UNASSIGNED: Photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL) stabilizes the corneal stroma and eliminates microorganisms. Numerous PACK-CXL protocols, using different energy sources and chromophores, have been applied in preclinical studies, including live animal studies, with various experimental designs and endpoints. So far, a systematic mapping of the applied protocols and consistency across studies seems lacking but is essential to guide future research.
UNASSIGNED: The scoping review protocol was in line with the JBI Manual for Evidence Synthesis. Electronic databases were searched (Embase, MEDLINE, Scopus, Web of Science) to identify eligible records, followed by a two-step selection process (title and abstract screening, full text screening) for record inclusion. We extracted information on (1) different PACK-CXL protocol characteristics; (2) infectious pathogens tested; (3) study designs and experimental settings; and (4) endpoints used to determine antimicrobial and tissue stabilizing effects. The information was charted in frequency maps.
UNASSIGNED: The searches yielded 3654 unique records, 233 of which met the inclusion criteria. With 103 heterogeneous endpoints, the researchers investigated a wide range of PACK-CXL protocols. The tested microorganisms reflected pathogens commonly associated with infectious keratitis. Bacterial solutions and infectious keratitis rabbit models were the most widely used models to study the antimicrobial effects of PACK-CXL.
UNASSIGNED: If preclinical PACK-CXL studies are to guide future translational research, further cross-disciplinary efforts are needed to establish, promote, and facilitate acceptance of common endpoints relevant to PACK-CXL.
UNASSIGNED: Systematic mapping of PACK-CXL protocols in preclinical studies guides future translational research.

BACKGROUND: Riboflavin (vitamin B2) is a water-soluble micronutrient considered to be a precursor of the nucleotides flavin adenine dinucleotide and flavin mononucleotide. This vitamin makes up mitochondrial complexes and participates as an enzymatic cofactor in several mechanisms associated with energy metabolism.
OBJECTIVE: This systematic review collected and discussed the most relevant results on the role of riboflavin in the energy metabolism of lipids, proteins, and carbohydrates.
METHODS: A systematic search was carried out in the PubMed-Medline, Scopus, Embase, and Web of Science databases using the PICOS (Population, Intervention, Comparison, Outcome, Study design) strategy.
METHODS: The screening of studies went through 2 stages following predefined eligibility criteria. The information extracted covered reference details, study design, population characteristics, experimental model, treatment parameters and dosage, route of administration, duration of treatment, and results found.
METHODS: The risk of bias was assessed using the SYRCLE Risk of Bias (RoB) tool for in vivo studies and the QUIN tool adapted for in vitro studies, utilizing 10 domains, including selection bias, performance bias, detection bias, attrition bias, reporting bias, and other biases, to evaluate the methodological quality of the included studies.
CONCLUSIONS: This review concludes that riboflavin regulates energy metabolism by activating primary metabolic pathways and is involved in energy balance homeostasis.

Corneal crosslinking (CXL) represents a paradigm shift in the management of corneal ectatic disorders. Before CXL was introduced, patients would need specialty contact lenses and possible corneal transplantation. CXL involves a biochemical reaction in which ultraviolet A light is used in conjunction with Riboflavin to form crosslinks in between corneal stromal collagen. This leads to strengthening and stabilizing of the collagen lamellae, resulting in mechanical stiffening of the cornea. Multiple protocols have been proposed including epithelium on versus off and varying light intensity and duration of treatment. All protocols appear to be safe and effective with few reported complications including infection, stromal haze, scarring, and endothelial toxicity. Overall, CXL has demonstrated to halt the progression of the disease clinically and in keratometry readings and improve the quality of life for patients. It is a minimally invasive, cost-effective procedure that can be performed in an outpatient setting with a fast recovery time and long-lasting results.

OBJECTIVE: To report the first case of Rhizopus sp keratitis in a 15-year-old male patient who had undergone a conventional Epi-off CXL procedure for progressive keratoconus.
METHODS: A 15-year-old male studying at school presented with defective vision in both eyes recently. He was diagnosed with progressive keratoconus in the right eye more than left eye. After the conventional CXL procedure, the patient developed corneal ulcer on third postoperative day.
RESULTS: The microbiological diagnosis of both BCL and ulcer revealed Rhizopus sp. The patient responded to topical antifungals, and the ulcer entirely healed with a large central scar.
CONCLUSIONS: Rhizopus keratitis is rare in a healthy individual. Ours is the first case report of Rhizopus keratitis in patient undergone CXL.

OBJECTIVE: The objective of the current study is to compare the treatment effects of different vitamins on essential hypertension to provide an initial basis for developing evidence-based practices.
METHODS: Systematic review and network meta-analysis.
METHODS: Five electronic databases (PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) were searched from their inception to 25 September 2023.
RESULTS: The primary outcomes were the difference between the intervention group and the control group in changes in office systolic blood pressure (SBP) and office diastolic blood pressure (DBP) from baseline. The secondary outcomes were the difference between the intervention group and the control group in changes in 24-hour mean ambulatory systolic blood pressure (24 hours SBP), 24-hour mean ambulatory diastolic blood pressure (24 hours DBP) and heart rate (HR) from baseline.
RESULTS: A total of 23 studies comparing five vitamins (vitamin B2, vitamin C, vitamin D, vitamin E, folic acid) and involving 2218 participants were included. The included trials were all vitamin versus placebo, so the network was star-shaped. Among the five vitamins, only vitamin E was significantly more effective at reducing SBP (mean difference: -14.14 mm Hg, 95% credible intervals: -27.62 to -0.88) than placebo. In addition, no evidence was found that any of the five vitamins influenced DBP, 24 hours SBP, 24 hours DBP, or HR. The dose of vitamins, geographical region and percentage of males (only SBP) might be sources of heterogeneity. Sensitivity and subgroup analysis revealed that the effect of vitamin intervention on blood pressure varies according to different doses of vitamins.
CONCLUSIONS: According to the results, vitamin E might be an effective measure to reduce SBP, but more research is needed to validate this finding.
UNASSIGNED: CRD42022352332.

Corneal crosslinking (CXL) is used for treating keratoconus and post-laser in situ keratomileusis ectasia. However, refractive surgery is not usually performed with prophylactic CXL. Therefore, we performed a meta-analysis comparing outcomes of refractive surgeries with vs without prophylactic CXL. We systematically searched databases for studies comparing refractive surgeries for myopic correction with vs without prophylactic corneal crosslinking. Review Manager 5.4.1 was used to perform statistical analysis. We included 2820 eyes from 28 studies. Compared with refractive surgery alone, surgery with prophylactic CXL resulted in decreased central corneal thickness, corrected distance visual acuity logMAR, and safety and efficacy indices. There were no significant differences in postoperative uncorrected distance visual acuity of 20/20 or better at ≥12 months and other visual outcomes among both groups. More randomized controlled trials with standard crosslinking protocols are needed to analyze the prophylactic use of crosslinking with refractive surgeries.

The history of corneal cross-linking (CXL) dates back to 2003 when some German scientists investigated possible treatments to harden the corneal structure to increase its resistance in ectatic corneal diseases. Nowadays, CXL is considered the most effective therapy in ectatic corneal diseases due to its proven efficacy in hardening the cornea, thus halting the development of the disease. Since 2003, CXL applications have dramatically expanded and have been implemented in several other areas such as infectious keratitis, corneal edema, and before performing keratoplasty for various purposes. Moreover, several irradiation patterns are being studied to correct refractive errors, taking into account the corneal refractive changes that occur after the procedure. Currently, scleral cross-linking is also being investigated as a potential therapy in cases of progressive myopia and glaucoma. In this article, we provide a comprehensive overview of the available applications of cross-linking in nonectatic ocular conditions and highlight the possible future indications of this procedure.

Only a few studies have explored relationships between riboflavin intake and function and a few studies have examined the effects of supplements on various clinical or biochemical outcomes. None of these studies, however, make a useful contribution to understanding requirements in healthy populations. Thus, there is no strong evidence to change the recommendations. The requirement for riboflavin is estimated based on the relationship between intake and biochemical indices of riboflavin status, including urinary excretion and enzyme activities.

Brain oxygen deprivation causes morphological damage involved in the formation of serious pathological conditions such as stroke and cerebral palsy. Therapeutic methods for post-hypoxia/anoxia injuries are limited and still have deficiencies in terms of safety and efficacy. Recently, clinical studies of stroke have reported the use of drugs containing riboflavin for post-injury clinical rehabilitation, however, the effects of vitamin B2 on exposure to cerebral oxygen deprivation are not completely elucidated. This review aimed to investigate the potential antioxidant, anti-inflammatory and neuroprotective effects of riboflavin in cerebral hypoxia/anoxia. After a systematic search, 21 articles were selected, 8 preclinical and 12 clinical studies, and 1 translational study. Most preclinical studies used B2 alone in models of hypoxia in rodents, with doses of 1-20 mg/kg (in vivo) and 0.5-5 µM (in vitro). Together, these works suggested greater regulation of lipid peroxidation and apoptosis and an increase in neurotrophins, locomotion, and cognition after treatment. In contrast, several human studies have administered riboflavin (5 mg) in combination with other Krebs cycle metabolites, except one study, which used only B2 (20 mg). A reduction in lactic acidosis and recovery of sensorimotor functions was observed in children after treatment with B2, while adults and the elderly showed a reduction in infarct volume and cognitive rehabilitation. Based on findings from preclinical and clinical studies, we conclude that the use of riboflavin alone or in combination acts beneficially in correcting the underlying brain damage caused by hypoxia/anoxia and its inflammatory, oxidative, and behavioral impairments.

Beyond their nutritional benefits, vitamins could decrease the risk of chronic diseases due to their potent antioxidant capacity. The present work is aimed at reviewing the state of the art regarding (1) the vitamins involved in oxidative stress prevention in accordance with the requirements established by the European Food Safety Authority (EFSA) and (2) the foods of plant origin that are sources of those vitamins and have potential benefits against oxidative stress in humans. According to the European regulations based on EFSA scientific evidence, riboflavin, vitamin C, and vitamin E are those vitamins subjected to the approved health claim \"contribute to the protection of cells from oxidative stress\". Scientific studies conducted in humans with some natural food sources of riboflavin (almonds, wheat germ, mushrooms, oat bran), vitamin C (guava, kale, black currant, Brussels sprouts, broccoli, orange), and vitamin E (hazelnuts, almonds, peanuts, pistachio nuts, extra virgin olive oil, dates, rye) have been performed and published in the literature. However, no food of plant origin has obtained a favorable EFSA opinion to substantiate the approval of health claims related to its potential properties related to oxidative stress prevention. Further studies (concretely, well-controlled human intervention studies) must be carried out in accordance with EFSA requirements to provide the highest level of scientific evidence that could demonstrate the potential relationship between foods of plant origin and antioxidant capacity. This review could be useful for the scientific community to study the application of health claims referring to the antioxidant capacity potentially exerted by foods of plant origin.