Organoleptic characteristics and compositional profile of meat of growing Japanese quail fed different levels of poultry byproducts compost.

The poultry industry generates a lot of waste, including dead birds, manure, and poultry litter. Poultry waste should never be disposed of improperly because it can seriously harm the environment. The waste can be recycled as a feedstock for use in poultry feed by composting the litter and deceased birds. The compositional profile and organoleptic properties of the meat of growing Japanese quail were examined over the course of a 4-week trial to ascertain the effect of adding compost to the diet. In a completely randomized design (CRD), 1200 newly hatched quail chicks (Coturnix coturnix japonica) were divided into five treatment groups (diets with 0, 2.5, 5, 7.5, and 10% compost), each consisting of 40 birds with six replicates. The addition of compost to the diet had no noticeable effects on the organoleptic qualities of appearance, color, aroma, taste, texture, juiciness, tenderness, and acceptability (P>0.05). The compositional profile characteristics for chicks given compost at any level compared to chicks fed the control diet showed no differences (P>0.05). These findings suggest that the sensory characteristics and compositional profile of growing meat quails can be maintained when fed diets including up to 10% compost.

Assessing effect of feeding poultry byproducts compost on organoleptic characteristics and compositional profile of meat of broiler chickens.

Large amounts of waste, including dead birds, manure, and poultry litter, are produced by the poultry industry. Poultry waste should be disposed of properly to avoid major pollution and health risks. Composting litter and dead birds could be an option to recycle the waste and use in poultry feed. A study was conducted to investigate the effects of feeding composted poultry waste on the organoleptic qualities and compositional profile of the meat of broiler chickens. A total of 300 day-old broiler chicks (500-Cobb) were randomly allocated to five treatment groups replicated six times with 10 birds each, under a completely randomized design (CRD). Five iso-caloric and iso-nitrogenous diets including composted poultry byproducts at concentrations of 0, 2.5, 5, 7.5, and 10% were fed ad libitum to the birds from day 0 to day 35. The sensory grading and meat composition profile of 500 Cobb broiler chickens were tested at 35 days of age. The findings showed that there were no variations in the sensory profiles of the meat from birds given various diets (P>0.05). Although the results were somewhat lower for the chicks fed compost-containing diets than for the control group, this difference was deemed to be insignificant (P>0.05). Similarly, there were no variations in the compositional profile values of the meat between meat from birds fed various diets (P>0.05). These findings imply that broiler chickens may be raised on diets containing up to 10% poultry byproduct compost without any negative impacts on the meat's sensory quality or composition. Additionally, using compost into broiler diets may help to lower the cost of feed.

Identification of an Orally Bioavailable, Brain-Penetrant Compound with Selectivity for the Cannabinoid Type 2 Receptor.

Modulation of the endocannabinoid system (ECS) is of great interest for its therapeutic relevance in several pathophysiological processes. The CB2 subtype is largely localized to immune effectors, including microglia within the central nervous system, where it promotes anti-inflammation. Recently, a rational drug design toward precise modulation of the CB2 active site revealed the novelty of Pyrrolo[2,1-c][1,4]benzodiazepines tricyclic chemotype with a high conformational similarity in comparison to the existing leads. These compounds are structurally unique, confirming their chemotype novelty. In our continuing search for new chemotypes as selective CB2 regulatory molecules, following SAR approaches, a total of 17 selected (S,E)-11-[2-(arylmethylene)hydrazono]-PBD analogs were synthesized and tested for their ability to bind to the CB1 and CB2 receptor orthosteric sites. A competitive [3H]CP-55,940 binding screen revealed five compounds that exhibited >60% displacement at 10 µM concentration. Further concentration-response analysis revealed two compounds, 4k and 4q, as potent and selective CB2 ligands with sub-micromolar activities (Ki = 146 nM and 137 nM, respectively). In order to support the potential efficacy and safety of the analogs, the oral and intravenous pharmacokinetic properties of compound 4k were sought. Compound 4k was orally bioavailable, reaching maximum brain concentrations of 602 ± 162 ng/g (p.o.) with an elimination half-life of 22.9 ± 3.73 h. Whether administered via the oral or intravenous route, the elimination half-lives ranged between 9.3 and 16.7 h in the liver and kidneys. These compounds represent novel chemotypes, which can be further optimized for improved affinity and selectivity toward the CB2 receptor.

In-vitro tribological study and submodeling finite element technique in analyzing wear of zirconia toughened alumina against alumina with bio-lubricants for hip implants.

Tribological study of zirconia toughened alumina against alumina is investigated using ball-on-disk tribometer with different bio-lubricants. Friction and wear coefficients are estimated for these bio-lubricants under four different loading conditions which are equivalent to regular and risky human gait activities. Experiments are carried out for a total sliding distance of 10 km with each bio-lubricant to estimate its friction and wear coefficients. Using submodeling finite element approach, cumulative linear and volumetric wear is estimated with the help of contact pressure. The sesame oil bio-lubricant showed better wear coefficient for risky gait activities and Ringer's solution exhibited minimum wear coefficient for normal walking gait activity. Overall minimum cumulative linear and volumetric wear for 2 million cycles was obtained for Ringer's solution.

First In Class (S,E)-11-[2-(Arylmethylene)Hydrazono]-PBD Analogs As Selective CB2 Modulators Targeting Neurodegenerative Disorders.

Newly designed pyrrolo[2,1-c][1,4]benzodiazepines tricyclic skeleton has shown potential clusters of cannabinoid receptors CB1/CB2 selective ligands. CB2 plays a critical role in microglial-derived neuroinflammation, where it modulates cell proliferation, migration, and differentiation into M1 or M2 phenotypes. Beginning with computer-based docking studies accounting the recently discovered X-ray crystal structure of CB2, we designed a series of PBD analogs as potential ligands of CB2 and tested their binding affinities. Interestingly, computational studies and theoretical binding affinities of several selected (S,E)-11-[2-(arylmethylene)hydrazono]-PBD analogs, have revealed the presence of potential selectivity in binding attraction towards CB1 and CB2. Reported here is the discovery of the first representatives of this series of selective binding to CB2. Preliminary data showed that this class of molecules display potential binding efficacy towards the cannabinoid receptors tested. Intriguingly, initial cannabinoid binding assay showed a selective binding affinity of 4g and 4h showed K i of 0.49 and 4.7 µM towards CB2 receptors while no binding was observed to CB1. The designed leads have shown remarkable stability pattern at the physiological pH magnifying their therapeutic values. We hypothesize that the PBD tricyclic structure offers the molecule an appropriate three-dimensional conformation to fit snugly within the active site of CB2 receptors, giving them superiority over the reported CB2 agonists/inverse agonists. Our findings suggested that the attachment of heterocyclic ring through the condensation of diazepine hydrazone and S- or N-heterocyclic aldehydes enhances the selectivity of CB2 over CB1.

Happiness among dentists: a multi-scale, multi-national study from 21 countries.

OBJECTIVES: The extent to which dentists are happy with their profession and their life has not been well studied. The present study aimed to explore the level of happiness, satisfaction with life and psychological well-being among a sample of dental professionals from 21 countries. MATERIALS AND METHODS: The sample comprised 2,200 dentists from 21 countries. Three scales - Subjective Happiness Scale (SHS), Satisfaction With Life Scale (SWLS), and Affect Balance Scale (ABS) - were used to measure the subjective responses. Data related to demographic and social characteristics were recorded. Mann-Whitney and Kruskal-Wallis tests were used as appropriate. Scales were correlated, and multiple linear regression analyses were employed to identify the independent determinants of SHS, SWLS and ABS. Data were analysed using the SPSS software program; a value of P <0.05 was considered significant. RESULTS: The overall mean scores of SHS, SWLS and ABS were 18.53 ± 5.06, 23.06 ± 6.25 and 1.26 ± 2.40, respectively, with significant differences found across countries: dentists working in Croatia, Peru and Serbia recorded the highest scores, unlike dentists practicing in Yemen, Syria, and Iraq, who recorded the lowest scores. There were significant, moderately positive correlations between the various scales: SHS and SWLS: r = 0.535, P < 0.001; SHS and ABS: r = 0.58, P < 0.001; and SWLS and ABS: r = 0.533, P < 0.001. Country of practice, age, qualification and monthly income were the significant independent predictors of SHS, SWLS and ABS. CONCLUSION: Country of residence and social characteristics were associated with dentists' responses regarding their feelings and subjective well-being.

Assessment of Mesial Canals Morphology of Mandibular First Molars Using CBCT: An In-vitro Study / Avaliação da morfologia dos canais mesiais dos primeiros molares inferiores usando TCCB: um estudo in vitro

Objective: The current study aimed to investigate the relationship between canal configuration, distance between mesiobuccal (MB) and mesiolingual (ML) orifices and the degree of canals curvature in the mesial root of permanent mandibular first molars in a sample of Sudanese population using cone-beam computed tomography (CBCT). Material and Methods: A total of 143 extracted mandibular first molars were processed and scanned with CBCT to determine the configuration of the mesial root canals according to the Vertucci classification. The interorificial distance and the degree of canal curvature in clinical (CV) and proximal (PV) views using Schneider technique were assessed. Results: The commonest canal configuration was type IV (53.1%). The interorificial distance was significantly shorter in type VI compared to other types (P < 0.05). Significant association was found for type IV between the MB and ML canal in the primary curvature regarding CV and PV, and for type II regarding PV in primary and secondary curvature (P < 0.05). In type IV the degree of secondary curvature of MB canal regarding PV, and in the ML canal in CV was significantly lower compared to other types (P < 0.05). Significant correlation was seen in PV of primary curvature in the MB for type VI (P < 0.05). Conclusion: The interorificial distance and secondary curvatures in CV for MB canal were found to be key factors for predicting root canal patterns in PV (AU)

Objetivo: O presente estudo teve como objetivo investigar a relação entre a configuração do canal, a distância entre os orifícios de entrada dos canais mesiovestibular (MB) e mesiolingual (ML) e o grau de curvatura dos canais na raiz mesial dos primeiros molares inferiores permanentes em uma amostra da população sudanesa usando tomografia computadorizada cone-beam(TCCB). Material and Methods: Um total de 143 primeiros molares inferiores extraídos foram processados e escaneados com TCCB para determinar a configuração dos canais radiculares mesiais de acordo com a classificação de Vertucci. A distância inter orificios e o grau de curvatura do canal nas vistas clínica (CV) (acredito que a tradução seja essa mesma, seria como uma foto intra oral clínica/perguntei a um endodontista, mas não soube me responder) e proximal (PV) usando a técnica de Schneider foram avaliados. Resultado: A configuração mais comum do canal foi do tipo IV (53,1%). A distância inter-orificios foi significativamente menor no tipo VI em comparação com outros tipos (P <0,05). Correlação significativa foi observada na PV da curvatura primária no MB para o tipo VI (P <0,05). Conclusão: A distância inter orifícios e as curvaturas secundárias na CV para o canal MB foram consideradas fatores-chave na predição dos padrões do canal radicular na PV (AU)

An inhibitory compound produced by a soil isolate of Rhodococcus has strong activity against the veterinary pathogen R. equi.

Complete genome sequencing of dozens of strains of the soil bacterium Rhodococcus has revealed the presence of many cryptic biosynthetic gene clusters, presumably dedicated to the production of small molecules. This has sparked a renewed interest in this underexplored member of the Actinobacteria as a potential source of new bioactive compounds. Reported here is the discovery of a potent inhibitory molecule produced by a newly isolated strain of Rhodococcus, strain MTM3W5.2. This small inhibitory molecule shows strong activity against all Rhodococcus species tested, including the veterinary pathogen R. equi, and some closely related genera. It is not active against other Gram positive or Gram negative bacteria. A screen of random transposon mutants identified a gene required to produce this inhibitory compound. This gene is a large multi-domain, type I polyketide synthase that is part of a very large multi-gene biosynthetic gene cluster in the chromosome of strain MTM3W5.2. The high resolution mass spectrum of a major chromatogram peak from a broth culture extract of MTM3W5.2 shows the presence of a compound at m/z 911.5490 atomic mass units. This compound is not detected in the culture extracts from a non-producing mutant strain of MTM3W5.2. A large gene cluster containing at least 14 different type I polyketide synthase genes is proposed to be required to synthesize this antibiotic-like compound.

Translation and validation of the Arabic version of the 5-item Oral health impact profile: OHIP5-Ar.

PURPOSE: The aim of this study was to translate and validate an Arabic version of the 5-item Oral Health Impact Profile (OHIP). METHODS: A total of 320 subjects (aged 18 years and above) were consecutively recruited from dental clinics. The self-administered OHIP5-Ar was distributed and the data were collected and analyzed. The dimensionality of the instrument was investigated using confirmatory factor analyses (CFA). Reliability was assessed as the instruments internal consistency using Cronbach's alpha and test-retest-reliability using intraclass correlation coefficient (ICC). Convergent validity was tested by correlation between perceived global oral and general health questions with the latent factor (OHRQoL) using structural equation modelling analysis and with OHIP5-Ar total score using spearman's correlation coefficient. Known-groups validity was tested among groups with known differences and sensitivity to change was also investigated after dental treatments. RESULTS: The OHIP5-Ar was fitted well in the unidimensional model as indicated by the CFA with fit indices (RMSEA: 0.00, SRMR: 0.010, GFI: 0.998, TLI: 1). Cronbach's alpha was 0.78 and the ICC agreement was 0.88. The validity tests indicated satisfactory validity of the instrument and the sensitivity to change of the instrument revealed significant change in the OHIP5-Ar total score after the provision of dental treatments (effect sizes: 0.55-1.49). CONCLUSION: The OHIP5-Ar showed satisfactory psychometric properties among Arabic-speaking population. This instrument is sensitive to the changes of oral health and can be used to measure the OHRQoL with one total score.

Synthesis and biological activity of fused tetracyclic Pyrrolo[2,1-c][1,4]benzodiazepines.

Cancer remains the second major cause of death in the world. Thus, there is a pressing need to identify potential synthetic route for the development of novel anticancer agents which will serve as lead compounds to effectively combat this life-threatening epidemic. Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) have sparked a great interest as lead compounds because of their cancerostatic and anti-infective properties. The twisted molecular structure of PBD analogs provides both helical and chiral elements. In an effort to expand novel PBDs that interact with the key exocyclic amino group of the DNA-guanine base, we hypothesized that construction of a fused cyclic active system, would likely serve as an electrophilic site when compared to traditional electrophilic C11-N10 imine group. To examine our theory, we report herein the synthesis and cell viability/cytotoxicity of a series of PBD analogs using NCI-60 cell lines screening. Thus, compounds 1-13 were synthesized and fully characterized. The selected PBDs were found to have marginal inhibition of growth, up to 30%, for certain cell lines.

Marine Inspired 2-(5-Halo-1H-indol-3-yl)-N,N-dimethylethanamines as Modulators of Serotonin Receptors: An Example Illustrating the Power of Bromine as Part of the Uniquely Marine Chemical Space.

In previous studies, we have isolated several marine indole alkaloids and evaluated them in the forced swim test (FST) and locomotor activity test, revealing their potential as antidepressant and sedative drug leads. Amongst the reported metabolites to display such activities was 5-bromo-N,N-dimethyltryptamine. Owing to the importance of the judicious introduction of halogens into drug candidates, we synthesized two series built on a 2-(1H-indol-3-yl)-N,N-dimethylethanamine scaffold with different halogen substitutions. The synthesized compounds were evaluated for their in vitro and in vivo antidepressant and sedative activities using the mouse forced swim and locomotor activity tests. Receptor binding studies of these compounds to serotonin (5-HT) receptors were conducted. Amongst the prepared compounds, 2-(1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide (1a), 2-(5-bromo-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide (1d), 2-(1H-indol-3-yl)-N,N-dimethylethanamine (2a), 2-(5-chloro-1H-indol-3-yl)-N,N-dimethylethanamine (2c), 2-(5-bromo-1H-indol-3-yl)-N,N-dimethylethanamine (2d), and 2-(5-iodo-1H-indol-3-yl)-N,N-dimethylethanamine (2e) have been shown to possess significant antidepressant-like action, while compounds 2c, 2d, and 2e exhibited potent sedative activity. Compounds 2a, 2c, 2d, and 2e showed nanomolar affinities to serotonin receptors 5-HT1A and 5-HT7. The in vitro data indicates that the antidepressant action exerted by these compounds in vivo is mediated, at least in part, via interaction with serotonin receptors. The data presented here shows the valuable role that bromine plays in providing novel chemical space and electrostatic interactions. Bromine is ubiquitous in the marine environment and a common element of marine natural products.

Specificity and mechanism of mandelamide hydrolase catalysis.

The best-studied amidase signature (AS) enzyme is probably fatty acid amide hydrolase (FAAH). Closely related to FAAH is mandelamide hydrolase (MAH), whose substrate specificity and mechanism of catalysis are described in this paper. First, we developed a convenient chromogenic substrate, 4-nitrophenylacetamide, for MAH. The lack of reactivity of MAH with the corresponding ethyl ester confirmed the very limited size of the MAH leaving group site. The reactivity of MAH with 4-nitrophenyl acetate and methyl 4-nitrophenyl carbonate, therefore, suggested formation of an "inverse" acyl-enzyme where the small acyl-group occupies the normal leaving group site. We have interpreted the specificity of MAH for phenylacetamide substrates and small leaving groups in terms of its active site structure, using a homology model based on a FAAH crystal structure. The relevant structural elements were compared with those of FAAH. Phenylmethylboronic acid is a potent inhibitor of MAH (Ki = 27 nM), presumably because it forms a transition state analogue structure with the enzyme. O-Acyl hydroxamates were not irreversible inactivators of MAH but some were found to be transient inhibitors.

A phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of alitretinoin (BAL4079) in the treatment of severe chronic hand eczema refractory to potent topical corticosteroid therapy.

Severe chronic hand eczema (sCHE) is a persistent, disfiguring disease that responds poorly to conventional treatment and causes substantial physical and psychological disability. The objective of this study was to evaluate efficacy and safety of oral alitretinoin in sCHE in a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study comparing alitretinoin with placebo. Efficacy was assessed every 4 weeks during treatment and 4 weeks after end of treatment (EOT, 24 weeks); responders were assessed every 4 weeks for a further 48 weeks after EOT. The study was conducted at academic and private dermatology centers. The participants were 596 patients with sCHE refractory to potent topical corticosteroids. Patients were treated with daily oral alitretinoin 30 mg or placebo for up to 24 weeks. Primary endpoint was proportion of responding patients based on Physician Global Assessment (PGA) of "clear" or "almost clear" at EOT. Key secondary endpoints: Patient Global Assessment (PaGA), change in modified Total Lesion Symptom Score (mTLSS), time to response (TTR), extent of disease at EOT, and duration of response (DOR). At EOT, 40% of alitretinoin-treated patients were responders vs 15% placebo-treated patients (odds ratio [OR] = 3.78; P < .001); a greater proportion of alitretinoin-treated patients achieved a PaGA of "cleared" or "almost cleared" (OR = 4.05; P< .001). A greater decrease in mTLSS occurred from baseline to EOT in alitretinoin- vs placebo-treated patients (treatment difference -24% P< .001). Median TTR for responders at EOT was shorter with alitretinoin vs placebo (65 vs 117 days; P< .001). Greater decreases in extent of disease at EOT were observed with alitretinoin vs placebo (treatment difference -22%; P< .001). The most common treatment-emergent adverse event was headache. Alitretinoin significantly improved signs/symptoms of sCHE, was well tolerated in patients refractory to potent topical corticosteroids, and may provide benefit to this population.

Determination of genetic variation among chickpea genotypes and their F1 crosses with RAPD markers.

The intensity of genetic diversity amongst chickpea genotypes and their crosses is unknown. The current study investigated the genetic diversity of chickpea genotypes and their F1 crosses by using random amplified polymorphic DNA (RAPD) markers. We assessed the variation among six chickpea genotypes and 15 F1 crosses with the RAPD markers. The six parents and their 21 hybrids were carefully studied based on the presence or absence of bands. The level of polymorphism varied with different primers. Out 28 primers used, 21 amplified the genomic DNA in all the varieties, 15 generated polymorphic bands among all the varieties, and six produced similar banding patterns.

ß-Peptide coatings by surface-initiated polymerization.

Homopolymers of ß-lactams can be grown by surface-initiated polymerization. These surface-linked ß-peptides are living polymers with the potential to be utilized as tunable, protease-resistant interfaces in multiphase structural composites where the characteristics of the interface influence bulk properties.

4-quinolones as noncovalent inhibitors of high molecular mass penicillin-binding proteins.

Penicillin-binding proteins (PBPs) are important bacterial enzymes that carry out the final steps of bacterial cell wall assembly. Their DD-transpeptidase activity accomplishes the essential peptide cross-linking step of the cell wall. To date, all attempts to discover effective inhibitors of PBPs, apart from ß-lactams, have not led to new antibiotics. Therefore, the need for new classes of efficient inhibitors of these enzymes remains. Guided by a computational fragment-based docking procedure, carried out on Escherichia coli PBP5, we have designed and synthesized a series of 4-quinolones as potential inhibitors of PBPs. We describe their binding to the PBPs of E. coli and Bacillus subtilis. Notably, these compounds bind quite tightly to the essential high molecular mass PBPs.

2-N-Methyl modifications and SAR studies of manzamine A.

Quaternary carbolinium salts have been reported to show improved antimalarial activity and reduced cytotoxicity as compared to electronically neutral beta-carbolines. In this study, mono- and di-methylated quaternary carbolinium cations of manzamine A were synthesized and evaluated for their in vitro antimalarial and antimicrobial activity, cytotoxicity, and also their potential for glycogen synthase kinase (GSK-3beta) inhibition using molecular docking studies. Among the analogs, 2-N-methylmanzamine A (2) exhibited antimalarial activity (IC(50) 0.7-1.0microM) but was less potent than manzamine A. However the compound was significantly less cytotoxic to mammalian kidney fibroblasts and the selectivity index was in the same range as manzamine A.

Hypoplastic circumflex retroesophageal right-sided cervical aortic arch with unusual vascular arrangement and severe coarctation.

We report the case of a 12-year-old boy with a hypoplastic retroesophageal circumflex right-sided cervical aortic arch and coarctation. After the incidental finding of a heart murmur when the boy was 9 years old, cardiac magnetic resonance showed a right-sided cervical aortic arch, hypoplastic transverse arch, and separate origin of the left common carotid, right common carotid, right vertebral, and right subclavian arteries. The left subclavian artery arose from the proximal descending aorta next to the coarctation. An extra-anatomical ascending to descending aorta tube graft was inserted through a right lateral thoracotomy with good results.