Evidence on the inhibitory effect of Brassica plants against Acinetobacter baumannii lipases: phytochemical analysis, in vitro, and molecular docking studies.

BACKGROUND: Infections caused by Acinetobacter baumannii are becoming a rising public health problem due to its high degree of acquired and intrinsic resistance mechanisms. Bacterial lipases penetrate and damage host tissues, resulting in multiple infections. Because there are very few effective inhibitors of bacterial lipases, new alternatives for treating A. baumannii infections are urgently needed. In recent years, Brassica vegetables have received a lot of attention since their phytochemical compounds have been directly linked to diverse antimicrobial actions by inhibiting the growth of various Gram-positive and Gram-negative bacteria, yeast, and fungi. Despite their longstanding antibacterial history, there is currently a lack of scientific evidence to support their role in the management of infections caused by the nosocomial bacterium, A. baumannii. This study aimed to address this gap in knowledge by examining the antibacterial and lipase inhibitory effects of six commonly consumed Brassica greens, Chinese cabbage (CC), curly and Tuscan kale (CK and TK), red and green Pak choi (RP and GP), and Brussels sprouts (BR), against A. baumannii in relation to their chemical profiles. METHODS: The secondary metabolites of the six extracts were identified using LC-QTOF-MS/MS analysis, and they were subsequently correlated with the lipase inhibitory activity using multivariate data analysis and molecular docking. RESULTS: In total, 99 metabolites from various chemical classes were identified in the extracts. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) revealed the chemical similarities and variabilities among the specimens, with glucosinolates and phenolic compounds being the major metabolites. RP and GP showed the highest antibacterial activity against A. baumannii, followed by CK. Additionally, four species showed a significant effect on the bacterial growth curves and demonstrated relevant inhibition of A. baumannii lipolytic activity. CK showed the greatest inhibition (26%), followed by RP (21%), GP (21%), and TK (15%). Orthogonal partial least squares-discriminant analysis (OPLS-DA) pinpointed 9 metabolites positively correlated with the observed bioactivities. Further, the biomarkers displayed good binding affinities towards lipase active sites ranging from -70.61 to -30.91 kcal/mol, compared to orlistat. CONCLUSION: This study emphasizes the significance of Brassica vegetables as a novel natural source of potential inhibitors of lipase from A. baumannii.

Comparison between using inlet circular jet and elliptic jet in combustion chamber by using twin jet flow propane and methanol.

The current work aimed to improve the combustion behavior of a non-premixed twin-jet inlet. The effect of fuel and air inlet shape under different velocities was studied using ANSYS as the process takes place in species transport and finite rate/eddy dissipation, and the flow is considered to be turbulent. Two different shapes (circular-circular and circular-elliptic inlet jets) were investigated, and the results show that the behavior and intensity of the fire are affected by variations in the speed and, geometry of the inlet which affects temperature, heat release rate, combustion efficiency, and equivalent ratios. The optimum air/fuel velocities were found to be 2.5/1.5 with circular-circular inlet jets.

Does Obesity Affect the Rate of Force Development in Plantar Flexor Muscles among Older Adults?

The literature offers limited information on the effect of obesity on the rate of force development (RFD), a critical parameter for mobility in older adults. The objectives of this study were to explore the influence of obesity on the RFD in older adults and to examine the association between this neuromuscular parameter and walking speed. The participants (42 older adults) were classified into two groups: the control group (CG, n = 22; mean age = 81.13 ± 4.02 years; body mass index (BMI) = 25.13 ± 3.35 kg/m2), and the obese group (OG, n = 20; mean age = 77.71 ± 2.95 years; BMI = 34.46 ± 3.25 kg/m2). Walking speed (m/s) was measured using the 10 m walking test. Neuromuscular parameters of the plantar flexors were evaluated during a maximal voluntary contraction test using a dynamometer. The RFD was calculated from the linear slop of the force-time curve in the following two phases: from the onset of the contraction to 50 ms (RFD0-50) and from 100 to 200 ms (RFD100-200). The gait speed was lower in the OG compared to the CG (p < 0.001). The RFD50/100 and RFD100/200 were lower in the OG compared to the CG (p < 0.001). The RFD50/100 was found to be the predominant influencer on gait speed in the OG. In conclusion, obesity negatively impacts the RFD in older adults and RFD stands out as the primary factor among the studied parameters influencing gait speed.

Dihydrophenazine: a multifunctional new weapon that kills multidrug-resistant Acinetobacter baumannii and restores carbapenem and oxidative stress susceptibilities.

AIMS: The current work aims to fully characterize a new antimicrobial agent against Acinetobacter baumannii, which continues to represent a growing threat to healthcare settings worldwide. With minimal treatment options due to the extensive spread of resistance to almost all the available antimicrobials, the hunt for new antimicrobial agents is a high priority. METHODS AND RESULTS: An Egyptian soil-derived bacterium strain NHM-077B proved to be a promising source for a new antimicrobial agent. Bio-guided fractionation of the culture supernatants of NHM-077B followed by chemical structure elucidation identified the active antimicrobial agent as 1-hydroxy phenazine. Chemical synthesis yielded more derivatives, including dihydrophenazine (DHP), which proved to be the most potent against A. baumannii, yet it exhibited a marginally safe cytotoxicity profile against human skin fibroblasts. Proteomics analysis of the cells treated with DHP revealed multiple proteins with altered expression that could be correlated to the observed phenotypes and potential mechanism of the antimicrobial action of DHP. DHP is a multipronged agent that affects membrane integrity, increases susceptibility to oxidative stress, interferes with amino acids/protein synthesis, and modulates virulence-related proteins. Interestingly, DHP in subinhibitory concentrations re-sensitizes the highly virulent carbapenem-resistant A. baumannii strain AB5075 to carbapenems providing great hope in regaining some of the benefits of this important class of antibiotics. CONCLUSIONS: This work underscores the potential of DHP as a promising new agent with multifunctional roles as both a classical and nonconventional antimicrobial agent that is urgently needed.

The Moraxella catarrhalis AdhC-FghA system is important for formaldehyde detoxification and protection against pulmonary clearance.

Multidrug-resistant clinical isolates of Moraxella catarrhalis have emerged, increasing the demand for the identification of new treatment and prevention strategies. A thorough understanding of how M. catarrhalis can establish an infection and respond to different stressors encountered in the host is crucial for new drug-target identification. Formaldehyde is a highly cytotoxic compound that can be produced endogenously as a by-product of metabolism and exogenously from environmental sources. Pathways responsible for formaldehyde detoxification are thus essential and are found in all domains of life. The current work investigated the role of the system consisting of the S-hydroxymethyl alcohol dehydrogenase (AdhC), a Zn-dependent class III alcohol dehydrogenase, and the S-formyl glutathione hydrolase (FghA) in the formaldehyde detoxification process in M. catarrhalis. Bioinformatics showed that the components of the system are conserved across the species and are highly similar to those of Streptococcus pneumoniae, which share the same biological niche. Isogenic mutants were constructed to study the function of the system in M. catarrhalis. A single fghA knockout mutant did not confer sensitivity to formaldehyde, while the adhC-fghA double mutant is formaldehyde-sensitive. In addition, both mutants were significantly cleared in a murine pulmonary model of infection as compared to the wild type, demonstrating the system's importance for this pathogen's virulence. The respective phenotypes were reversed upon the genetic complementation of the mutants. To date, this is the first study investigating the role of the AdhC-FghA system in formaldehyde detoxification and pathogenesis of M. catarrhalis.

Discovery of Novel Pyridazine-Tethered Sulfonamides as Carbonic Anhydrase II Inhibitors for the Management of Glaucoma.

As a progressive neuropathic condition, glaucoma can cause lifelong blindness if left untreated. Novel phenylpyridazine-tethered sulfonamides were designed as selective inhibitors for carbonic anhydrase (CA) isoform II to find effective therapeutic agents for glaucoma. Subsequently, the target inhibitors were synthesized and assessed for their inhibitory action against cytosolic CA I and II. Interestingly, the synthesized molecules poorly inhibited CA I while exhibiting low subnanomolar potency against CA II. Compound 7c disclosed the most potent activity (IC50 = 0.63 nM) with high selectivity against CA II (605-fold than acetazolamide selectivity). Moreover, compound 7c also showed significant in vivo IOP-reducing properties in the in vivo model of glaucoma. Furthermore, the binding of compound 7c to CA II was assessed at the molecular level, exploiting the molecular docking approach.

Phytochemical Screening and chemical investigation of lipoidal matter of the leaves of Latania verschaffeltii Lem. Family Arecaceae cultivated in Egypt

Abstract This study presents the first preliminary phytochemical screening and investigation of the lipoidal matter of Latania verschaffeltii Lem. leaves, belonging to the Arecaceae family. Gas chromatography coupled with mass spectroscopy (GC/MS) was used to analyze and identify compounds of saponifiable and unsaponifiable content. The preliminary phytochemical screening of total methanolic extract of Latania verschaffeltii Lem. leaves revealed the presence of unsaturated sterols and/or triterpenes, carbohydrates and/or glycosides, flavonoids, tannins, saponins, and phenolic acids in the leaves. However, cardenolides, cyanogenic compounds, alkaloids, and iridoids were not detected. The results of the gas chromatography/mass spectrometry (GC/MS) analysis indicated that the percentage of saturated fatty acids (83.82%) is higher than that of unsaturated fatty acids (9.42%). The predominant methyl ester of a saturated fatty acid detected in the sample was hexadecanoic acid methyl ester, accounting for 41.68% of the total. The composition of the unsaponifiable matter consisted of hydrocarbons (5.66%), fatty alcohols (0.96%), terpenes (85.97%), and sterols (2.18%). The major terpenes observed were phytol (43.62%) and squalene (39.27%).

Retention of hybrid-abutment-crowns with offset implant placement: influence of Crown materials and Ti-base height.

BACKGROUND: The purpose of the current study was to assess the impact of three esthetic CAD/CAM material, titanium base height and their interaction on the retention strength of a hybrid-abutment-crown. METHODS: A total of 42 hybrid-abutment crowns with identical external geometries were designed in CAD software to fit two different Ti-Base abutment heights (n = 42/abutment height): either short (S) with 4 mm (n = 21) or long (L) 7 mm (n = 21) height. Each main group was divided into 3 subgroups (n = 7), according to esthetic crown material, Zirconia (Z), Lithium disilicate (L) and Hybrid ceramic (V). A universal primer and an adhesive resin cement were used for bonding according to the manufacturer instructions. Artificial aging in form of water storage (30 days), chewing simulation (50,000-cycles, 49 N, 1.67 Hz) and thermal cyclic (5000 cycles at 5-55 °C) were applied, specimens were pulled-out under tension load in (N) using a universal testing machine. Two and one-way ANOVA and Post Hoc Tukey test were used for statistical analysis. RESULTS: Long lithium disilicate (LL) group showed the highest retention (738.7 ± 178.5) followed by short lithium disilicate (LS) group (688.6 ± 169.9). Meanwhile, short zirconia (ZS) showed the lowest retention strength (231.1 ± 86.9). CONCLUSION: CAD/CAM fabricated lithium disilicate hybrid-abutment-crown can be used instead of conventional crowns over implant abutment. Etchable ceramics are recommended as a material of choice for CAD/CAM fabricated hybrid-abutment-crowns instead of zirconia in terms of retention durability.

Is Subtle Cavovarus a Problem for Athletes?

Cavovarus or high-arched foot is a common foot deformity that occurs due to the disruption of the foot-driven equilibrium between the first metatarsal, fifth metatarsal, and the heel. This imbalance leads to an increase in the foot's normal plantar concavity. Cavovarus deformity ranges from a mild and flexible malalignment to a fixed, complex, and severe deformation. Subtle cavovarus foot, the mild form of the cavus foot, was first described by Manoli and colleagues.

Evaluation of small hydropower turbines installed downstream of Nile River branches (Egypt).

The current study proposes a new strategy for using small hydroelectric turbines in downstream river branches with the least amount of construction and the lowest cost by comparing two different methods of installing the turbines, the first by installing the turbines at the river's bottom and the second by installing the turbines on floating boats. The methodology of this article is based on predicting the distribution of velocities through the watercourse using experimental data collected at various points in the river's depth, and then predicting the resulting electrical power for different sizes of turbines, as well as estimating the number of turbines for each row and the number of rows along the river. Therefore, Investigate the proposed systems. The proposed small hydropower system's economic viability and environmental impact are investigated in this article. According to the nature of the waterway, the best diameter of a turbine that can be used is 1.5 m based on water velocities and river depths. The proposed power plant generated 25.8 kW per single turbine row, with an estimated cost of produced power (0.035 USD/kWh) of approximately 20 turbines installed per row. Compared to other renewable energy sources, the proposed hydropower system is cost-effective and environmentally friendly, as generating electricity with the proposed small hydropower plant could reduce annual carbon dioxide emissions by 368 tones of CO2 per single turbine row.

Exploring novel aryl/heteroaryl-isosteres of phenylthiazole against multidrug-resistant bacteria.

Antimicrobial resistance has become a concern as a worldwide threat. A novel scaffold of phenylthiazoles was recently evaluated against multidrug-resistant Staphylococci to control the emergence and spread of antimicrobial resistance, showing good results. Several structural modifications are needed based on the structure-activity relationships (SARs) of this new antibiotic class. Previous studies revealed the existence of two key structural features essential for the antibacterial activity, the guanidine head and lipophilic tail. In this study, a new series of twenty-three phenylthiazole derivatives were synthesized utilizing the Suzuki coupling reaction to explore the lipophilic part. The in vitro antibacterial activity was evaluated against a range of clinical isolates. The three most promising compounds, 7d, 15d and 17d, with potent MIC values against MRSA USA300 were selected for further antimicrobial evaluation. The tested compounds exhibited potent results against the tested MSSA, MRSA, and VRSA strains (concentration: 0.5 to 4 µg mL-1). Compound 15d inhibited MRSA USA400 at a concentration of 0.5 µg mL-1 (one-fold more potent than vancomycin) and showed low MIC values against ten clinical isolates, including linezolid-resistant strain MRSA NRS119 and three vancomycin-resistant isolates VRSA 9/10/12. Moreover, compound 15d retained its potent antibacterial activity using the in vivo model by the burden reduction of MRSA USA300 in skin-infected mice. The tested compounds also showed good toxicity profiles and were found to be highly tolerable to Caco-2 cells at concentrations of up to 16 µg mL-1, with 100% of the cells remaining viable.

Fracture load of ultrathin occlusal veneers: Effect of thickness and surface conditioning.

OBJECTIVE: This in-vitro study is planned to analyze the effect of different thicknesses of ceramic occlusal veneers and different surface treatments on fracture resistance. MATERIALS AND METHODS: A total of 48 sound mandibular molars are anatomically prepared from the occlusal surface with two different thicknesses (1.0 and 0.5 mm). CAD/CAM zirconia-reinforced glass ceramic blocks (Vita Suprinity) are used for fabricating occlusal veneers. The teeth are randomly divided into two primary groups A and B (n=24) according to occlusal veneer thickness. Each group is subdivided according to surface conditioning into three equal subgroups (n=8)-subgroup HF: etching with hydrofluoric acid and ceramic primer application; subgroup APF: etching with acidulated phosphate fluoride and ceramic primer application; subgroup EP: conditioning with etch and prime only. Dual-cure adhesive resin cement (Multilink Automix) is utilized to adhesively bond the veneers. All specimens are subjected to 240,000 cycles of dynamic load aging prior to the fracture resistance test. The fracture resistance is measured in Newton (N). The Failure mode patterns are analyzed and categorized using a scanning electron microscope (SEM). The results are analyzed using a two-way ANOVA with Bonferroni's Post-Hoc test, followed by a one-way ANOVA for each factor. That is in addition to one-way ANOVA for surface treatment under each thickness, each followed by Bonferroni's Post-Hoc test. Then, a T-test is used to compare the two thicknesses under each surface treatment. All tests are set at 0.05 significance level. RESULTS: The two-way ANOVA test revealed that restoration thickness and surface treatment both significantly affect the fracture resistance values (p<0.05). The highest fracture resistance mean (2672±216N) is obtained from HF at 1.0 mm thickness, while the lowest mean (2104±299N) is obtained from APF at 0.5 mm thickness. CONCLUSION: All test groups, regardless of thickness, demonstrated fracture resistance values that exceeded both normal and parafunctional bite forces. The veneers that bonded after hydrofluoric acid etching followed by ceramic primer application showed more favourable fracture patterns.

Influence of thickness and surface conditioning on fracture resistance of occlusal veneer.

BACKGROUND: The purpose of the current study was to assess the impact of restoration thickness, surface conditioning and the interaction between them on the fracture resistance of CAD/CAM fabricated lithium disilicate occlusal veneers. METHODS: A total of 42 maxillary molars were prepared to receive CAD/CAM fabricated lithium disilicate occlusal veneer either with 0.5 mm (n = 21) or 1 mm (n = 21) thickness. Each main group was divided into 3 subgroups (n = 7), according to surface treatment, HF acid (HF-1, HF-0.5), acidulated phosphate fluoride (APF-1, APF-0.5) and Monobond etch & prime (MON-1, MON-0.5). Multilinik N (Ivoclar-Vivadent) adhesive resin cement was used for bonding according to the manufacturer instructions. One hour after bonding, specimens were stored in water bath for 75 days followed by cyclic loading fatigue for 240,000 cycles to simulate clinical situation. Finally, specimens were fractured under compressive load in (N) using a universal testing machine. Two and one-way ANOVA and Post Hoc Tukey test were used for statistical analysis. RESULTS: The means ± SD (N) fracture load for each group were calculated. MON-1 group showed the highest fracture load (1644.7 ± 155.3) followed by HF-1 group (1514.6 ± 212.5). Meanwhile, APF-0.5 showed the lowest fracture load (962 ± 249.6). CONCLUSION: CAD/CAM fabricated lithium disilicate occlusal veneers can be used with a thickness of 0.5 mm instead of conventional crowns. Monobond etch & prime is recommended as a surface treatment for CAD/CAM fabricated lithium disilicate occlusal veneer due to biological hazards of Hydrofluoric acid.

Pancreas transplantation today: quo vadis?

Successful pancreas or islet transplantation is currently the only cure for type 1 diabetes mellitus. Since the first pancreas transplant in 1966, there have been various refinements of surgical technique along with improved immunosuppressive regimens, resulting in significantly improved outcomes, with contemporary research into graft monitoring and newer biomarkers, potentially lengthening graft survival rates further. Patients with insulin-dependent diabetes mellitus who are eligible for pancreas or islet transplantation represent a select group, the tip of the iceberg for a significant global diabetes disease burden. In the last 50 years, there have been quantum advances in alternative technologies in diabetes therapy, both experimental and translational. Further development and improved access are required to treat the larger proportion of people suffering from diabetes. Emerging stem cell therapy is still experimental whereas alternatives including automated insulin delivery systems and islet cell transplantation are already used in some countries. Whilst automated insulin delivery systems have increased in efficacy, they still do not achieve the near physiological control of blood sugar, which can be achieved by successful pancreas or islet transplantation. This state-of-the-art review provides a summary of pancreas and islet transplantation to its current place in diabetes therapy, along with alternative and future therapies, including the obstacles associated with the dissemination of these new therapies. With the advent of these modern cellular and technological advances, this review addresses the question: are we entering an era where whole organ pancreas transplantation could be replaced entirely by modern technological advances in diabetes therapy?

Expanding the structure-activity relationships of alkynyl diphenylurea scaffold as promising antibacterial agents.

With the continuous and alarming threat of exhausting the current antimicrobial arsenals, efforts are urgently needed to develop new effective ones. In this study, the antibacterial efficacy of a set of structurally related acetylenic-diphenylurea derivatives carrying the aminoguanidine moiety was tested against a panel of multidrug-resistant Gram-positive clinical isolates. Compound 18 was identified with a superior bacteriological profile than the lead compound I. Compound 18 demonstrated an excellent antibacterial profile in vitro: low MIC values, extended post-antibiotic effect, refractory ability to resistance development upon extended repeated exposure, and high tolerability towards mammalian cells. Finally, when assessed in a MRSA skin infection animal model, compound 18 showed considerable healing and less inflammation, decrease in the bacterial loads in skin lesions, and it surpassed fusidic acid in controlling the systemic dissemination of S. aureus. Collectively, compound 18 represents a promising lead anti-MRSA agent that merits further investigation for the development of new anti-staphylococcal therapeutics.

Multidrug-Resistant Acinetobacter baumannii Infections in the United Kingdom versus Egypt: Trends and Potential Natural Products Solutions.

Acinetobacter baumannii is a problematic pathogen of global concern. It causes multiple types of infection, especially among immunocompromised individuals in intensive care units. One of the most serious concerns related to this pathogen is its ability to become resistant to almost all the available antibiotics used in clinical practice. Moreover, it has a great tendency to spread this resistance at a very high rate, crossing borders and affecting healthcare settings across multiple economic levels. In this review, we trace back the reported incidences in the PubMed and the Web of Science databases of A. baumannii infections in both the United Kingdom and Egypt as two representative examples for countries of two different economic levels: high and low-middle income countries. Additionally, we compare the efforts made by researchers from both countries to find solutions to the lack of available treatments by looking into natural products reservoirs. A total of 113 studies reporting infection incidence were included, with most of them being conducted in Egypt, especially the recent ones. On the one hand, this pathogen was detected in the UK many years before it was reported in Egypt; on the other hand, the contribution of Egyptian researchers to identifying a solution using natural products is more notable than that of researchers in the UK. Tracing the prevalence of A. baumannii infections over the years showed that the infections are on the rise, especially in Egypt vs. the UK. Further concerns are linked to the spread of antibiotic resistance among the isolates collected from Egypt reaching very alarming levels. Studies conducted in the UK showed earlier inclusion of high-throughput technologies in the tracking and detection of A. baumannii and its resistance than those conducted in Egypt. Possible explanations for these variations are analyzed and discussed.

Endoscopic third ventriculostomy for management of hydrocephalus associated with Chiari malformation type II in children.

BACKGROUND: Hydrocephalus is commonly associated with Chiari malformation (CM) particularly CM type II. The traditional treatment of hydrocephalus in these patients has been cerebrospinal fluid diversion by shunts. Endoscopic third ventriculostomy (ETV) has emerged as an alternative procedure in these patients. PURPOSE: Assessment of the clinical and radiological outcomes of ETV in the management of hydrocephalus in children with CM II. METHODS: This is a prospective study conducted on 18 patients with CM II associated with hydrocephalus admitted to Cairo University hospitals between January 2020 and June 2021. These patients had been managed surgically by ETV. Clinical outcome was assessed based on improvement of manifestations of increased intracranial pressure while radiological outcome was based on the findings of postoperative computed tomography. In cases with early failure, serial lumbar puncture (LP) was performed for 2 days. RESULTS: ETV was performed as a secondary procedure in 4 cases. The overall success rate of the procedure was 72%, and its success rate as a secondary procedure was 100%. Serial LP was effective in decreasing early failure in 44.4% of cases. Radiological regression of hydrocephalic changes was detected in 50% of the cases. CONCLUSION: ETV is an efficient and safe procedure in the treatment of hydrocephalus in children with Chiari malformation II, particularly when performed as a secondary procedure. Serial LP following the procedure increases the success rate in patients with early failure.

Key Anthropometric Variables Associated With Front-Crawl Swimming Performance in Youth Swimmers: An Allometric Approach.

ABSTRACT: Sammoud, S, Negra, Y, Chaabene, H, Bouguezzi, R, Attia, A, Granacher, U, Younes, H, and Nevill, AM. Key anthropometric variables associated with front-crawl swimming performance in youth swimmers: an allometric approach. J Strength Cond Res 37(6): 1259-1263, 2023-This study aimed to establish key anthropometric characteristics (e.g., optimal body height, limb-segment length, and girth/breadth ratios) related to 100-m front-crawl performance in young swimmers. In total, 74 swimmers (boys [ n = 41; age: 18.1 ± 3.5 years]; girls [ n = 33; age: 15.9 ± 3.1 years]) participated in this study. We adopted a multiplicative allometric log-linear regression model to identify key anthropometric characteristics associated with 100-m front-crawl swimming performance. The main outcomes indicated that length ratio = ([height/leg length]), foot length and ankle girth, biacromial breadth, and % of body fat were associated with 100-m front-crawl mean swimming speed performance. These findings highlight the importance of assessing anthropometric characteristics in young front-crawl swimmers for talent identification and development.