Classical and alternative receptors for SARS-CoV-2 therapeutic strategy.

Understanding the molecules that are essential for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) entry can provide insights into viral infection and dissemination. Recently, it has been identified from several studies that angiotensin-converting enzyme 2 receptor and transmembrane serine protease 2 are the main entry molecules for the SARS-CoV-2, which produced the pandemic of Covid-19. However, additional evidence showed several other viral receptors and cellular proteases that are also important in facilitating viral entry and transmission in the target cells. In this review, we summarized the types of SARS-CoV-2 entry molecules and discussed their crucial roles for virus binding, protein priming and fusion to the cellular membrane important for SARS-CoV-2 infection.

Should Aquaporin-4 Antibody Test Be Performed in all Patients With Isolated Optic Neuritis?

BACKGROUND: Optic neuritis (ON) may be the initial manifestation of neuromyelitis optica spectrum disorder (NMOSD). Aquaporin-4 antibody (AQP4 Ab) is used to diagnose NMOSD. This has implications on prognosis and is important for optimal management. We aim to evaluate if clinical features can distinguish AQP4 Ab seropositive and seronegative ON patients. METHODS: We reviewed patients with first episode of isolated ON from Tan Tock Seng Hospital and Singapore National Eye Centre who tested for AQP4 Ab from 2008 to 2017. Demographic and clinical data were compared between seropositive and seronegative patients. RESULTS: Among 106 patients (120 eyes) with first episode of isolated ON, 23 (26 eyes; 22%) were AQP4 Ab positive and 83 (94 eyes; 78%) were AQP4 Ab negative. At presentation, AQP4 Ab positive patients had older mean onset age (47.9 ± 13.6 vs 36.8 ± 12.6 years, P < 0.001), worse nadir VA (OR 1.714; 95% CI, 1.36 to 2.16; P < 0.001), less optic disc swelling (OR 5.04; 95% CI, 1.682 to 15.073; p = 0.004), and higher proportions of concomitant anti-Ro antibody (17% vs 4%, p = 0.038) and anti-La antibody (17% vs 1%, p = 0.008). More AQP4 Ab positive patients received steroid-sparing immunosuppressants (74% vs 19%, p < 0.001) and plasma exchange (13% vs 0%, p = 0.009). AQP4 Ab positive patients had worse mean logMAR VA (visual acuity) at 12 months (0.70 ± 0.3 vs 0.29 ± 0.5, p = 0.051) and 36 months (0.37±0.4 vs 0.14 ± 0.2, p = 0.048) follow-up. CONCLUSION: Other than older onset age and retrobulbar optic neuritis, clinical features are non-discriminatory for NMOSD. We propose a low threshold for AQP4 Ab serology testing in inflammatory ON patients, particularly in high NMOSD prevalence populations, to minimize diagnostic and treatment delays.

Ethnic variation in medial orbital wall anatomy and its implications for decompression surgery.

BACKGROUND: To describe the inter-ethnic variation in medial orbital wall anatomy between Chinese, Malay, Indian and Caucasian subjects. METHODS: Single-centre, retrospective, Computed Tomography (CT)-based observational study. 20 subjects of each ethnicity, were matched for gender and laterality. We excluded subjects younger than 16 years and those with orbital pathology. OsiriX version 8.5.1 (Pixmeo., Switzerland) and DICOM image viewing software CARESTREAM Vue PACS (Carestream Health Inc., USA) were used to measure the ethmoidal sinus length, width and volume, medial orbital wall and floor angle and the relative position of the posterior ethmoid sinus to the posterior maxillary wall. Statistical analyses were performed using Statistical Package for Social Sciences version 25.0 (IBM, USA). RESULTS: There were 12 males (60 %) in each group, with no significant difference in age (p = 0.334-0.994). The mean ethmoid sinus length in Chinese, Malay, Indian and Caucasian subjects, using the Chinese as reference, were 37.2, 36.9, 38.0 and 37.4mm, the mean width was 11.6, 10.5, 11.4 and 10.0mm (p = 0.020) and the mean ethmoid sinus volume were 3362, 3652, 3349 and 3898mm3 respectively. The mean medial orbital wall and floor angle was 135.0, 131.4, 131.0 and 136.8 degrees and the mean relative position of posterior ethmoid sinus to posterior maxillary wall were - 2.0, -0.2, -1.5 and 1.6mm (p = 0.003) respectively. CONCLUSIONS: No inter-ethnic variation was found in decompressible ethmoid sinus volume. Caucasians had their posterior maxillary sinus wall anterior to their posterior ethmoidal walls unlike the Chinese, Malay and Indians. Awareness of ethnic variation is essential for safe orbital decompression.

Antimutagenic, Cytoprotective and Antioxidant Properties of Ficus deltoidea Aqueous Extract In Vitro.

Ficus deltoidea var. deltoidea is used as traditional medicine for diabetes, inflammation, and nociception. However, the antimutagenic potential and cytoprotective effects of this plant remain unknown. In this study, the mutagenic and antimutagenic activities of F. deltoidea aqueous extract (FDD) on both Salmonella typhimurium TA 98 and TA 100 strains were assessed using Salmonella mutagenicity assay (Ames test). Then, the cytoprotective potential of FDD on menadione-induced oxidative stress was determined in a V79 mouse lung fibroblast cell line. The ferric-reducing antioxidant power (FRAP) assay was conducted to evaluate FDD antioxidant capacity. Results showed that FDD (up to 50 mg/mL) did not exhibit a mutagenic effect on either TA 98 or TA 100 strains. Notably, FDD decreased the revertant colony count induced by 2-aminoanthracene in both strains in the presence of metabolic activation (p < 0.05). Additionally, pretreatment of FDD (50 and 100 µg/mL) demonstrated remarkable protection against menadione-induced oxidative stress in V79 cells significantly by decreasing superoxide anion level (p < 0.05). FDD at all concentrations tested (12.5-100 µg/mL) exhibited antioxidant power, suggesting the cytoprotective effect of FDD could be partly attributed to its antioxidant properties. This report highlights that F. deltoidea may provide a chemopreventive effect on mutagenic and oxidative stress inducers.

Efficacy of Modified Amnion-Assisted Conjunctival Epithelial Redirection (ACER) for Partial Limbal Stem Cell Deficiency.

Background and objectives: the aim of this study was to analyze the efficacy of a modified "amnion-assisted conjunctival epithelial redirection (ACER)" technique for the treatment of partial limbal stem cell deficiency (LSCD). Materials and methods: the medical records of three patients with partial LSCD who underwent corneal surface reconstruction with modified ACER following superficial keratectomy were retrospectively studied. Briefly, in this technique, an inner amniotic membrane (AM) layer was applied on the corneal surface to promote corneal re-epithelialization. The outer AM layer was applied as a barrier to prevent the invasion of conjunctival epithelial cells into the cornea before the corneal surface was completely covered by corneal epithelial cells derived from the remaining intact limbal stem cells. Results: in all three cases, the outer AM layer successfully kept the conjunctival epithelium away from the corneal surface and prevented an admixture of conjunctival epithelial cells with corneal epithelial cells. In all three patients, the cornea was completely re-epithelized with epithelial cells derived from the remaining healthy limbal stem cells, and a clear visual axis was maintained without recurrence for a mean follow-up period of 37.3 ± 8.6 months. Conclusions: the preliminary results suggest that modified ACER appears to be a viable option for patients with partial LSCD.

Zingiber zerumbet L. (Smith) extract alleviates the ethanol-induced brain damage via its antioxidant activity.

BACKGROUND: Zingiber zerumbet (L.) Smith belongs to the Zingiberaceae family that is widely distributed throughout the tropics, particularly in Southeast Asia. It is locally known as 'Lempoyang' and traditionally used to treat fever, constipation and to relieve pain. It is also known to possess antioxidant and anti-inflammatory activities. Based on these antioxidant and anti-inflammatory activities, this study was conducted to investigate the effects of ethyl-acetate extract of Z. zerumbet rhizomes against ethanol-induced brain damage in male Wistar rats. METHOD: Twenty-four male Wistar rats were divided into four groups which consist of normal, 1.8 g/kg ethanol (40% v/v), 200 mg/kg Z. zerumbet extract plus ethanol and 400 mg/kg Z. zerumbet plus ethanol. The extract of Z. zerumbet was given once daily by oral gavage, 30 min prior to ethanol exposure via intraperitoneal route for 14 consecutive days. The rats were then sacrificed. Blood and brain homogenate were subjected to biochemical tests and part of the brain tissue was sectioned for histological analysis. RESULT: Treatment with ethyl-acetate Z. zerumbet extract at 200 mg/kg and 400 mg/kg significantly reduced the level of malondialdehyde (MDA) and protein carbonyl (p < 0.05) in the brain homogenate. Both doses of extracts also significantly increased the level of serum superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities as well as glutathione (GSH) level (p < 0.05). However, administration of ethyl-acetate Z. zerumbet extract at 400 mg/kg showed better protective effects on the ethanol-induced brain damage as shown with higher levels of SOD, CAT, GPx and GSH in the brain homogenate as compared to 200 mg/kg dose. Histological observation of the cerebellum and cerebral cortex showed that the extract prevented the loss of Purkinje cells and retained the number and the shape of the cells. CONCLUSION: Ethyl-acetate extract of Z. zerumbet has protective effects against ethanol-induced brain damage and this is mediated through its antioxidant properties. Z. zerumbet extract protects against ethanol-induced brain damage via its antioxidant properties.

Development and Validation of a Deep Learning System for Diabetic Retinopathy and Related Eye Diseases Using Retinal Images From Multiethnic Populations With Diabetes.

Importance: A deep learning system (DLS) is a machine learning technology with potential for screening diabetic retinopathy and related eye diseases. Objective: To evaluate the performance of a DLS in detecting referable diabetic retinopathy, vision-threatening diabetic retinopathy, possible glaucoma, and age-related macular degeneration (AMD) in community and clinic-based multiethnic populations with diabetes. Design, Setting, and Participants: Diagnostic performance of a DLS for diabetic retinopathy and related eye diseases was evaluated using 494 661 retinal images. A DLS was trained for detecting diabetic retinopathy (using 76 370 images), possible glaucoma (125 189 images), and AMD (72 610 images), and performance of DLS was evaluated for detecting diabetic retinopathy (using 112 648 images), possible glaucoma (71 896 images), and AMD (35 948 images). Training of the DLS was completed in May 2016, and validation of the DLS was completed in May 2017 for detection of referable diabetic retinopathy (moderate nonproliferative diabetic retinopathy or worse) and vision-threatening diabetic retinopathy (severe nonproliferative diabetic retinopathy or worse) using a primary validation data set in the Singapore National Diabetic Retinopathy Screening Program and 10 multiethnic cohorts with diabetes. Exposures: Use of a deep learning system. Main Outcomes and Measures: Area under the receiver operating characteristic curve (AUC) and sensitivity and specificity of the DLS with professional graders (retinal specialists, general ophthalmologists, trained graders, or optometrists) as the reference standard. Results: In the primary validation dataset (n = 14 880 patients; 71 896 images; mean [SD] age, 60.2 [2.2] years; 54.6% men), the prevalence of referable diabetic retinopathy was 3.0%; vision-threatening diabetic retinopathy, 0.6%; possible glaucoma, 0.1%; and AMD, 2.5%. The AUC of the DLS for referable diabetic retinopathy was 0.936 (95% CI, 0.925-0.943), sensitivity was 90.5% (95% CI, 87.3%-93.0%), and specificity was 91.6% (95% CI, 91.0%-92.2%). For vision-threatening diabetic retinopathy, AUC was 0.958 (95% CI, 0.956-0.961), sensitivity was 100% (95% CI, 94.1%-100.0%), and specificity was 91.1% (95% CI, 90.7%-91.4%). For possible glaucoma, AUC was 0.942 (95% CI, 0.929-0.954), sensitivity was 96.4% (95% CI, 81.7%-99.9%), and specificity was 87.2% (95% CI, 86.8%-87.5%). For AMD, AUC was 0.931 (95% CI, 0.928-0.935), sensitivity was 93.2% (95% CI, 91.1%-99.8%), and specificity was 88.7% (95% CI, 88.3%-89.0%). For referable diabetic retinopathy in the 10 additional datasets, AUC range was 0.889 to 0.983 (n = 40 752 images). Conclusions and Relevance: In this evaluation of retinal images from multiethnic cohorts of patients with diabetes, the DLS had high sensitivity and specificity for identifying diabetic retinopathy and related eye diseases. Further research is necessary to evaluate the applicability of the DLS in health care settings and the utility of the DLS to improve vision outcomes.

Features Associated With Vision in Eyes With Subfoveal Fibrosis From Neovascular Age-Related Macular Degeneration.

PURPOSE: To report the characteristics and correlation of visual acuity in eyes treated for neovascular age-related macular degeneration (nAMD) and developed fibrosis. DESIGN: Case-control study. METHODS: Three hundred fifty-six treatment-naive nAMD eyes that were treated for 12 months were included. Fibrosis was defined as present if well-defined hyperreflective material (HRM) were present between the neurosensory retina and the Bruch membrane on optical coherence tomography (OCT) that correlated with well-defined regions of yellowish pallor on fundus photography and/or staining on fluorescence angiography. OCT features of subfoveal fibrosis and the overlying retina were correlated with visual acuity at month 12. RESULTS: Sixty-three eyes (20.3%) developed incident fibrosis at month 12. Compared with eyes that did not develop fibrosis, these eyes had lower baseline vision (49 vs 54 letters, P = .02) and more of them had type 2 macular neovascularization (15.0 vs 8.8%, P = .03), larger lesion area (29.6 vs 15.1 mm2, P = .02), and subretinal hemorrhage ≥4 disc diameters (44.4% vs 19.8%, P < .01). Visual acuity was worse in the incident fibrosis compared with the group that never developed fibrosis by month 12. (-1.4±17.1 versus +6.0±17.4 letters, P < .01). In 83 eyes that had subfoveal fibrosis, better vision was associated with intact ellipsoid zone-external limiting membrane complex (ß coefficient 29.4, 95% CI 14.2-44.6, P < .01), whereas worse vision was associated with retinal pigment epithelium (RPE)-involving HRM, HRM above the RPE, and width of HRM (ß coefficients -25.4 [95% CI -36.3 to -14.6], P < .01; -23.5 [95% CI -39.0 to -7.9], P < .01; and -3.8 [95% CI -7.2 to -0.4], P = .03, respectively). CONCLUSION: Although fibrosis is associated with poorer visual outcome, preservation of external limiting membrane and level of fibrosis relative to the RPE are associated with visual outcomes.

A case of secondary multiple evanescent white dot syndrome in a patient with preexisting wet age-related macular degeneration.

Purpose: To report a case of secondary Multiple Evanescent White Dot Syndrome in a patient with preexisting wet age-related macular degeneration. Observation: A 75-year-old male on treat and extend regimen for wet age-related macular degeneration (AMD) presented with a sudden loss of vision and saw central dark shadow in the right eye (RE) for a duration of 1 week. There was no significant history preceding the visual loss. Examination showed a visual acuity (VA) of counting fingers at 1 meter in the right eye and 20/25 in the left eye. Anterior segment examination was unremarkable with dilated fundus examination showing a clear vitreous, tortuous blood vessel, a hyperemic disc and fibrosis at the macula. The left eye (LE) examination was unremarkable. Optical Coherence Tomography (OCT) showed fibrosis due to the previous wet AMD and hyperreflective excrescences projecting from the retinal pigment epithelium (RPE) outside of the old area of wet AMD. Fundus Fluorescein Angiogram (FFA) showed hyperfluorescent spots in a wreath-like pattern increasing in intensity in the early phase and showing late staining towards the late phase while Indocyanine green angiography (ICGA) did not clearly delineate the lesions. Fundus autofluorescence (FAF) revealed hyper Autofluorescence (AF) at the posterior pole. Optical Coherence Tomography Angiography (OCTA) revealed a flow reduction in the choriocapillaris of the affected area. Basic blood investigations with Venereal Disease Research Laboratory (VDRL), syphilitic IgM and IgG antibodies, Quantiferon TB gold test, complete renal function tests and liver function tests were performed. All the blood investigations were within normal limits and the workup for syphilis and tuberculosis was negative. The patient was started on 1mg/kg body weight of oral prednisolone (after the non-response to low dose of oral steroids) with the diagnosis of secondary multiple evanescent white dot syndrome (MEWDS) secondary to wet AMD. The patient was followed up every weekly and the last visit showed improvement in visual acuity to 20/50 with resolution of lesions on FAF and OCT macula. Conclusion and importance: Secondary MEWDS is extremely rare and unique in terms of its presentation and its association with preexisting chorioretinal disease where there is damage to the choriocapillaris- Bruch's membrane-RPE complex. This case report highlights one such rare case scenario and how multimodal imaging helps in the diagnosis, management and follow-up of patients with secondary MEWDS.

Clinical utility of ultra-widefield fluorescein angiography and optical coherence tomography angiography for retinal vein occlusions.

Retinal vein occlusions (RVOs) are the second most common retinal vascular disease after diabetic retinopathy, and are a significant cause of visual impairment, especially in the elderly population. RVOs result in visual loss due to macular ischemia, cystoid macular edema (CME), and complications related to neovascularization. Vascular assessment in RVOs traditionally relies on standard fluorescein angiography (FA) for assessment of macular and retinal ischemia, which aids in prognostication and guides intervention. Standard FA has significant limitations-it is time-consuming, requires invasive dye administration, allows for limited assessment of the peripheral retina, and is usually evaluated semi-qualitatively, by ophthalmologists with tertiary expertise. More recently, the introduction of ultra-widefield FA (UWF FA) and optical coherence tomography angiography (OCTA) into clinical practice has changed the tools available for vascular evaluation in RVOs. UWF FA allows for evaluation of peripheral retinal perfusion, and OCTA is non-invasive, rapidly-acquired, and provides more information on capillary perfusion. Both modalities can be used to provide more quantitative parameters related to retinal perfusion. In this article, we review the clinical utility and impact of UWF FA and OCTA in the evaluation and management of patients with RVOs.

Lysosomal dysfunction induced cytosolic vacuolation and increased intracellular amyloid-beta 42 (Aß42) in human brain endothelial cells (HBEC-5i).

Lysosome is a primary degradative organelle and is crucial in cellular homeostasis. A reduction in its function due to ageing has been associated with the development of Alzheimer's disease (AD), a common neurodegenerative disorder characterised by the deposition of neurotoxic amyloid plaque in the brain and cerebral vessel walls. The breakdown of the blood-brain barrier (BBB) plays a vital role in the pathogenesis of AD. However, the impact of lysosomal dysfunction on brain endothelial cells, the key component of the BBB, in the disease progression is yet to be fully understood. In this study, human brain endothelial cells (HBEC-5i) were exposed to a lysosomotropic compound, chloroquine (CQ) for 24 h. Cell viability was assessed with the 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay to determine the inhibitory concentration (IC) at IC10 (17.5 µM), IC25 (70.5 µM), and IC50 (125 µM). The morphological changes observed include vacuoles arrested in the cytosols and cell shrinkage that were more prominent at IC25 and IC50. Lysosomal dysfunction was evaluated by measuring the lysosomal-associated membrane protein-1 (LAMP-1) and microtubule-associated protein light chain 3-II (LC3-II) using the capillary-based immunoassay. LC3-II was significantly increased at IC25 and IC50 (p < 0.05 and p < 0.001, respectively). The concentration of intracellular and extracellular Aß42 was quantitated using the enzyme-linked immunosorbent assay, which demonstrated a significant increase (p < 0.05) in intracellular Aß42 at IC25. This study showed that perturbation of lysosomal function impairs autophagy that leads to intracellular increment of Aß, indicating the important roles of lysosomes in endothelial cells homeostasis and disease progression.

Molecularly imprinted polymers for per- and polyfluoroalkyl substances enrichment and detection.

Per- and polyfluoroalkyl substances (PFAS) are highly toxic pollutants of significant concern as they are being detected in water, air, fish and soil. They are extremely persistent and accumulate in plant and animal tissues. Traditional methods of detection and removal of these substances use specialised instrumentation and require a trained technical resource for operation. Molecularly imprinted polymers (MIPs), polymeric materials with predetermined selectivity for a target molecule, have recently begun to be exploited in technologies for the selective removal and monitoring of PFAS in environmental waters. This review offers a comprehensive overview of recent developments in MIPs, both as adsorbents for PFAS removal and sensors that selectively detect PFAS at environmentally-relevant concentrations. PFAS-MIP adsorbents are classified according to their method of preparation (e.g., bulk or precipitation polymerization, surface imprinting), while PFAS-MIP sensing materials are described and discussed according to the transduction methods used (e.g., electrochemical, optical). This review aims to comprehensively discuss the PFAS-MIP research field. The efficacy and challenges facing the different applications of these materials in environmental water applications are discussed, as well as a perspective on challenges for this field that need to be overcome before exploitation of the technology can be fully realised.

Corrigendum: Effects of aerobic exercise and dietary flavonoids on cognition: a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fphys.2023.1216948.].

Effects of aerobic exercise and dietary flavonoids on cognition: a systematic review and meta-analysis.

Introduction: Studies have shown that exercise increases angiogenesis and perfusion in the hippocampus, activates neurogenesis in the dentate gyrus and increases synaptic plasticity, as well as increases the complexity and number of dendritic spines, all of which promote memory function and protect against cognitive decline. Flavonoids are gaining attention as antioxidants in health promotion due to their rich phenolic content, particularly for their modulating role in the treatment of neurodegenerative diseases. Despite this, there has been no comprehensive review of cognitive improvement supplemented with flavonoid and prescribed with exercise or a combination of the two interventions has been conducted. The purpose of this review is to determine whether a combined intervention produces better results when given together than when given separately. Methods: Relevant articles assessing the effect of physical exercise, flavonoid or in combination on cognitive related biomarkers and neurobehavioral assessments within the timeline of January 2011 until June 2023 were searched using three databases; PubMed, PROQUEST and SCOPUS. Results: A total of 705 articles were retrieved and screened, resulting in 108 studies which are in line with the objective of the current study were included in the analysis. Discussion: The selected studies have shown significant desired effect on the chosen biomarkers and neurobehavioral assessments. Systematic Review Registration: identifier: [CRD42021271001].

Long COVID active case detection initiative among COVID-19 patients in Port Dickson, Malaysia: a retrospective study on the positive outcomes, the proportion of patients with long COVID and its associated factors.

Background: Long COVID is new or ongoing symptoms at four weeks or more after the start of acute COVID-19. However, the prevalence and factors associated with long COVID are largely unknown in Malaysia. We aim to determine the proportion and factors associated with long COVID among COVID-19 patients in Port Dickson, Malaysia. The positive outcomes of our long COVID active detection initiative were also described. Methods: This was a retrospective analysis of long COVID data collected by the Port Dickson District Health Office between 1 September 2021 to 31 October 2021. Monitoring long COVID symptoms was our quality improvement initiative to safeguard residents' health in the district. The study population was patients previously diagnosed with COVID-19 who resided in Port Dickson. The inclusion criteria were adults aged 18 years and above and were in the fifth week (day 29 to 35) post-COVID-19 diagnosis during the data collection period. We called all consecutive eligible patients to inquire regarding long COVID symptoms. Long COVID was defined as new or ongoing symptoms lasting more than 28 days from the date of positive SARS-CoV-2 by polymerase chain reaction test. Binary multivariate logistic regression was conducted to determine factors associated with long COVID. Results: Among 452 patients, they were predominantly male (54.2%), Malays (68.8%) and aged 18-29 years (58.6%). A total of 27.4% (95% CI [23.4-31.8]) of patients experienced long COVID symptoms and were referred to government clinics. The most frequent long COVID symptoms experienced were fatigue (54.0%), cough (20.2%), muscle pain (18.5%), headache (17.7%) and sleep disturbance (16.1%). Females, patients with underlying cardiovascular disease, asthma and chronic obstructive airway disease, those who received symptomatic care, and patients with myalgia and headaches at COVID-19 diagnosis were more likely to have long COVID. Three patients with suspected severe mental health problems were referred to the district psychologist, and ten patients with no/incomplete vaccination were referred for vaccination. Conclusion: Long COVID is highly prevalent among COVID-19 patients in Port Dickson, Malaysia. Long-term surveillance and management of long COVID, especially among the high-risk groups, are needed as we transition to living with COVID-19.

Effects of Valproic Acid and Mitomycin C Combination Therapy in a Rabbit Model of Minimally Invasive Glaucoma Surgery.

Purpose: This study aimed to compare the effectiveness of combination therapy consisting of low-dose mitomycin C (MMC) and valproic acid (VPA) against high-dose MMC for improving the scar phenotype in minimally invasive glaucoma surgery (MIGS). Methods: A rabbit model of MIGS incorporating the PreserFlo MicroShunt was treated with high (0.4 mg/mL) or low (0.1 mg/mL) doses of MMC or with combination therapy consisting of low-dose (0.1 mg/mL) MMC and VPA. Operated eyes were examined by live ocular imaging, histochemical evaluation, multiphoton quantitation of collagen characteristics, and molecular analyses. Results: Although high-dose MMC obliterated the vasculature, combination therapy vastly improved the postoperative tissue morphology by maintaining the vasculature without increased vascularization. Combination therapy also altered collagen morphology and reduced encapsulation of the MicroShunt distal end, which remained at risk with MMC treatment alone. Multiphoton quantitation indicated that the combination therapy significantly reduced collagen density and fiber dimensions compared with monotherapy. At the molecular level, combination therapy significantly reduced Vegfa, Vegfc, and Vegfd expression and inhibited Col1a1 upregulation from baseline levels, all of which low-dose MMC alone was unable to achieve. Notably, COL1A1 protein levels appeared more consistently suppressed by combination therapy compared with high-dose MMC alone. Conclusions: Compared with high-dose MMC, combination therapy was less toxic by sparing the vasculature and potentially more effective in reducing scarring via the regulation of collagen content and organization. Translational Relevance: VPA may be combined with low-dose MMC to replace high-dose MMC to deliver safe and effective anti-scarring outcomes.

Effect of valproic acid on functional bleb morphology in a rabbit model of minimally invasive surgery.

PURPOSE: To determine the effect of valproic acid (VPA) on bleb morphology and scar characteristics in a rabbit model of minimally invasive glaucoma surgery (MIGS). METHODS: Nine New Zealand white rabbits were subjected to MIGS with intraoperative implantation of the PreserFlo MicroShunt. Rabbits were then administered with subconjunctival injections of phosphate buffered saline (PBS) (n=4) or with VPA (n=5). Bleb morphology was examined by slit-lamp biomicroscopy and in vivo confocal microscopy. Postoperative day 28 tissues were examined by immunohistochemical evaluation and label-free multiphoton microscopy to visualise the collagen matrix, by terminal deoxynucleotidyl transferase dUTP nick-end labelling assay and immunofluorescent labelling for Ki67 expression to detect apoptosis and cell growth, and by real-time quantitative PCR to measure Col1a1, Fn, and Smad6 transcript expression. RESULTS: VPA-treated blebs were detectable on day 28, while the PBS-treated blebs were not detectable by day 14. VPA-treated blebs were diffuse, extended posteriorly with near normal conjunctival vascularity and featured a combination of reticular/blurred stromal pattern with evidence of relatively large stromal cysts. Instead of the deposition of thick, disorganised collagen fibres characteristic of the PBS bleb, the VPA bleb contained conspicuously thinner collagen fibres which were associated with similarly thinner fibronectin fibres. In corroboration, Col1a1 and Fn mRNA expression was reduced in the VPA blebs, while increased Smad6 expression implicated the disruption of the transforming growth factor beta pathway. Apoptosis and cell growth profiles appeared similar with both treatments. CONCLUSIONS: The results support the application of VPA to enhance bleb morphology associated with good bleb function in MIGS with no apparent cytotoxicity.

The Impact of Listening to, Reciting, or Memorizing the Quran on Physical and Mental Health of Muslims: Evidence From Systematic Review.

Objectives: Listening to or memorizing the Quran has been suggested to affect the psychosocial health and well-being of Muslims. Muslims who memorized Quran have a higher quality of life (QoL) and lower anxiety and stress. Hence, this systematic review was conducted to evaluate the studies that assessed the effect of listening to, reciting, or memorizing the Quran on physical and mental health. Methods: This review was performed on articles published from the inception and April 2021. Databases including ProQuest, PubMed and Web of Science were searched on 19 April 2021. Keywords such as "Quran", "al- Quran," "al- Kareem," "Holy Quran," "memori," "Tahfiz," "Huffaz," "listening" and "reciting" were used for databases searching. The risk of bias was assessed using Cochrane risk of bias tool and Joanna Briggs Institute (JBI). Only 20 articles were included in data synthesis out of a total of 230. Results: The findings revealed that listening to, reciting or memorizing the Quran had a favorable effect on depression, anxiety, physiologic parameters, quality of life, quality of sleep and intelligence quotient. Conclusion: The current evidence suggests that, listening to, reciting or memorizing the Quran may be useful as an intervention to improve physical and mental health.

Development and Validation of Huffaz ProHealth 1.0©: A Module to Improve the Well-Being of Tahfiz Students in Selangor, Malaysia.

The increase in the number of Tahfiz schools in Malaysia indicates a high demand from the community for Tahfiz education. Tahfiz schools provide a Quran memorization syllabus as the main part of the curriculum at the primary and secondary levels. There is no holistic module that combines learning and health for Tahfiz students in Malaysia. Huffaz ProHealth 1.0© Module is a health intervention module developed explicitly for Tahfiz students by a group of researchers from Universiti Kebangsaan Malaysia Kuala Lumpur (UKMKL). The module encompasses educational and motivational components for the Tahfiz students, and acts as a guide for their teachers and staff to improve the students' health and quality of life. The module consists of three components: physical health, nutritional and psychological well-being. Each component is divided into several units with specific activities. The Sidek Module Development Model (SDMM) was used as a reference model. The study involved two phases: the development (Phase I) and evaluation (Phase II). In Phase I, a needs assessment was conducted among students and teachers from Tahfiz schools to evaluate their knowledge, attitude, and practice on the related topics. Meanwhile, the module's validity and feasibility were assessed by healthcare experts and Tahfiz teachers in Phase II. The item-content validity index (I-CVI), content validity value, Tool to Evaluate Materials used in Patient Education (TEMPtEd) score, and expert feedback were evaluated. In conclusion, the Huffaz ProHealth 1.0© module was successfully developed and evaluated. Strong validity values were observed in all components, indicating high suitability to be employed at Tahfiz schools.

Serum Metabolomics Profiling of Commercially Mixed Functional Foods-Effects in Beta-Amyloid Induced Rats Measured Using 1H NMR Spectroscopy.

Functional foods such as pomegranate, dates and honey were shown by various previous studies to individually have a neuroprotective effect, especially in neurodegenerative disease such as Alzheimer's disease (AD). In this novel and original study, an 1H NMR spectroscopy tool was used to identify the metabolic neuroprotective mechanism of commercially mixed functional foods (MFF) consisting of pomegranate, dates and honey, in rats injected with amyloid-beta 1-42 (Aß-42). Forty-five male albino Wistar rats were randomly divided into five groups: NC (0.9% normal saline treatment + phosphate buffer solution (PBS) solution injection), Abeta (0.9% normal saline treatment + 0.2 µg/µL Aß-42 injection), MFF (4 mL/kg MFF treatment + PBS solution injection), Abeta-MFF (4 mL/kg MFF treatment + 0.2 µg/µL Aß-42 injection) and Abeta-NAC (150 mg/kg N-acetylcysteine + 0.2 µg/µL Aß-42 injection). Based on the results, the MFF and NAC treatment improved the spatial memory and learning using Y-maze. In the metabolic analysis, a total of 12 metabolites were identified, for which levels changed significantly among the treatment groups. Systematic metabolic pathway analysis found that the MFF and NAC treatments provided a neuroprotective effect in Aß-42 injected rats by improving the acid amino and energy metabolisms. Overall, this finding showed that MFF might serve as a potential neuroprotective functional food for the prevention of AD.