Rates of glaucomatous visual field change before and after transscleral cyclophotocoagulation: a retrospective case series

BACKGROUND: The primary goal of glaucoma treatment is to lower and control intraocular pressure (IOP) and thereby prevent functional deterioration. For glaucomas that are refractory to medical and incisional surgical therapies, transscleral diode cyclophotocoagulation (TCP) is a well-established procedure to effectively decrease IOP. This study investigated rates of visual field (VF) change in patients with glaucoma before and after TCP. METHODS: This retrospective case series investigated rates of VF changes in glaucoma patients before and after they underwent TCP. At least four VF examinations were required, two before and two after surgery. VF examinations were performed using standard automated perimetry and rates of change were calculated by linear regression analysis of mean deviation (MD) values measured over time. RESULTS: A total of 46 eyes of 43 patients were included and followed on average 3.6 years before and 2.1 years after TCP. 67 % of the eyes showed further progression of glaucoma following surgery. Mean preoperative MD change was -0.21 dB/year (SE = 0.08, 95 % CI [-0.06, -0.37]). Postoperatively the mean change was -0.26 dB/year (SE = 0.22 95 % CI [0.38, -0.48]) which results in a difference between pre- and postoperative MD rate of 0.05 dB/year (p = 0.824). The mean MD value was worse after surgery and dropped by 1.73 dB (SE = 0.58, 95 % CI [-0.59, -2.87], p = 0.003). Intraocular pressure (IOP) decreased from 23.2 mmHg (SD = 4.67) before TCP to 14.3 mmHg (SD = 3.17) after TCP (p < 0.001). For each 1 mmHg of IOP reduction after surgery, postoperative rate of VF loss decreased by 0.15 dB/year. CONCLUSION: Rates of glaucomatous visual field loss did not significantly change after TCP and the majority of the eyes showed further progression of glaucoma after surgery. Mean MD value was considerably lower after TCP

Ultrafast structural changes direct the first molecular events of vision

視覚に関わるタンパク質の超高速分子動画 --薄暗いところで光を感じる仕組み--. 京都大学プレスリリース. 2023-03-23.Vision is initiated by the rhodopsin family of light-sensitive G protein-coupled receptors (GPCRs). A photon is absorbed by the 11-cis retinal chromophore of rhodopsin, which isomerizes within 200 femtoseconds to the all-trans conformation, thereby initiating the cellular signal transduction processes that ultimately lead to vision. However, the intramolecular mechanism by which the photoactivated retinal induces the activation events inside rhodopsin remains experimentally unclear. Here we use ultrafast time-resolved crystallography at room temperature to determine how an isomerized twisted all-trans retinal stores the photon energy that is required to initiate the protein conformational changes associated with the formation of the G protein-binding signalling state. The distorted retinal at a 1-ps time delay after photoactivation has pulled away from half of its numerous interactions with its binding pocket, and the excess of the photon energy is released through an anisotropic protein breathing motion in the direction of the extracellular space. Notably, the very early structural motions in the protein side chains of rhodopsin appear in regions that are involved in later stages of the conserved class A GPCR activation mechanism. Our study sheds light on the earliest stages of vision in vertebrates and points to fundamental aspects of the molecular mechanisms of agonist-mediated GPCR activation

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Genetic & epigenetic differences between borderline personality disorder patients & healthy controls

The aim of the present study was to compare BPD patients with healthy controls on the score of single nucleotid polymorphisms (rs2030324, rs988748, rs6265, rs7124442) and length polymorphisms (BDNF-LCPR and BDNF microsatellite) on the BNDF gene. Furthermore, BDNF methylations levels (BDNF promoter 4 and BDNF 81B) should be compared between the two groups. An additionally goal was to assess the effect of I-DBT on methylation levels at the BDNF gene

Improving the metabolic stability of cultured cells during extended HR-MAS NMR measurements by prior heating

Introduction: 1HHRMAS NMR is an established tool for metabolic characterization of biological samples. However, the accuracy of biomarker detection depends on the sample stability over measurement time. Previously, Duarte et al. found enhanced metabolite visibility and different lipid profiles in lysed compared to frozen cells [1]. Here we investigated effects of shorttime heating prior to HRMAS measurements on metabolite stability of cells. We hypothesized that cell heating has only minor effects on initial metabolite contents (i.e. initially similar spectra with and without heating) and results in increased temporal metabolite stability due to reduced enzymatic activity. Methods: The metabolite content of six lysed nonheated (LFB) and six lysed heated fibroblastsamples (LHFB) was measured as a function of time. Additionally, one sample each of nonheated and heated lysed adrenal cells (LAD & LHAD), which are less robust than fibroblasts, were measured. After lysis according to [1], half of the samples were heated (70°C) for 20min. 1HPROJECT [2] spectra were obtained on a Bruker AvanceII spectrometer (500.13MHz, 277K, MAS=3kHz) at different times over 9 hours. Individual peak analysis was performed investigating temporal changes. For fibroblasts, statistical methods were applied including PCA. Results and Discussion: PCA results and individual peak analysis clearly confirmed our hypothesis: The temporal metabolite stability for LHFB was largely maintained in contrast to LFB. Average temporal variation of all peaks was 14.4% for LHFB compared to 43.1% for LFB. Additionally, the PCA plot demonstrated close clustering for LHFB, whereas LFB were spreading out over time. Also LHAD showed temporal metabolic stability, while LAD exhibited strong changes. Our results suggest using cell lysis in combination with heating for extended longterm HRMAS NMR measurements, in order to minimize metabolite content modifications over measurement time. References: 1. Duarte IF, et al. Anal. Chem. 2009;81:5023. 2. Aguilar JA, et al. Chemical Communications 2012;48:811

Premigratory and migratory neural crest cells are multipotent in vivo

The neural crest (NC) is an embryonic stem/progenitor cell population that generates a diverse array of cell lineages, including peripheral neurons, myelinating Schwann cells, and melanocytes, among others. However, there is a long-standing controversy as to whether this broad developmental perspective reflects in vivo multipotency of individual NC cells or whether the NC is comprised of a heterogeneous mixture of lineage-restricted progenitors. Here, we resolve this controversy by performing in vivo fate mapping of single trunk NC cells both at premigratory and migratory stages using the R26R-Confetti mouse model. By combining quantitative clonal analyses with definitive markers of differentiation, we demonstrate that the vast majority of individual NC cells are multipotent, with only few clones contributing to single derivatives. Intriguingly, multipotency is maintained in migratory NC cells. Thus, our findings provide definitive evidence for the in vivo multipotency of both premigratory and migrating NC cells in the mouse