Cortisol Responses to Naturally Occurring Psychosocial Stressors Across the Psychosis Spectrum: A Systematic Review and Meta-Analysis.

BACKGROUND: Individuals with established psychosis and those at high-risk for the disorder have been found to show abnormalities within the hypothalamic-pituitary-adrenal (HPA) axis, including elevations in basal and diurnal cortisol, but a blunted cortisol awakening response. However, the extent to which these features are associated with psychosocial stressors encountered in the natural environment (which are known to be more commonly experienced by these groups, and more distressing) is currently unclear. We therefore conducted a systematic review and meta-analysis to investigate the concordance between naturally-occurring psychosocial stressors and cortisol levels in these populations. METHODS: PubMed, PsycINFO, and EMBASE were searched up to November 2019 to identify studies examining the concordance between psychosocial stressors and cortisol in healthy controls and individuals on the psychosis spectrum (patients with established psychosis and/or high-risk individuals). An overall meta-analysis (including data for all stressor-cortisol pairings) was performed to determine the degree of concordance irrespective of group status, with meta-regression employed to test whether the degree of concordance differed in established psychosis and high-risk groups compared to controls. Planned stratified analyses were then performed to examine group differences (where established psychosis and high-risk groups were combined) within individual stressor-cortisol pairings. RESULTS: Eighteen studies (16 datasets) were eligible for inclusion. The overall model, comprising 134 effect sizes, showed that stressors and cortisol measures were only weakly correlated [r=0.05 (95% CI: -0.00 to 0.10), p=0.059] and that neither established psychosis status (r=0.01, p=0.838) nor high-risk status (r=0.02, p=0.477) had a significant effect of the strength of correlation. In stratified analyses, significant differences between healthy controls and psychosis spectrum groups were observed for only one of the six stressor-cortisol pairings examined, where life event exposure and diurnal cortisol were positively correlated in controls [r=0.25 (95% CI: 0.01 to 0.46)], but negatively correlated in the psychosis spectrum group [r=-0.28 (95% CI: -0.49 to -0.04)]. CONCLUSIONS: Overall, we observed poor concordance between naturally-occurring psychosocial stressors and cortisol irrespective of stressor type, cortisol measure, or group status. We consider a range of methodological factors that may have obscured the ability to detect "true" associations and provide recommendations for future studies in this field.

Feasibility and acceptability of ambulatory glucose profile in children with Type 1 diabetes mellitus: A pilot study.

BACKGROUND: Insulin administration and self-monitoring of blood glucose (SMBG) are pillars in the management of diabetes in children. Introduction of continuous glucose monitoring (CGM) has made it possible to understand the glycemic profiles which are not picked up by SMBG. Recent advent of flash glucose monitoring with inbuilt software to obtain ambulatory glucose profile (AGP) has emerged as a novel method to study glycemic patterns in adults with Type I diabetes. However, the use of AGP in children is yet to be explored. METHODS: AGP was used in 46 children with Type 1 diabetes mellitus. Feasibility was measured regarding data and sensor failure. Acceptability was measured using a questionnaire. RESULTS: Forty-six children (22 girls and 24 boys) with a mean age of 10.07 years and mean diabetes duration of 3.4 years were included in the study. In this cohort, for 30 (65.21%) subjects, the sensor remained in situ for a complete duration of 14 days. Except for minor discomfort, AGP was well accepted by most of the children and their parents. CONCLUSION: AGP is a feasible option for monitoring glycemic status in children with diabetes with a high rate of acceptance.

Adult vision screenings in Omaha, Nebraska.

PURPOSE: The purpose of this study was to examine the association between risk factors and failing vision screening tests to better identify populations at high risk for age-related eye diseases and vision impairments. METHODS: A retrospective review of 839 vision screening forms from an ongoing vision screening program in Omaha, Nebraska, was conducted. Univariate and multivariate logistic regression analyses were used. RESULTS: Sex, age, ethnicity, and persistent pain were independently associated with failing the visual field test in multivariate analysis. Persistent pain and glaucoma diagnosis were independently associated with failing the visual acuity test. CONCLUSIONS: Female sex, age older than 65, African American or Hispanic ethnicity, glaucoma diagnosis, and persistent eye pain were significant risk factors for failing a vision screening test. Vision screenings should focus on targeting populations that exhibit these risk factors.

Mutational analysis of the poly(ADP-ribosyl)ation sites of the transcription factor CTCF provides an insight into the mechanism of its regulation by poly(ADP-ribosyl)ation.

Poly(ADP-ribosyl)ation of the conserved multifunctional transcription factor CTCF was previously identified as important to maintain CTCF insulator and chromatin barrier functions. However, the molecular mechanism of this regulation and also the necessity of this modification for other CTCF functions remain unknown. In this study, we identified potential sites of poly(ADP-ribosyl)ation within the N-terminal domain of CTCF and generated a mutant deficient in poly(ADP-ribosyl)ation. Using this CTCF mutant, we demonstrated the requirement of poly(ADP-ribosyl)ation for optimal CTCF function in transcriptional activation of the p19ARF promoter and inhibition of cell proliferation. By using a newly generated isogenic insulator reporter cell line, the CTCF insulator function at the mouse Igf2-H19 imprinting control region (ICR) was found to be compromised by the CTCF mutation. The association and simultaneous presence of PARP-1 and CTCF at the ICR, confirmed by single and serial chromatin immunoprecipitation assays, were found to be independent of CTCF poly(ADP-ribosyl)ation. These results suggest a model of CTCF regulation by poly(ADP-ribosyl)ation whereby CTCF and PARP-1 form functional complexes at sites along the DNA, producing a dynamic reversible modification of CTCF. By using bioinformatics tools, numerous sites of CTCF and PARP-1 colocalization were demonstrated, suggesting that such regulation of CTCF may take place at the genome level.

Somatically acquired hypomethylation of IGF2 in breast and colorectal cancer.

The imprinted insulin-like growth factor 2 (IGF2) gene is expressed predominantly from the paternal allele. Loss of imprinting (LOI) associated with hypomethylation at the promoter proximal sequence (DMR0) of the IGF2 gene was proposed as a predisposing constitutive risk biomarker for colorectal cancer. We used pyrosequencing to assess whether IGF2 DMR0 methylation is either present constitutively prior to cancer or whether it is acquired tissue-specifically after the onset of cancer. DNA samples from tumour tissues and matched non-tumour tissues from 22 breast and 42 colorectal cancer patients as well as peripheral blood samples obtained from colorectal cancer patients [SEARCH (n=case 192, controls 96)], breast cancer patients [ABC (n=case 364, controls 96)] and the European Prospective Investigation of Cancer [EPIC-Norfolk (n=breast 228, colorectal 225, controls 895)] were analysed. The EPIC samples were collected 2-5 years prior to diagnosis of breast or colorectal cancer. IGF2 DMR0 methylation levels in tumours were lower than matched non-tumour tissue. Hypomethylation of DMR0 was detected in breast (33%) and colorectal (80%) tumour tissues with a higher frequency than LOI indicating that methylation levels are a better indicator of cancer than LOI. In the EPIC population, the prevalence of IGF2 DMR0 hypomethylation was 9.5% and this correlated with increased age not cancer risk. Thus, IGF2 DMR0 hypomethylation occurs as an acquired tissue-specific somatic event rather than a constitutive innate epimutation. These results indicate that IGF2 DMR0 hypomethylation has diagnostic potential for colon cancer rather than value as a surrogate biomarker for constitutive LOI.

Optic disc melanocytoma and glaucoma.

An 82-year-old man presented with optic disc melanocytoma and glaucomatous optic neuropathy. The coexistence of these findings is particularly challenging, as there is no specific means for differentiating whether the optic nerve damage is glaucoma- or melanocytoma-related.

Intracameral 2.3% sodium hyaluronate to treat postoperative hypotony in patients with glaucoma.

BACKGROUND AND OBJECTIVE: To evaluate the intracameral use of Healon5 (2.3% sodium hyaluronate) (Advanced Medical Optics, Santa Ana, CA) in patients with hypotony. PATIENTS AND METHODS: Fifteen consecutive patients with glaucoma who had hypotony for at least 7 days were prospectively recruited. Indications for the intracameral injection of Healon5 were an intraocular pressure (IOP) of less than 6 mm Hg with negative results on Seidel test. RESULTS: The mean IOP readings at baseline, 1 to 2 weeks post-injection, and 4 to 6 weeks post-injection were 3.8 +/- 1.58, 6.58 +/- 2.62, and 6.50 +/- 2.24 mm Hg, respectively. The increase in IOP at both follow-up points was significant (P < .01). The visual acuity improvement was small but significant at the 4 to 6 week point (P = .05). In the early-onset cases, IOP increased significantly from baseline at both follow-up points (P< .05), but visual acuity did not. No significant change from baseline IOP or visual acuity occurred among the late-onset cases. The existing hypotony-related conditions consistently improved by the 4 to 6 week point. CONCLUSIONS: Intracameral injection of Healon5 raised IOP more in early-onset hypotony cases than in late-onset cases. Although the improvements in IOP and visual acuity were statistically significant, the overall clinical picture did not change because the endpoint IOP was still hypotonus. Twenty percent of the patients had IOP spikes that required medical treatment.

Level of disagreement between Proview phosphene tonometer and Goldmann applanation tonometer intraocular pressure readings.

PURPOSE: To evaluate the agreement of intraocular pressure (IOP) readings obtained with the Proview phosphene tonometer and those obtained by Goldmann applanation tonometry as well as the effect of regular use of the Proview on patients' anxiety about their glaucoma. METHODS: One hundred thirty-five consecutive patients with glaucoma, 35 designated as controls, were enrolled in a 10-month randomized prospective clinical trial. The study patients but not the controls used the Proview outside the office. At office visits IOP was measured by an ophthalmologist with the Goldmann applanation tonometer (GAT) as well as by examiners and patients using the Proview. Patients in the treatment group (n = 100) were asked to measure and record their IOP at home as well. Using ANOVA, we examined the relationship between demographic variables and the level of agreement between the Proview readings and those measured by GAT at the final office visit. All participants also were asked to complete a questionnaire regarding their anxiety about their IOP at the baseline and final office visits. The primary outcome measure was the level of agreement of the Proview measurements with those obtained by GAT. Secondary outcome measures included patients' anxiety about their glaucoma. RESULTS: The absolute mean difference between GAT and Proview readings at the final visit was 3.5 +/- 2.9 mm Hg (median, 2.8 mm Hg). The treatment group reported significantly less anxiety about their glaucoma after 4 to 6 weeks of using the Proview (P = .024). CONCLUSIONS: There was considerable discrepancy between Proview and GAT readings. However, regular use of the Proview tonometer significantly reduced patients' anxiety about their glaucoma.

Results of the use of the Ex-PRESS miniature glaucoma implant in technically challenging, advanced glaucoma cases: a clinical pilot study.

PURPOSE: To report results of implantation of the Ex-PRESS Miniature Glaucoma Implant (Optonol, Neve Ilan, Israel) shunt directly under the conjunctiva in advanced glaucoma. DESIGN: Noncomparative case series. METHODS: Chart review of eleven cases of Ex-PRESS implantation. Outcome measures included intraocular pressure (IOP), complications, visual acuity, and additional interventions. Failure was defined as unacceptably high IOP requiring revision or explantation. RESULTS: Four patients (36%) failed. Ten (91%) experienced hypotony during postoperative week one. In the seven nonfailures, mean pre and postoperative IOPs were 30.3 +/- 9.3 mm Hg and 13.6 +/- 4.4 mm Hg, respectively (P = .006). The logMAR visual acuity did not change significantly from baseline to follow up (logMAR 1.1 +/- 0.9 and 1.4 +/- 0.9, respectively, P = .13). There were no intraoperative complications. Postoperative complications in the 11 eyes included choroidal detachment in 3 (27%) and suprachoroidal hemorrhage in 2 (18%). Of the 7 successful cases, additional interventions were required in 4 (57%). CONCLUSIONS: Despite significant IOP reduction, the incidence of complications following Ex-PRESS implantation directly under the conjunctiva was unacceptably high in this group of patients.