Blind Conditions Research Articles

Drug Discovery Strategies for Inherited Retinal Degenerations.

Simple SummaryInherited retinal degeneration is a group of heterogeneous genetic disorders impairing vision. In these diseases, photoreceptor or retinal ganglion cells become dysfunctional and degenerate. Currently, no cures exist for these devastating blinding conditions. In this review, we will discuss targets and drug discovery strategies for inherited retinal degeneration using animal models, stem cells, and small molecule screening with updates on preclinical developments.Inherited retinal degeneration is a group of blinding disorders afflicting more than 1 in 4000 worldwide. These disorders frequently cause the death of photoreceptor cells or retinal ganglion cells. In a subset of these disorders, photoreceptor cell death is a secondary consequence of retinal pigment epithelial cell dysfunction or degeneration. This manuscript reviews current efforts in identifying targets and developing small molecule-based therapies for these devastating neuronal degenerations, for which no cures exist. Photoreceptors and retinal ganglion cells are metabolically demanding owing to their unique structures and functional properties. Modulations of metabolic pathways, which are disrupted in most inherited retinal degenerations, serve as promising therapeutic strategies. In monogenic disorders, great insights were previously obtained regarding targets associated with the defective pathways, including phototransduction, visual cycle, and mitophagy. In addition to these target-based drug discoveries, we will discuss how phenotypic screening can be harnessed to discover beneficial molecules without prior knowledge of their mechanisms of action. Because of major anatomical and biological differences, it has frequently been challenging to model human inherited retinal degeneration conditions using small animals such as rodents. Recent advances in stem cell-based techniques are opening new avenues to obtain pure populations of human retinal ganglion cells and retinal organoids with photoreceptor cells. We will discuss concurrent ideas of utilizing stem-cell-based disease models for drug discovery and preclinical development.

Glaucoma drainage implant exposure: A review of aetiology, risks and repair considerations.

In recent years, there has been a paradigm shift in glaucoma surgical procedures. Glaucoma drainage implant (GDI) surgeries are being performed much more commonly. Thus, it is important for surgeons to be cognisant of potential complications and their management. Exposure of a GDI is a well-known complication, and prompt recognition and treatment are required to prevent endophthalmitis, a potentially blinding condition. In this review, we discuss the mechanisms and risk factors for GDI exposure, highlight important considerations for repair, and discuss repair techniques, with the aim of improving patient outcomes and minimising the risk of re-exposure.

Diabetes a major risk factor for blinding condition of Neovascular Glaucoma

Importance: Neovascular glaucoma (NVG) is a severe form of secondary glaucoma has a varying prevalence of 0.01 to 3.9% of all glaucoma in different regions of world. Majority of them are affected with proliferative diabetic retinopathy. Although NVG overall prevalence is low but it is a dreadful condition led to blindness. If not detected earlier of the disease by latest investigating majors and treated systematically on different stages of the disease along with taking care of the alleviation of different aggravating factors for retinal hypoxia. Objectives: To summarize published evidence on etiopathogenesis, clinical feature, stages of NVG and to provide treatment recommendation on different stages of the NVG for ophthalmologists based on published evidence. Evidence Review: A literature search of PubMed was conducted from January 1, 1974 to June 30, 2022. Publications describing prevalence, etiopathogenesis, clinical staging, investigation and treatment modality were included in the study. Findings: NVG is characterized by development of new vessels on iris and fibrovascular tissue proliferation in the anterior chamber angle with increase in IOP, principally driven by Retinal ischemia and among the commonest causes are proliferative diabetic neuropathy (PDR), central retinal venous occlusion, and ocular ischemic syndrome (OIS).

Innovative Design of Intelligent Health Equipment for Helping the Blind in Smart City.

The rapid advancement of information technology in today's modern society is contributing to an increase in the general degree of civilization in society. People are pleased with technological progress, but they are also becoming more aware that a major challenge confronting the advancement of social civilization at the moment is determining how to alleviate the difficulties associated with traveling and participating in social activities for the blind, as well as increasing the frequency with which they go out, travel, and participate in other activities. The blindness equipment that is now accessible in China is no longer suitable to meet the needs of blind people, but the growth of smart cities offers an opportunity to change this. Guide devices are crucial among the numerous types of equipment to assist the blind, and in order to better fulfill their various demands, we must upgrade and optimize the existing devices. The Chinese People's Daily highlights some of the key barriers to blind people's access in its 2019 article: random parking that blocks blind lanes; and “snake” and “broken” blind lanes that are not created with blind people's access in mind. In a smart city, accurate placement via smart maps helps alleviate a number of traffic-related issues for blind individuals. In this paper, we propose an intelligent guide device and interactive software to provide a more intelligent way for blind people to travel, which can effectively improve blind people's traffic conditions and make their travel easy, convenient, and safe, reflecting society's concern for blind people.

Successful surgery and institutional incidence of rhegmatogenous retinal detachments in Teaching Hospital, Kurunegala, Sri Lanka: 3-year results from a tertiary care centre in North-Western province of Sri Lanka

Introduction: Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition if not treated. Major proportion of RRDs in Teaching Hospital were complex RRDs.Objectives: To assess the surgical success (reattachment) and other characteristics of RRD repairs and to determine the yearly institutional incidence of RRDs in Teaching Hospital, Kurunegala, Sri Lanka.Methods: Observational study of retrospective case review of RRDs operated by single vitreoretinal surgeon from 30.09.2018 to 30.09.2021. Retinal reattachment is the primary outcome measure. Modalities of treatment were either pars planar vitrectomy (TPPV) or scleral buckling (SB). Perfluoropropane or Silicone oil 1000cst was used as tamponading agent indicated by the complexity of RRD. All the cases were performed without endolaser, or a wideangle viewing system and cryopexy used for primary sealing of tears. When indicated TPPV was combined with SB. Failed SBs reoperated with TPPV and tamponade.Results: Study involved 309 eyes of 306 patients where 248 (80.26%) eyes of 246 offered TPPV and 61 (19.74%) eyes out of 60 offered SB. Mean age was 51.32y (7-80y) and 198 (65%) males and 108 (35%) females. Mean number of surgical interventions 1.608 (1-6). Overall surgical success over 3 years in TPPV group was 87.096% (216/248) and in SB group 77.049% (47/61) and average surgical success in both groups was 82.072% (263/309). Steady rise in surgical success in TPPV group observed over years achieving 93.55% in 2021. Average institutional incidence of RRDs was 1.346 per 100 eye admissions to eye unit.Conclusion: In a low facility setup for vitreoretinal services high success rate achieved has helped to prevent blindness due to RRD.

Latent fingermark development on fired and unfired brass ammunition under controlled and blind conditions

There has been growing interest in the Foster+Freeman RECOVER® Latent Fingerprint Technology system to develop fingermarks from fired ammunition. Over a six-month period, 1540 fingermarks were deposited on brass.223 ammunition, the majority of which were then fired after different time intervals. Samples were subjected to a cleaning protocol and/or processed with disulfur dinitride, cyanoacrylate/Brilliant Yellow 40, and/or vacuum metal deposition. Overall, 121 out of 1304 (9.3%) of natural fingermarks deposited were deemed identifiable post-firing and processing. This translated to 102 out of 652 (15.6%) of fired cartridges having identifiable fingermarks. A pseudo-operational study, which involved processing 1000 fired brass ammunition of various caliber using disulfur dinitride with and without a cleaning protocol, was conducted; only 18 (1.8%) comparable fingermarks were developed. This study demonstrates the need for more robust research involving this challenging substrate and novel technology, with which several issues were identified.

A defective structural zipper in photoreceptors causes inherited blindness.

Being able to see the beauty of this world is a wonderful thing unfortunately unavailable to people with inherited blindness. In this issue of PLOS Biology, Mercey and colleagues present optimized expansion microscopy for retinal tissue, which represents a huge step forward in our ability to study these blinding conditions.

A 10-Year Review of the Management of Ocular Mucous Membrane Pemphigoid: A Private Practice Experience.

Ocular mucous membrane pemphigoid (OcMMP) is a rare and potentially blinding condition for which consensus treatment guidelines do not exist. The purpose of this study was to assess the effectiveness and safety of various immunomodulatory agents in the treatment of OcMMP in a private practice setting. We conducted a 10-year retrospective chart review of patients managed with OcMMP (n = 22). The median age at diagnosis was 73 (range: 35-91) years, and 59% (13/22) of patients were female. Visual acuity, Foster stage, and adverse effects (AEs) were documented. Treatment outcomes for each treatment episode were qualified at 3 months as complete response (CR), response (R), or failure (F). After 3 months, CR was then further subqualified as sustained CR, reactivation after initial CR, or AE after initial CR. The Fisher exact test P values were calculated for each outcome in comparison with mycophenolate. Twenty patients were treated with an immunomodulatory agent for a total of 55 treatment episodes. In comparison to dapsone, mycophenolate was more likely to achieve sustained CR (50% vs. 0%, P = 0.022) and R (100% vs. 50%, P = 0.007), and less likely to fail (0% vs. 50%, P = 0.007). Dapsone was also more likely to be discontinued because of AEs than mycophenolate (40% vs. 6%, P = 0.041). Mycophenolate is a superior first-line agent to dapsone in the treatment of OcMMP. Although not statistically significant, mycophenolate trends toward superiority over methotrexate as well. Mycophenolate is very effective when used in combination with rituximab. Azathioprine remains a reasonable second-line agent.

AAV2-mediated gene therapy for Bietti crystalline dystrophy provides functional CYP4V2 in multiple relevant cell models

Bietti crystalline dystrophy (BCD) is an inherited retinal disease (IRD) caused by mutations in the CYP4V2 gene. It is a relatively common cause of IRD in east Asia. A number of features of this disease make it highly amenable to gene supplementation therapy. This study aims to validate a series of essential precursor in vitro experiments prior to developing a clinical gene therapy for BCD. We demonstrated that HEK293, ARPE19, and patient induced pluripotent stem cell (iPSC)-derived RPE cells transduced with AAV2 vectors encoding codon optimization of CYP4V2 (AAV2.coCYP4V2) resulted in elevated protein expression levels of CYP4V2 compared to those transduced with AAV2 vectors encoding wild type CYP4V2 (AAV2.wtCYP4V2), as assessed by immunocytochemistry and western blot. Similarly, we observed significantly increased CYP4V2 enzyme activity in cells transduced with AAV2.coCYP4V2 compared to those transduced with AAV2.wtCYP4V2. We also showed CYP4V2 expression in human RPE/choroid explants transduced with AAV2.coCYP4V2 compared to those transduced with AAV2.wtCYP4V2. These preclinical data support the further development of a gene supplementation therapy for a currently untreatable blinding condition—BCD. Codon-optimized CYP4V2 transgene was superior to wild type in terms of protein expression and enzyme activity. Ex vivo culture of human RPE cells provided an effective approach to test AAV-mediated transgene delivery.

A method for assessing and monitoring consistency of nonclinical ECG analysis

Cardiovascular safety is a key area of concern for new drugs in development, and the collection and analysis of electrocardiograms (ECGs) is a standard and major component of nonclinical testing. Digital data capture technology allows for high-throughput and long-duration ECG collections, resulting in large volumes of data. Consistent analysis of these ECG data is critical for detecting meaningful changes during nonclinical drug development. We developed a method to assess the consistency of nonclinical ECG analysis for a group of analysts over time. Eight‑lead ECGs were collected from conscious dogs using Ponemah (v5.2, DSI). Analysts placed Pstart, Qstart, Rpeak, Send, and Tend marks on six waveforms for each animal. The ECG files were randomized and re-marked under blinded conditions 4 to 14 days following initial mark placement. Averages of each parameter measured (RR interval, QRS duration, PR interval, and QT interval) were compiled for each marking session and analyst. A Gage R&R evaluation was completed. Graphical output from the Gage R&R evaluation showed distinct variability on group and individual analyst levels. Differences in inter- and intra-analyst variability (reproducibility and repeatability, respectively) were observed between trained analysts and analysts in training. The Gage R&R method is an effective tool for assessing consistency of digital ECG mark placement at a group level. Furthermore, it is able to identify areas of improvement for individual ECG analysts and to assess ECG analyst consistency during their training period. The assessment results are useful for facilitating discussions on best practices and maintaining consistency of mark placement.

Severity of myopia in children presented at KDA district head quarter teaching hospital Kohat.

Objective: To evaluate the severity and relationship of myopia with age of the children. Study Design: Descriptive Cross Sectional study. Setting: Eye OPD DHQ Teaching Hospital KDA Kohat. Period: January 2021 to June 2021. Material & Methods: The sample size was 200 children with myopia and the age limit was 5-19 years. To determine the severity of myopia in children of age limit 5-19 years presented at DHQ and teaching hospital Kohat, the children were included into the study based on the inclusion criteria, the cycloplegic refraction was done and then the spherical equivalent of the refractive error was recorded and based on that the children were categorised as having mild, moderate, high, and severe myopia. All the data was collected and processed through SPSS 23.0 software. Results: Cumulatively out of 200 participants, 98 children had mild myopia, 87 had moderate myopia, 10 had high myopia and 5 children had severe myopia. Mild myopia was mostly prevalent in children of age limit 8-10 years, moderate myopia was mostly prevalent in children of age limit 11-13 years, while high myopia was mostly prevalent in children with age limit 14-16 years, and severe myopia was mostly prevalent in children of age limit 17-19 years. Conclusion: It is clear from the results that the most prevalent type of myopia in children is mild myopia and myopia severity increases with increase in children age. As the myopia is the most common type of refractive error in children and high myopia is a major risk factor of blinding ocular condition so, the myopia type and severity should be recognized as soon as possible in children and should be managed to control the progression of myopia.

Octacalcium Phosphate/Gelatin Composite (OCP/Gel) Enhances Bone Repair in a Critical-sized Transcortical Femoral Defect Rat Model.

Bone grafting is widely used to treat large bone defects. A porous composite of a bioactive octacalcium phosphate material with gelatin sponge (OCP/Gel) has been shown to biodegrade promptly and be replaced with new bone both in animal models of a membranous bone defect and a long bone defect. However, it is unclear whether OCP/Gel can regenerate bone in more severe bone defects, such as a critical-size transcortical defect. Using an in vivo rat femur model of a standardized, transcortical, critical-size bone defect, we asked: Compared with a Gel control, does OCP/Gel result in more newly formed bone as determined by (1) micro-CT evaluation, (2) histologic and histomorphometric measures, and (3) osteocalcin staining and tartrate-resistant acid phosphatase staining? Thirty-four 12-week-old male Sprague-Dawley rats (weight 356 ± 25.6 g) were used. Gel and OCP/Gel composites were prepared in our laboratory. Porous cylinders 3 mm in diameter and 4 mm in height were manufactured from both materials. The OCP/Gel and Gel cylinders were implanted into a 3-mm-diameter transcortical critical-size bone defect model in the left rat femur. The OCP/Gel and Gel were randomly assigned, and the cylinders were implanted. The biological responses of the defect regions were evaluated radiologically and histologically. At 4 and 8 weeks after implantation, CT evaluation, histological examination of decalcified samples, and immunostaining were quantitatively performed to evaluate new bone formation and remaining bone graft substitutes and activity of osteoblasts and osteoclast-like cells (n = 24). Qualitative histological evaluation was performed on undecalcified samples at 3 weeks postimplantation (n = 10). CT and decalcified tissue analysis was not performed blinded, but an analysis of undecalcified specimens was performed under blinded conditions. Radiologic analysis revealed that the OCP/Gel group showed radiopaque regions around the OCP granules and at the edge of the defect margin 4 weeks after implantation, suggesting that new bone formation occurred in two ways. In contrast, the rat femurs in the Gel group had a limited radiopaque zone at the edge of the defect region. The amount of new bone volume analyzed by micro-CT was higher in the OCP/Gel group than in the Gel group at 4 and 8 weeks after implantation (​​4 weeks after implantation: OCP/Gel versus Gel: 6.1 ± 1.6 mm 3 versus 3.4 ± 0.7 mm 3 , mean difference 2.7 [95% confidence interval (CI) 0.9 to 4.5]; p = 0.002; intraclass correlation coefficient [ICC] 0.72 [95% CI 0.29 to 0.91]; 8 weeks after implantation: OCP/Gel versus Gel: 3.9 ± 0.7 mm 3 versus 1.4 ± 1.1 mm 3 , mean difference 2.5 [95% CI 0.8 to 4.3]; p = 0.004; ICC 0.81 [95% CI 0.47 to 0.94]). Histologic evaluation also showed there was a higher percentage of new bone formation in the OCP/Gel group at 4 and 8 weeks after implantation (​​4 weeks after implantation: OCP/Gel versus Gel: 31.2% ± 5.3% versus 13.6% ± 4.0%, mean difference 17.6% [95% CI 14.2% to 29.2%]; p < 0.001; ICC 0.83 [95% CI 0.53 to 0.95]; 8 weeks after implantation: OCP/Gel versus Gel: 28.3% ± 6.2% versus 9.5% ± 1.9%, mean difference 18.8% [95% CI 11.3% to 26.3%]; p < 0.001; ICC 0.90 [95% CI 0.69 to 0.97]). Bridging of the defect area started earlier in the OCP/Gel group than in the Gel group at 4 weeks after implantation. Osteocalcin immunostaining showed that the number of mature osteoblasts was higher in the OCP/Gel group than in the Gel group at 4 weeks (OCP/Gel versus Gel: 42.1 ± 6.5/mm 2 versus 17.4 ± 5.4/mm 2 , mean difference 24.7 [95% CI 16.2 to 33.2]; p < 0.001; ICC 0.99 [95% CI 0.97 to 0.99]). At 4 weeks, the number of osteoclast-like cells was higher in the OCP/Gel composite group than in the Gel group (OCP/Gel versus Gel: 3.2 ± 0.6/mm 2 versus 0.9 ± 0.4/mm 2 , mean difference 2.3 [95% CI 1.3 to 3.5]; p < 0.001; ICC 0.79 [95% CI 0.35 to 0.94]). OCP/Gel composites induced early bone remodeling and cortical bone repair in less time than did the Gel control in a rat critical-size, transcortical femoral defect, suggesting that OCP/Gel could be used as a bone replacement material to treat severe bone defects. In a transcortical bone defect model of critical size in the rat femur, the OCP/Gel composite demonstrated successful bone regeneration. Several future studies are needed to evaluate the clinical application of this interesting bone graft substitute, including bone formation capacity in refractory fracture and spinal fusion models and the comparison of bone strength after repair with OCP/Gel composite to that of autologous bone.

Analysis of physiological and non-contact signals to evaluate the emotional component in consumer preferences.

Emotions are an essential drive in decision making and may influence consumer preference. In this study we assessed the influence of brands in product preference after tasting 2 soft-drinks (Coca Cola vs. Cola beverage), by using physiological measurements, namely the skin conductance, the respiratory rate and heart rate variability (HRV) extracted using contactless sensors. The experimental protocol enrolled twenty-five young subjects which were asked to taste 2 soft drinks in random order, without knowing the brand (blind condition) and then knowing the brand (not blind condition). After each phase the subject was asked to choose the preferred beverage. Our main hypothesis is that if the subject knows the brand there is an arousal effect, independently from the absolute appreciation of the product. In order to evaluate the emotional components, the skin conductance, respiratory and Video-Photoplethysmographic (PPG) signals were continuously recorded throughout the experiment. The Video-PPG was then processed to extract HRV parameters. We observed that the arousal levels changed among beverages and conditions, going from higher arousal for Coca-Cola in the blind condition, to higher arousal for Cola in the not blind condition. Moreover, 44% of the subjects changed their preference when the brand was uncovered: from blind to not blind conditions, 6 subjects went from Cola to Coca-Cola as preferred drink and 5 went from Coca-Cola to Cola. Opposite results were found for the two beverages when comparing the physiological response when the beverage was/was not preferred. Finally, differences were found also between consumers and not consumers of Coca-Cola and the blind/not blind comparison. We conclude that the brand is a fundamental element in a request for choice and it can affect the first emotional response of a subject.

Topical Capsaicin in Poly(lactic-co-glycolic)acid (PLGA) Nanoparticles Decreases Acute Itch and Heat Pain.

Background: Capsaicin, the hot pepper agent, produces burning followed by desensitization. To treat localized itch or pain with minimal burning, low capsaicin concentrations can be repeatedly applied. We hypothesized that alternatively controlled release of capsaicin from poly(lactic-co-glycolic acid) (PLGA) nanoparticles desensitizes superficially terminating nociceptors, reducing burning. Methods: Capsaicin-loaded PLGA nanoparticles were prepared (single-emulsion solvent evaporation) and characterized (size, morphology, capsaicin loading, encapsulation efficiency, in vitro release profile). Capsaicin-PLGA nanoparticles were applied to murine skin and evaluated in healthy human participants (n = 21) for 4 days under blinded conditions, and itch and nociceptive sensations evoked by mechanical, heat stimuli and pruritogens cowhage, β-alanine, BAM8-22 and histamine were evaluated. Results: Nanoparticles (loading: 58 µg capsaicin/mg) released in vitro 23% capsaicin within the first hour and had complete release at 72 h. In mice, 24 h post-application Capsaicin-PLGA nanoparticles penetrated the dermis and led to decreased nociceptive behavioral responses to heat and mechanical stimulation (desensitization). Application in humans produced a weak to moderate burning, dissipating after 3 h. A loss of heat pain up to 2 weeks was observed. After capsaicin nanoparticles, itch and nociceptive sensations were reduced in response to pruritogens cowhage, β-alanine or BAM8-22, but were normal to histamine. Conclusions: Capsaicin nanoparticles could be useful in reducing pain and itch associated with pruritic diseases that are histamine-independent.

Assessing the Ability of Reiki Practitioners to Detect Human Energy Fields

Reiki is a form of energy healing that has gained popularity in the United States, but there remains skepticism about its scientific validity. This study examines the ability of Reiki practitioners (RP) to detect human energy fields (HEF). Volunteer RP were asked to identify the location of a human hand under blinded conditions for a total of 20 trials. Four potential options existed for subjects (right, left, both, or neither); thus, random chance would predict a success rate of 25%. A success rate of &gt;40% was considered significant, and these individuals would be asked to conduct another 40 trials. A control group of non-energy trained volunteers were also asked to complete the same task. A total of 67, mainly female (91%), RP participated in this study. The majority were Reiki Masters (90%) and practiced Reiki an average of 11.4 years (±6.2, 1.5-24). They had a mean success rate of detecting HEF of 25.4%, (median 5 ± 1.8, 1-10), while the control group (n = 25) had an average success rate of 24.2% (median 5 ± 1.6, 2-8). One subject met criteria for repeat testing for a final 42% accuracy rate. Level of training (masters versus level II), years of experience (&gt;10), age (&gt;60), female sex, handedness, or time to detect HEF (average &gt;20 sec) did not correlate to an increase in accuracy for RP. RPs’ ability to HEF was equivalent to chance and similar to the control group of non-energy trained volunteers. The mechanism by which reiki provides benefits to patients is still unknown, and while this study indicates that it may not be through the manipulation of energy fields, alternate explanations include physical touch and healing touch, both of which should be explored in future research.

The association between intestinal microbiome and autoimmune uveitis.

The microbiome is strongly implicated in a wide spectrum of immune-mediated diseases, whereas gut commensal microbiota plays a pivotal role in immune and intestinal homeostasis. A thorough literature search was performed in PubMed database. An additional search was made in Google Scholar to complete the collected items. Due to complex interactions with the host genetics and other factors, intestinal dysbiosis has been linked to various immune-mediated disorders. In particular, the role of intestinal microbiota in the pathogenesis of uveitis has been demonstrated by several studies, indicating that changes in the microbiome can trigger autoimmune ocular inflammatory processes or affect their severity. This review summarizes how alterations in the intestinal microbiota can conduce to immune-mediated ocular pathologies and how microbiome can be targeted in order to form novel therapeutic approaches to treat these severe and potentially blinding conditions.

Quantifying light energy from 450 nm, 650 nm, 810 nm, and 980 nm wavelength lasers delivered through dental hard tissue

PurposeThe energy available to treat the dental pulp after transmittance through overlying structures is clinically important for determining photobiological effects. This ex vivo study aimed to quantify laser energy delivery though the dental crown to the pulp from an initial energy of 5 J using four common laser wavelengths (λ = 450, 650, 810, and 980 nm).Material and methodsA total of 30 extracted healthy human teeth (anterior n = 10; premolar n = 10; molar n = 10) were longitudinally sectioned (Project Number: 2021/421, University of Sydney, NSW, Australia). Each sample was methodically exposed in random order to the four wavelengths. Each wavelength was operated at the same power (0.50 W) for 10 s to deliver 5.0 J with a total energy delivery of 10 J/cm2. Laser light was delivered with an 8-mm-diameter fiber bundle probe directed perpendicularly to the buccal cervical-third of the crown. The transmitted energy was measured twice and averaged using a periodically pre-calibrated power meter in blinded conditions. Data were analyzed using a general linear model with logarithmic transformation.ResultsWavelength and tooth thickness were significant predictors of optical transmittance (P < 0.05) while tooth type was significant only for the 450 nm wavelength. The average attenuation coefficients (µ) were 2.55, 2.45, 1.87, and 5.42 cm−1 (± 10%) for the 980, 810, 650, and 450 nm groups, respectively.ConclusionClinicians should recognize that significant attenuation occurs during laser energy delivery to the pulp, influenced by the wavelength, thickness, and tooth type. Our findings support the potential for laser energy delivery to the pulp for photobiomodulation applications.

Müller Glia maintain their regenerative potential despite degeneration in the aged zebrafish retina.

Ageing is a significant risk factor for degeneration of the retina. Müller glia cells (MG) are key for neuronal regeneration, so harnessing the regenerative capacity of MG in the retina offers great promise for the treatment of age‐associated blinding conditions. Yet, the impact of ageing on MG regenerative capacity is unclear. Here, we show that the zebrafish retina undergoes telomerase‐independent, age‐related neurodegeneration but that this is insufficient to stimulate MG proliferation and regeneration. Instead, age‐related neurodegeneration is accompanied by MG morphological aberrations and loss of vision. Mechanistically, yes‐associated protein (Yap), part of the Hippo signalling, has been shown to be critical for the regenerative response in the damaged retina, and we show that Yap expression levels decline with ageing. Despite this, morphologically and molecularly altered aged MG retain the capacity to regenerate neurons after acute light damage, therefore, highlighting key differences in the MG response to high‐intensity acute damage versus chronic neuronal loss in the zebrafish retina.

Hidden in the Eyes-Recurrence of Systemic Hemopathies Reportedly "In Remission": Six Cases and Review of Literature.

Background and Objectives: Secondary ocular localizations of hematological malignancies are blinding conditions with a poor prognosis, and often result in a delay in the diagnosis. Materials and Methods: We describe a series of rare cases of ocular involvement in six patients with hematological malignancies, reportedly in remission, who presented secondary ocular localizations, challenging to diagnose. Two patients had an acute lymphoblastic leukemia (ALL) and developed either a posterior scleritis or a pseudo-panuveitis with ciliary process infiltration. One patient had iris plasmacytoma and developed an anterior uveitis as a secondary presentation. Two patients had a current systemic diffuse large B-cell lymphoma (DLBCL) and were referred either for intermediate uveitis or for papilledema and vitritis with secondary retinitis. Finally, one patient with an acute myeloid leukemia (AML) presented a conjunctival localization of a myeloid sarcoma. We herein summarize the current knowledge of ophthalmologic manifestations of extramedullary hematopathies. Results: Inflammatory signs were associated with symptomatic infiltrative lesions well displayed in either the iris, the retina, the choroid, or the cavernous sinus, from the admission of the patients in the ophthalmological department. These findings suggest that patients with ALL, AML, systemic DLBCL, and myeloma can present with ophthalmic involvement, even after having been reported as in remission following an effective systemic treatment and/or allograft. Conclusions: Early detection of hidden recurrence in the eyes may permit effective treatment. Furthermore, oncologists and ophthalmologists should be aware of those rare ocular malignant locations when monitoring patient’s progression after initial treatment, and close ophthalmologic examinations should be recommended when detecting patient’s ocular symptoms after treatment.

Integrating a Real-Life Experience with Consumer Evaluation: Sensory Acceptance and Willingness to Pay for Coffee Drinks in a Real Café

Consumer experiments in real-life environments that capture consumer responses in context and link them to consumers' daily habits are valuable for reflecting multi-faceted decision environments, reducing consumer cognitive burden, and other empirical biases. The objective of this study was to investigate and link consumers’ sensory acceptance and willingness to pay (WTP) in a real-life study situation by taking the example of oat and pea protein milk. A total of 144 German consumers were recruited in a café in a middle-sized town in Germany. Under blind conditions, consumers were asked to indicate their hedonic liking, willingness to pay a premium for cappuccino prepared with plant-based milk, and their adaptability and motivation for integrating the plant-based milk alternatives into their daily diet. The sensory evaluation of this study showed good acceptance of cappuccino prepared with oat milk and pea protein milk; high acceptance was reflected in reasonable and realistic WTP estimates.