P2-PKCß pathway. Thus, our findings provided important mechanistic insight for Synj1-regulated DAT trafficking integral to dysfunctional DA signaling in early parkinsonism.

Female authorship trends and the effect of COVID-19 on cataract and refractive surgery literature.

PURPOSE: To evaluate whether gender barriers persist specifically in the cataract and refractive surgery (CRS) literature. In addition, no literature exists investigating the long-term effect of COVID-19 on female authorship in ophthalmology past 2020. SETTING: Scopus 2015 to 2022. DESIGN: Retrospective data review. METHODS: Articles published in the Journal of Refractive Surgery and the Journal of Cataract & Refractive Surgery were recorded from January 2015 to February 2022 from Scopus. Articles with only 1 author or where gender could not be identified were excluded. The first author (FA) gender, senior author (SA) gender, affiliated country, type of literature, and number of citations were collected. Pearson chi-squared tests with phi coefficients and multivariate logistic regression were performed. RESULTS: 3153 articles were included in analysis. There were 910 works with female FAs and 648 with female SAs. Gender did not predict publishing in one journal over the other (P > .050). Women made up less than 30% of authorship of all types of literature, except for prospective/observational studies as FA (31.3%). Compared with before 2020, female FAs from 2020 onward were associated with increased retrospective analysis (phi = 0.072, P = .030) and letters/editorials (phi = 0.134, P < .001) but decreased case reports (phi = 0.087, P = .009) and "others" (phi = -0.164, P < .001). Similar associations were observed for female SAs. Females were more likely to publish in Asian countries. Female SAs predicted an increased likelihood of female FAs (odds ratio, 1.401, 95% CI, 1.165-1.684, P < .001). CONCLUSIONS: Gender disparities exist in authorship of the CRS literature. COVID-19 has altered the types of literature published by women, but men still publish most of all types of CRS research.

Effects of Lifestyle Modification Interventions to Prevent and Manage Child and Adolescent Obesity: A Systematic Review and Meta-Analysis.

The objective of this review was to assess the impact of lifestyle interventions (including dietary interventions, physical activity, behavioral therapy, or any combination of these interventions) to prevent and manage childhood and adolescent obesity. We conducted a comprehensive literature search across various databases and grey literature without any restrictions on publication, language, or publication status until February 2020. We included randomized controlled trials and quasi-experimental studies from both high income countries (HIC) and low-middle-income countries (LMICs). Participants were children and adolescents from 0 to 19 years of age. Studies conducted among hospitalized children and children with any pre-existing health conditions were excluded from this review. A total of 654 studies (1160 papers) that met the inclusion criteria were included in this review. A total of 359 studies targeted obesity prevention, 280 studies targeted obesity management, while 15 studies targeted both prevention and management. The majority of the studies (81%) were conducted in HICs, 10% of studies were conducted in upper middle income countries, while only 2% of the studies were conducted in LMICs. The most common setting for these interventions were communities and school settings. Evidence for the prevention of obesity among children and adolescents suggests that a combination of diet and exercise might reduce the BMI z-score (MD: -0.12; 95% CI: -0.18 to -0.06; 32 studies; 33,039 participants; I2 93%; low quality evidence), body mass index (BMI) by 0.41 kg/m2 (MD: -0.41 kg/m2; 95% CI: -0.60 to -0.21; 35 studies; 47,499 participants; I2 98%; low quality evidence), and body weight (MD: -1.59; 95% CI: -2.95 to -0.23; 17 studies; 35,023 participants; I2 100%; low quality evidence). Behavioral therapy alone (MD: -0.07; 95% CI: -0.14 to -0.00; 19 studies; 8569 participants; I2 76%; low quality evidence) and a combination of exercise and behavioral therapy (MD: -0.08; 95% CI: -0.16 to -0.00; 9 studies; 7334 participants; I2 74%; low quality evidence) and diet in combination with exercise and behavioral therapy (MD: -0.13; 95% CI: -0.25 to -0.01; 5 studies; 1806 participants; I2 62%; low quality evidence) might reduce BMI z-score when compared to the control group. Evidence for obesity management suggests that exercise only interventions probably reduce BMI z-score (MD: -0.13; 95% CI: -0.20 to -0.06; 12 studies; 1084 participants; I2 0%; moderate quality evidence), and might reduce BMI (MD: -0.88; 95% CI: -1.265 to -0.50; 34 studies; 3846 participants; I2 72%) and body weight (MD: -3.01; 95% CI: -5.56 to -0.47; 16 studies; 1701 participants; I2 78%; low quality evidence) when compared to the control group. and the exercise along with behavioral therapy interventions (MD: -0.08; 95% CI: -0.16 to -0.00; 8 studies; 466 participants; I2 49%; moderate quality evidence), diet along with behavioral therapy interventions (MD: -0.16; 95% CI: -0.26 to -0.07; 4 studies; 329 participants; I2 0%; moderate quality evidence), and combination of diet, exercise and behavioral therapy (MD: -0.09; 95% CI: -0.14 to -0.05; 13 studies; 2995 participants; I2 12%; moderate quality evidence) also probably decreases BMI z-score when compared to the control group. The existing evidence is most favorable for a combination of interventions, such as diet along with exercise and exercise along with behavioral therapy for obesity prevention and exercise alone, diet along with exercise, diet along with behavioral therapy, and a combination of diet, exercise, and behavioral therapy for obesity management. Despite the growing obesity epidemic in LMICs, there is a significant dearth of obesity prevention and management studies from these regions.