Probiotic Bacillus species and Saccharomyces boulardii improve performance, gut histology and immunity in broiler chickens

The aim of this study was to compare the effects of a new multispecies probiotic containing four Bacillus species and Saccharomyces boulardii (Microguard®) with a commercial probiotic (Protexin®) and a commonly used antibiotic in broilers. Six hundred one-day-old male Ross 308 broilers were randomized to six experimental treatments, with five replicates of 20 chicks each, for 42 days, receiving an ad libitum corn-soybean basal diet. Treatments were added to the basal diet and consisted of tetracycline as an antibiotic growth promoter (500 g/ton), three dosages of Microguard (50, 100 and150 g/ton) or Protexin (100 g/ton). The control group received the basal diet with no additive. The group fed with Microguard at 150 g/ton showed increased final bodyweight, weight gain, high density lipoprotein, triglyceride, and antibody titres against Newcastle disease (ND) and avian influenza (AI) levels. Improved feed conversion ratio, increased villus height, and villus highest crypt depth ratio, along with lower plasma gamma-glutamyl transpeptidase, alkaline phosphatase, alanine aminotransferase, were found in probiotic-supplemented broilers. Carcass yield, liver weights, breast muscle values, and abdominal fat weights were reduced in groups fed with 100 or 150 g/ton of Microguard. Caecal coliforms, Salmonella and Escherichia coli numbers decreased in groups fed with 100 or 150 g/ton of Microguard. These results show that Microguard at 150 g/ton is a promising probiotic to replace antibiotics in broiler feed as a growth-promoter while enhancing immune system responses and inducing beneficial modulations in the caecal microflora.Keywords: blood biochemistry, broiler chicks, carcass traits, performance, probioti

Assessment of a probiotic Containing Bacillus Subtilis on the Performance and Gut Health of Laying Japanese Quails (Coturnix Coturnix Japonica)

Keywords Japanese quails, egg production, gut health, immune response. ABStRACt The present study was carried out to determine the effects of the inclusion of a spore-forming probiotic (Bacillus subtilis) in laying Japanese quail diets as an alternative to growth-promoting antibiotics to help produce healthy eggs and meat. This experiment was conducted as a completely randomized design with three treatments (control, 0.05% bacitracin methylene disalicylate (BMD), or 0.1% Bacillus subtilis) of five replicates of 11 quails each. Feed intake and egg production were recorded daily on cage basis. Body weight was determined at the beginning and end of the trial (36 and 42 weeks). At the end of the experiment (42 weeks), antibodies against Newcastle disease and avian influenza, egg components, Haugh units, eggshell quality and breaking strength, blood parameters, cecal microbial population, villus length, and crypt depth were measured. The dietary inclusion of Bacillus subtilis and BMD significantly (p≤0.05) increased egg production and egg weight; however, eggshell thickness and breaking strength, Haugh units, and eggshell percentages were not affected. The dietary addition of both products significantly (p≤0.05) decreased plasma cholesterol levels and increased LDL levels, as well as antibody levels against Newcastle disease and avian influenza (p≤0.01). In birds fed Bacillus subtilis and BMD, crypt depth was reduced, but villus height and villus to crypt ratio were significantly increased (p≤0.001) compared with those fed the basal diet. Cecal coliforms, E. coli, and Salmonella counts were reduced (p≤0.01) in quails fed the diets containing Bacillus subtilis and BMD compared those quails fed the non-supplemented diet. The results of this study demonstrated that in absence of AGPs, the inclusion of a spore-forming probiotic partially improves the performance of laying quails

Indole-3-carbinol suppresses NF-κB activity and stimulates the p53 pathway in pre-B acute lymphoblastic leukemia cells

B cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common type of cancer in children. Dramatic improvements in primary therapy for childhood ALL have led to an overall cure rate of 80 , providing opportunities for innovative combined-modality strategies that would increase cure rates while reducing the toxic side effects of current intensive regimens. In this study, we report that indole-3-carbinol (I3C), a natural phytochemical found in cruciferous vegetables, had anti-leukemic properties in BCP-ALL NALM-6 cells. I3C induced cell growth inhibition by G1 cell cycle arrest and triggered apoptosis in a dose- and time-dependent manner. p53, p21, and Bax proteins showed increased expression after I3C treatment. Real-time PCR analysis of pro-apoptotic p53 target genes revealed up-regulation of PUMA, NOXA, and Apaf-1. I3C also suppressed constitutive nuclear factor-κB (NF-κB) activation and inhibited the protein expression of NF-kappa B-regulated antiapoptotic (IAP1, Bcl-xL, Bcl-2, XIAP) and proliferative (c-Myc) gene products. Coadministration of I3C with the topoisomerase II inhibitor, doxorubicin, potentiates cytotoxic effects compared with either agent alone. Apoptosis induction by the drug combination was associated with enhanced caspase-9 activation and PARP cleavage. Furthermore, I3C abolished doxorubicin-induced NF-κB activity as evidenced by decreased nuclear accumulation of p65, inhibition of IκBα phosphorylation and its degradation, and decreased NF-κB DNA-binding activity. Western blot analysis revealed that doxorubicin-induced Bcl-2 protein expression was inhibited by I3C. Overall, our results indicated that using nontoxic agents, such as I3C, in combination with anthracyclines might provide a new insight into the development of novel combination therapies in childhood BCP-ALL. © 2015, International Society of Oncology and BioMarkers (ISOBM)

Temporal Artery Biopsy for Diagnosing Giant Cell Arteritis: A Ten-year Review

Purpose: To assess the use of temporal artery biopsy (TAB) in diagnosing giant cell arteritis (GCA) and to evaluate patients� clinical and laboratory characteristics. Methods: We conducted a retrospective chart review of patients with suspected GCA who underwent TAB and had complete workup in a tertiary center in Iran between 2008 and 2017. The 2016 American College of Rheumatology (ACR) revised criteria for early diagnosis of GCA were used for each patient for inclusion in this study. Results: The mean age of the 114 patients in this study was 65.54 ± 10.17 years. The mean overall score according to the 2016 ACR revised criteria was 4.17 ± 1.39, with 5.82 ± 1.28 for positive biopsies and 3.88 ± 1.19 for negative biopsies (p <0.001). Seventeen patients (14.9) had a positive biopsy. Although the mean post-fixation specimen length in the biopsy-positive group (18.35 ± 6.9 mm) was longer than that in the biopsy-negative group (15.62 ± 8.4 mm), the difference was not statistically significant (P = 0.21). There was no statistically significant difference between the groups in terms of sex, serum hemoglobin, platelet count, and erythrocyte sedimentation rate. There were statistically significant differences between the biopsy-negative and biopsy-positive groups with respect to patients� age and C-reactive protein level (P < 001 and P = 0.012, respectively). Conclusion: The majority of TABs were negative. Reducing the number of redundant biopsies is necessary to decrease workload and use of medical services. We suggest that the diagnosis of GCA should be dependent on clinical suspicion. © 2020 JOURNAL OF OPHTHALMIC AND VISION RESEARC

Dehydration of potato slices following brief dipping in osmotic solutions: effect of conditions and understanding the mechanism of water loss

A novel variant of osmotic dehydration, named here as post-dipping dehydration – where a material is dipped in a salt or sugar solution for a very short time followed by simple exposure to ambient conditions was explored with the aim of lowering water content of potato slices but at the same time not gain a high level of sugar/salt. The rate of water loss, which was rapid initially, was found to approach equilibrium. This paper also explored whether the water loss process could subsequently be kick started once again, by employing a multi-stage process, where each stage consisted of osmotic solution dipping followed by ambient holding of the potato slices that had reached equilibrium in the earlier stage. Water loss values comparable to conventional osmotic dehydration could be achieved thus, but with significantly lower overall solid gain (less than 50%) – which can potentially yield a significantly healthy product option

Safety and effectiveness of high-dose vitamin C in patients with COVID-19: a randomized open-label clinical trial

Background: Vitamin C is an essential water-soluble nutrient that functions as a key antioxidant and has been proven to be effective for boosting immunity. In this study, we aimed to assess the efficacy of adding high-dose intravenous vitamin C (HDIVC) to the regimens for patients with severe COVID-19 disease. Methods: An open-label, randomized, and controlled trial was conducted on patients with severe COVID-19 infection. The case and control treatment groups each consisted of 30 patients. The control group received lopinavir/ritonavir and hydroxychloroquine and the case group received HDIVC (6 g daily) added to the same regimen. Results: There were no statistically significant differences between two groups with respect to age and gender, laboratory results, and underlying diseases. The mean body temperature was significantly lower in the case group on the 3rd day of hospitalization (p = 0.001). Peripheral capillary oxygen saturations (SpO2) measured at the 3rd day of hospitalization was also higher in the case group receiving HDIVC (p = 0.014). The median length of hospitalization in the case group was significantly longer than the control group (8.5 days vs. 6.5 days) (p = 0.028). There was no significant difference in SpO2 levels at discharge time, the length of intensive care unit (ICU) stay, and mortality between the two groups. Conclusions: We did not find significantly better outcomes in the group who were treated with HDIVC in addition to the main treatment regimen at discharge. Trial registration irct.ir (IRCT20200411047025N1), April 14, 2020 © 2021, The Author(s)

A Dominant-Negative Approach That Prevents Diphthamide Formation Confers Resistance to Pseudomonas Exotoxin A and Diphtheria Toxin

Diphtheria toxin (DT), Pseudomonas aeruginosa Exotoxin A (ETA) and cholix toxin from Vibrio cholerae share the same mechanism of toxicity; these enzymes ADP-rybosylate elongation factor-2 (EF-2) on a modified histidine residue called diphthamide, leading to a block in protein synthesis. Mutant Chinese hamster ovary cells that are defective in the formation of diphthamide have no distinct phenotype except their resistance to DT and ETA. These observations led us to predict that a strategy that prevents the formation of diphthamide to confer DT and ETA resistance is likely to be safe. It is well documented that Dph1 and Dph2 are involved in the first biochemical step of diphthamide formation and that these two proteins interact with each other. We hypothesized that we could block diphthamide formation with a dominant negative mutant of either Dph1 or Dph2. We report in this study the first cellular-targeted strategy that protects against DT and ETA toxicity. We have generated Dph2(C-), a dominant-negative mutant of Dph2, that could block very efficiently the formation of diphthamide. Cells expressing Dph2(C-) were 1000-fold more resistant to DT than parental cells, and a similar protection against Pseudomonas exotoxin A was also obtained. The targeting of a cellular component with this approach should have a reduced risk of generating resistance as it is commonly seen with antibiotic treatments

Organoids and organ chips in ophthalmology

Recent advances have driven the development of stem cell-derived, self-organizing, three-dimensional miniature organs, termed organoids, which mimic different eye tissues including the retina, cornea, and lens. Organoids and engineered microfluidic organ-on-chips (organ chips) are transformative technologies that show promise in simulating the architectural and functional complexity of native organs. Accordingly, they enable exploration of facets of human disease and development not accurately recapitulated by animal models. Together, these technologies will increase our understanding of the basic physiology of different eye structures, enable

The global burden of childhood and adolescent cancer in 2017: an analysis of the Global Burden of Disease Study 2017

© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Accurate childhood cancer burden data are crucial for resource planning and health policy prioritisation. Model-based estimates are necessary because cancer surveillance data are scarce or non-existent in many countries. Although global incidence and mortality estimates are available, there are no previous analyses of the global burden of childhood cancer represented in disability-adjusted life-years (DALYs). Methods: Using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 methodology, childhood (ages 0–19 years) cancer mortality was estimated by use of vital registration system data, verbal autopsy data, and population-based cancer registry incidence data, which were transformed to mortality estimates through modelled mortality-to-incidence ratios (MIRs). Childhood cancer incidence was estimated using the mortality estimates and corresponding MIRs. Prevalence estimates were calculated by using MIR to model survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated by multiplying age-specific cancer deaths by the difference between the age of death and a reference life expectancy. DALYs were calculated as the sum of YLLs and YLDs. Final point estimates are reported with 95% uncertainty intervals. Findings: Globally, in 2017, there were 11·5 million (95% uncertainty interval 10·6–12·3) DALYs due to childhood cancer, 97·3% (97·3–97·3) of which were attributable to YLLs and 2·7% (2·7–2·7) of which were attributable to YLDs. Childhood cancer was the sixth leading cause of total cancer burden globally and the ninth leading cause of childhood disease burden globally. 82·2% (82·1–82·2) of global childhood cancer DALYs occurred in low, low-middle, or middle Socio-demographic Index locations, whereas 50·3% (50·3–50·3) of adult cancer DALYs occurred in these same locations. Cancers that are uncategorised in the current GBD framework comprised 26·5% (26·5–26·5) of global childhood cancer DALYs. Interpretation: The GBD 2017 results call attention to the substantial burden of childhood cancer globally, which disproportionately affects populations in resource-limited settings. The use of DALY-based estimates is crucial in demonstrating that childhood cancer burden represents an important global cancer and child health concern. Funding: Bill & Melinda Gates Foundation, American Lebanese Syrian Associated Charities (ALSAC), and St. Baldrick's Foundation

Global, regional, and national burden of respiratory tract cancers and associated risk factors from 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Prevention, control, and treatment of respiratory tract cancers are important steps towards achieving target 3.4 of the UN Sustainable Development Goals (SDGs)—a one-third reduction in premature mortality due to non-communicable diseases by 2030. We aimed to provide global, regional, and national estimates of the burden of tracheal, bronchus, and lung cancer and larynx cancer and their attributable risks from 1990 to 2019. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 methodology, we evaluated the incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs) of respiratory tract cancers (ie, tracheal, bronchus, and lung cancer and larynx cancer). Deaths from tracheal, bronchus, and lung cancer and larynx cancer attributable to each risk factor were estimated on the basis of risk exposure, relative risks, and the theoretical minimum risk exposure level input from 204 countries and territories, stratified by sex and Socio-demographic Index (SDI). Trends were estimated from 1990 to 2019, with an emphasis on the 2010-19 period. Findings Globally, there were 2·26 million (95% uncertainty interval 2·07 to 2·45) new cases of tracheal, bronchus, and lung cancer, and 2·04 million (1·88 to 2·19) deaths and 45·9 million (42·3 to 49·3) DALYs due to tracheal, bronchus, and lung cancer in 2019. There were 209 000 (194 000 to 225 000) new cases of larynx cancer, and 123 000 (115 000 to 133 000) deaths and 3·26 million (3·03 to 3·51) DALYs due to larynx cancer globally in 2019. From 2010 to 2019, the number of new tracheal, bronchus, and lung cancer cases increased by 23·3% (12·9 to 33·6) globally and the number of larynx cancer cases increased by 24·7% (16·0 to 34·1) globally. Global age-standardised incidence rates of tracheal, bronchus, and lung cancer decreased by 7·4% (−16·8 to 1·6) and age-standardised incidence rates of larynx cancer decreased by 3 ·0% (−10·5 to 5·0) in males over the past decade; however, during the same period, age-standardised incidence rates in females increased by 0·9% (−8·2 to 10·2) for tracheal, bronchus, and lung cancer and decreased by 0·5% (−8·4 to 8·1) for larynx cancer. Furthermore, although age-standardised incidence and death rates declined in both sexes combined from 2010 to 2019 at the global level for tracheal, bronchus, lung and larynx cancers, some locations had rising rates, particularly those on the lower end of the SDI range. Smoking contributed to an estimated 64·2% (61·9–66·4) of all deaths from tracheal, bronchus, and lung cancer and 63·4% (56·3–69·3) of all deaths from larynx cancer in 2019. For males and for both sexes combined, smoking was the leading specific risk factor for age-standardised deaths from tracheal, bronchus, and lung cancer per 100 000 in all SDI quintiles and GBD regions in 2019. However, among females, household air pollution from solid fuels was the leading specific risk factor in the low SDI quintile and in three GBD regions (central, eastern, and western sub-Saharan Africa) in 2019. Interpretation The numbers of incident cases and deaths from tracheal, bronchus, and lung cancer and larynx cancer increased globally during the past decade. Even more concerning, age-standardised incidence and death rates due to tracheal, bronchus, lung cancer and larynx cancer increased in some populations—namely, in the lower SDI quintiles and among females. Preventive measures such as smoking control interventions, air quality management programmes focused on major air pollution sources, and widespread access to clean energy should be prioritised in these settings