Notes

Isoprenylcysteine Carboxylmethyltransferase-Based Therapy with regard to Hutchinson-Gilford Progeria Malady.
Intraocular pressure (IOP) reduction is key to controlling primary open angle glaucoma (POAG). Pharmacotherapies for POAG or ocular hypertension (OHT) commonly lower IOP by increasing uveoscleral outflow or decreasing aqueous humor production. Netarsudil (Rhopressa), a Rho kinase inhibitor, reduces IOP by improving trabecular outflow facility, which is reduced in POAG. We investigated the effects of netarsudil on aqueous humor dynamics in patients with POAG or OHT.

Double-masked, randomized, vehicle-controlled, Phase 2 trial.

Netarsudil 0.02% was instilled in 1 eye and vehicle into the contralateral eye of 20 patients once daily in the morning for 7 days. The primary endpoint was change in mean diurnal outflow facility on day 8 versus that on day 1 (baseline). Outflow facility was measured by using Schiøtz tonography, IOP by pneumotonometry, and episcleral venous pressure (EVP) by automated venomanometry.

Eighteen patients (90%) completed the study. KPT-185 Mean diurnal outflow facility increased 0.039 versus 0.007 µL/min/mm Hg from baseline in the netarsudil- and the vehicle-treated groups, respectively (P < .001 vs. baseline for netarsudil), a treatment difference of 0.03 µL/min/mm Hg (P ≤ .001). Mean diurnal IOP change from baseline at day 8 was -4.52 mm Hg for netarsudil versus -0.98 mm Hg for vehicle, a treatment difference of -3.54 mm Hg (P < .0001). Mean diurnal EVP change from baseline was -0.79 mm Hg in the netarsudil-treated group versus 0.10 mm Hg for vehicle, a treatment difference of -0.89 mm Hg (P < .001). All patients reporting an adverse event reported conjunctival hyperemia of mild or moderate severity.

Netarsudil acts on the conventional outflow pathway, both proximal and distal, to significantly reduce IOP in POAG and OHT by improving trabecular outflow facility and decreasing EVP.
Netarsudil acts on the conventional outflow pathway, both proximal and distal, to significantly reduce IOP in POAG and OHT by improving trabecular outflow facility and decreasing EVP.
To investigate the longitudinal changes in circumpapillary capillary density (cpCD) and retinal nerve fiber layer thickness (cpRNFLT) and their association with visual field (VF) progression in open-angle glaucoma (OAG) eyes at different stages of glaucoma.

Retrospective, observational case series METHODS This study enrolled 158 eyes of 158 OAG patients classified into early (89 eyes) and moderate-to-advanced (69 eyes) stage based on VF mean deviation (MD; -6 dB). Serial cpCD and cpRNFLT measurements were performed using optical coherence tomography (OCT) angiography and OCT during a mean follow-up of 2.66 years. The reference standard of glaucoma progression was determined by VF progression. The rates of longitudinal change in cpCD and cpRNFLT were evaluated using linear mixed effects models and compared between progressors and nonprogressors. The factors associated with VF progression, including the rates of longitudinal change in cpCD and cpRNFLT, were assessed using logistic regression analyses.

Theof glaucoma stage.
In OAG eyes, the rate of longitudinal cpCD loss was significantly associated with VF progression regardless of glaucoma stage.DNA methylation and hydroxymethylation represent important epigenetic modifications involved in cell differentiation. DNA hydroxymethylation can be used to classify independent biological samples by tissue type. Relatively little is known regarding the genomic abundance and function of 5-hydroxymethylcytosine (5-hmC) in ocular tissues. The choroid supplies oxygen and nutrients to the outer retina through its dense network of blood vessels. This connective tissue is mainly composed of pigmented melanocytes, and stromal fibroblasts. Since DNA hydroxymethylation level is relatively high in cutaneous melanocytes, we investigated the presence of 5-hmC in choroidal melanocytes, as well as the expression of ten-eleven translocation methylcytosine dioxygenases (TETs) and isocitrate dehydrogenases (IDHs) implicated in this DNA demethylation pathway. Immunofluorescence, DNA slot blots and liquid chromatography coupled to tandem mass spectrometry performed with choroidal tissues and melanocytes within these tissues revealed that they have a relatively high level of 5-hmC. We also examined the expression of TET1/2 and IDH1/2 in choroidal melanocytes by gene expression profiling, qPCR and Western blotting. In addition, we detected decreased levels of 5-hmC when choroidal melanocytes were exposed to a lower concentration of oxygen. Our study therefore demonstrates that DNA hydroxymethylation is present in choroidal melanocytes, and that the abundance of this epigenetic mark is impacted by hypoxia.Presbyopia is a growing problem in view of an aging global population and increasingly patients desire spectacle-free solutions to address this condition. Surgically implanted corneal inlays have been the topic of renewed research efforts in the past several years as a treatment option for presbyopia, with several approaches being used to modify the refractive properties of the cornea and enhance near vision. In this review we discuss historical approaches to corneal inlay surgery, critically appraise the current generation of presbyopia-correcting corneal inlays and their associated complications and consider the future prospects for emerging corneal inlay technologies that aim address the shortcomings of currently available inlays.Among the in vivo experimental models, the chick embryo chorioallantoic membrane (CAM) has been routinely used to implant several malignant cell lines or tumor tissues to study their angiogenic and metastatic capability. Since the chick embryo is naturally immunodeficient, the CAM can support the engraftment of tumor cells, and their growth therein can faithfully recapitulate most of the characteristics of the carcinogenic process including growth, invasion, angiogenesis and colonization of distant tissues. This review article is focused on the discussion of the more recent literature data concerning the use of the CAM to investigate the metastatic process.Pulpitis refers to inflammation of the inner pulp by invading microbes, and tissue repair occurs due to odontogenic differentiation of human dental pulp cells (hDPCs) with multidifferentiation potential. Long noncoding RNAs (lncRNAs) can modulate numerous pathological and biological processes; however, the role of lncRNAs in the inflammation and regeneration of the dentin-pulp complex in pulpitis is unclear. Here, we performed high-throughput sequencing to identify differentially expressed lncRNAs between human normal and inflamed pulp and concluded that lncMEG3 (lncRNA maternally expressed gene 3, MEG3) was significantly upregulated in both inflamed pulp and LPS-treated hDPCs. MEG3 expression in the pulp tissue was detected using the RNAscope® technique. RNA pulldown assays identified the MEG3-interacting proteins and the potential mechanisms. With MEG3 knockdown, we investigated the role of MEG3 in the secretion of inflammatory cytokines in LPS-treated hDPCs and odontogenic differentiation of hDPCs. MEG3 downregulation inhibited the secretion of TNF-α, IL-1β and IL-6 in LPS-treated hDPCs, and the p38/MAPK signaling pathway may be related to this effect. MEG3 knockdown promoted odontogenic differentiation of hDPCs by regulating the Wnt/β-catenin signaling pathway. Our study suggested that MEG3 has a negative effect on inflammation and regeneration of the dentin-pulp complex in pulpitis.The traditional segmentectomy involves each segment as the least surgical unit to preserve more pulmonary parenchyma than lobectomy, which is also excessive for small ground glass opacity-dominated lung cancer. We report a novel technique of sublobar resection based on subsegment. Under the guidance of three-dimensional computed tomography bronchography and angiography, the nodules were classified according to their subsegmental location and removed by individual sublobar resection. That assists in removing malignant nodules with safe margins and preserves more pulmonary parenchyma. However, the oncologic efficacy and pulmonary function protection warrant follow-up.
The objective of this study was to determine how thoracic surgeons manage intraoperative esophagectomy positive margins and how these decisions may relate to overall (OS) and progression-free survival (PFS) in esophageal cancer.

A survey was sent to thoracic surgeons to understand the management of intraoperative positive esophagectomy margins. Primary data at two high volume esophageal cancer institutions from 1994-2017 were retrospectively reviewed to identify patients who had intraoperative positive frozen section margins during esophagectomy. Patient characteristics and survival were collected and analyzed. OS and PFS were assessed using a Cox model.

85% of thoracic surgeons responding to a survey reported the utilization of frozen pathologic evaluation during esophagectomy with attempts at re-resection to achieve negative margin. Our esophagectomy database identified 94 patients with intraoperative positive margins. Of those re-resected (n=67, 63%), 44 patients (46.8%) were converted to R0 resectioars to be related to PFS.
Cardiac surgery-associated acute kidney injury (CS-AKI) is common in infants and is associated with negative outcomes. Nadir indexed oxygen delivery (DO
i) during cardiopulmonary bypass (CPB) is associated with the occurrence of postoperative CS-AKI, with critical thresholds for DO
i reported to be 262 to 300 mL/min/m
in adults. However, given that infants have a higher metabolic rate and oxygen demand, the critical DO
i in infants is not comparable with existing adult standards. This study aimed to explore the critical DO
i threshold during pediatric CPB.

Between March 2019 and April 2020, 106 consecutive infants undergoing cardiac surgery with CPB were admitted to this prospective observational cohort study. The DO
i levels of each patient were monitored during CPB. Pre- and intraoperative factors were tested for independent association with CS-AKI. The postoperative outcomes of patients with or without CS-AKI were compared.

In our patient population (n= 83), we identified 25 patients (38.5%) with postoperative CS-AKI. Multivariate analysis revealed 2 independent risk factors for onset of CS-AKI CPB duration and nadir DO
i. The lowest suitable DO
i during CPB in the present population was 353 mL/min/m
(sensitivity, 65.6%; specificity, 74.5%). CS-AKI during pediatric CPB remained significantly associated with an increased morbidity, related mainly to a postoperative low cardiac output syndrome, but not to mortality.

The lowest suitable DO
i during CPB in the infant population undergoing cardiac surgery was 353 mL/min/m
. Below this threshold, there was a high probability of inducing CS-AKI.
The lowest suitable DO2i during CPB in the infant population undergoing cardiac surgery was 353 mL/min/m2. Below this threshold, there was a high probability of inducing CS-AKI.A 21-year old female with a history of Turner syndrome presented with a diastolic heart murmur, dizziness, dyspnea, and intermittent chest pain. Preoperative imaging revealed a fistula from the right sinus of Valsalva into the right atrium. Turner syndrome is associated with both aortopathy and congenital heart malformations. Acquired sinus of Valsalva fistula is a rare disorder and has not been previously reported in association with Turner syndrome.
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