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Background Hearing deficit is one of the side effects of 1st generation iron chelators in β-thalassemia, however the risk of hearing deficits following 2nd generation iron chelators is not well known. Aim To assess hearing status of Transfusion Dependent β-thalassemia children on oral iron chelating agents and detect risk factors for hearing impairment. Methods This is a cross-sectional study recruited sixty children and adolescent with confirmed diagnosis of transfusion dependent β-thalassemia. Demographic and clinical characteristics collected, audiological testing were performed by the same audiologist using the same equipment for all patients including tympanometry, pure tone audiometry, speech audiometry, transient evoked otoacoustic emissions and distortion product otoacoustic emissions. Results Recruited children and adolescents with transfusion dependent β-thalassemia were 32 (53.3%) boys and 28 (46.7%) girls and their mean age was 11.34 ± 3.08, majority of patients 48 (80%) were on single Deferasirox. Our study revealed that among the 60 children evaluated, 16.6% exhibited some form of hearing loss. Sensorineural hearing loss (SNHL) was observed in 6.6% of the participants, while 10% had conductive hearing loss (CHL). Bilateral SNHL in 5% and bilateral CHL in 8.3% of all the cases. Hearing impairment was mild in nature, but predominantly affected high-frequency ranges, the most affected frequencies being 4000 Hz and 8000 Hz. There was no significant difference between studied thalassemia children with and without hearing impairment regarding gender, age at study entry, age at diagnosis, duration of disease and duration or dose of chelating agent ( P  > 0.05). Our study revealed significant difference between studied thalassemia children with and without hearing impairment regarding age of starting blood transfusion ( p -value = 0.024), affected patients started blood transfusion at older age, also statistically significant difference in both groups regarding median serum ferritin was found ( p -value = 0.028), lower levels were found in affected patients. Conclusion No significant effect of using oral iron chelation drugs was observed on frequency and type of hearing loss among the studied patients but instead the age at starting regular blood transfusion did. Screening of such group of patients for hearing impairment at diagnosis and at regular periods is recommended.

Background Klebsiella pneumoniae ( K. pneumoniae ) is an opportunistic pathogen belonging to Enterobacteriaceae family. It is present in the intestinal tract of animals and humans, and is considered as a major threat to public health. A total of 33 previously identified K. pneumoniae strains isolated from of broiler chicken ( n  = 20) and, humans ( n  = 13) were tested for their antimicrobial sensitivity and virulence genes detection. Results The antimicrobial sensitivity testing of broiler chickens K. pneumoniae strains, showed complete phenotypic resistance towards ampicillin (100%), colistin (100%), fosfomycin (100%), trimethoprim/sulphamethaxole (100%) followed by gentamicin (90%), cefotaxime (90%) and chloramphenicol (75%). However, all the isolates were sensitive to imipenem (100%). K. pneumoniae human strains showed complete phenotypic resistance to fosfomycin (100%), followed by ampicillin (92.3%), colistin (92.3%), and ciprofloxacin and trimethoprim/sulfamethaxole (76.9%, each). The resistance gene profiling of the chicken strains was cml A (65%), dfr A1 (65%), mcr 1 (60%), tet A (50%), fos A (40%), and sul 1 (35%), and the most prevalent virulence gene was rmp A (85%), that was detected either alone in 9 isolates (52.9%), or in combination with the mag A gene in 8 isolates (47.1%), and with fim H gene in 8 isolates (47.1%), followed by fim H (55%) and mag A genes (40%). On the other hand, the human strains gene profiling showed mcr 1 (61.5%), cml A (53.8%), and sul 1 (46.2%) genes, while dfr A1 was not detected. The most prevalent virulence genes in the human strains were rmp A and mag A genes (46.2%, each), followed by fim H gene (38.5%). Overall, multidrug-resistant (MDR) (33.3%), extensively-drug resistant (XDR) (57.6%) and pan-drug resistant (PDR) (9.1%) isolates were detected. Conclusion The distribution of such virulent and resistant K. pneumoniae isolates among apparently healthy broiler chicken, highlights their potential role in the transmission of both resistance and virulence attributes to the surrounding environment and human contacts. Moreover, spreading of carbabenem resistant K. pneumoniae among human isolates, suggest the urgent need for more strict measures for the uncontrolled usage of antibiotics.

Background Flipped learning excessively boosts the conceptual understanding of students through the reversed arrangement of pre-learning and in classroom learning events and challenges students to independently achieve learning objectives. Using a gamification method in flipped classrooms can help students stay motivated and achieve their goals.  Methods This study adopted a randomized controlled study design with a pre-test and post-test and involved 128 nursing students at Mansoura University. This study randomly divided the students into the study and control groups. Data were collected at three time points using six tools . In the intervention group, Moodle was gamified for 6 weeks.  Results A significant difference in the students’ self-confidence ( p  = 0.021), skills knowledge ( p  < 0.001), intensity of preparation ( p  < 0.001), and motivation ( p  < 0.001) was observed between the two groups; however, no difference in the students’ skills performance ( p  = 0.163) was observed between the two groups after using gamified flipped classrooms. Conclusions Compared with the traditional flipped classrooms, gamified flipped classrooms improved nursing students’ motivation, intensity of preparation, skills knowledge, and self-confidence during laboratory clinical practice. Thus, gamification is a learning approach that can be implemented in conjunction with the flipped classroom model to motivate students to participate in the learning process. Trial registration. Prospectively registered with ClinicalTrials.gov on 26/04/2021; registration number NCT04859192.

Background The effects of safflower oil and vitamin C (Vit. C) inclusion in broiler chicken diets on the growth performance, apparent ileal digestibility coefficient “AID%” of amino acids, intestinal histology, behavior, carcass traits, fatty acid composition of the breast muscle, antioxidant and immune status for a 35-day feeding period were evaluated. A total of 300 three-day-old Ross chicks (58.25 g ± 0.19) were randomly allotted in a 2 × 3 factorial design consisting of two levels of vitamin C (0 and 400 mg/kg diet) and three levels of safflower oil (0, 5, and 10 g/kg diet). Results An increase in the final body weight, total body weight gain, total feed intake, and the relative growth rate ( P  <  0.05) were reported by safflower oil and vitamin C inclusion. Dietary supplementation of safflower oil and vitamin C had a positive effect ( P <  0.05 ) on the ingestive, resting, and feather preening behavior. Vitamin C supplementation increased ( P <  0.05 ) the AID% of lysine, threonine, tryptophan, arginine, and valine. Safflower inclusion (10 g/kg) increased ( P <  0.05 ) the AID% of methionine and isoleucine. Safflower oil inclusion increased ( P <  0.05 ) the levels of stearic acid, linoleic acid, saturated fatty acids, and omega-3 fatty acids (ω-3) in the breast muscle. In contrast, the supplementation of only 10 g of safflower oil/kg diet increased ( P = 0.01 ) the omega-3/omega-6 (ω-3/ω-6) fatty acids ratio. Vit. C supplementation increased ( P <  0.05 ) the CAT serum levels, SOD, and GSH enzymes. Dietary supplementation of safflower oil and vitamin C improved the intestinal histology. They increased the villous height and width, crypt depth, villous height/crypt depth ratio, mucosal thickness, goblet cell count, and intra-epithelium lymphocytic lick cell infiltrations. The serum levels of IgA and complement C3 were increased ( P <  0.01 ) by Vit. C supplementation and prominent in the 400 vit. C +  10 safflower Oil group. Conclusion A dietary combination of safflower oil and vitamin C resulted in improved growth rate, amino acids AID%, intestinal histology, welfare, immune and antioxidant status of birds, and obtaining ω-3 and linoleic acid-enriched breast muscles. The best inclusion level was 400 vit. C +  10 safflower Oil.

Background Drought is a major determinant for growth and productivity of all crops, including cereals, and the drought-induced detrimental effects are anticipated to jeopardize world food security under the ongoing global warming scenario. Biostimulants such as humic acid (HA) can improve drought tolerance in many cereals, including maize and sorghum. These two plant species are genetically related; however, maize is more susceptible to drought than sorghum. The physiological and biochemical mechanisms underlying such differential responses to water shortage in the absence and presence of HA, particularly under field conditions, are not fully understood. Results Herein, the effects of priming maize and sorghum seeds in 100 mg L −1 HA on their vegetative growth and physiological responses under increased levels of drought (100%, 80%, and 60% field capacity) were simultaneously monitored in the field. In the absence of HA, drought caused 37.0 and 58.7% reductions in biomass accumulation in maize compared to 21.2 and 32.3% in sorghum under low and high drought levels, respectively. These responses were associated with differential retardation in overall growth, relative water content (RWC), photosynthetic pigments and CO 2 assimilation in both plants. In contrast, drought increased root traits as well as H 2 O 2 , malondialdehyde, and electrolyte leakage in both species. HA treatment significantly improved the growth of both plant species under well-watered and drought conditions, with maize being more responsive than sorghum. HA induced a 29.2% increase in the photosynthetic assimilation rate in maize compared to 15.0% in sorghum under high drought level. The HA-promotive effects were also associated with higher total chlorophyll, stomatal conductance, RWC, sucrose, total soluble sugars, total carbohydrates, proline, and total soluble proteins. HA also reduced the drought-induced oxidative stress via induction of non-enzymic and enzymic antioxidants at significantly different extents in maize and sorghum. Conclusion The current results identify significant quantitative differences in a set of critical physiological biomarkers underlying the differential responses of field-grown maize and sorghum plants against drought. They also reveal the potential of HA priming as a drought-alleviating biostimulant and as an effective approach for sustainable maize and sorghum production and possibly other crops in drought-affected lands.

The use of dried olive pomace as complementary energy sources in poultry feed is still limited due to its low protein and high fiber contents. Bioconversion of olive pomace through solid-state fermentation with or without exogenous enzymes is considered as a trial for improving its nutritional value. This study aimed to evaluate the effects of fermented olive pomace with or without enzymatic treatment on the growth, modulations of genes encoding digestive enzymes and glucose transporters, meat oxidative stability, and economic efficiency of broiler chickens. A total of 1400 day-old broiler chicks (Ross 308) were randomly allocated to seven dietary treatments with 10 replicates of 20 birds/replicate. Treatments included control (basal corn–soybean diet) and other six treatments in which basal diet was replaced by three levels (7.5, 15, and 30%) of fermented olive pomace (FOPI) or enzymatically fermented olive pomace (FOPII) for 42 days. The highest body weight gain was observed in groups fed 7.5 and 15% FOPII (increased by 6.6 and 12.5%, respectively, when compared with the control group). Also, feeding on 7.5 and 15% FOPII yielded a better feed conversion ratio and improved the digestibility of crude protein, fat, and crude fiber. The expression of the SGLT-1 gene was upregulated in groups fed FOPI and FOPII when compared with the control group. Moreover, the expression of the GLUT2 gene was elevated in groups fed 7.5 and 15% FOPII. By increasing the levels of FOPI and FOPII in diets, the expression of genes encoding pancreatic AMY2A, PNLIP , and CCK was upregulated ( p < 0.05) when compared with the control. Fat percentage and cholesterol content in breast meat were significantly reduced ( p < 0.05) by nearly 13.7 and 16.7% in groups fed FOPI and FOPII at the levels of 15 and 30%. Total phenolic and flavonoid contents in breast meat were significantly increased in groups fed 15 and 30% FOPI and FOPII when compared with the control group and even after a long period of frozen storage. After 180 days of frozen storage, the inclusion of high levels of FOP significantly increased ( p < 0.05) the levels of glutathione peroxide and total superoxide dismutase and meat ability to scavenge free radical 1,1-diphenyl-2-picrylhydrazyl. Furthermore, the highest net profit and profitability ratio and the lowest cost feed/kg body gain were achieved in groups fed 7.5 and 15% of FOPII, respectively. The results of this study indicated that dietary inclusion of 15% FOPII could enhance the growth performance and economic efficiency of broiler chickens. Moreover, a higher inclusion level of FOPI or FOPII could enhance the quality and increase the oxidative stability of frozen meat and extend the storage time.

Natural products have been extensively used for treating a wide variety of disorders. In recent times, Brucine (BRU) as one of the natural medications extracted from seeds of nux vomica, was investigated for its anticancer activity. As far as we know, this is the first study on BRU anticancer activity against skin cancer. Thus, the rational of this work was implemented to develop, optimize and characterize the anticancer activity of BRU loaded ethosomal gel. Basically, thin film hydration method was used to formulate BRU ethosomal preparations, by means of Central composite design (CCD), which were operated to construct (32) factorial design. Two independent variables were designated (phospholipid percentage and ethanol percentage) with three responses (vesicular size, encapsulation efficiency and flux). Based on the desirability function, one formula was selected and incorporated into HPMC gel base to develop BRU loaded ethosomal gel. The fabricated gel was assessed for all physical characterization. In-vitro release investigation, ex-vivo permeation and MTT calorimetric assay were performed. BRU loaded ethosomal gel exhibited acceptable values for the characterization parameters which stand proper for topical application. In-vitro release investigation was efficiently prolonged for 6 h. The flux from BRU loaded ethosome was enhanced screening optimum SSTF value. Finally, in-vitro cytotoxicity study proved that BRU loaded ethosomal gel significantly improved the anticancer activity of the drug against A375 human melanoma cell lines. Substantially, the investigation proposed a strong motivation for further study of the lately developed BRU loaded ethosomal gel as a prospective therapeutic strategy for melanoma treatment.

The escalating threat of microbial resistance underscores the urgent need for innovative solutions, including natural agents capable of attenuating virulence. This study explores the antimicrobial and anti-virulence potential of essential oils (EOs) derived from Sphagneticola trilobata against Pseudomonas aeruginosa . Through GC/MS analysis, volatile metabolites from the flower heads and leaves/stems of Egyptian S. trilobata were identified, revealing 43 and 62 components, respectively. Key compounds included α-phellandrene, α-pinene, D-limonene, and α-thujene. The Minimum Inhibitory Concentrations (MIC) of flower head and leaf/stem EOs against P. aeruginosa were 1.17% and 1.75% v/v , respectively. At sub-MIC doses (1/8th of the MIC), the EOs exhibited significant anti-virulence properties, including complete inhibition of protease activity and disruption of biofilm formation, which are crucial for bacterial survival and pathogenicity. Additionally, they effectively suppressed the expression of quorum sensing genes, which are essential for bacterial communication and virulence. Virtual screening of four major EO components (+)-(R)-limonene, (±)-α-pinene, α-phellandrene, and α-thujene against five critical protein targets involved in biofilm formation, quorum sensing, virulence, and protease activity in P. aeruginosa further supported their anti-virulence and antibiofilm actions, showing high affinity for these targets. These findings suggest that the EOs of S. trilobata hold great potential as natural virulence attenuating agents, particularly against biofilm-forming pathogens like P. aeruginosa .

Dual nano encapsulation of multi-strain probiotic bacteria can enhance their viability within the avian gastrointestinal tract and improve their effectiveness in disease prevention. So that this study spotted the light on the effect of dual nano encapsulated multi strain of probiotics (LEBB-NPs) contained Enterococcus faecium NCTC 7171, Bacillus amyloliquefaciens probiotic CECT 5940, Lacticasei bacillus casei ATTC334 and Bifidobacterium breve JCM1192 on laying performance, egg quality, immune defence, and resistance against Salmonella Typhimurium challenge. A total of 250 Ross 308 laying breeder hens, 20 weeks of age, were randomly allocated into five experimental groups (five replicates per group; 10 hens per replicate). The control group received a basal diet only and was not challenged. Infected control: hens received basal diet only and challenged with S. Typhimurium (1 × 10 6 CFU/hen) at week 34 of age. Groups LEBB-NPsI, LEBB-NPsII and LEBB-NPsIII fed basal diet supplemented with dual nano encapsulated multi strain of probiotics at levels of 1 × 10 6 CFU/kg diet, 1 × 10 8 CFU/kg diet and 1 × 10 10 CFU/kg diet respectively and challenged with Salmonella Typhimurium (1 × 10 6 CFU/hen) at weeks 34 of age. The results indicated that hens receiving LEBB-NPs showed improved egg production and net feed efficiency during the pre-challenge and early laying periods. Additionally, they restored normal egg production performance following the challenge during the mid-laying period. Challenge at 34 weeks with S. Typhimurium had prominently decreased fertility, hatchability and increased egg embryonic death while dietary fortification with LEBB-NPsIII restored these parameters to normal levels. Dietary supplementation with LEBB-NPs enhanced immune defense, as evidenced by increased phagocytic activity, higher levels of IgM, IgG, lysozymes, and complement C3, both before and after the challenge. Furthermore, upregulation of tight junction genes ( JAM , MUC-2 , ZO-1 , ZO-2 , OCLN , and cldn-4 ), anti-inflammatory mediators ( IL-4 and IL-10 ), and avian β defensinins ( AvBD6 and AvBD6 ) expression levels was noticed before and after challenge in all groups fed LEBB-NPs especially in LEBB-NPsIII fed group. Additionally, the expression of inflammatory mediators ( IL-1β , IL-6 , TNF-α , CCL4 , CCL20 and iNos ) had been down regulated in groups supplemented by LEBB-NPs compared to infected control group. A noticeable decrease in S. Typhimurium counts was observed at various intervals post-infection in the cecum, feces, liver, ovaries, and eggs in groups fed LEBB-NPs, particularly in the LEBB-NPsIII group. This reduction was accompanied by inhibition of virulence-related genes ( HilA and SopD ), compared to the infected control group. Overall, the encouraging results obtained from LEBB-NPs suggest their potential application in breeder feed, due to their positive effects on egg production, egg fertility, and hatchability, as well as their stimulatory role in immune defense and resistance to S. Typhimurium challenge.

The effect of phenolic-rich onion extract (PROE), as a feed additive, was evaluated on the growth, carcass traits, behavior, welfare, intestinal histology, amino acid ileal digestibility \"AID%,\" and the immune status of broiler chicks for 35 days. A total number of 400, 1-day-old broiler chicks (45.38 g ± 1.35) were allocated to four different treatments with 10 replicates each (100 chicks/treatment) consisting of: T1, basal diet without additives (control treatment) (PROE0); T2, basal diet + phenolic-rich onion extract (1 g/kg diet) (PROE1); T3, basal diet + phenolic-rich onion extract (2 g/kg diet) (PROE2); and T4, basal diet + phenolic-rich onion extract (3 g/kg diet) (PROE3). An increase in the final body weight \"FBW,\" bodyweight gain \"BWG,\" and feed consumption was observed ( < 0.05) at different PROE levels. Also, the thymus and bursa percentages were increased in the PROE2 and PROE3 treatments ( < 0.05). The chicks fed on PROE supplemented diets had increased frequency of feeding and drinking and showed comfortable behavior ( < 0.05) with lesser aggression ( < 0.05). Additionally, an increase was observed in the antioxidant enzyme activity, phagocytic %, phagocytic index, and serum lysozyme activity in PROE supplemented treatments, with the best outcome reported in the PROE3 treatment ( < 0.01). IgM was increased in the birds fed with PROE2 and PROE3 diets ( < 0.01). PROE supplementation increased the AID% of lysine and methionine ( <0.01), PROE3 treatment increased the AID% of threonine ( < 0.05), and PROE2 and PROE3 treatments increased the AID% of leucine and isoleucine ( < 0.05). Besides, PROE2, and PROE3 treatments increased the villus height and width, mucosal thickness, and goblet cell count from the duodena, jejuna, and ilea ( < 0.05) compared to control treatment. Based on these results, we concluded that the dietary addition of phenolic-rich onion extracts can improve the growth rate of broiler chicken by improving the AID% of amino acids and intestinal histology. Also, it can improve the welfare, antioxidant enzymes activity, and immune status of the birds. Phenolic-rich onion extracts can be used as a natural growth promoter in the poultry feed for good health and improved performance.