Functional Diversity of Memory CD8 T Cells is Spatiotemporally Imprinted.

Tissue-resident memory CD8 T cells (TRM) kill infected cells and recruit additional immune cells to limit pathogen invasion at barrier sites. Small intestinal (SI) TRM cells consist of distinct subpopulations with higher expression of effector molecules or greater memory potential. We hypothesized that occupancy of diverse anatomical niches imprints these distinct TRM transcriptional programs. We leveraged human samples and a murine model of acute systemic viral infection to profile the location and transcriptome of pathogen-specific TRM cell differentiation at single-transcript resolution. We developed computational approaches to capture cellular locations along three anatomical axes of the small intestine and to visualize the spatiotemporal distribution of cell types and gene expression. TRM populations were spatially segregated: with more effector- and memory-like TRM preferentially localized at the villus tip or crypt, respectively. Modeling ligand-receptor activity revealed patterns of key cellular interactions and cytokine signaling pathways that initiate and maintain TRM differentiation and functional diversity, including different TGFß sources. Alterations in the cellular networks induced by loss of TGFßRII expression revealed a model consistent with TGFß promoting progressive TRM maturation towards the villus tip. Ultimately, we have developed a framework for the study of immune cell interactions with the spectrum of tissue cell types, revealing that T cell location and functional state are fundamentally intertwined.

Identification of CD8 + T-Cell-Immune Cell Communications in Ileal Crohn's Disease.

INTRODUCTION: Crohn's disease (CD) is a major subtype of inflammatory bowel disease (IBD), a spectrum of chronic intestinal disorders caused by dysregulated immune responses to gut microbiota. Although transcriptional and functional changes in a number of immune cell types have been implicated in the pathogenesis of IBD, the cellular interactions and signals that drive these changes have been less well-studied. METHODS: We performed Cellular Indexing of Transcriptomes and Epitopes by sequencing on peripheral blood, colon, and ileal immune cells derived from healthy subjects and patients with CD. We applied a previously published computational approach, NicheNet, to predict immune cell types interacting with CD8 + T-cell subsets, revealing putative ligand-receptor pairs and key transcriptional changes downstream of these cell-cell communications. RESULTS: As a number of recent studies have revealed a potential role for CD8 + T-cell subsets in the pathogenesis of IBD, we focused our analyses on identifying the interactions of CD8 + T-cell subsets with other immune cells in the intestinal tissue microenvironment. We identified ligands and signaling pathways that have implicated in IBD, such as interleukin-1ß, supporting the validity of the approach, along with unexpected ligands, such as granzyme B, which may play previously unappreciated roles in IBD. DISCUSSION: Overall, these findings suggest that future efforts focused on elucidating cell-cell communications among immune and nonimmune cell types may further our understanding of IBD pathogenesis.

Small intestine and colon tissue-resident memory CD8+ T cells exhibit molecular heterogeneity and differential dependence on Eomes.

Tissue-resident memory CD8+ T (TRM) cells are a subset of memory T cells that play a critical role in limiting early pathogen spread and controlling infection. TRM cells exhibit differences across tissues, but their potential heterogeneity among distinct anatomic compartments within the small intestine and colon has not been well recognized. Here, by analyzing TRM cells from the lamina propria and epithelial compartments of the small intestine and colon, we showed that intestinal TRM cells exhibited distinctive patterns of cytokine and granzyme expression along with substantial transcriptional, epigenetic, and functional heterogeneity. The T-box transcription factor Eomes, which represses TRM cell formation in some tissues, exhibited unexpected context-specific regulatory roles in supporting the maintenance of established TRM cells in the small intestine, but not in the colon. Taken together, these data provide previously unappreciated insights into the heterogeneity and differential requirements for the formation vs. maintenance of intestinal TRM cells.

Kinetic Profiling of Homogeneous and Heterogeneous Biocatalysts in Continuous Flow by Online Mass Spectrometry.

Enzyme kinetics is normally assessed by performing individual kinetic measurements using batch-type reactors (test tubes, microtiter plates), in which enzymes are mixed with different substrates. Some drawbacks of conventional methods are the large amounts of experimental materials, long analysis times, and limitations of spectrophotometry. Therefore, we have developed a method for facile determination of enzyme kinetics using online flow-based mass spectrometry. A concentration ramp of substrate or product was created by dynamically adjusting flow rates of pumps delivering stock solution of substrate and diluent. Precise kinetic measurements were performed by reaction product quantification and initial rate calculation. In the presence of ascending substrate concentrations, the rate of a target enzyme (penicillinase)-catalyzed hydrolysis was varied. By measuring the reaction product continuously, Michaelis constants (KM) could be calculated. The enzyme kinetic measurements for hydrolysis of penicillins were conducted based on this simple, rapid, and low sample consumption online flow device. In the homogeneous reaction, the KM values for amoxicillin, ampicillin, penicillin G, and penicillin V were 254.9 ± 14.5, 29.2 ± 0.3, 2.6 ± 0.1, and 5.4 ± 0.1 µM, respectively. In the heterogeneous reaction, the KM values for amoxicillin, ampicillin, penicillin G, and penicillin V were 408.9 ± 75.1, 114.4 ± 8.0, 21.8 ± 0.7, and 83.3 ± 4.8 µM, respectively. Apart from enzyme assay, the showcased method for the generation of temporal concentration ramps can be utilized to perform rapid quantity calibrations for mass spectrometric analyses.

The Radiation Dose to the Left Supraclavicular Fossa is Critical for Anastomotic Leak Following Esophagectomy - A Dosimetric Outcome Analysis.

Purpose: For locally advanced esophageal cancer, definitive concurrent chemoradiotherapy (CCRT) with a radiation dose of 50-50.4 Gy/25-28 Fx is prescribed, followed by adjuvant esophagectomy for better local control or salvage treatment if locoregional recurrence occurs. However, radiation injury before surgery may delay wound healing. We performed cervical anastomosis directly inside the left supraclavicular fossa (SCF), the irradiation target for esophageal cancer. The significance of radiation injury in patients with cervical anastomotic leak (AL) remains unclear. Thus, we assessed the influence of radiation on cervical AL in patients undergoing preoperative CCRT followed by esophagectomy. Patients and Methods: We defined the SYC zone, a portion of the region overlapping the left SCF. The radiation dose to the SYC zone was analyzed and correlated with AL in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were administered preoperative CCRT (radiation dose with 50-50.4 Gy/25-28 Fx to the primary esophageal tumor) followed by esophagectomy between October 2009 and January 2018. Receiver operating characteristic curve analysis and logistic regression were used to identify the optimal radiation factor to predict AL and the cutoff value. Results: The optimal radiation factor to predict AL was the mean dose to the SYC zone (area under the curve (AUC)=0.642), and the cutoff point of the mean dose was 48.55 Gray (Gy). For a mean SYC zone dose ≥48.55 Gy, the AL risk was sevenfold greater than that for <48.55 Gy (OR = 7.805; 95% CI: 1.184 to 51.446; P value = 0.033). Conclusion: Recognizing the SYC zone as an organ at risk and performing radiation evaluation are meaningful. A reduced mean dose of the SYC zone below 48.55 Gy results in a lower cervical AL rate following esophagectomy.

The Impact of Weight Loss during Chemoradiotherapy for Unresectable Esophageal Cancer: Real-World Results.

Weight loss is a common phenomenon presented in unresectable esophageal cancer (EC) patients during their definitive chemoradiotherapy (dCRT) treatment course. This study explored the prognostic value of weight changes during dCRT in unresectable EC patients. From 2009 to 2017, 69 cT4b thoracic EC patients undergoing complete curative dCRT without baseline malnutrition were included. Clinical factors were analyzed via the Cox proportional hazards model and survival was analyzed by the Kaplan−Meier method. During dCRT, the median weight loss percentage was 5.51% (IQR = 2.77−8.85%), and the lowest body weight was reached at 35 days (IQR = 23−43 days). Median OS of these patients was 13.5 months. Both univariate and multivariate analysis demonstrated that weight loss ≤ 4% during dCRT was significantly associated with superior OS with a hazard ratio of 2.61 (95% CI: 1.40−4.85, p = 0.002). The median OS for patients with weight loss ≤ 4% and >4% during dCRT was 59.6 months and 9.7 months, respectively (p = 0.001). Our study demonstrated that weight loss ≤ 4% during dCRT course is a favorable prognostic factor for cT4b EC patients. This index could serve as a nutrition support reference for unresectable EC patients receiving dCRT in the future.

Thinner Central Corneal Thickness is Associated with a Decreased Parapapillary Vessel Density in Normal Tension Glaucoma.

This retrospective cross-sectional study, which enrolled 124 normal tension glaucoma (NTG) eyes and 68 healthy eyes as the control, determined the association between central corneal thickness (CCT) and ocular parameters in NTG. CCT was measured using the Pentacam® system, optical coherence tomography angiography (OCT-A) was adopted to measure the peripapillary and macular area VDs, and spatial data were based on the Garway-Heath map as illustrated in OCT-A. Univariate and multivariate linear regressions were used to statistically analyze for associations between CCT and other factors. In this study, the mean age was similar for both the NTG and control groups. The mean CCT of the NTG group was significantly thinner than that of the control group (533.97 ± 33.11 µm vs. 546.78 ± 38.21 µm; p = .022). Considering all the factors, CCT negatively correlated with visual field (VF) pattern standard deviation (univariate, p = .045). To analyze structural and functional factors separately, we found a significant positive correlation between CCT and whole disc radial peripapillary capillary VD (VDRPC; multivariate, p = .019). To analyze the relationship between all factors and sectoral changes in VDRPC, a significant positive correlation was observed between CCT and inferior temporal VDRPC (univariate, p = .039) and inferior nasal VDRPC (VDRPC IN; univariate, p = .048). In conclusion, this novel study shows that among NTG participants, a thinner cornea correlated with weaker biomechanical properties susceptible to optic nerve tissue displacement, especially in response to mild transient elevation of IOP, leads to compromised ocular microcirculation.

Preventive effect and safety of Chinese herbal medicine for oral mucositis during radiotherapy in patients with head and neck cancer: Study protocol for a randomized trial.

Background: Oral mucositis (OM) is a common side effect of radiotherapy (RT) that can have severe implications in patients with head and neck cancer (HNC). Traditional Chinese medicine (TCM) formula is widely applied in treating OM, but little substantial evidence exists to clarify it effects. The study intends to determine whether the TCM-based prescription in treating HNC with RT can improve the OM when compared with RT alone. Methods: A single-center, randomized, two-arm parallel-group, open-label controlled clinical trial will be conducted to determine whether the Zi-Yin-Liang-Ge-San (ZYLGS), which contains Rx. Scutellariae, Rx. Glycyrrhizae, Hb. Dendrobii, Rx. Ophiopogonis, and Hb. Menthae Haplocalycis, combined with RT can improve the incidence and severity of OM. Two hundred participants will randomly 1:1 to receive at least 6 weeks of RT plus ZYLGS powder or control. The primary outcome measures are onset, gradation of OM (Common Terminology Criteria for Adverse Events v5.0), and oral pain (visual analogue scale). The secondary outcome measures include nutritional status, the EORTC Quality of Life Core Questionnaire and head and neck module. The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, serious adverse events, and blood and biochemical analysis will be recorded to evaluate the safety. Visits will be performed for each week during the RT treatment period and then 2 weeks in the follow-up period. Discussion: The study's result will provide a high-level evidence for TCM-based formulation for HNC patients with RT on the effect of OM prevention and management.

Efficacy of modified levator-muscle resection using Putterman ptosis clamp versus traditional levator-muscle resection for aponeurotic ptosis: A retrospective analysis.

BACKGROUND/OBJECTIVES: In recent years, a modified levator muscle resection using Putterman ptosis clamp was developed. We used a retrospective case-control study to compare the effects of the modified and traditional levator muscle resection methods. METHODS: Patients with moderate-to-severe ptosis who underwent the traditional or modified method for levator muscle resection were divided into two groups: Group I received the traditional method in 2013 and Group II received the modified method using Putterman clamp in 2015. During each postoperative visit, in addition to imaging, changes in the margin reflex distance 1 (MRD 1), and adverse events were recorded. Surgical time and final result in the last follow-up were recorded. RESULTS: Group I had 35 patients (54 eyes) and Group II had 33 patients (59 eyes). After the surgery, the MRD 1 in both groups was significantly improved at 1 week and at the final visit compared to baseline. Significant differences were observed in MRD 1 change at 1-week post-operation and the change at the final visit and the surgical time between Groups I and II (P < 0.05). Group II had a shorter surgical time than Group I. Compared with Group I (20.37%), the revision rate was lower in Group II (10.16%). CONCLUSIONS: The modified levator muscle resection using Putterman ptosis clamp and traditional levator muscle resection can both improve ptosis. Comparison results showed that using Putterman ptosis clamp assisted in levator muscle surgery had shorter operation time, faster postoperative recovery, and lower revision rate than the traditional method. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Significant Reduction in Vertebral Artery Dose by Intensity Modulated Proton Therapy: A Pilot Study for Nasopharyngeal Carcinoma.

Intensity modulated proton therapy (IMPT) with the vertebral artery (VA)-sparing technique has been initially proposed in our institution. This pilot study was conducted to compare the dose to VAs between IMPT and volumetric-modulated arc therapy (VMAT) for patients with nasopharyngeal carcinoma (NPC). A total of six patients with NPC treated by IMPT were enrolled in the study. Target volumes and organs at risk (OARs) were delineated, including 12 samples of right and left VAs, respectively, for each patient. Treatment planning by IMPT and dual-arc VMAT was carried out for comparison. The IMPT plan significantly reduced VA mean dose, V10, V20, V30, V40, and V50, compared to the VMAT plan in all 12 samples (p < 0.001). The average mean dose to VAs for IMPT was 35.2% (23.4-46.9%), which was less compared to VMAT (p < 0.001). Adequate dose coverage was achieved with both IMPT and VMAT plans for three different dose levels of target volumes for all patients. IMPT significantly reduces VA dose while maintaining adequate dose coverage of all target volumes. For patients with head and neck cancer who seek to preserve their blood flow to the brain in order to decrease late vascular and neurologic sequelae, IMPT should be considered. A prospective study with longer follow-up is ongoing to confirm our preliminary results.

Nursing Students' Perceptions of Menstrual Distress during Clinical Practice: A Q-Methodology Study.

This study aimed to explore the cluster patterns of female nursing students' perceptions of the effects of menstrual distress during clinical practice. This study adopted the Q-methodology study design. We recruited female nursing students from a college in northern Taiwan. Forty-seven Q-statements were constructed to explore participants' experiences of the impact of menstrual distress on clinical learning. In total, 58 participants subjectively ranked Q-statements concerning menstrual distress experiences during clinical practice and were classified. After Q-sorting, the subjective ranking process PQ Method (version 2.35, Schmolck, Emmendingen, Germany) was employed for factor analysis. Four patterns of shared perspectives, accounting for 46.6% of the total variance, were identified: (a) influencing clinical learning and making good use of painkillers; (b) responsible attitudes and diversified relief of discomfort; (c) seeking peer support and effect on mood; (d) negative impact on learning ability and conservative self-care. Clinical practice is a major component of nursing education; menstrual distress affects female nursing students' clinical learning and performance. The exploration of clustering different nursing students' perceptions may facilitate customized strategies to enable more appropriate assistance.

Optical Coherence Tomography Angiography Vessel Density Changes in Normal-tension Glaucoma Treated With Carteolol, Brimonidine, or Dorzolamide.

PRECIS: In patients with normal-tension glaucoma (NTG), topical dorzolamide might enhance the vessel density (VD), topical carteolol decreased the VD in the inferior-temporal peripapillary retina, whereas topical brimonidine did not change the VD. PURPOSE: Topical antiglaucoma medications may improve ocular perfusion pressure or microcirculation in the optic nerve head. The study evaluated responses of retinal VD to topical carteolol, brimonidine, and dorzolamide in NTG using optical coherence tomography angiography. PATIENTS AND METHODS: This is a retrospective, nonrandomized, comparative study. The study included 131 individuals (77 men, 54 women) diagnosed with NTG, without systemic medication use, who visited the glaucoma clinic of Chang Gung Memorial Hospital, Taiwan, between January 2019 and May 2020. If both eyes were diagnosed with NTG, only the right eye was included. Of these, there were 80 carteolol-treated eyes, 27 brimonidine-treated eyes, and 24 dorzolamide-treated eyes. We studied the response of optical coherence tomography angiography parameters and retinal nerve fiber layer (RNFL) thickness to drugs, 6 months after treatment. RESULTS: In dorzolamide-treated eyes, increases in the peripapillary superficial retinal VD, especially in the superior-nasal area, were significant; however, no RNFL thickness changes were observed. In contrast, the superficial retinal VD decreased at the inferior-temporal peripapillary area, and RNFL thickness decreased in the inferior-nasal peripapillary area of carteolol-treated eyes. Finally, in brimonidine-treated eyes, changes in either VD parameters or RNFL thickness were not significant. CONCLUSIONS: Topical dorzolamide possibly enhanced the VD of the peripapillary retina in NTG eyes. On the contrary, topical carteolol possibly decreased VD in the inferior-temporal peripapillary retina. Finally, in cases treated with topical brimonidine, peripapillary microcirculation remained unchanged. The study shows preliminary results and future large-scale studies are needed to confirm findings.

Mitochondrial dynamics and bioenergetics regulated by netrin-1 in oligodendrocytes.

Mitochondria are dynamic organelles that produce energy and molecular precursors that are essential for myelin synthesis. Unlike in neurons, mitochondria in oligodendrocytes increase intracellular movement in response to glutamatergic activation and are more susceptible to oxidative stress than in astrocytes or microglia. The signaling pathways that regulate these cell type-specific mitochondrial responses in oligodendrocytes are not understood. Here, we visualized mitochondria migrating through thin cytoplasmic channels crossing myelin basic protein-positive compacted membranes and localized within paranodal loop cytoplasm. We hypothesized that local extracellular enrichment of netrin-1 might regulate the recruitment and function of paranodal proteins and organelles, including mitochondria. We identified rapid recruitment of mitochondria and paranodal proteins, including neurofascin 155 (NF155) and the netrin receptor deleted in colorectal carcinoma (DCC), to sites of contact between oligodendrocytes and netrin-1-coated microbeads in vitro. We provide evidence that Src-family kinase activation and Rho-associated protein kinase (ROCK) inhibition downstream of netrin-1 induces mitochondrial elongation, hyperpolarization of the mitochondrial inner membrane, and increases glycolysis. Our findings identify a signaling mechanism in oligodendrocytes that is sufficient to locally recruit paranodal proteins and regulate the subcellular localization, morphology, and function of mitochondria.

Correlation of Visual Field With Peripapillary Vessel Density Through Optical Coherence Tomography Angiography in Normal-Tension Glaucoma.

Purpose: To investigate the retinal vessel density (VD) in healthy and normal-tension glaucoma (NTG) eyes through optical coherence tomography angiography (OCTA) and to determine the correlation between VD and the retinal nerve fiber layer (RNFL) thickness and functional visual field (VF) defects for different locations. Methods: A total of 74 NTG eyes and 24 healthy eyes were included. OCTA VD at 4.5 × 4.5 mm peripapillary region and 3.0 × 3.0 mm macula area, RNFL thickness, and VF pattern deviation results were individually analyzed on the basis of the Garway-Heath sectorization. Correlations between VD and VF/RNFL and VF were compared. Results: In the NTG group, peripapillary VD, superficial macula VD, RNFL thickness, and ganglion cell complex thickness were significantly lower. In the whole peripapillary area and inferotemporal sector, anatomic correlations between VD and VF pattern deviation values were significantly higher than those between the RNFL thickness and VF values. In the subgroup analysis, VD was anatomically correlated with VF in early-, moderate-, and severe-stage NTG eyes, whereas the RNFL thickness was correlated with VF in moderate- and severe-stage NTG eyes. Conclusions: We observed VD reduction in the peripapillary retina and superficial macula area in NTG eyes. The microvascular dropout of VD in the peripapillary retina, especially in the inferotemporal sector, provided a more accurate anatomic correlation with functional VF defects than that of the RNFL thickness, especially in early-stage NTG eyes. Translational Relevance: In patients who cannot comply VF exam, VD is a good tool for disease detection.

Folate-Targeted Curcumin-Encapsulated Micellar Nanosystem for Chemotherapy and Curcumin-Mediated Photodynamic Therapy.

Curcumin (CUR) is a natural phenolic product used as a high-efficiency and low-toxicity anticancer drug and photosensitizer. However, it has a poor aqueous solubility and a lack of target specificity, which limits its clinical applications. Hence, we developed a folate-conjugated polymeric micelle to enhance the efficient delivery of CUR for effective cancer cell targeting and anticancer efficiency. A series of biocompatible folate-conjugated poly(2-(methacryloyloxy)ethylphosphoryl- choline)-b-poly(ε-caprolactone) (FPM) was synthesized with different hydrophobic lengths and folate contents. The prepared CUR-loaded micelles (CUR-FPM) possessed several superior properties, including an excellent drug loading capacity (6.3 ± 1.2%), improved CUR aqueous stability, fast-sustained CUR release in an acidic environment, and efficient intracellular production of reactive oxygen species. The in vitro cytotoxicity demonstrated that the CUR-FPM micelles efficiently suppressed the growth of HeLa cells (folate-receptor overexpression) compared to that of HT-29 cells, and a competition study showed less cytotoxic effect when free folic acid blocked the folate receptor, indicating the folate conjugation played the role of targeting the specific cells well. Moreover, the CUR-mediated photodynamic therapy (PDT) by CUR-FPM micelles under irradiation further inhibited the proliferation of cancer cells. All these results indicate that the CUR-FPM micelles could be a promising delivery system for folate-overexpressing cancer cells, complementary chemotherapy, and CUR-mediated photodynamic therapy.

Outcomes in patients with lacrimal gland carcinoma treated with definitive radiotherapy or eye-sparing surgery followed by adjuvant radiotherapy.

BACKGROUND: The optimal treatment for lacrimal gland cancer remains unclear. Eye-preserving surgery, as opposed to exenteration, followed by adjuvant radiotherapy (RT), has recently been reported to deliver satisfactory outcomes, but evidence is sparse. The aim of the present study was to evaluate outcomes in patients with lacrimal gland cancer treated at two tertiary medical centers. METHODS: We retrospectively examined data from patients with lacrimal gland cancer who had received eye-preserving surgical treatment followed by adjuvant RT with or without chemotherapy, or (if the tumor was inoperable) needle biopsy with definitive RT with or without chemotherapy. Baseline clinical and pathological characteristics were considered. Outcomes of interest included post-treatment complications, overall survival (OS), locoregional progression-free survival (LPFS), and distant metastasis-free survival (DMFS). RESULTS: Eighteen patients were included. Two-year OS, LPFS, and DMFS rates were 69.0, 76.7, and 71.4%, respectively. Patients with early-stage (T1-T2) lacrimal gland cancer had significantly better outcomes than those with advanced-stage disease (T3-T4). Two-year OS, LPFS, and DMFS rates were each 100% in patients with disease stages T1-T2, and 37.5, 50, and 37.5%, respectively, in those with disease stages T3-T4 (P < 0.05). Orbital complications were well tolerated. CONCLUSIONS: Eye-sparing surgery with adjuvant RT can achieve satisfactory results in patients with T1-T2 lacrimal gland carcinoma. Disease stage T3 and above was associated with poor outcomes even with post-operative RT, likely due to distant metastasis. Adding neoadjuvant chemotherapy or adjuvant chemotherapy to current treatment strategies might be a suitable choice for this group of patients.

Effects of Biotin on survival, ensheathment, and ATP production by oligodendrocyte lineage cells in vitro.

Mechanisms implicated in disease progression in multiple sclerosis include continued oligodendrocyte (OL)/myelin injury and failure of myelin repair. Underlying causes include metabolic stress with resultant energy deficiency. Biotin is a cofactor for carboxylases involved in ATP production that impact myelin production by promoting fatty acid synthesis. Here, we investigate the effects of high dose Biotin (MD1003) on the functional properties of post-natal rat derived oligodendrocyte progenitor cells (OPCs). A2B5 positive OPCs were assessed using an in vitro injury assay, culturing cells in either DFM (DMEM/F12+N1) or "stress media" (no glucose (NG)-DMEM), with Biotin added over a range from 2.5 to 250 µg/ml, and cell viability determined after 24 hrs. Biotin reduced the increase in OPC cell death in the NG condition. In nanofiber myelination assays, biotin increased the percentage of ensheathing cells, the number of ensheathed segments per cell, and length of ensheathed segments. In dispersed cell culture, Biotin also significantly increased ATP production, assessed using a Seahorse bio-analyzer. For most assays, the positive effects of Biotin were observed at the higher end of the dose-response analysis. We conclude that Biotin, in vitro, protects OL lineage cells from metabolic injury, enhances myelin-like ensheathment, and is associated with increased ATP production.

Early versus Delayed Phacoemulsification and Intraocular Lens Implantation for Acute Primary Angle-Closure.

PURPOSE: To compare the effects of early phacoemulsification and intraocular lens implantation (phaco/IOL), delayed phaco/IOL after initial laser peripheral iridotomy (LPI), and conventional LPI alone in patients with acute primary angle-closure (PAC). METHODS: Patients with acute PAC were included in the study, and those with secondary glaucoma, prior ocular trauma, or other ocular diseases and those who had undergone ocular surgeries previously were excluded. Patients were categorized into three groups: Group A, which underwent primary phaco/IOL after acute PAC; Group B, which underwent LPI initially after acute PAC, followed by phaco/IOL within 6 months; and Group C, which underwent LPI alone. The IOP control success at 12 months as well as changes in ocular characteristics and the number of antiglaucoma medications used after the treatment among the groups were evaluated. RESULTS: Eighty-one eyes were included in the study: 24 eyes in Group A, 23 eyes in Group B, and 34 eyes in Group C. The linear mixed model analysis demonstrated considerable IOP control in Groups A and B. Visual acuity, anterior chamber depth (ACD), and angle width improved significantly in Groups A and B, but not in Group C. The number of antiglaucoma medications used was significantly higher in Group C than in Groups A and B. CONCLUSIONS: Patients who underwent phaco/IOL had better IOP control, improved vision, deeper ACD, and wider angle and required less antiglaucoma medications than those who underwent LPI alone. Performing phaco/IOL weeks to months after the initial LPI did not appear to adversely affect outcomes compared with those of early phaco/IOL.