Unravelling the Antimicrobial, Antibiofilm, Suppressing Fibronectin Binding Protein A (fnba) and cna Virulence Genes, Anti-Inflammatory and Antioxidant Potential of Biosynthesized Solanum lycopersicum Silver Nanoparticles.

Background and Objectives: Urinary tract infections [UTIs] are considered the third most known risk of infection in human health around the world. There is increasing appreciation for the pathogenicity of Gram-positive and Gram-negative strains in UTIs, aside from fungal infection, as they have numerous virulence factors. Materials and Methods: In this study, fifty urine samples were collected from patients suffering from UTI. Among the isolates of UTI microbes, six isolates were described as MDR isolates after an antibiotic susceptibility test carried out using ten different antibiotics. An alternative treatment for microbial elimination involved the use of biosynthesized silver nanoparticles (AgNPs) derived from Solanum lycopersicum [S. cumin]. Results: The sizes and shapes of AgNPs were characterized through TEM imaging, which showed spherical particles in a size range of 35-80 nm, of which the average size was 53 nm. Additionally, the silver nanoparticles (AgNPs) demonstrated inhibitory activity against Staphylococcus aureus (OR648079), exhibiting a 31 mm zone of inhibition at a minimum inhibitory concentration (MIC) of 4 mg/mL and a minimum bactericidal concentration (MBC) of 8 mg/mL. This was followed by Aspergillus niger (OR648075), which showed a 30 mm inhibition zone at an MIC of 16 mg/mL and a minimum fungicidal concentration (MFC) of 32 mg/mL. Then, Enterococcus faecalis (OR648078), Klebsiella pneumoniae (OR648081), and Acinetobacter baumannii (OR648080) each displayed a 29 mm zone of inhibition at an MIC of 8 mg/mL and an MBC of 16 mg/mL. The least inhibition was observed against Candida auris (OR648076), with a 25 mm inhibition zone at an MIC of 16 mg/mL and an MFC of 32 mg/mL. Furthermore, AgNPs at different concentrations removed DPPH and H2O2 at an IC50 value of 13.54 µg/mL. Also, AgNPs at 3 mg/mL showed remarkable DNA fragmentation in all bacterial strains except Enterococcus faecalis. The phytochemical analysis showed the presence of different active organic components in the plant extract, which concluded that rutin was 88.3 mg/g, garlic acid was 70.4 mg/g, and tannic acid was 23.7 mg/g. Finally, AgNPs concentrations in the range of 3-6 mg/mL showed decreased expression of two of the fundamental genes necessary for biofilm formation within Staphylococcus aureus, fnbA (6 folds), and Cna (12.5 folds) when compared with the RecA gene, which decreased by one-fold when compared with the control sample. These two genes were submitted with NCBI accession numbers [OR682119] and [OR682118], respectively. Conclusions: The findings from this study indicate that biosynthesized AgNPs from Solanum lycopersicum exhibit promising antimicrobial and antioxidant properties against UTI pathogens, including strains resistant to multiple antibiotics. This suggests their potential as an effective alternative treatment for UTIs. Further research is warranted to fully understand the mechanisms of action and to explore the therapeutic applications of these nanoparticles in combating UTIs.

Efficacy of silver nanoparticles against Trichinella spiralis in mice and the role of multivitamin in alleviating its toxicity.

Trichinellosis is a worldwide zoonotic disease. The majority of currently available anti-trichinellosis medications exhibit inadequate efficacy. The efficacy of a natively prepared new formulation of silver nanoparticles (Ag-NPs) was evaluated in the treatment of Trichinella spiralis (T. spiralis) infection in mice alone and combined with multivitamin-mineral (MM). After investigating the product's biological and pharmacological characteristics, its therapeutic dose was estimated to be Ag-NPs at 21.5 mg/kg B.W. This dose was orally inoculated to experimentally infected mice at 3-5 days post-inoculation (dpi) against the mature worms, at 8-10 dpi against the newborn larvae, and at 33-35th dpi against the encapsulated larvae. Each treatment's efficacy was assessed by scarifying control and treated mice 3 days post-treatment. The drug alone or in supplement form has a high trichinocidal effect exceeding that of the reference drug. Early treatment (3-5 dpi) by Ag-NPs or Ag-NPs + MM and albendazole revealed high efficacy against the intestinal stage, reaching 93.3%, 94.7%, and 90.6% for the three treatments, respectively. The materials causing a significant (P-value < 0.001) decrease in the mean encapsulated larvae reached 86.61%, 89.07%, and 88.84%/gm of muscles using the three treatments, respectively. Moreover, all larvae extracted from Ag-NPs-treated groups failed to induce infection post-inoculation in new mice. Additionally, combining the material with MM proved to overcome the reversible adverse effects of silver material on the estimated redox parameters and liver and kidney biomarkers, denoting its ability to alleviate Ag-NP toxicity. In conclusion, the high trichinocidal effect of Ag-NPs against the adult and encapsulated larvae during a short inoculation period introduced Ag-NPs as an alternative to other nematicidal drugs.

Maternal supplementation of curcumin-olive oil nanocomposite improves uteroplacental blood flow, placental growth and antioxidant capacity in goats.

This experiment was designed to investigate the impact of curcumin-olive oil nanocomposite (CONC) supplementation on uteroplacental hemodynamics and ultrasonographic measurements as well as maternal oxidative status in midgestating goats. Twelve synchronized pregnant goats (85.58 ± 1.08 days of gestation; mean ± SD) were uniformly assigned to two groups (n = 6/group); the first group received daily oral supplementation of CONC (3 mg/kg body weight; nanocurcumin [NC] group) for 32 days, and the second group was offered physiological saline (control) following the NC group timeline. The goats of both groups were examined at 3-day intervals for middle uterine (MUA) and umbilical (UMA) arteries hemodynamics (pulsatility index [PI], resistive index [RI], systole/diastole [S/D] and blood flow rate [BFR]) and diameters, uteroplacental thickness (UPT), placentomes' diameter (PD) and echogenicity, steroid hormones (progesterone and estradiol 17ß), oxidative biomarkers (total antioxidant capacity [TAC], catalase [CAT], malondialdehyde [MDA]), nitric oxide (NO) and blood cells DNA integrity. The UPT (p = 0.012) and PD (p = 0.021) values were higher in the NC group than in their counterparts' control group (D11-32). There were increases in diameter (p = 0.021 and p = 0.012) and decreases (p = 0.021, p = 0.016 and p = 0.041 [MUA]; p = 0.015, p = 0.023 and p = 0.011 [UMA] respectively) in Doppler indices (PI, RI and S/D) of the MUA and UMA in the NC group compared to the control group (D14-32). On D20-32 (MUA) and D14-32 (UMA), the NC goats had higher BFR than the control group (p = 0.021, 0.018 respectively). The means of blood cells with fragmented DNA were lower (p = 0.022) in the NC group than in the control group on Days 8 and 21 postsupplementation. There were increases in CAT and NO (D20-32; p = 0.022 and p = 0.004 respectively), and TAC (D17-32; p = 0.007) levels in the NC goats compared to the control ones. The NC group had lower (p = 0.029) concentrations of MDA than the control group on Day 20 postsupplementation onward. In conclusion, oral supplementation of CONC improved uteroplacental blood flow and the antioxidant capacity of midgestating goats.

Pancreatic cyst features predict future development of pancreatic cancer: results of a nested case-control study.

BACKGROUND AND AIMS: Risk factors for pancreatic cancer among patients with pancreatic cysts are incompletely characterized. The primary aim of this study was to evaluate risk factors for development of pancreatic cancer among patients with pancreatic cysts. METHODS: We conducted a retrospective case-control study of U.S. veterans with a suspected diagnosis of branch-duct intraductal papillary mucinous neoplasm from 1999 to 2013. RESULTS: Age (hazard ratio [HR], 1.03 per year; 95% confidence interval [CI], 1.00-1.06), larger cyst size at cyst diagnosis (HR, 1.03 per mm; 95% CI, 1.01-1.04), cyst growth rate (HR, 1.22 per mm/y; 95% CI, 1.14-1.31), and pancreatic duct dilation (5-9.9 mm: HR, 3.78; 95% CI, 1.90-7.51; ≥10 mm: HR, 13.57; 95% CI, 5.49-33.53) were found to be significant predictors for pancreatic cancer on multivariable analysis. CONCLUSIONS: Age, cyst size, cyst growth rate, and high-risk or worrisome features were associated with a higher risk of developing pancreatic cancer. Applying current and developing novel strategies is required to optimize early detection of pancreatic cancer after cyst diagnosis.

FolE gene expression for folic acid productivity from optimized and characterized probiotic Lactobacillus delbrueckii.

BACKGROUND: Lactobacillus delbrueckii was one of the most common milk lactic acid bacterial strains (LAB) which characterized as probiotic with many health influencing properties. RESULTS: Among seven isolates, KH1 isolate was the best producer of folic acid with 100 µg/ml after 48 h of incubation; FolE gene expression after 24 h of incubation was in the highest value in case of KH1 with three folds. Lactose was the best carbon source for this KH1, besides the best next isolates KH80 and KH98. The selected three LAB isolates were identified through 16S rDNA as Lactobacillus delbrueckii. These three isolates have high tolerance against acidic pH 2-3; they give 45, 10, and 22 CFUs at pH 3, besides 9, 6, and 4 CFUs at pH2, respectively. They also have resistance against elevated bile salt range 0.1-0.4%. KH1 recorded 99% scavenging against 97.3% 1000 µg/ml ascorbic acid. Docking study exhibits the binding mode of folic acid which exhibited an energy binding of - 8.65 kcal/mol against DHFR. Folic acid formed four Pi-alkyl, Pi-Pi, and Pi-sigma interactions with Ala9, Ile7, Phe34, and Ile60. Additionally, folic acid interacted with Glu30 and Asn64 by three hydrogen bonds with 1.77, 1.76, and 1.96 Å. CONCLUSION: LAB isolates have probiotic properties, antioxidant activity, and desired organic natural source for folic acid supplementation that improve hemoglobin that indicated by docking study interaction.

Trichinocidal activity of a novel formulation of curcumin-olive oil nanocomposite in vitro.

Curcumin-olive oil nanocomposite (CO-NC), a novel formulation of nano-curcumin, was produced and characterized. By evaluating the death rate and DNA damage inflicted on adult Trichinella spiralis (T. spiralis) worms using the comet test and Scanning electron microscopy (SEM) analysis, the effectiveness of the substance against these worms was assessed in vitro. The mortality effects of CO-NC on the parasite adult worms were increased with the upgrading in the concentration and exposure time from 1 to 24 h using concentrations from 10 to 100 ppm. LC50 was determined to be 10.0 ppm/18 h, 20.0 ppm/9 h, 40.0 ppm/6 h, 80.0 ppm/2 h, and 100.0 ppm/1 h, while LC100 was 40.0 ppm/24 h, 80.0 ppm/12 h, and 100.0 ppm/6 h. The comet assay was utilized to examine DNA damage in control and dead worms exposed to varying doses. A direct correlation (P ≤ 0.05) was found between the increase in CO-NC dose and the degree of DNA damage as indicated by alterations in DNA % in the tail segment, tail length (µm), tail moment (µm), and olive tail moment with the control samples. The sub-epidermal layer was detached, the cuticle was partially sloughed off, and the usual creases, ridges, and annulations were altered in the T. spiralis exposed worms. As a result, the tested new trichinocidal drug formulation of nano-curcumin on an oil base was confirmed to be an efficient, secure, and environmentally friendly alternative. The medication has the potential to severely and irreversibly harm the DNA and ultrastructural morphology of adult worms.

Evaluation of the wound healing effect of neomycin-silver nano-composite gel in rats.

Objectives: Both nano silver and neomycin have wound healing properties. Silver nanoparticles have been used as main compounds for therapeutic drug delivery systems against various ailments. The present study aimed to prepare a neomycin silver nano-composite gel easily, rapidly, and cheaply method to improve wound healing. Methods: Forty-five Wistar rats (150-200 g) divided into nine groups: wound untreated, wound fusidic acid treated, wound neomycin treated, three groups with wound and neomycin silver nano-composite gel at 1:1, 1:2, and 1:3 concentrations, respectively, and three groups wound treated silver nano gel at the previous concentrations, respectively. Percentages of wound healing and histopathological examination of the wound area were assessed in all groups. Results: Atomic force microscopy (AFM) and transmission electron microscopy (TEM) images demonstrated the spherical shape of neomycin silver nano-composite gel without aggregation but homogenous dispersion in a gel matrix. Dynamic light scattering (DLS) showed a 4 nm size of nano silver, which agrees with AFM image data analysis but not with TEM image due to the good coating of the gel matrix to silver nanoparticles. Dynamic light scattering Zeta potential was -21 mV, illustrating the high bioactivity of the neomycin silver nano-composite. The groups receiving neomycin silver nano-composite gel showed a significantly higher and dose dependent wound healing compared to other treatment groups. Conclusion: The present work confirmed the potential wound healing activity of neomycin silver nano-composite gel compared to either alone.

Comparison of cold snare and hot snare polypectomy for the resection of sporadic nonampullary duodenal adenomas.

BACKGROUND AND AIMS: Nonampullary duodenal adenomas can undergo malignant transformation, making endoscopic resection, often by hot snare (HSP) or cold snare polypectomy (CSP), necessary. Although CSP has been shown to be safer for removal of colon polyps, data comparing these techniques for the resection of duodenal adenomas are limited. Our aim was to compare the safety and efficacy of CSP and HSP for the removal of nonampullary duodenal adenomas. METHODS: We performed a retrospective cohort study of patients referred to 2 academic medical centers with a histologically confirmed sporadic, nonampullary duodenal adenoma who underwent endoscopic snare polypectomy between January 1, 2007 and March 1, 2021. Patients with underlying polyposis syndromes were excluded. Outcomes included postprocedural adverse events and polyp recurrence. RESULTS: Of 110 total patients, 69 underwent HSP and 41 underwent CSP. Intraprocedural bleeding was similar between both groups, but 7 patients in the HSP group experienced delayed adverse events versus none in the CSP group (P = .04). Fifty-four patients had complete polyp resection and subsequent surveillance endoscopies. Multivariate analysis showed polyp size to be associated with recurrence (per mm; odds ratio, 1.11; 95% confidence interval, 1.04-1.20; P < .01). Endoscopic resection technique (HSP vs CSP) was not a predictor of recurrence (P = .18). CONCLUSIONS: HSP led to more delayed adverse events compared with CSP, whereas no significant differences on outcomes were noted, suggesting that CSP is equally effective and potentially safer for the removal of duodenal adenomas.

Pancreas Cancer Incidence and Pancreas Cancer-Associated Mortality Are Low in National Cohort of 7211 Pancreas Cyst Patients.

BACKGROUND AND AIMS: Pancreatic cancer incidence and mortality among patients with pancreas cysts are unclear. The aims of this study are to evaluate incidence of pancreatic cancer and cause-specific mortality among patients with pancreatic cysts using a large national cohort over a long follow-up period. METHODS: We conducted a retrospective cohort study of US Veterans diagnosed with a pancreatic cyst 1999-2013, based on International Classification of Diseases, 9th edition (ICD9) coding within national Department of Veterans Affairs (VA) data. Pancreatic cancer incidence was ascertained using VA cancer registry data, ICD-9 codes, and the National Death Index, a national centralized database of death records, including cause-specific mortality. RESULTS: Among 7211 Veterans with pancreatic cysts contributing 31,501 person-years of follow-up (median follow-up 4.4 years), 79 (1.1%) developed pancreatic cancer. A total of 1982 patients (27.5%) died during the study follow-up period. Sixty-three patients (3.2% of deaths; 0.9% of pancreas cyst cohort) died from pancreatic cancer, but the leading causes of death in the cohort were non-pancreatic cancer (n = 498, 25% of deaths) and cardiovascular disease (n = 398, 20% of deaths). CONCLUSIONS: Pancreas cancer incidence and pancreatic cancer-associated mortality are very low in a large national cohort of VA pancreatic cyst patients with long-term follow-up. Most deaths were from non-pancreas cancers and cardiovascular causes, and only a minority (3.2%) were attributable to pancreas cancer. Given death from pancreas cancer is rare, future research should focus on identifying criteria for selecting individuals at high risk for death from pancreatic cancer for pancreatic cyst surveillance.

A 51-Year-Old Woman With Rapidly Progressive Dyspnea.

CASE PRESENTATION: A 51-year-old woman with a history of diabetes mellitus and anemia sought treatment at the emergency room for a 2-month history of dry cough and shortness of breath and a 1-week history of substernal chest tightness. One month before her presentation, she was seen at a separate hospital for dyspnea and was found to be anemic. She underwent chest radiography and CT scanning of the chest that was unrevealing to the cause of dyspnea. She received a blood transfusion, although no cause of the anemia was found. One week before presentation, she started experiencing dyspnea on exertion with associated chest pressure, prompting her to seek treatment at the emergency room. On presentation, she reported no fevers, night sweats, joint pain, paroxysmal nocturnal dyspnea, orthopnea, edema, palpitations, lightheadedness, or syncope. She noted a 10- to 20-pound involuntary weight loss over 5 to 6 months. Of note, she had never undergone esophagogastroduodenoscopy or colonoscopy. Medications included an oral diabetic medication. She had no significant family history. She never smoked and had no history of illicit drug or alcohol use.

Protected code blue: using in situ simulation to develop a protected code blue and modify staff training protocol-experience in a large community teaching hospital during the COVID-19 pandemic.

The surge in clinical demand, shortage in personal protective equipment and high-exposure risk for healthcare workers during the COVID-19 pandemic has challenged hospital common practices and forced a reassessment of care delivery models. Code blue teams are highly specialised units that partake in life-saving situations that can jeopardise the safety of team members. There is a paucity of guidance in regards to proper infection control measures to protect the responders.This study describes a methodical approach to assessing vulnerabilities to transmission of SARS-CoV-2 within existing code blue practices, modalities to limit the number of code blue team responders and modifications to the protocol at a large community teaching hospital. The effort undertaken faced challenges due to the nature of the pandemic and the increased demand on healthcare workers. Quality improvement methods facilitated our protocol design and implementation. To this date, there has been no identified COVID-19 disease in any protected code blue (PCB) team members. We recommend that similar practices be considered and adopted widely and practised periodically.

Ingestion of A Common Plant's Leaves Leads to Acute Respiratory Arrest and Paralysis: A Case Report.

BACKGROUND: Nicotiana glauca is a plant known to cause acute toxicity upon ingestion or dermal exposure due to the nicotinic alkaloid, anabasine. Nicotinic alkaloids cause toxicity by acting as agonists on nicotinic-type acetylcholine receptors (nAChRs). Initial stimulation of these receptors leads to symptoms such as tachycardia, miosis, and tremors. The effects of high doses of nicotinic alkaloids are biphasic, and eventual persistent depolarization of nAChRs at the neuromuscular junction occurs. This causes apnea, paralysis, and cardiovascular collapse. CASE REPORT: In this report, we present a case of respiratory arrest due to nicotinic alkaloid poisoning from the ingestion of Nicotiana glauca. The diagnosis was suspected after the patient's family gave a history of the patient ingesting a plant prior to arrival. They were able to also provide a physical sample of the plant. CONCLUSION: The phone application, "Plant Snap", determined the plant species and helped confirm the diagnosis. This case describes how modern technology and thorough history taking can combine to provide the best possible patient care.

Analgesia-first sedation in critically ill adults: A U.S. pilot, randomized controlled trial.

PURPOSE: To determine the feasibility of conducting a multicenter ICU RCT of AFS compared to either protocol-directed sedation (PDS) or both PDS and daily sedation interruption (DSI) in North America. MATERIALS AND METHODS: This single-center RCT compared AFS [fentanyl (bolus ± infusions) to reach CPOT ≤2; if RASS ≥1, CPOT ≤2 and additional fentanyl failed to reach RASS goal (-2 to 0), low-dose propofol (up to 6 h) was given] with either PDS or both PDS and DSI daily in adults mechanically ventilated (MV) ≥48 h. Relevant feasibility, safety, and clinical outcomes were defined and evaluated. RESULTS: 90 of 160 eligible patients were enrolled [AFS = 27; PDS = 28; PDS + DSI = 31]; rate = 3/month. Time from intubation to randomization was 17.5 ±â€¯11.6 h. Study days fully adherent to the study intervention [AFS = 95%; PDS = 99%; PDS + DSI = 96%] and time spent in the first 48 h after randomization without pain (CPOT ≤2)[AFS = 82%; PDS = 78%; PDS + DSI = 77%] and at goal RASS[AFS = 88%; PDS = 83%; PDS + DSI = 95%] were high and similar. Nurse-perceived [median (IQR)] study workload (10-point VAS) was higher with AFS [4(2-6)] than PDS [1(1-3)] or PDS + DSI [2(1-5)]; p = .002). Unplanned extubation was rare (AFS = 1; PDS = 0; PDS + DSI = 1). Days [median (IQR)] free of MV in the 28d after intubation [AFS 24(23,26); PDS 24(20,26); PDS + DSI 24(21,26)] was not different (p = .62). CONCLUSION: A multicenter RCT evaluating AFS is feasible to conduct in North America.

Intestinal Tuberculosis Masquerading as Crohn's Disease? A Case of Disseminated Tuberculosis after Anti-TNF Therapy for Suspected Crohn's Disease.

Intestinal tuberculosis (ITB) and Crohn's disease (CD) very closely resemble each other in symptomatology, imaging, appearance, and pathology. While ITB is rare in the United States, its prevalence is significantly higher in endemic areas, thus presenting a diagnostic dilemma in immigrant populations from high-risk countries. This patient was diagnosed with CD and treated with anti-TNF agents after indeterminate screening for latent tuberculosis. He was then admitted with septic shock and intestinal perforation due to disseminated tuberculosis. This case demonstrates the importance the consideration of ITB when a patient with risk factors for TB fails to respond to treatment for CD.

Application of some nanoparticles in the field of veterinary medicine.

Nanotechnology is a fast-growing technology that plays an important great impact on various fields of therapeutic applications. It is capable for solving several problems related to animal health and production. There are different nano-systems such as liposomes, metallic nanoparticles, polymeric micelles, polymeric nanospheres, functionalized fullerenes, carbon nanotubes, dendrimers, polymer-coated nanocrystals and nanoshells. In this review, we mentioned different methods for the preparation and characterization of nanoparticles. This review is concerned mainly on nanoparticle systems for antibiotic delivery which suffer from poor bioavailability and many side effects. Nanoparticles are characterized by many features include their minimal size, colossal surface zone to mass extent. The development of antimicrobials in nanoparticle systems is considered an excellent alternative delivery system for antimicrobials for the treatment of microbial diseases by increasing therapeutic effect and overcoming the side effects. In this paper, we reviewed some antimicrobial nanoparticle preparations and we focused on florfenicol and neomycin nanoparticle preparations as well as chitosan and silver nanoparticles preparations to prepare, characterize and compare their different pharmacological effects.