Cereal bar enriched with ora-pro-nóbis (Pereskia aculeata Miller): physicochemical and sensory characterization.

Ora-pro-nobis (OPN) is an unconventional food plant with high nutritional value, and its nutritional composition can be altered according to cultivation. Cereal bars are a popular nutrient-poor foods, and OPN could be incorporated to improve the nutritional quality. This study aimed to evaluate the physicochemical characteristics and sensory acceptability of cereal bars enriched with OPN flour (OpnF) from different forms of cultivation. OpnF was obtained by dehydrating and grinding OPN leaves collected in rural (ROpnF) and urban (UOpnF) municipalities. Two formulations of cereal bars, peanut flavor (Bpn) and mango flavor (Bmg), each with 10% OpnF, were prepared. The macronutrients and mineral composition, oxalate content, water activity, texture, color profile, and acceptability were evaluated. ROpnF had the highest protein, iron, and manganese content, whereas UOpnF had the highest ash and magnesium content. The oxalic acid/calcium ratio was 1.43 and did not imply calcium bioavailability. In addition to nutritional and protein values, Bpn and Bmg presented a good sensory acceptability index of > 77.5% with market potential. Bmg has the highest mineral content and is a source of iron, manganese, and magnesium. OpnF can be used in cereal bars and potentially improve nutritional attributes and used in other foods in a similar way.

ROBIN: a randomised, double-masked, placebo-controlled Phase IIa study of the AOC3 inhibitor BI 1467335 in diabetic retinopathy.

OBJECTIVE: To evaluate the safety and efficacy of BI 1467335 in patients with non-proliferative diabetic retinopathy (NPDR). METHODS: ROBIN is a Phase IIa, double-masked, randomised, placebo-controlled study (NCT03238963). Patients with NPDR and without centre-involved diabetic macular oedema were included; all had a best corrected visual acuity letter score of ≥70 Early Treatment Diabetic Retinopathy Study letters in the study eye at screening. Patients received oral BI 1467335 10 mg or placebo once daily for 12 weeks. Post-treatment follow-up was 12 weeks. The primary endpoint was the proportion of patients over the 24 weeks with ocular adverse events (AEs). Secondary endpoints were the proportion of patients with ≥2-step improvement from baseline in DRSS severity level at Week 12 and the proportion of patients with non-ocular AEs at 24 weeks. RESULTS: Seventy-nine patients entered the study (BI 1467335, n = 40; placebo, n = 39). The proportion of patients with ocular AEs over 24 weeks was greater in the BI 1467335 versus the placebo group (35.0% vs 23.1%, respectively). Treatment-related AEs were reported for similar numbers of patients in the placebo and BI 1467335 group (7.7% vs 7.5%, respectively). At Week 12, 5.7% (n = 2) of patients in the BI 1467335 group had a 2-step improvement in DRSS severity level from baseline, compared with 0% in the placebo group. CONCLUSIONS: BI 1467335 was well tolerated by patients with NPDR. There was a high variability in DRSS levels for individual patients over time, with no clear efficacy signal.

Pachira aquatica: biological activity and chemical composition of leaves, flowers, and seeds.

The chemical composition of Pachira aquatica crude extracts flowers, leaves, and seeds was obtained by UHPLC-ESI/qTOF and GC/MS. The antiproliferative activity was evaluated against the human tumour cell lines AGS (gastric), CaCo-2 (colorectal), MCF-7 (breast), and NCI-H460 (lung). The anti-inflammatory and cellular antioxidant activities were also studied. Flavonoids, phenolic acids, coumarins, and saturated fatty acids were identified in the samples. The concentration of extracts responsible for inhibiting 50% of nitric oxide production ranged from (149 to > 400 µg mL-1). Antiproliferative activity against the tumour cell lines was: AGS (GI50 175 to > 400 µg mL-1), Caco-2 (GI50 215 to > 400 µg mL-1), MCF7 (GI50 232 to > 400 µg mL-1) and NCI-H460 (GI50 208 to > 400 µg mL-1). Cellular antioxidant activity remained between 73% to > 2000%. The selectivity index (SI) ranged from 1.00 to 2.78, indicating low antiproliferative activity.

The Natural History of Retinal Sensitivity Loss in Diabetic Macular Ischemia over One Year Evaluated by Microperimetry.

Background/Objectives: This one-year prospective observational study, conducted at two centers, aimed to report the natural history of retinal sensitivity (RS) loss in diabetic macular ischemia (DMI). Methods: Patients with stable-treated proliferative diabetic retinopathy (PDR) were recruited if there was evidence of DMI on optical coherence tomography angiography, defined as a foveal avascular zone ≥ 0.5 mm2 or parafoveal capillary dropout ≥ 1 quadrant. The minimal visual acuity required for performing microperimetry (MP) was ≥54 Early Treatment Diabetic Retinopathy Study letters (Snellen equivalent 20/80). The overall RS (oRS) and pointwise sensitivity (PWS) within the 3 × 3 mm macula were assessed at baseline and twelve months. A value <25 decibels (dB) was defined as impaired RS, and a decrease of 2 and 7 dB was regarded as mild and severe loss, respectively. Results: A total of 88 patients (97 eyes) were included. No statistically significant MP changes were detected at one year. However, 10% of the cohort lost oRS ≥ 2 dB, and 73% lost ≥2 dB PWS in ≥5 loci, whereas 1% lost oRS ≥ 7 dB, and 4% lost ≥7 dB PWS in ≥5 loci. The foveola and temporal parafovea were the most vulnerable to severe RS loss. Compared to their counterpart, eyes with baseline oRS ≥ 25 dB had significantly more RS loss in the macula and superior parafovea (55% versus 32% and 53% versus 28%, both p = 0.01). Conclusions: Rather than oRS loss, ≥2 dB loss in PWS in ≥5 loci is a more feasible outcome measure for clinical trials in DMI.

Subretinal transient hyporeflectivity in neovascular age-related macular degeneration and its response to a loading phase of aflibercept: PRECISE report 4.

PURPOSE: To describe the prevalence of subretinal transient hyporeflectivity (STHR) in exudative neovascular age-related macular degeneration (nAMD) and its response to a loading phase of aflibercept. METHODS: Optical coherence tomography (OCT) scans of treatment-naïve nAMD patients captured at baseline and after a loading phase of aflibercept were graded for presence of STHR, defined as a small, well-defined, round, subretinal, hyporeflective area, delimited between the ellipsoid zone (EZ) and the retinal pigmented epithelium/Bruch membrane complex. OCT parameters recorded were macular neovascularisation (MNV) subtypes, location of retinal fluids (subretinal fluid, SRF and intraretinal fluid, IRF), central retinal and choroidal thickness. Response was defined as absence of IRF and SRF. Factors associated with completely resolved STHR versus persistent STHR post-loading phase were compared. RESULTS: 2039 eyes of 1901 patients were analysed. STHR was observed in 79 eyes of 78 patients, with an estimated prevalence of 3.87% (95% CI 3.08-4.81%). STHR were seen in 44 type 1 MNV (56%), 27 with type 2 (34%), and 8 with type 3 (10%). At baseline, a total of 303 STHR were present, ranging between 1-22 per eye. The total number of STHR reduced significantly after the loading phase to 173 (p = 0.002). Complete disappearance of STHR was seen in 44 eyes (56%) and persistent STHR in the rest (44%). CONCLUSIONS: STHR may represent a marker of low-grade exudation in nAMD eyes with good response to a loading phase of aflibercept. However, its potential role as an independent nAMD activity biomarker is limited as most resolve after the loading phase.

Associations of presenting visual acuity with morphological changes on OCT in neovascular age-related macular degeneration: PRECISE Study Report 2.

PURPOSE: To study associations of optical coherence tomography (OCT) features with presenting visual acuity (VA) in treatment naive neovascular age-related macular degeneration (nAMD). METHODS: Patients with nAMD initiated on aflibercept therapy were recruited from December 2019 to August 2021. Demographic and OCT (Spectralis, Heidelberg Engineering) features associated with good VA (VA ≥ 68 ETDRS letters, Snellen ≥ 6/12) and poor VA (VA < 54 letters, Snellen < 6/18) were analysed using Generalised Estimating Equations to account for inter-eye correlation. RESULTS: Of 2274 eyes of 2128 patients enrolled, 2039 eyes of 1901 patients with complete data were analysed. Mean age was 79.4 (SD 7.8) years, female:male 3:2 and mean VA 58.0 (SD 14.5) letters. On multivariable analysis VA < 54 letters was associated with increased central subfield thickness (CST) (OR 1.40 per 100 µm; P < 0.001), foveal intraretinal fluid (OR 2.14; P < 0.001), polypoidal vasculopathy (PCV) relative to Type 1 macular neovascularisation (MNV) (OR 1.66; P = 0.049), presence of foveal subretinal hyperreflective material (SHRM) (OR 1.73; P = 0.002), foveal fibrosis (OR 3.85; P < 0.001), foveal atrophy (OR 5.54; P < 0.001), loss of integrity of the foveal ellipsoid zone (EZ) or external limiting membrane (ELM) relative to their preservation (OR 3.83; P < 0.001) and absence of subretinal drusenoid deposits (SDD) (presence vs absence; OR 0.75; P = 0.04). These features were associated with reduced odds of VA ≥ 68 letters except MNV subtypes and SDD. CONCLUSION: Presence of baseline fovea-involving atrophy, fibrosis, intraretinal fluid, SHRM, PCV EZ/ELM loss and increased CST determine poor presenting VA. This highlights the need for early detection and treatment prior to structural changes that worsen baseline VA.

Topographic Correlation of Microperimetry With Structural Characteristics in Diabetic Macular Ischemia.

PURPOSE: This study aimed to determine the threshold for defining abnormal retinal sensitivity (RS) that correlates with structural changes in diabetic macular ischemia (DMI) patients with stable treated proliferative diabetic retinopathy (PDR). DESIGN: Prospective cross-sectional study. METHODS: In a single center, we recruited 85 eyes (67 patients) with stable treated PDR with best-corrected visual acuity (BCVA) ≥54 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (Snellen equivalent 20/80) and optical coherence tomography angiography evidence of DMI. The function-function and function-structure correlation were assessed. Two preselected thresholds in overall RS (oRS), 25 decibels (dB) and age-matched normative data (AMND), were tested on their ability to reflect abnormal anatomy in DMI. Finally, a multivariable regression model was established to depict the relationship between the oRS and various parameters. RESULTS: The oRS showed only a modest correlation with BCVA and low-luminance visual acuity (LLVA). The whole-image deep vessel density (wiDVD) was the most reliable vascular metric correlated with RS. For every 1% decline in the wiDVD, the oRS decreased by 0.37 dB (P < .001) after multivariable adjustment. Furthermore, both a reduction of oRS to <25 dB or below AMND could differentiate eyes with FAZ ≥0.5 mm2, whole image superficial vessel density (wiSVD) <37.7%, wiDVD <41.9%, and the presence of disorganization of the retinal inner layers (DRIL) from their counterparts. CONCLUSIONS: The absolute value of 25 dB in oRS is worth considering as a trial endpoint, because it does not require complex calculation and closely reflects the structural abnormalities in DMI.

Baseline characteristics of eyes with early residual fluid post loading phase of aflibercept therapy in neovascular AMD: PRECISE study report 3.

PURPOSE: To compare the baseline characteristics in patients with and without early residual fluid (ERF) after aflibercept loading phase (LP) in patients with treatment naïve neovascular age related macular degeneration (nAMD). METHODS: Patients with nAMD initiated on LP of three intravitreal aflibercept doses were recruited from December 2019 to August 2021. Baseline demographic and OCT features associated with any ERF were analysed using Generalised Estimating Equations to account for inter-eye correlation. Receiver operating characteristic (ROC) curve was performed for selection of CST threshold. RESULTS: Of 2128 patients enrolled, 1999 eyes of 1862 patients with complete data were included. After LP, ERF was present in 1000 (50.0%), eSRF in 746(37.3%) and eIRF in 428 (21.4%) eyes. In multivariable analysis of baseline features, eyes with increased central subfield thickness (CST) (OR 1.31 per 100 microns increase [95% CI 1.22 to 1.41]; P < 0.001), eyes with IRF and SRF at baseline (1.62 [95% CI 1.17 to 2.22]; P = 0.003), and those with SRF only (OR 2.26 [95% CI 1.59 to 3.20]; P < 0.001) relative to IRF only were determinants of ERF. CST ≥ 418 microns had 57% sensitivity and 58% specificity to distinguish ERF from no ERF at visit 4. CONCLUSION: On average, 50% of eyes have ERF after aflibercept LP. Clinically relevant baseline determinants of ERF include CST ≥ 418 µ and presence of only SRF. These eyes may require further monthly treatment before extending treatment intervals.

The Optical Coherence Tomography and Microperimetry Biomarker Evaluation in Patients with Geographic Atrophy (OMEGA) Study: Design and Baseline Characteristics - OMEGA Report 1.

INTRODUCTION: The aim of this study was to describe the design and the participants' baseline characteristics of a prospective natural history study of geographic atrophy (GA) secondary to age-related macular degeneration. METHODS: The optical coherence tomography (OCT) and microperimetry biomarker evaluation in patients with GA (OMEGA) study was conducted at a tertiary referral center (ClinicalTrials.gov identifier: NCT05963646). Participants were followed for 12 months during 4 visits (baseline and follow-up exams at weeks 12, 24, and 48) with best-corrected Early Treatment of Diabetic Retinopathy Study visual acuity, low-luminance visual acuity (LLVA), and quick contrast sensitivity function testing. Further, participants underwent spectral-domain OCT, OCT angiography, fundus autofluorescence imaging, and mesopic microperimetry testing. RESULTS: Thirty participants (median [IQR] age of 79 [77, 84] years) and 37 study eyes were included with a (median [IQR]) GA area of 1.40 mm2 (0.49, 5.24) at baseline. Out of 37 study eyes, six developed macular neovascularizations (16%). The study-eye best-corrected visual acuity was (median [IQR]) 0.18 logarithm of the minimum angle of resolution (logMAR) (0.06, 0.26), LLVA 0.66 logMAR (0.36, 0.88), and the microperimetry mean sensitivity 18.4 dB (9.21, 20.9). The highest correlation between square root GA area and a visual function test was evident for LLVA (R2 of 0.578), followed by area under the log contrast sensitivity function curve (0.519) and microperimetral retinal sensitivity (0.487). CONCLUSION: This report lays out the design and baseline characteristics of the OMEGA study, which aims to contribute to the understanding of the natural history of GA. The OMEGA study will provide estimates of the ability to detect change and retest reliability for a panel of structure and functional assessments.

Lentinus crinitus: Traditional use, phytochemical and pharmacological activities, and industrial and biotechnological applications.

The saprophytic basidiomycete Lentinus crinitus (L.) Fr is a Brazilian native fungus with pantropical occurrence. L. crinitus produces edible fruiting bodies with medicinal, nutritional, and biotechnological applications. The compounds from fungal fruiting bodies can be applied to the preparation of products in the food, cosmetic, biomedical, and pharmaceutical industries. Our aim was to review the literature on L. crinitus concerning its botanical description, geographical distribution, phytochemistry, pharmacological properties, nutritional value, and biotechnology potential (in vitro cultivation and enzyme production). Scientific search engines, including ScienceDirect, CAPES Journals Portal, Google Scholar, PubMed, SciELO, MEDLINE, LILACS, and SciFinder, were consulted to gather data on L. crinitus. The present review is an up-to-date and comprehensive analysis of the phytochemical compounds, phytopharmacological activities, and biotechnological value of L. crinitus. Extracts from L. crinitus have been reported to exhibit numerous in vitro pharmacological activities such as antioxidant, antifungal, antibacterial, antiviral, and anticancer. The substances in these extracts belong to different classes of chemical compounds such as polysaccharides, fatty acids, terpenes, phenolic acids, and flavonoids. Reviews on Brazilian native fungi are of great importance for scientific knowledge, with great applicability as a mirror for species of the same family. The ethnobotanical, phytochemical, pharmacological, ethnomedicinal, and biotechnological properties of L. crinitus highlighted in this review provide information for future studies and commercial exploitation, and reveal that this fungus has enormous potential for pharmaceutical, nutraceutical, biotechnological, and ecological applications.

A Multi-Modal AI-Driven Cohort Selection Tool to Predict Suboptimal Non-Responders to Aflibercept Loading-Phase for Neovascular Age-Related Macular Degeneration: PRECISE Study Report 1.

Patients diagnosed with exudative neovascular age-related macular degeneration are commonly treated with anti-vascular endothelial growth factor (anti-VEGF) agents. However, response to treatment is heterogeneous, without a clinical explanation. Predicting suboptimal response at baseline will enable more efficient clinical trial designs for novel, future interventions and facilitate individualised therapies. In this multicentre study, we trained a multi-modal artificial intelligence (AI) system to identify suboptimal responders to the loading-phase of the anti-VEGF agent aflibercept from baseline characteristics. We collected clinical features and optical coherence tomography scans from 1720 eyes of 1612 patients between 2019 and 2021. We evaluated our AI system as a patient selection method by emulating hypothetical clinical trials of different sizes based on our test set. Our method detected up to 57.6% more suboptimal responders than random selection, and up to 24.2% more than any alternative selection criteria tested. Applying this method to the entry process of candidates into randomised controlled trials may contribute to the success of such trials and further inform personalised care.

Study protocol on prevalence of non-exudative macular neovascularisation and its contribution to prediction of exudation in fellow eyes with unilateral exudative AMD (EYE-NEON).

PURPOSE: Fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) are at risk of developing macular neovascularisation (MNV). These eyes may first develop subclinical non-exudative MNV (neMNV) before they leak to form exudative MNV (eMNV). The EYE NEON study is a 2-year study aimed at estimating the prevalence and incidence of neMNV and evaluating its role as a predictor for conversion to neovascular AMD. METHODS: EYE NEON is a multicentre study that will run in retinal clinics across 25 National Health Service with the aim to recruit 800 patients with new onset nAMD in the first eye. The fellow-eye with no evidence of nAMD at baseline will be the study eye. All study eyes will have OCT and OCTA done at first and second year following first anti-VEGF treatment to the first eye (non-study eye), with new onset nAMD. We will estimate the prevalence and incidence of neMNV over 2 years, rate of conversion from neMNV to eMNV and numbers initiated on treatment for neovascular AMD in the study eye will be reported. Predictive models of conversion including neMNV with other demographic and imaging parameters will be developed. CONCLUSION: The study design with proposed target sample size is sufficient to evaluate the retinal imaging characteristics of the study eyes with and without neMNV and develop predictive models to inform risk of conversion to nAMD.

Biosorption of methylene blue by residue from Lentinus crinitus mushroom cultivation.

Conventional textile effluent treatments cannot remove methylene blue, a mutagenic azo dye, and an endocrine disruptor, that remains in the drinking water after conventional water treatment. However, the spent substrate from Lentinus crinitus mushroom cultivation, a waste, could be an attractive alternative to remove persistent azo dyes in water. The objective of this study was to assess the methylene blue biosorption by spent substrate from L. crinitus mushroom cultivation. The spent substrate obtained after mushroom cultivation had been characterized by the point of zero charge, functional groups, thermogravimetric analysis, Fourier transform infrared spectroscopy, and scanning electron microscopy. Moreover, the spent substrate biosorption capacity was determined in function of pH, time, and temperature. The spent substrate had a point of zero charge value of 4.3 and biosorbed 99% of methylene blue in pH from 3 to 9, with the highest biosorption in the kinetic assay of 15.92 mg g- 1, and in the isothermal assay of 120.31 mg g- 1. Biosorption reached equilibrium at 40 min after mixing and best fitted the pseudo-second-order model. Freundlich model best fitted the isothermal parameters and each 100 g spent substrate biosorbed 12 g dye in an aqueous solution. The spent substrate of L. crinitus cultivation is an effective biosorbent of methylene blue and an alternative to removing this dye from water, adding value to the mushroom production chain, and supporting the circular economy.

Antimicrobial activity of Tetradenia riparialeaf essential oil / Actividad antimicrobiana del aceite esencial de hoja de Tetradenia riparia

Food spoilage is a widely neglected problem and the constant use of synthetic fungicides could develop resistant fungi. The objective of this study was to evaluate the chemical composition and antimicrobial activity of Tetradenia riparialeaf essential oil against foodborne disease microorganisms. Leaf essential oil was obtained by hydrodistillation and identified by gas chromatography coupled to mass spectrometry. The antimicrobial activity was studied by broth microdilution. The major compounds identified were oxygenated sesquiterpenes (43.6%): 14-hydroxy-9-epi-(E)-cariophylene (20.8%) and τ-cadinol (18.4%); followed by oxygenated diterpenes (24.6%): 6,7-dehydroroyleanone (12.6%) and 9ß, 13ß-epoxy-7-abiethene (10.6%); sesquiterpenic hydrocarbons (17.1%) and oxygenated monoterpenes (7.4%): fenchone (5.6%). The essential oil had broad antibacterial and antifungal activity, mainly against A. versicolor and P. ochrochloron with fungistatic and fungicidal activities and B. cereus, L. monocytogenes, and S. aureuswith bacteriostatic and bactericidal activities. T. riparialeaf essential oil is a potential alternative to control microorganisms-

El deterioro de los alimentos es un problema ampliamente desatendido y el uso constante de fungicidas sintéticos podría desarrollar hongos resistentes. El objetivo de este estudio fue evaluar la composición química y la actividad antimicrobiana del aceite esencial de hoja de Tetradenia riparia contra microorganismos patógenos transmitidos por los alimentos. El aceite esencial de hoja se obtuvo por hidrodestilación y se identificó mediante cromatografía de gases acoplada a espectrometría de masas. La actividad antimicrobiana estudiada fue por microdilución en caldo. Los compuestos principales del aceite esencial se identificaron como sesquiterpenos oxigenados (43,6%): 14-hidroxi-9-epi-(E)-cariofileno (20,8%) y τ-cadinol (18,4%); seguido de diterpenos oxigenados (24,6%): 6-7-deshidroroileanona (12,6%) y 9ß, 13ß-epoxi-7-abieteno (10,6%); hidrocarburos sesquiterpénicos (17,1%) y monoterpenos oxigenados (7,4%): fenchona (5,6%). Tenía amplia actividad antibacteriana y antifúngica, principalmente contra A. versicolor y P. ochrochloron con actividades fungistáticas y fungicidas, y principalmente contra B. cereus, L. monocytogenes y S. aureus con actividades bacteriostáticas y bactericidas. El aceite esencial de hoja de T. riparia es una alternativa potencial para controlar microorganismos.

Factors That Can Prolong Ocular Treatment Duration in Age-Related Macular Degeneration.

Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are used to treat wet age-related macular degeneration (wAMD); however, they are associated with a considerable treatment burden and poor real-world outcomes. The molecular size and charge of anti-VEGF agents influence drug pharmacokinetics in the vitreous and peak drug efficacy. This article reviews the established and novel strategies to prolong drug action, in the vitreal cavity, and thus reduce dosing frequency. Increased ocular residency can be attained by increasing drug size as with large molecules, such as KSI-301; adding polyethylene glycol to pegcetacoplan (APL-2) or avacincaptad pegol to increase molecular size; or binding to other targets that increase molecular size, such as vitreal albumin in the case of BI-X. Faricimab is a bispecific antibody in which the fragment crystallizable portion is engineered to prolong ocular residency and reduce systemic exposure. Conversely, small VEGF-binding molecules, such as brolucizumab, can be administered at higher clinical doses, with the potential for prolonged clinical activity versus larger molecules. Other important considerations include sustained drug delivery routes, such as the ranibizumab port delivery system or subconjunctival or suprachoroidal injection. More effective and longer-lasting treatments are needed for wAMD to prolong drug action and reduce dosing frequency. Several strategies are under investigation and the prevention of vision loss in patients with AMD or other retinal diseases may be attainable in the near future.

Tomato as a Natural Source of Dyes in the Food Industry: A Patent Data Analysis.

BACKGROUND: Foods that promote health benefits are being increasingly used. Innovative techniques, such as nanotechnology, have been used to improve functional properties, sensory characteristics, or the conservation of foods. OBJECTIVE: The objective of this study was to identify the technological domain of patents for tomato products with or without nanotechnology and elucidate the technological advances associated with the recent use of tomatoes as a natural food dye in the food industry by exploring patent documents. METHODS AND RESULTS: The search was conducted using the Espacenet and INPI databases. There was an increase in patent document applications employing nanotechnology in 2013, with a peak between 2017 and 2018. China is the lead country in the number of patent applications. In Brazil, the patent applications are variable, and the food industry is most involved in studies on tomatoes as a natural food dye. Most patent deposits using nanotechnology were from companies, and the main sources of the patent application were the food and pharmaceutical industries. CONCLUSION: There is an increasing trend for the use of tomatoes as natural food dyes, produced with or without nanotechnology, and number of patents filed yearly. New technologies are being developed in several application areas.

Light conditions affect the growth, chemical composition, antioxidant and antimicrobial activities of the white-rot fungus Lentinus crinitus mycelial biomass.

The mycelial biomass of basidiomycetes is a promising source of compounds and represents an alternative for industrial and biotechnological applications. Fungi use light as information and hold photoresponse mechanisms, in which sensors respond to light wavelengths and regulate various biological processes. Therefore, this study aimed to investigate the effects of blue, green, and red lights on the growth, chemical composition, and antioxidant and antimicrobial activity of Lentinus crinitus mycelial biomass. The chemical composition of the mycelial biomass was determined by chromatographic methods, antioxidant activity was analyzed by in vitro assays, and antimicrobial activity was investigated by the microdilution assay. The highest mycelial biomass yield was observed under blue-light cultivation. Many primordia arose under blue or green light, whereas the stroma was formed under red light. The presence of light altered the primary fungal metabolism, increasing the carbohydrate, tocopherol, fatty acid, and soluble sugar contents, mostly mannitol, and reducing the protein and organic acid concentrations. Cultivation under red light increased the phenol concentration. In contrast, cultivation under blue and green lights decreased phenol concentration. Benzoic and gallic acids were the main phenolic acids in the hydroalcoholic extracts, and the latter acids increased in all cultures under light, especially red light. Mycelial biomass cultivated under red light showed the highest antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The ferric reducing antioxidant power (FRAP) method showed that all light wavelengths increased the antioxidant activity of mycelial biomass, with the highest value under red light. Moreover, the ß-carotene/linoleic acid co-oxidation (BCLA) assay demonstrated that the antioxidant activity was affected by light cultivation. Mycelial biomass grown under all conditions exhibited antibacterial and antifungal activities. Thus, mycelial biomass cultivation of L. crinitus under light conditions may be a promising strategy for controlling the mycelial chemical composition and biomass yield.

Characterization of the Structural and Functional Alteration in Eyes with Diabetic Macular Ischemia.

OBJECTIVE: To investigate the relative effect of disorganization of the retinal inner layers (DRIL) and ellipsoid zone (EZ) loss on visual function in diabetic macular ischemia (DMI). DESIGN: Prospective cross-sectional observational study. PARTICIPANTS: Patients with stable treated proliferative diabetic retinopathy (PDR) without center-involved diabetic macular edema were recruited at the Moorfields Eye Hospital from December 2019 to November 2021. The main inclusion criteria were best-corrected visual acuity (BCVA) of ≥ 40 ETDRS letters (Snellen equivalent 20/160) with OCT angiography (OCTA) evidence of DMI in ≥ 1 eye. METHODS: Each eligible eye of the recruited patients was assessed for BCVA, OCT, and OCTA metrics. The prespecified OCT parameters were DRIL and subfoveal EZ loss. Generalized estimating equations were used. MAIN OUTCOMES MEASURES: The frequency of DRIL and EZ loss, their relative contributions to vision loss, and their associations with microvascular alterations were evaluated. RESULTS: A total of 125 eyes of 86 patients with PDR were enrolled; 104 (83%) eyes had a BCVA of ≥ 70 letters. Disorganization of the retinal inner layers was more prevalent than EZ loss (46% [58 eyes] vs. 19% [24 eyes]). On average, the presence of DRIL had a more pronounced impact on vision, retinal thickness, and microvascular parameters than EZ loss. After multivariable adjustment, the odds of coexisting DRIL increased by 12% with every letter decrease in BCVA; however, there was no statistically significant association of subfoveal EZ loss with BCVA. In eyes with DRIL in the absence of EZ loss, the BCVA declined significantly by 6.67 letters compared with eyes with no DRIL nor EZ loss (95% confidence interval [CI], -9.92 to -3.41; P < 0.001). However, if DRIL and EZ loss coexisted, the resultant BCVA was 13.22 letters less than eyes without these structural abnormalities (95% CI, -18.85 to -7.59; P < 0.001). CONCLUSIONS: In patients with DMI with a Snellen visual acuity of 20/160 or better, eyes with DRIL were associated with more visual function loss and retinal blood circulation alterations than those with subfoveal EZ loss only.

Utilization of Agro-Industrial Residues in the Rearing and Nutritional Enrichment of Zophobas atratus Larvae: New Food Raw Materials.

Edible insects are a potential alternative food source of high feed conversion efficiency and protein content. Zophobas atratus is an edible insect that adapts to different diets, enabling sustainable rearing by adding value to by-products and agro-industrial residues. This study aimed to evaluate the performance and nutritional characterization of Zophobas atratus larvae fed with different proportions of grape residue. Physicochemical analysis of the diets and larvae (AOAC procedures), fatty acid profile (chromatographic techniques), metals and non-metals (inductively coupled plasma optical emission spectrometry), larval mass gain, feed conversion efficiency, and mortality rate were assessed. The replacement of 25% of the conventional diet with grape residue increased lipid, ash, and fiber contents and reduced protein, carbohydrates, and energy. It promoted greater mass gain, lower mortality rate, and reduced larval growth time by 51%. Among the replacements, 25% resulted in the second-highest content of calcium, sodium, magnesium, and zinc, and the lowest content of potassium and phosphorus in the larvae. The 100% replacement resulted in the highest amounts of C18:2n6 (27.8%), C18:3n3 (2.2%), and PUFA (30.0%). Replacing 25% of the conventional diet with grape residue is equivalent to the conventional diet in many aspects and improves several larvae performance indices and nutritional values.

HORNBILL: a phase I/IIa trial examining the safety, tolerability and early response of BI 764524 in patients with diabetic retinopathy and diabetic macular ischaemia-rationale, study design and protocol.

BACKGROUND: Diabetic macular ischaemia (DMI) is a complication of diabetic retinopathy that leads to irreversible vision loss. DMI is characterised by reduced retinal vessel density and enlargement of the foveal avascular zone (FAZ). Despite its clinical burden, there is no formal consensus on the definition of DMI, and no approved treatment. Semaphorin 3A (Sema3A) is an axonal guidance molecule that blocks revascularisation of the ischaemic retina. Sema3A modulation is therefore a promising mechanism of action for the treatment of ischaemic eye diseases. BI 764524 is an intravitreal anti-Sema3A ischaemia modulator agent. METHODS: HORNBILL (NCT04424290) is a phase I/IIa trial comprising a non-randomised, open-label, single rising dose (SRD) part and a randomised, masked, sham-controlled multiple dose (MD) part to investigate the safety, tolerability and early biological response of ischaemia modulator BI 764524 in adults (≥18 years) with DMI. DMI will be defined using optical coherence tomography angiography (OCTA) as either any degree of disruption in the retinal vascularity (SRD) or a FAZ of ≥0.5 mm2 (MD). Subjects in the SRD part will receive 0.5, 1.0 or 2.5 mg of BI 764524; the maximum tolerated dose will then be used in the MD part. A minimum of 12 subjects will be enrolled into the SRD part; planned enrollment is 30 for the MD part. The primary endpoint of the SRD part is the number of subjects with dose-limiting adverse events (AEs) until day 8. The primary endpoint of the MD part is the number of subjects with drug-related AEs from baseline to end of study, and secondary endpoints include change from baseline in the size of the FAZ, best-corrected visual acuity and central retinal thickness. DISCUSSION: DMI is a poorly defined condition with no treatment options. HORNBILL is the first clinical trial to assess a treatment for DMI and to use OCTA as a means to define and examine DMI. The OCTA data generated in this trial could form the basis of formal diagnostic criteria for DMI. Furthermore, the novel mechanism of action (Sema3A modulation) explored in this trial has the potential to revolutionise the treatment landscape for patients with DMI. TRIAL REGISTRATION: ClinicalTrials.gov NCT04424290 ; EudraCT 2019-004432-28. Registered on 9 June 2020.