A TET homologue protein from Coprinopsis cinerea (CcTET) that biochemically converts 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine.

DNA methylation (5-methylcytosine, 5mC) plays critical biological functions in mammals and plants as a vital epigenetic marker. The Ten-Eleven translocation dioxygenases (TET1, 2, and 3) have been found to oxidize 5mC to 5-hydroxymethylcytosine (5hmC) and then to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in mammalian cells. We report herein three mushroom TET homologues from Coprinopsis cinerea that can mediate 5mC oxidation. Specifically, one homologue (CC1G_05589, CcTET) shows similar activity to its mammalian TET homologues. Biochemically, CcTET actively converts 5mC to 5hmC, 5fC, and 5caC under natural conditions (pH 7.0). Interestingly, CcTET also converts the majority of 5mC to 5fC under slightly acidic (pH 5.8) and neutral conditions. Kinetics analyses of the oxidation by CcTET under neutral conditions indicate that conversion of 5mC to 5hmC and 5hmC to 5fC are faster than that of 5fC to 5caC, respectively. Our results provide an example of a TET homologue in a non-mammalian organism that exhibits full 5mC-to-5caC oxidation activity and a slight preference to producing 5fC. The preferential accumulation of 5fC in the in vitro oxidation reactions under both neutral and acidic conditions may have biological implications for 5mC oxidation in fungi species.

Closed-globe injuries of the ocular surface associated with combat blast exposure.

PURPOSE: To describe closed-globe conjunctival and corneal injuries and endothelial cell abnormalities associated with blast exposure and their relationships to other closed-globe injuries and blast-event characteristics. DESIGN: Observational cross-sectional study. PARTICIPANTS: Veterans with a history of blast-related traumatic brain injury (TBI). METHODS: History and ocular examination, including slit-lamp biomicroscopy, gonioscopy, specular microscopy. MAIN OUTCOME MEASURES: Type and location of blast injuries to the conjunctiva and cornea. RESULTS: Ocular surface injuries were present in 25% (16 of 65) of blast-exposed veterans with TBI. Injuries included partial-thickness anterior stromal corneal scars (15 eyes), Descemet membrane ruptures (6 eyes), and conjunctival or corneal foreign bodies (7 eyes). Based on normative information from an age-matched comparison group, endothelial cell abnormalities were identified in 37% of participants. Eyes with ocular surface injury were more likely to have lower endothelial cell density, higher coefficient of variation of cell area, and lower percentage of hexagonal cells compared with eyes without injury. Presence of ocular surface injury or endothelial cell abnormalities was associated with elevated rates of other anterior and posterior segment injuries, as well as impairment of visual acuity. We found no relationship between ballistic eyewear use or severity level of TBI and presence of ocular surface injuries from blast. CONCLUSIONS: Independent of TBI severity or use of protective eyewear, ocular surface injuries and endothelial cell abnormalities were found in significant numbers of veterans with blast-related brain injury. Descemet membrane ruptures from blast exposure were described. Ocular surface trauma was associated with other ocular injuries throughout the globe. Potential mechanisms for the types and locations of ocular injuries seen were discussed. Any corneal or conjunctival injury in a blast survivor should prompt a thorough ocular trauma examination, including gonioscopy and specular microscopy, with appropriate follow-up for associated injuries. Longitudinal studies are required to determine long-term visual outcomes after blast exposure.

Ketamine-enhanced prolonged exposure therapy in veterans with PTSD: A randomized controlled trial protocol.

BACKGROUND: The 2023 VA/DoD Clinical Practice Guideline for the Management of PTSD recommends individual, manualized trauma-focused such as Prolonged Exposure (PE) over pharmacologic interventions for the primary treatment of PTSD. Unfortunately, clinical trials of trauma-based therapies in the military and veteran population showed that 30% to 50% of patients did not demonstrate clinically meaningful symptom change. Ketamine, an FDA-approved anesthetic with potent non-competitive glutamatergic N-methyl-d-aspartate antagonistic properties, has demonstrated to enhance the recall of extinction learning and decrease fear renewal without interference of extinction training in preclinical studies. METHODS: We plan to conduct a single site RCT comparing three ketamine treatment vs. active placebo (midazolam) adjunct to PE therapy among Veterans with PTSD. Pharmacological phase will start simultaneously with PE session 1. Infusions will be administered 24 h. prior to PE session for the first 3 weeks. After PE is completed (session 10), patients will be assessed during a 3-month follow-up period at various time points. We estimate that out of 100 veterans, 80 will reach time point for primary outcome measure and will be considered for primary analysis. Secondary outcomes include severity of depression and anxiety scores, safety and tolerability of ketamine-enhanced PE therapy, cognitive performance during treatment and early improvement during PE related to the rate of dropouts during PE therapy. DISCUSSION: Results of the proposed RCT could provide scientific foundation to distinguish the essential components of this approach, enhance the methodology, elucidate the mechanisms involved, and identify sub-PTSD populations that most likely benefit from this intervention.

Nursing opinions on collaborating with residents in new and legacy OB/GYN programs.

Collaboration among physicians and nurses is vital and has shown to lead to better patient care and improve outcomes. Our study surveyed two groups of Labor and Delivery nurses in two regionally similar community hospitals in midwestern United States: one group from a new Obstetrics and Gynecology (OB/GYN) residency program (n = 49) and another from an established (legacy) OB/GYN residency program (n = 49). The survey asked nurses from the hospital with new and legacy residency program about preparedness for working with residents, perceptions of nurse-resident-patient relationships, collaboration and opinions about how resident physicians impact patient safety. Most nurses from the legacy residency program showed positive perceptions of collaboration with the residency and institutional support. In the new OB/GYN residency program, nurses were generally neutral and showed skepticism about collaboration with OB/GYN resident physicians and institutional support. Nurses from both hospitals felt similarly in their comfort escalating issues to administration and in their satisfaction with interprofessional collaboration within Labor and Delivery units. Providing nurses with opportunities to learn about the role of new medical residents in their patient care setting as well as intentional collaboration between nursing and residency program administration might result in more effective collaboration between physician residents and nursing staff.

Persistent Fetal SVT in a COVID-19 Positive Pregnancy.

BACKGROUND: Rapid introduction and spread of SARS-CoV-2 have posed unique challenges in understanding the disease, role in vertical transmission, and in developing management. We present a case of a patient with COVID-19 infection and fetus with new-onset fetal SVT. CASE: A 26-year-old gravida 4 para 2012 with third trimester COVID-19 infection was diagnosed with new onset fetal SVT. Successful cardioversion was achieved with flecainide. The patient was followed outpatient until induction of labor at 39 and 3/7 weeks of gestational age resulting in an uncomplicated vaginal delivery. Postpartum course was uncomplicated. CONCLUSION: Fetal SVT is a potential complication of maternal COVID-19 infection. The use of transplacental therapy with flecainide is an appropriate alternative to digoxin in these cases.

Comparison of Using One Trabecular Microbypass Stent versus Two during Cataract Surgery at Two Sites: One-Year Follow-Up.

PURPOSE: To compare IOP and ocular hypotensive medication reduction of using one trabecular microbypass stent versus two in patients with open-angle glaucoma. Setting. Palo Alto Veterans Affairs (VA) Hospital and the Byers Eye Institute at Stanford University, Palo Alto, California, USA. DESIGN: Retrospective case series. METHODS: A chart review included patients who underwent trabecular microbypass implantation with cataract surgery in 2015-2017, with at least one-year follow-up. Subjects were divided into two groups by location (always one stent at Stanford versus two stents at the VA). Primary outcome measures included IOP and medication reduction at baseline and 12-month follow-up. RESULTS: 132 subjects (166 eyes) were included. The preoperative IOP was 16.3 ± 3.4 mmHg on 2.6 ± 1.1 medications in the one-stent group (N = 85) and 17.5 ± 3.1 mmHg on 2.7 ± 0.6 medications in the two-stent group (N = 81). There was no significant difference between the two groups (p = 0.06). At the 12-month visit, there was a 13.37% ± 2.93 reduction in IOP in the 1-stent group (p ≤ 0.001) and 13.49% ± 2.69 in the 2-stent group (p ≤ 0.001); both were not significantly different from each other (p = 0.074). At 12 months, there was also a 14.5% reduction in medication use for the 1-stent group and 15.3% reduction in the 2-stent group, both statistically significant from baseline, (p = 0.022 and p = 0.037, respectively). CONCLUSIONS: Implantation with either one or two stents during cataract surgery in patients with glaucoma demonstrated similar IOP and med reduction in both groups between the two sites.

Photodynamic therapy with and without adjunctive intravitreal triamcinolone acetonide: a retrospective comparative study.

BACKGROUND AND OBJECTIVE: To compare photodynamic therapy (PDT) with and without adjunctive intravitreal triamcinolone acetonide (IVTA) in the treatment of choroidal neovascularization secondary to age-related macular degeneration. PATIENTS AND METHODS: Sixty-six eyes received PDT with IVTA and 73 eyes received PDT only. Outcome measures included changes in visual acuity and greatest linear dimension (GLD), the presence of angiographic leakage, the re-treatment rate, and adverse events. RESULTS: Patients treated with PDT with IVTA had reduced mean GLD compared to patients treated with PDT only at all study time points (3 [P = .0049], 6 [P = .003], and 12 [P = .05] months). Forty-four percent of patients in the PDT with IVTA group and 22% of patients in the PDT only group achieved angiographic closure at 3 months (P = .027). There were no significant differences in the final visual acuity outcome or the re-treatment rate between the two groups. CONCLUSION: PDT with IVTA therapy has a favorable outcome on GLD. There is a modest improvement in visual acuity with PDT with IVTA therapy, which diminishes over time.

Total plasma homocysteine and primary open-angle glaucoma.

PURPOSE: To evaluate total plasma homocysteine (tHcy) levels in patients diagnosed with primary open-angle glaucoma (POAG) and normal subjects. DESIGN: Case-control study. METHODS: This study involved 55 POAG patients, 16 patients with secondary open-angle glaucoma or angle-closure glaucoma (non-POAG group), and 39 control healthy subjects undergoing ocular surgery. All glaucoma patients had characteristic glaucomatous optic disk damage and visual field loss. Fasting tHcy concentrations of all study participants were determined using high-performance liquid chromatography. Analysis of variance was used to compare homocysteine levels among the three diagnostic groups, and multivariate analysis was conducted to assess the associations between tHcy and diagnostic group, age, gender, smoking status, systemic hypertension, hyperlipidemia, and cardiovascular or cerebrovascular disease. RESULTS: Mean +/- standard deviation of tHcy levels in POAG individuals, non-POAG patients and control subjects was 14.90 +/- 6.45 micromol/l, 14.30 +/- 4.35 micromol/l, and 14.81 +/- 4.56 micromol/l, respectively (P =.93; ANOVA). No statistically significant difference was found in the proportion of patients with abnormal tHcy levels among the three diagnostic groups. In multivariate analysis, only age and positive smoking status were significantly correlated with total plasma homocysteine levels. CONCLUSION: No significant difference was found in plasma homocysteine levels among POAG patients and normal control individuals.

Synthesis of a FTO inhibitor with anticonvulsant activity.

We describe the rationale for and the synthesis of a new class of compounds utilizing a modular approach that are designed to mimic ascorbic acid and to inhibit 2-oxoglutarate-dependent hydroxylases. Preliminary characterization of one of these compounds indicates in vivo anticonvulsant activity (6 Hz mouse model) at nontoxic doses, inhibition of the 2-oxoglutarate-dependent hydroxylase FTO, and expected increase in cellular N(6)-methyladenosine. This compound is also able to modulate various microRNA, an interesting result in light of the recent view that modulation of microRNAs may be useful for the treatment of CNS disease.

Extensive intracorneal deposition after compression sutures for the treatment of hypotony maculopathy.

PURPOSE: To report a case of extensive intrastromal corneal infiltration with opacification after compression suture placement for hypotony maculopathy. DESIGN: Retrospective case report. METHODS: A 24-year-old Indian male with hypotony maculopathy after trabeculectomy was referred to us for management of overfiltration. Compression sutures were placed to reduce bleb size and area of filtration. Slit lamp photographs and bleb/corneal imaging with anterior segment optical coherence tomography were performed to document corneal infiltration. RESULTS: After placement of the compression sutures in an attempt to delimit the large bleb, there was normalization of the intraocular pressure and improvement in visual acuity. However, the patient developed a wide area of corneal intrastromal deposition that did not extend into the visual axis and was not visually significant. The intrastromal location of the infiltration was delineated on cross-sectional anterior segment optical coherence tomography imaging. CONCLUSIONS: The placement of compression sutures near the scleral flap may create upward tension that we hypothesize can lead to subsequent corneal intrastromal deposition. Despite this rare complication, compression sutures remain a good option for the treatment of an overfiltering bleb.

Eyelid retraction and incomplete eyelid closure secondary to human immunodeficiency virus-associated muscle wasting.

Human immunodeficiency virus (HIV)-associated weight loss remains a significant problem, even in the era of highly active antiretroviral therapy. This interventional case report describes eyelid retraction and poor eyelid closure caused by orbicularis atrophy in the setting of HIV-associated muscle wasting. A 65-year-old HIV-infected man sought treatment for chronic ocular irritation. On examination, he was thin with marked temporal wasting. Corneal epithelial defects were present bilaterally. There was 2 mm of superior scleral show in the right eye and trace inferior scleral show bilaterally. With attempted closure, lagophthalmos approached 1 cm in the right eye and was 3 mm in the left eye. The remainder of the examination was unremarkable. Gold weight placement achieved symptomatic improvement with adequate eyelid closure. Biopsy demonstrated fibrous tissue with an absence of identifiable muscle fibers. In the setting of HIV-associated muscle wasting, orbicularis oculi muscle atrophy may result in eyelid retraction, lagophthalmos, and ocular surface disease.