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Nucleic acid delivery requires vectorization for protection from nucleases, preventing clearance by the reticuloendothelial system, and targeting to allow cellular uptake. Nanovectors meeting the above specifications should be safe for the patient, simple to manufacture, and display long-term stability. Our nanovectors were obtained via the green process of polyelectrolyte complexation, carried out at 25 °C in water at a low shear rate using chitosan (a polycationic biocompatible polysaccharide of specific molar mass and acetylation degree) and dextran sulfate as a polyanionic biocompatible polysaccharide. These complexes formed nanoassemblies of primary nanoparticles (20–35 nm) and maintained their colloidal stability for over 1 year at 25 °C. They could be steam sterilized, and a model nucleic acid could be either encapsulated or surface adsorbed. A targeting agent was finally bound to their surface. This work serves as a proof of concept of the suitability of chitosan-based polyelectrolyte complexes as nanovectors by sequential multilayered adsorption of various biomacromolecules.

The uricase enzyme yields allantoin, hydrogen peroxide, and carbon dioxide by catalyzing the oxidative opening of the purine ring in the urate pathway. This enzyme is important for biochemical diagnosis and reduces toxic urate accumulation during various diseases (hyperuricemia, gout, and bedwetting). Direct urate oxidase injection is recommended in renal complications-associated gout and to prevent chemotherapy-linked hyperuricemia disorders. Thus, uricase is a promising enzyme with diverse applications in medicine. Microbial production of uricase is featured by high growth rates, cost-effective bioprocessing, and easy optimization of the medium. Microbes produce the enzyme extracellular or intracellular. Extracellular uricase is preferred for biotechnological applications as it minimizes time, effort, and purification processes. This review provides insights into uricase-producing microbes, bacterial uric acid degradation pathways, degrading enzymes, and uricase-encoding genes.

Pet reptiles are gaining popularity among Saudi citizens but owners lack public health-associated awareness. Generally, the pet shops do not properly guide about reptile handling and health precautions. This study features molecular characterization of Salmonellaisolates from pet reptiles to detect potential human pathogenic serovars. Previously identified five Salmonellasp. isolates from pet reptiles in private households were subjected to PCR amplification of 16S rRNA gene followed by Sanger sequencing and phylogenetic analysis. Sequencing confirmed all five isolates as Salmonella entericasubsp. entericaserovar Typhimurium. Different strains shared a common ancestor but were divided into different clades in various host species (snakes and lizards). All reptiles could be a potential source of zoonotic Salmonellaspp. and multidrug resistance (MDR) of Salmonellacan further worsen the situation. The feed, confined shared living spaces of multiple animals, environmental conditions, and pets’ interaction with wild animals could enhance the probability of Salmonellaspp. occurrence in pet reptiles. This study necessitates the pet owners’ awareness regarding Salmonellaspp. transmission routes and associated human health repercussions while keeping pet reptiles.

Pathogenic microorganisms and cancer continue to be the most difficult problem in public health care and the incidence of diseases caused by such resistant strains and cancer cells are growing. Recent advances in nanotechnology open up new possibilities for creating novel, exciting nanoparticles that are safe for human cells and may be used as smart antibacterial and anticancer medicines. The novelty of the present study is the extracellular green synthesis of zinc oxide nanoparticles (ZnO NPs), and gold (Au) NPs using the cell filtrate of the endophytic fungus Fusarium chlamydosporumMW341592.1 isolated from healthy leaves of Eucalyptus sideroxylonplant. Eco-friendly synthesized ZnO NPs and Au NPs were screening for their activity against select carcinomic cell lines and some multidrug-resistant bacteria. The synthesized ZnO NPs and Au NPs were characterized by UV-Vis. spectroscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), transition electron microscopy (TEM), and energy-dispersive X-ray spectroscopy (EDX). The UV-Vis. absorption spectra of the produced ZnO NPs showed bands in the UV area at 320 nm, whereas the Au NPs showed bands in the UV region at 530 nm. TEM revealed average sizes for ZnO NPs, and Au NPs as 19.3 nm and 22.1 nm, respectively, while shape revealed both ZnO NPs and Au NPs with spherical-like shape. Biological assay showed that raising in the synthesized NP concentration lowers the number of HCT-116 human colon cancer cells and CACO2 human intestinal cancer cells, as well as associated pathogens such as Escherichia coliand Pseudomonas aeruginosa.

The objective of this study is to assess the chemical composition, nutritional values, and bioactivities of four macroalgae from the Egyptian Red Sea coasts using standard methods. Of these, three Rhodophyceae species, Digenea simplex(D. simplex), Laurencia papillosa(L. papillosa), and Galaxaura oblongata(G. oblongata), and one Phyaeophyceae species, Turbinaria decurrens(T. decurrens), were selected. The results of proximate and chemical composition analyses based on the algal dry weight (DW) showed that carbohydrate content was the highest, ranging from 32.47 ± 1.03% to 45.5 ± 1.23%. Other algal constituents, including ash, protein, moisture, sulfate, lipid, phenolics, and flavonoids, have contents that depend on the algal species. Besides, HPLC analysis revealed that each algal extract contained varying amounts of nine phenolic acids. Atomic absorption spectrometry, the HPLC-Pico-Tag method, the ion chromatography technique, and GC/MS analyses were used to determine the chemical profiles of the elemental, amino acid, halide, and fatty acid of each algal extract. Bioactivities revealed that both the •DPPH and ABTS assays showed that all the algae studied had a significant ability to scavenge free radicals in a dosage-dependent way. They also had strong selective cytotoxic activity against HEPG-2 and HCT-116 cell lines, but only weak activity against MCF-7 and A549 cell lines. Finally, our findings suggested that the selected algae might be efficiently used as nutraceuticals and functional foods, indicating an increase in their proliferation.

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ObjectivesWe studied neonates with suspected early-onset sepsis (EOS, sepsis developing in the first 72 hours after delivery) in Malawi to (1) describe clinical characteristics and microbiological findings, (2) identify which patient characteristics may be associated with pathogen positivity on blood culture, and (3) describe mortality and its potential determinants.DesignProspective observational study (May 2018–June 2019).SettingNeonatal ward in Queen Elizabeth Central Hospital, the largest government hospital in Malawi.PatientsAll neonates with suspected EOS in whom a blood culture was obtained.ResultsOut of 4308 neonatal admissions, 1244 (28.9%) had suspected EOS. We included 1149 neonates, of which 109 blood cultures had significant growth (9.5%). The most commonly isolated pathogens were Staphylococcus aureus, Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coliand Acinetobacter baumanii. Many of the Gram negatives were extended-spectrum beta lactamase-producing Enterobacteriaceae, and these were 40–100% resistant to first-line and second-line antimicrobials. Gestational age (GA) of <32 weeks was associated with pathogen-positive blood cultures (<28 weeks: adjusted OR (AOR) 2.72, 95% CI 1.04 to 7.13; 28–32 weeks: AOR 2.26, 95% CI 1.21 to 4.21; p=0.005). Mortality was 17.6% (202/1149) and associated with low birth weight (<1000 g: AOR 47.57, 95% CI 12.59 to 179.81; 1000–1500 g: AOR 11.31, 95% CI 6.97 to 18.36; 1500–2500 g: AOR 2.20, 95% CI 1.42 to 3.39; p<0.001), low Apgar scores at 5 min (0–3: AOR 18.60, 95% CI 8.81 to 39.27; 4–6: AOR 4.41, 95% CI 2.81 to 6.93; p<0.001), positive maternal venereal disease research laboratory status (AOR 2.53, 95% CI 1.25 to 5.12; p=0.001) and congenital anomalies (AOR 7.37, 95% CI 3.61 to 15.05; p<0.001). Prolonged rupture of membranes was inversely associated with mortality (AOR 0.43, 95% CI 0.19 to 0.98; p 0.007).ConclusionIn Malawi, EOS was suspected in nearly a third of neonatal admissions and had a high mortality. Ten per cent were culture-confirmed and predicted by low GA. To reduce the impact of suspected neonatal sepsis in least developed countries, improved maternal and antenatal care and development of rapid point of care methods to more accurately guide antimicrobial use could simultaneously improve outcome and reduce antimicrobial resistance.

ObjectivesThis study investigated occupational risk factors and exposure–response relationships for airway disease among health workers (HWs) exposed to cleaning agents in two tertiary hospitals in South Africa and Tanzania.MethodsIn this cross-sectional study, 697 participants completed questionnaire interviews while 654 underwent fractional exhaled nitric oxide (FeNO) testing. Asthma Symptom Score (ASS) was computed based on the sum of answers to five questions on asthma-related symptoms in the past 12 months. For exposure–response analyses, cleaning agent-related self-reported exposure variables were categorised into three levels (cleaning product not used; use of a cleaning product for up to 99 min per week and use of a cleaning product for ≥100 min per week).ResultsAsthma-related outcomes (ASS and FeNO) demonstrated positive associations with medical instrument cleaning agents (orthophthalaldehyde and enzymatic cleaners) and tasks (instruments precleaning and changing sterilisation solutions) as well as patient care activities (disinfection prior to procedures and disinfecting wounds). A particularly pronounced dose–response relationship was observed between work-related ocular-nasal symptoms and medical instrument cleaning agents (orthophthalaldehyde, glutaraldehyde, enzymatic cleaners, alcohols and bleach) (OR range: 2.37–4.56) and tasks (OR range: 2.92–4.44). A strong association was also observed between ASS and use of sprays for fixed surface cleaning (mean ratio 2.81; 95% CI 1.41 to 5.59).ConclusionsSpecific agents for medical instrument disinfection for example, orthophthalaldehyde and enzymatic cleaners, patient care activities and use of sprays are important occupational risk factors for airway disease among HWs.

Fungal infections (mycoses) represent a major health issue in humans. They have emerged as a global concern for medical professionals by causing high morbidity and mortality. Fungal infections approximately impact one billion individuals per annum and account for 1.6 million deaths. The diagnosis of Candidainfections is a challenging task. Laboratory-based Candidaspecies identification techniques (molecular, commercial, and conventional) have been reviewed and summarized. This review aims to discuss the mycoses history, taxonomy, pathogenicity, and virulence characteristics.

Milk is a putrescible commodity that is extremely prone to microbial contamination. Primarily, milk and dairy products are believed to be easily contaminated by pathogenic microorganisms, including Listeria monocytogenes, Salmonellaspp., and Staphylococcus aureus. The microbiological quality of raw milk and dairy products regarding foodborne pathogens is of paramount importance due to concern of human health. In this study 400 buffalo raw milk samples were screened for assessing the prevalence of L. monocytogenes, Salmonellaspp., and S. aureus. This study implemented uniplex-polymerase chain reaction (u-PCR) and multiplex-polymerase chain reaction (m-PCR) assays for the fast simultaneous detection of these pathogens comparing to the conventional culturing methods. Raw milk samples were found contaminated with the prevalence of 2.2%, 4.0%, and 14.2% for L. monocytogenes, Salmonellaspp., and S. aureus, respectively. These pathogens were detected with the optimized polymerase chain reaction assays after 6 h of enrichment. u-PCR and m-PCR demonstrated the limit of detection as 104, 102, and 10 cells/mL after 6, 12, 18, and 24 h for each culture of the pathogens. A high sensitivity (10 colony-forming unit [CFU]/mL) of the m-PCR protocol was noted. The developed protocol is a cost-effective and rapid method for the simultaneous detection of pathogens associated with raw milk and dairy industries.

This research examines the impact of using hybrid nano-sustainable materials such as nano-silica and nano-slag, at three designated contents (2, 4, and 6%) by the cement weight. Mechanical and physical characteristics were studied at 7 and 28 ages. Overall, the experimental results showed the positive impacts of used hybrid nano-sustainable additives on fresh and hardened properties of modified cement mortar. The compressive strength of mortar containing nano-slag with 2, 4, and 6% enhanced as 11, 33, and 32% at 28 days, respectively, and correspondingly, direct tensile strength enhanced as 16, 39, and 30% at 28 days, respectively. Furthermore, the compressive strength of cement mortar containing 2, 4, and 6% of nano-silica improved by 20, 44, and 59% at 28 days, respectively. Besides direct tensile strength improved by 19, 37, and 46% at 28 days, respectively, as compared with reference cement mortar. The 4% nano-slag and the 6% nano-silica showed the optimum results of improvements of the compressive strength and direct tensile strength as 33 and 39% and 59 and 46% at 28 days, respectively. Hence, the optimization results of selected cement mortar comprising hybrid nano-sustainable materials as 6 wt% nano-silica and 4 wt% nano-slag produce a greater enhancement of mortar strength. Compressive and direct tensile strength improved by 73 and 53% at 28 days, respectively.

Unsteady study of the natural convection of aluminum oxide-water nanofluid within a trapezoidal geometry containing a circular cylinder located at its center. Finite Element method has been considered for the numerical analysis. The proposed investigation handled the impact of Rayleigh number (103–105), chemical reaction parameter (0–4), aluminum oxide nanoparticles volume fraction (0–0.06), magnetic field (0–63) and its inclination angle (0°–90°), and circular obstacle diameter (0.3–0.7) effects on time-dependent natural convection of Al2O3–H2O nanofluid. On the other hand, the value of Prandtl number has kept constant at (Pr = 6.2). Since the nanofluid mobility at φ= 0.02, Ha = 3, and Fk= 1 significantly improved, the heat transfer rate achieved its maximum intensity at Ra = 105. Research also reveals a little effect on heat transfer by increasing the fraction of nanoparticles. Additionally, as Ha intensifies from 0 to 63, a final change in the mean Nusselt number of 28.65 % is displayed. Finally, as the magnetic field angle of rotation is diminished, more enhancement in heat transmission is achieved. This research provides insights into the intricate relationship between natural convection and exothermic reaction under the influences of various conditions. This can illustrate the flow and thermal behaviors of nanofluid in such non-uniform shapes in many engineering applications.

To explore the prevalence of multidrug-resistant community-associated uropathogenic Escherichia coli(UPEC) and their virulence factors in Western Saudi Arabia. A total of 1,000 urine samples were examined for the presence of E. coliby selective plating on MacConkey, CLED, and sheep blood agar. Antimicrobial susceptibility patterns were determined using Vitek®2 Compact (MIC) and the disc diffusion method with Mueller-Hinton agar. Genes encoding virulence factors (kpsMTII, traT, sat, csgA, vat, and iutA) were detected by PCR. The overall prevalence of UTI-associated E. coliwas low, and a higher prevalence was detected in samples of female origin. Many of the isolates exhibited resistance to norfloxacin, and 60% of the isolates showed resistance to ampicillin. No resistance to imipenem, meropenem, or ertapenem was detected. In general, half of the isolates showed multiple resistance patterns. UPEC exhibited a weak ability to form biofilms, where no correlation was observed between multidrug resistance and biofilm-forming ability. All uropathogenic E. coliisolates carried the kpsMTII, iutA, traT, and csgAgenes, whereas the low number of the isolates harbored the satand vatgenes. The diversity of virulence factors harbored by community-associated UPEC may render them more virulent and further explain the recurrence/relapse cases among community-associated UITs. To the best of our knowledge, this study constitutes the first exploration of virulence, biofilm-forming ability, and its association with multidrug resistance among UPEC isolates in Saudi Arabia. Further investigations are needed to elucidate the epidemiology of community-associated UPEC in Saudi Arabia.

ABSTRACTObjectivesIrritable bowel syndrome (IBS) is the most frequently diagnosed functional gastrointestinal disorder, with a prevalence of up to 25% of the global population. IBS patients suffer from abnormal abdominal pain, or visceral hypersensitivity (VHS), associated with altered bowel habits in the absence of an organic detectable cause. The pathophysiology of the disease is incompletely understood, but the dysregulation of the brain-gut axis is well established in IBS.MethodsIBS onset is mainly triggered by infectious gastroenteritis, psychological factors, and dietary factors, but genetic predispositions and intestinal dysbiosis might also play a role. Additionally, immune activation, and particularly chronic mast cell activation, have been shown to underlie the development of abdominal pain in IBS.ResultsBy releasing increased levels of mediators, including histamine, mast cells sensitize enteric nociceptors and lead to VHS development. The mechanisms underlying aberrant mast cell activation in IBS are still under investigation, but we recently showed that a local break in oral tolerance to food antigens led to IgE-mediated mast cell activation and food-induced abdominal pain in preclinical models and in IBS patients.ConclusionThe concept of food-mediated VHS highlights the potential of therapies targeting upstream mechanisms of mast cell sensitization to treat IBS.

Fuel tank footings are usually subjected to cyclic loads caused by filling and emptying of these tanks. In addition, in a multitude of geotechnical applications, soils are subjected to cyclic loading. Besides vehicle and traffic loads, cyclic loads also play an important role in pile driving processes and during the dimensioning of foundations for offshore wind craft plants. Research on the cyclic vertical loading problem for sand is particularly scarce, and most has been in commercial confidence. This paper is conducted to study the experimental behavior of dry sandy soil under foundations subjected to vertical cyclic compression load. A total of sixty-three models have been tested to study the behavior of shallow footings under cyclic load of different rates. A new compression machine was manufactured to apply both monotonic and cyclic loading. Three relative densities of sand, two footing shapes, three depths of foundation embedment, and three rates of loading were tried. It was concluded that with more depth of the footing (Dfincreasing), the soil settlement decreases. In general, when other factors are remaining constant, the bearing capacity of the soil goes on increasing when the depth or width of the foundation increases. The total settlement of a footing continues to increase during the time of the load and reaches a maximum value at the end of dwell time. During the decay period of the load, the footing rebounds to some degree.

A genetic algorithm program, combined with the finite difference method (GA-FDM), was developed to obtain the optimum location of the cut-off wall under the hydraulic structures to solve the seepage issues. For the optimization formulation model, the objective function was considered to minimize the total cost of the hydraulic structure construction. The major nonlinear constraints were formulated to meet uplift pressure and exit gradient safety considerations. In two phases, the GA-FDM model provided here satisfies the criteria of an optimal hydraulic design. Initially, a numerical model that has been validated and coded using the finite difference method (FDM), was employed to investigate the seepage issue. This was followed by the use of the genetic algorithm optimization model coded by the MATLAB programming with a finite difference program as a sub-routine to find the optimum position and depth for the cut-off wall. The numerical and optimization models were linked using MATLAB code, resulting in a Simulation–Optimization (S–O) approach. According to the findings, the suggested GA-FDM approach would offer an efficient, safe and cost-effective cut-off wall design. When the proposed S–O approach is applied to determine the optimum locations and depths of the upstream and downstream cut-off walls with respect to minimizing the construction cost, the cost of the safe dam floor is reduced by 60–77%. Finally, the optimum location ratio is approximately 0.22 and 0.94 from the hydraulic structure’s floor’s toe for the upstream and downstream cut-offs, respectively.

Lipid accumulating fungi are promising tools as alternative lipid source with different applications. In this study, seven oleaginous fungal strains were isolated from dung samples from the Egyptian ecosystem which later investigated for lipid accumulation, and Mucor racemosusAH1 represented the highest one. Statistical optimization of M. racemosusAH1 for lipid production was carried out using Taguchi design. Accordingly, dry biomass, total lipids, and lipid content were 3.72 gL−1, 1.21 gL−1, and 32.4%, respectively. Fatty acid profile of the produced lipids at different temperatures from 5 to 35 °C was investigated using gas chromatography mass spectroscopy GC–MS. Results revealed that the best temperature range for unsaturated fatty acids production particularly polyunsaturated fatty acids (PUFAs) was between 10 and 20 °C in which unsaturated fatty acids (USFAs) were higher than saturated fatty acids (SFAs); 54.47% and 43.67%, respectively. In conclusion, a promising lipid accumulating and cold-adapted M. racemosusMG547571 are considered as hopeful source of USFAs particularly oleic and linoleic acids which can be recruited for pharmaceutical applications, additionally, the high lipid yield could be exploited for biodiesel production.

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Locally advanced and borderline resectable pancreatic cancers are being increasingly recognized as a result of significant improvements in imaging modalities. The main tools used in diagnosis of these tumors include endoscopic ultrasound, computed tomography, magnetic resonance imaging, and diagnostic laparoscopy. The definition of what constitutes a locally advanced or borderline resectable tumor is still controversial to this day. Borderline resectable tumors have been treated with neoadjuvant therapy approaches that aim at reducing tumor size, thus improving the chances of an R0 resection. Both chemotherapy and radiotherapy (solo or in combination) have been used in this setting. The main chemotherapy agents that have shown to increase resectability and survival are FOLFORINOX (a combination of folinic acid, fluorouracil, irinotecan, and oxaliplatin) and gemcitabine–nab-paclitaxel. Surgery on these tumors remains a significantly challenging task for pancreatic surgeons. More studies are needed to determine the best agents to be used in the neoadjuvant and adjuvant settings, biologic markers for prognostic and operative predictions, and validation of previously published retrospective results.

ABSTRACTObjective: Mixed-Martial-Arts (MMA) has witnessed a rapid growth over the recent years. This study aims to explore the patterns and trends of head injuries in MMA.Design: Descriptive epidemiological study.Setting: Ringside physician reports of the Ultimate Fighting Championship (UFC) fights between 2016 and 2019 (inclusive) were screened. Data were extracted from the Nevada State Athletic Commission (NSAC) database. Play-by-play video analysis was also conducted.Participants: UFC fighters involved in fights sanctioned by the NSAC, between 2016 and the end of 2019 (N = 816).Independent variables: Sex, location of head injury, type of head injury, injury mechanism, number of significant head strikes, type of finish, and weight division.Main outcome measures: Head injury rates were calculated. A one-way analysis of variance (ANOVA) was used to explore any statistically significant differences between injury rates of different locations, types, and types of finishes. An independent t-test was used to determine whether any significant differences existed between the two sexes, and a Joinpoint regression analysis was used to determine the statistical significance of the trends of head injury rates across different weight divisions. P-values <0.05 were considered significant (95% CI).Results: A total of 288 head injuries in 408 fights were recorded during our study period. Head injury rate constituted 35 injuries per 100 athletic-exposures (AE) in sanctioned fights. Traumatic brain injuries (TBI) were the most common type of injury, with a rate of 16 per 100AE, significantly greater than that of fractures (p = 0.003). Males had a head injury rate of 37 per 100AE, higher than that of females which was 23 per 100AE. Technical Knockout (TKO)/ Knockout(KO) was the type of finish with the highest rate of head injuries, significantly greater than that of decision or submission (p < 0.001). In general, head injury rates were higher as weight divisions increased.Conclusion: Head injuries are prevalent in MMA. Preventive measures need to be implemented to ensure fighter safety and limit injury risk.

Exposure to disinfectants and cleaning products (DCPs) is now a well-established risk factor for work-related asthma (WRA). However, questions remain on the specific causal agents and pathophysiological mechanisms. Few studies have also reported an association between DCPs and rhinitis or chronic obstructive pulmonary disease. This review discusses the recent evidence pertaining to airway diseases attributable to occupational exposure to DCPs. In contrast to other agents, the incidence of WRA due to DCPs has increased over time. The use of DCPs in spray form has clearly been identified as an added risk factor. The mechanisms for WRA associated with DCPs remain poorly studied; however, both allergic and nonallergic responses have been described, with irritant mechanisms thought to play a major role. An early diagnostic workup based on clinical assessment accompanied by evaluation of lung function and immunological and airway inflammatory markers is important to guide optimal care and exposure avoidance to the implicated agent. Future research should focus on the effects of “green” products, pathophysiological mechanisms, and quantitative exposure assessment including the use of barcode-based methods to identify specific agents. There is an urgent need to strengthen preventive measures and interventions to reduce the burden of airway diseases associated with DCPs.