Real world efficacy and durability of faricimab in patients with neovascular AMD (nAMD) who had sub-optimal response to prior anti-VEGF therapy.

BACKGROUND: Age-related macular degeneration (AMD) remains a primary cause of blindness, with neovascular AMD (nAMD) presenting particular treatment challenges. Despite anti-vascular endothelial growth factor (anti-VEGF) therapies, many patients exhibit a suboptimal response to the previously available anti-vascular endothelial growth factor (anti-VEGF) therapies. This study evaluates the efficacy and treatment interval extension of faricimab in this patient cohort. METHODS: In a retrospective single-centre study at University Hospitals of Bristol and Weston, UK, nAMD patients suboptimally responsive to previous anti-VEGF therapies were switched to faricimab. Treatment started with an initiation phase of 4 monthly injections followed by a 'Treat and Extend' protocol. Outcomes included best-recorded visual acuity (BRVA), central subfield thickness (CST), the presence of retinal fluid, and treatment intervals. RESULTS: Among 98 eyes of 79 patients, following faricimab treatment, significant reductions in CST and retinal fluid were noted, indicating decreased disease activity. While BRVA changes were not statistically significant, the anatomical improvements suggest a potential therapeutic benefit. Notably, 40% of patients achieved extended treatment intervals, reducing the treatment burden. CONCLUSION: Faricimab offers a promising alternative for nAMD patients with suboptimal responses to prior anti-VEGF treatments, demonstrating significant anatomical improvements and the possibility of extended dosing intervals. These findings highlight the need for prospective real-world studies to further assess faricimab's role in nAMD management and its long-term impact on patient outcomes.

Agro-industrial by-products as ruminant feed: Nutritive value and in vitro rumen fermentation evaluation.

In recent years, agricultural by-products have generated increasing interest as ruminant feed. In a completely randomized design with five experimental treatments, this in vitro study investigated the nutritional value of citrus pulp and onion peel as alternative feed for ruminants and their effects on rumen fermentation, digestibility, and gas production. The first group was the control (50% grass hay/50% concentrate mixture). The other four treatments represented citrus pulp and onion peel at inclusion levels of 10 and 20%, replacing the expensive, high-quality feed ingredients such as the concentrate mixture. The chemical composition showed that citrus pulp is an energy-rich material that could be included up to 20% to replace part of the concentrate in a mixed diet without any adverse impacts on rumen fermentation parameters. The onion peels were rich in fiber and minerals. Their inclusion in the diet of over 10% had detrimental effects on rumen fermentation. The inclusion of either citrus pulp or onion peel in the diet did not have the potential to reduce enteric methane production. In conclusion, citrus pulp showed promising results as a new feed for ruminants. It was effective when included in up to 20% of a ruminant diet, replacing the concentrate mixture.

Micro- and Macro-Algae Combination as a Novel Alternative Ruminant Feed with Methane-Mitigation Potential.

This study was conducted to provide alternative high-quality feed and to reduce methane production using a mixture of the minimum effective levels of Euglena gracilis, EG, and Asparagopsis taxiformis, AT. This study was performed as a 24 h in vitro batch culture. Chemical analysis demonstrated that EG is a highly nutritive material with 26.1% protein and 17.7% fat. The results showed that the supplementation of AT as a feed additive at 1 and 2.5% of the diet reduced methane production by 21 and 80%, respectively, while the inclusion of EG in the diet at 10 and 25% through partially replacing the concentrate mixture reduced methane production by 4 and 11%, respectively, with no adverse effects on fermentation parameters. The mixtures of AT 1% with both EG 10% and EG 25% had a greater reductive potential than the individual supplementation of these algae in decreasing methane yield by 29.9% and 40.0%, respectively, without adverse impacts on ruminal fermentation characteristics. These results revealed that the new feed formulation had a synergistic effect in reducing methane emissions. Thus, this approach could provide a new strategy for a sustainable animal production industry.

Navel orange peel hydroethanolic extract as a phytogenic feed supplement: impacts on growth, feed intake, nutrient digestibility, and serum metabolites of heat stressed growing rabbits.

Currently, using agricultural wastes in animal production has gained worldwide interest. Hence, herein, an eight-week trial was performed to explore the effects of supplemental navel orange peel extract (NPE) on the growth, feed utilization, nutrient digestibility, antioxidant, and hematological parameters of heat-stressed rabbits. In total, 75 weaned rabbits were randomly assigned into five groups. The first group was reared in the winter (mild weather) and fed an untreated pelleted diet (W-NPE-0; control). The other four groups were reared in the summer (hot climate) and fed the control diet fortified with 0 (S-NPE-0), 250 (S-NPE-250), 500 (S-NPE-500), or 1000 (S-NPE-1000) mg NPE/kg diet. The results indicated that thermal-stressed rabbits (S-NPE-0) had significantly lower feed intake, growth performance, hematological indices, serum lipid profile, and antioxidative status, but higher lipid peroxidation compared to the W-NPE-0 group. However, the highest final weight and feed intake were recorded in the S-NPE-1000 group compared with the S-NPE-0 group. Also, supplemental NPE in the growing rabbit diet, especially the S-NPE-1000 group, enhanced the hematological and antioxidative indicators. In conclusion, NPE supplementation in growing rabbit diets could be used to efficiently mitigate the detrimental effects of chronic temperature stress on performance, hematobiochemical features, and oxidative stability.

Recovery in Stroke Patients Treated With Fluoxetine Versus Placebo: A Pooled Analysis of 7,165 Patients.

BACKGROUND: Stroke is a major cause of disability and death. Stroke recovery outcomes range from functional impairment to disability. This study was designed to compare the recovery results of stroke patients treated with fluoxetine to those treated with placebo. REVIEW SUMMARY: Seventeen randomized clinical trials were identified by searching PubMed, Cochrane, Scopus, and Web of Science until June 2021. Fluoxetine enhances the National Institutes of Health Stroke Scale (NIHSS) score [mean difference (MD)=-0.67, 95% confidence interval (CI) (-1.19 to -0.15)] and the Fugl-Meyer Motor Scale (FMMS) score [MD=17.36, 95% CI (12.12-22.61)] at the 3-month follow up. However, the NIHSS score showed no significant difference between the 2 groups at 2 weeks [MD=-0.32, 95% CI (-0.72 to 0.07)] or at 6 months [MD=-0.17, 95% CI (-0.47 to 0.14)]. Fluoxetine-treated and placebo-treated patients had the same overall impact on FMMS scores at 1 month ( P =0.41). Barthel index showed no significant difference between the 2 arms at 3 months ( P =0.21) or 6 months ( P =0.68). Fluoxetine-treated patients were at a higher risk of broken bone [risk ratios (RR)=2.30, 95% CI (1.59-3.32)] and hyponatremia [RR=2.12, 95% CI (1.19-3.76)], and at lower risk of new depression [RR=0.72, 95% CI (0.61-0.84)] in comparison with placebo. CONCLUSION: The efficacy of fluoxetine on the NIHSS and FMMS is likely to take time to emerge and is expected to be transient. The Barthel index score did not differ between the fluoxetine and placebo groups. The use of fluoxetine increased the incidence of hyponatremia and bone fractures while decreasing the risk of new-onset depression.

Insects as Novel Ruminant Feed and a Potential Mitigation Strategy for Methane Emissions.

This study is the first to evaluate the chemical composition and impacts of four different edible insects, Acheta domesticus (A.d), Brachytrupes portentosus (B.p), Gryllus bimaculatus (G.b), and Bombyx mori (B.m), on the digestibility, rumen fermentation, and methane production when used as a substitute for 25% of the soybean meal (SBM) in a ruminant diet through in vitro incubation. The dietary treatments were 100% grass hay, 60% grass hay + 40% SBM, 60% grass hay + 30% SBM + 10% A.d, 60% grass hay + 30% SBM + 10% B.p, 60% grass hay + 30% SBM + 10% G.b, and 60% grass hay + 30% SBM + 10% B.m. The experiment was conducted as a short-term batch culture for 24 h at 39 °C, and the incubation was repeated in 3 consecutive runs. Chemical analysis of the insects showed that they were rich in fat (14-26%) with a high proportion of unsaturated fatty acids (60-70%). Additionally, the insects were rich in protein (48-61%) containing all essential amino acids and the amino acid profiles of the insects were almost the same as that of SBM. The inclusion of insects did not affect nutrient digestibility or the production of volatile fatty acids but did increase the production of ammonia-nitrogen. The addition of G.b and B.m led to decrease in methane production by up to 18% and 16%, respectively. These results reveal that substitution of 25% SBM in the diet with the tested insects had no negative impacts, and their potential to reduce methane production is an environmental benefit.

The Efficacy of Plant-Based Bioactives Supplementation to Different Proportion of Concentrate Diets on Methane Production and Rumen Fermentation Characteristics In Vitro.

This In Vitro study was conducted to investigate the impact of plant-bioactives extract (PE), a combination of garlic powder and bitter orange extract, on methane production, rumen fermentation, and digestibility in different feeding models. The dietary treatments were 1000 g grass/kg ration + 0 g concentrate/kg ration (100:0), 80:20, 60:40, 40:60, and 20:80. The PE was supplemented at 200 g/kg of the feed. Each group consisted of 6 replicates. The experiment was performed as an In Vitro batch culture for 24 h at 39 °C. This procedure was repeated in three consecutive runs. The results of this experiment showed that supplementation with PE strongly reduced methane production in all kinds of feeding models (p < 0.001). Its efficacy in reducing methane/digestible dry matter was 44% in the 100:0 diet, and this reduction power increased up to a 69.2% with the inclusion of concentrate in the 20:80 diet. The PE application significantly increased gas and carbon dioxide production and the concentration of ammonia-nitrogen, but decreased the pH (p < 0.001). In contrast, it did not interfere with organic matter and fiber digestibility. Supplementation with PE was effective in altering rumen fermentation toward less acetate and more propionate and butyrate (p < 0.001). Additionally, it improved the production of total volatile fatty acids in all feeding models (p < 0.001). In conclusion, the PE combination showed effective methane reduction by improving rumen fermentation characteristics without exhibiting adverse effects on fiber digestibility. Thus, PE could be used with all kinds of feeding models to effectively mitigate methane emissions from ruminants.

Egg Yolk IgY: A Novel Trend of Feed Additives to Limit Drugs and to Improve Poultry Meat Quality.

Drugs that are commonly used in poultry farms can potentially cause a detrimental effect on meat consumers as a result of chemical residues. Therefore, seeking a natural alternative is crucial for the health of the consumers. The egg yolk immunoglobulin Y (IgY) is a promising natural replacement for antibiotics in the broilers' diet. There is a scarce focus on the influence of probiotics and IgY on the quality and the nutritive values of broiler meat and whether it can efficiently displace the anti-microbial power of antibiotics. Herein we used 40 Ross chicks (1.2 ± 0.43 days old) and separated them into four groups with variant feed additives (basal diet "control," probiotic, IgY, and probiotic + IgY). Our findings showed that the combination of probiotic and IgY supplementation enhanced the carcass quality traits and decreased the pH values that could retard spoilage due to bacteria and improve shelf life and meat quality. The same group also achieved a significant reduction in thiobarbituric acid value, indicating an improvement of meat quality. Moreover, color, shear force, water holding capacity, and cooking loss were most acceptable in broiler meat supplemented with IgY, which confirmed the highest carcass quality. Notably, the weight gain in the combination group has been greatly increased. Also, the protein percentage was the highest (22.26 ± 0.29, P < 0.001) in this combined supplementation group, which revealed the highest nutritive values. Staphylococcus aureus and Escherichia coli could not be detected in the meat of the probiotics group and/or in the combined treatment group. Interestingly, the IgY group showed an evidence of the killing power (log colony-forming units per milliliter) of S. aureus and Listeria monocytogenes at 1,500 µg/ml. Our findings, in vitro as well as in vivo, revealed that the combination group had antimicrobial bioactivity and enhanced the chickens' immunity. Therefore, IgY, a novel trend of feed additives, can be used to limit drugs. Additionally, the mortality percentage recorded was zero in all groups that received feed supplementation, while the combination group reached the best financial advantages. We concluded that feeding IgY powder with probiotic is a frontier to improve the productivity, immunity, and meat quality of broilers.

The Impact of Probiotics and Egg Yolk IgY on Behavior and Blood Parameters in a Broiler Immune Stress Model.

Feed additives are used frequently in variable combinations to maximize broiler productivity and consumer safety. Therefore, we evaluated the efficiency of feed additives used in four different diets: a basal diet, a probiotic (PRO-PAC®) supplement diet, an egg yolk purified immunoglobulin Y (IgY) supplemented diet, and a combination of IgY and PRO-PAC® supplement (n = 15 for each group). We assessed the improvement of behavioral and hematological parameters of Ross broilers before and after an immune stress challenge using lipopolysaccharide (LPS). Behavioral as well as physiological parameters were analyzed. The standing frequency was the highest (P < 0.05) in broilers supplemented with a combination of probiotics and IgY. Likewise, latency approach score to a novel object improved (P < 0.01) in the combination group at week-3. After intraperitoneal injection of LPS, this combination group achieved the best gait score at week-3, followed by week-5, compared to birds fed the basal diet. The heterophil/lymphocyte (H/L) ratio, heterophil differential count, and eosinophil differential count in the basal diet group that was challenged with LPS were significantly increased (P < 0.01, P < 0.001, P < 0.05, respectively) compared to the combination groups. Therefore, we concluded that the combination of IgY and probiotics can significantly improve the behavior and the underlying physiological parameters of Ross broilers. Consequently, this combination can improve the broilers' health, welfare and produce a safe meat free from harmful chemical residues.

Impacts of Mootral on Methane Production, Rumen Fermentation, and Microbial Community in an in vitro Study.

Methane mitigation strategies have a two-sided benefit for both environment and efficient livestock production. This preliminary short-term in vitro trial using Mootral (garlic and citrus extracts), a novel natural feed supplement, was conducted to evaluate its efficacy on rumen fermentation characteristics, methane production, and the bacterial and archaeal community. The experiment was performed as a batch culture using rumen fluid collected from sheep, and Mootral was supplemented in three concentrations: 0% (Control), 10%, and 20% of the substrate (50% Grass:50% Concentrate). The rumen fermentation data and alpha diversity of microbial community were analyzed by ordinary one-way analysis of variance. The relative abundance and statistical significance of families and operational taxonomic units (OTUs) among the groups were compared by Kruskal-Wallis H test using Calypso software. After 24-h incubation at 39°C, Mootral in a dose-dependent manner improved the production of total volatile fatty acids and propionate while it reduced the acetate proportion and acetate/propionate ratio. The total produced gas was two times higher in the Mootral-supplemented groups than control (P < 0.01), while the proportion of methane in the produced gas was reduced by 22% (P < 0.05) and 54% (P < 0.01) for 10 and 20% Mootral, respectively. Mootral did not change pH, digestibility, and ammonia-nitrogen. Microbial community analyses showed that Mootral effectively changed the ruminal microbiome. The bacterial community showed an increase of the relative abundance of the propionate-producing family such as Prevotellaceae (P = 0.014) and Veillonellaceae (P = 0.030), while there was a decrease in the relative abundance of some hydrogen-producing bacteria by Mootral supplementation. In the archaeal community, Methanobacteriaceae was decreased by Mootral supplementation compared with control (P = 0.032), while the Methanomassiliicoccaceae family increased in a dose-dependent effect (P = 0.038). The results of the study showed the efficacy of the new mixture to alter the ruminal microbial community, produce more propionate, and reduce microbial groups associated with methane production, thus suggesting that Mootral is a promising natural mixture for methane reduction from ruminants.

Identification of serum N-glycoproteins as a biological correlate underlying chronic stress response in mice.

Glycosylation is a post-translational protein modification in eukaryotes and plays an important role in controlling several diseases. N-glycan structure is emerging as a new paradigm for biomarker discovery of neuropsychiatric disorders. However, the relationship between N-glycosylation pattern and depression is not well elucidated to date. This study aimed to explore whether serum N-glycan structures are altered in depressive-like behavior using a stress based mouse model. We used two groups of BALB/c mice; (i) treated group exposed to chronic unpredictable mild stress (CUMS) as a model of depression, and (ii) control group. Behavioral tests in mice (e.g., sucrose preference test, forced swimming test, and fear conditioning test) were used to evaluate the threshold level to which mice displayed a depressive-like phenotype. Serum N-glycans were analyzed carefully using glycoblotting followed by Matrix-assisted laser desorption ionization-time of flight/mass spectrometry (MALDI-TOF/MS) to exhibit N-glycan expression levels and to illustrate the changes in the N-glycome profile. N-glycan expression levels were commonly altered in the depressive-like model and correlated well with the behavioral data. Our results indicated that sialylated N-glycan was identified as a biomarker associated with depressive symptoms, which may have utility as a candidate biomarker for the clinical diagnosis and monitoring of depression.

Short wavelength automated perimetry can detect visual field changes in diabetic patients without retinopathy.

PURPOSE: The purpose of the following study is to compare short wave automated perimetry (SWAP) versus standard automated perimetry (SAP) for early detection of diabetic retinopathy (DR). MATERIALS AND METHODS: A total of 40 diabetic patients, divided into group I without DR (20 patients = 40 eyes) and group II with mild non-proliferative DR (20 patients = 40 eyes) were included. They were tested with central 24-2 threshold test with both shortwave and SAP to compare sensitivity values and local visual field indices in both of them. A total of 20 healthy age and gender matched subjects were assessed as a control group. RESULTS: Control group showed no differences between SWAP and SAP regarding mean deviation (MD), corrected pattern standard deviation (CPSD) or short fluctuations (SF). In group I, MD showed significant more deflection in SWAP (-4.44 ± 2.02 dB) compared to SAP (-0.96 ± 1.81 dB) (P = 0.000002). However, CPSD and SF were not different between SWAP and SAP. In group II, MD and SF showed significantly different values in SWAP (-5.75 ± 3.11 dB and 2.0 ± 0.95) compared to SAP (-3.91 ± 2.87 dB and 2.86 ± 1.23) (P = 0.01 and 0.006 respectively). There are no differences regarding CPSD between SWAP and SAP. The SWAP technique was significantly more sensitive than SAP in patients without retinopathy (p), but no difference exists between the two techniques in patients with non-proliferative DR. CONCLUSION: The SWAP technique has a higher yield and efficacy to pick up abnormal findings in diabetic patients without overt retinopathy rather than patients with clinical retinopathy.