Epidemiological insights into paratuberculosis in camels in Saudi Arabia: Bayesian estimation of true prevalence and identification of risk factors.

Paratuberculosis, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a significant concern in the camel population of Saudi Arabia. This study aimed to provide epidemiological insights into the disease by estimating the true prevalence in camels in the Eastern Province and Riyadh, using a Bayesian estimation framework, and exploring the associated risk factors through a frequentist approach. A total of 1200 camel blood samples were collected and analyzed using an indirect ELISA method. The true herd-level prevalence was estimated at 0.7 (95% probability interval: 0.57 to 0.81), and the mean expected true animal-level prevalence was 0.17 (0.14 to 0.20). Risk factors associated with Map seropositivity were identified, including sex, breed, raising system, and production type. Females, single breed camels, and nomadic raising systems were found to have lower odds of seropositivity, while camels used for racing and show had significantly higher odds. The study's Bayesian approach, adjusting for the imperfect accuracy of MAP tests, provides a nuanced understanding of the disease's prevalence in the region. The integration of true prevalence estimates with risk factor analysis offers a comprehensive framework that can guide future policies and strategies in the fight against paratuberculosis in Saudi Arabia. The findings emphasize the importance of targeted control measures, underscoring the urgent need for interventions in Saudi Arabia's camel population. By understanding the true disease prevalence and its associated risk factors, we can enhance disease management strategies, offering valuable insights for future control and eradication efforts in the region.

Revolutionizing Cancer Treatment: Unleashing the Power of Viral Vaccines, Monoclonal Antibodies, and Proteolysis-Targeting Chimeras in the New Era of Immunotherapy.

In the realm of cancer immunotherapy, a profound evolution has ushered in sophisticated strategies that encompass both traditional cancer vaccines and emerging viral vaccines. This comprehensive Review offers an in-depth exploration of the methodologies, clinical applications, success stories, and future prospects of these approaches. Traditional cancer vaccines have undergone significant advancements utilizing diverse modalities such as proteins, peptides, and dendritic cells. More recent innovations have focused on the physiological mechanisms enabling the human body to recognize and combat precancerous and malignant cells, introducing specific markers like peptide-based anticancer vaccines targeting tumor-associated antigens. Moreover, cancer viral vaccines, leveraging engineered viruses to stimulate immune responses against specific antigens, exhibit substantial promise in inducing robust and enduring immunity. Integration with complementary therapeutic methods, including monoclonal antibodies, adjuvants, and radiation therapy, has not only improved survival rates but also deepened our understanding of viral virulence. Recent strides in vaccine design, encompassing oncolytic viruses, virus-like particles, and viral vectors, mark the frontier of innovation. While these advances hold immense potential, critical challenges must be addressed, such as strategies for immune evasion, potential off-target effects, and the optimization of viral genomes. In the landscape of immunotherapy, noteworthy innovations take the spotlight from the use of immunomodulatory agents for the enhancement of innate and adaptive immune collaboration. The emergence of proteolysis-targeting chimeras (PROTACs) as precision tools for cancer therapy is particularly exciting. With a focus on various cancers, from melanoma to formidable solid tumors, this Review critically assesses types of cancer vaccines, mechanisms, barriers in vaccine therapy, vaccine efficacy, safety profiles, and immune-related adverse events, providing a nuanced perspective on the underlying mechanisms involving cytotoxic T cells, natural killer cells, and dendritic cells. The Review also underscores the transformative potential of cutting-edge technologies such as clinical studies, molecular sequencing, and artificial intelligence in advancing the field of cancer vaccines. These tools not only expedite progress but also emphasize the multidimensional and rapidly evolving nature of this research, affirming its profound significance in the broader context of cancer therapy.

Retraction: Superior Mesenteric Artery Thrombosis Following Severe COVID-19 Pneumonia.

[This retracts the article DOI: 10.7759/cureus.19954.].

Cold atmospheric plasma induces the curing mechanism of diabetic wounds by regulating the oxidative stress mediators iNOS and NO, the pyroptotic mediators NLRP-3, Caspase-1 and IL-1ß and the angiogenesis mediators VEGF and Ang-1.

It has been demonstrated that cold atmospheric plasma (CAP) accelerates the wound healing process, however the underlying molecular pathways behind this effect remain unclear. Thus, the goal of the proposed investigation is to elucidate the therapeutic advantages of CAP on angiogenesis, pyroptotic, oxidative stress, and inflammatory mediators during the wound-healing mechanisms associated with diabetes. Intraperitoneal administration of streptozotocin (STZ, 60 mg/Kg) of body weight was used to induce type-1 diabetes. Seventy-five male mice were randomized into 3 groups: the control non-diabetic group, the diabetic group that was not treated, and the diabetic group that was treated with CAP. The key mediators of pyroptosis and its impact on the slow healing process of diabetic wounds were examined using histological investigations employing H&E staining, immunohistochemistry, ELISA, and Western blotting analysis. Angiogenesis proteins (VEGF, Ang-1, and HO-1) showed a significant decline in expression concentrations in the diabetic wounds, indicating that diabetic animals' wounds were less likely to heal. Furthermore, compared to the controls, the major mediators of pyroptosis (NLRP-3, IL-1ß, and caspase-1), oxidative stress (iNOS and NO), and inflammation (TNF-α and IL-6) have higher expression levels in the diabetic wounds. These factors substantially impede the healing mechanism of diabetic wounds. Interestingly, our results disclosed the therapeutic impacts of CAP treatment in the healing process of diabetic wounds via significantly regulating the expression levels of angiogenesis, pyroptosis, oxidative stress and pro-inflammatory mediators. Our findings demonstrated the curative likelihood of CAP and the underlying mechanisms for enhancing the healing process of diabetic wounds.

Enumeration of olive derived lignan, pinoresinol for activity against recent Omicron variant spike protein for structure-based drug design, DFT, molecular dynamics simulations, and MMGBSA studies.

The coronavirus disease 2019 (COVID-19) was first found in Wuhan, China, in December 2019. Because the virus spreads quickly, it quickly became a global worry. Coronaviridae is the family that contains both SARS-CoV-2 and the viruses that came before (i.e., MERS-CoV and SARS-CoV). Recent sources portray that the COVID-19 virus has affected 344,710,576 people worldwide and killed about 5,598,511 people in the last 2 years. The B.1.1.529 strain, later called "Omicron," was named a Variant of Concern on November 24, 2021. The SARS-CoV-2 virus has gone through a never-ending chain of changes that have never happened before. As a result, it has many different traits. Most of these changes have occurred in the spike protein, where antibodies bind. Because of these changes, the Omicron type is very contagious and easy to pass on. There have been a lot of studies done to try to figure out this new challenge in the COVID-19 strains race, but there is still a lot that needs to be explained. This study focuses on virtual screening, docking, and molecular dynamic analysis; we aimed to identify therapeutic candidates for the SARS-CoV-2 variant Omicron based on their ability to inhibit non-structural proteins. We investigate the prediction of the properties of a substantial database of drug molecules obtained from the OliveNet™ database. Compounds that did not exhibit adequate gastrointestinal absorption and failed the Lipinski test are not considered for further research. The filtered compounds were coupled with our primary target, SARS-CoV-2 Omicron spike protein. We focused on SARS-CoV-2 Omicron spike protein and filtering potent olive compounds. Pinoresinol, the most likely candidate, is bound best (- 8.5 kcal/mol). Pinoresinol's strong interaction with the active site made the complex's dynamic structure more resilient. MD simulations explain the protein-ligand complex's stability and function. Pinoresinol may be a promising SARS-CoV-2 Omicron spike protein receptor lead drug, and additional research may assist the scientific community.

Increased NOTCH1 expression is associated with low survival in moderate/ poor differentiated human oral squamous cell carcinoma patients.

Notch deregulation has been reported in various types of cancers, including Oral squamous cell carcinomas (OSCCs). The role of Notch1 signaling in oral squamous cell carcinoma (OSCC) remains poorly understood. In this study, NOTCH1 was aberrantly expressed in human oral cancer tissues compared with that in normal marginal tissues and was associated with poor prognosis. The positive Notch 1 expression was significantly associated with poor tumor differentiation status. Kaplan-Meier survival curves revealed that elevated cytoplasmic NOTCH1 expression levels in OSCC patients were associated with poor overall survival. Moreover, multivariate COX proportional hazard models revealed that T N status, AJCC stage histological grade were independent prognostic factors for survival. Our result clearly demonstrates the oncogenic role of Notch1 in oral cancer and Notch1 may be a useful biomarker to target oral cancer patients.

Fusion of Magnetic Resonance Elastography Images With Computed Tomography and Magnetic Resonance Imaging Using the Human Visual System.

Magnetic resonance elastography (MRE) is used to assess the stiffness of the liver to rule out cirrhosis or fibrosis. The image, nevertheless, is regarded as shear-wave imaging and does not depict any anatomical features. Multimodality medical image fusion (MMIF), such as the fusion of MRE with computed tomography (CT) scan or magnetic resonance imaging (MRI), can help doctors optimize the advantages of each imaging technique. As a result, perceptions serve as valid and valuable assessment criteria. The contrast sensitivity function (CSF), which describes the rates of visual contrast sensitivity through the changing of spatial frequencies, is used mathematically to characterize the human visual system (HVS). As a result, we suggest novel methods for fusing images that use discrete wavelets transform (DWT) based on HVS and CSF models. Images from MRI or CT scan were combined with MRE images, and the outcomes were assessed both subjectively and objectively. Visual inspection of merging images was done throughout the qualitative analysis. The CT-MRE fused images in all four datasets were shown to be superior at maintaining bones and spatial resolution, despite the MRI-MRE being better at exhibiting soft tissues and contrast resolution. It is clear from all four datasets that the liver soft tissue in MRI and CT images mixed successfully with the red-colored stiffness distribution seen in MRE images. The proposed approach outperformed DWT, which produced visual artifacts such as signal loss. Quantitative evaluation using mean, standard deviation, and entropy showed that the generated images from the proposed technique performed better than the source images and DWT. Additionally, peak signal-to-noise ratio, mean square error, correlation coefficient, and structural similarity index measure were employed to compare the two fusion approaches, namely, MRI-MRE and CT-MRE. The comparison did not show the superiority of one approach over the other. In conclusion, both subjective and objective evaluation approaches revealed that the combined images contained more information and characteristics. Hence, the proposed method might be a useful procedure to diagnose and localize the stiffness regions on the liver soft tissue by fusion of MRE with MRI or CT.

Antimalarial drug discovery against malaria parasites through haplopine modification: An advanced computational approach.

The widespread emergence of antimalarial drug resistance has created a major threat to public health. Malaria is a life-threatening infectious disease caused by Plasmodium spp., which includes Apicoplast DNA polymerase and Plasmodium falciparum cysteine protease falcipain-2. These components play a critical role in their life cycle and metabolic pathway, and are involved in the breakdown of erythrocyte hemoglobin in the host, making them promising targets for anti-malarial drug design. Our current study has been designed to explore the potential inhibitors from haplopine derivatives against these two targets using an in silico approach. A total of nine haplopine derivatives were used to perform molecular docking, and the results revealed that Ligands 03 and 05 showed strong binding affinity compared to the control compound atovaquone. Furthermore, these ligand-protein complexes underwent molecular dynamics simulations, and the results demonstrated that the complexes maintained strong stability in terms of RMSD (root mean square deviation), RMSF (root mean square fluctuation), and Rg (radius of gyration) over a 100 ns simulation period. Additionally, PCA (principal component analysis) analysis and the dynamic cross-correlation matrix showed positive outcomes for the protein-ligand complexes. Moreover, the compounds exhibited no violations of the Lipinski rule, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions yielded positive results without indicating any toxicity. Finally, density functional theory (DFT) and molecular electrostatic potential calculations were conducted, revealing that the mentioned derivatives exhibited better stability and outstanding performance. Overall, this computational approach suggests that these haplopine derivatives could serve as a potential source for developing new, effective antimalarial drugs to combat malaria. However, further in vitro or in vivo studies might be conducted to determine their actual effectiveness.

Development of a new drug candidate for the inhibition of Lassa virus glycoprotein and nucleoprotein by modification of evodiamine as promising therapeutic agents.

The Lassa virus (LASV), an RNA virus prevalent in West and Central Africa, causes severe hemorrhagic fever with a high fatality rate. However, no FDA-approved treatments or vaccines exist. Two crucial proteins, LASV glycoprotein and nucleoprotein, play vital roles in pathogenesis and are potential therapeutic targets. As effective treatments for many emerging infections remain elusive, cutting-edge drug development approaches are essential, such as identifying molecular targets, screening lead molecules, and repurposing existing drugs. Bioinformatics and computational biology expedite drug discovery pipelines, using data science to identify targets, predict structures, and model interactions. These techniques also facilitate screening leads with optimal drug-like properties, reducing time, cost, and complexities associated with traditional drug development. Researchers have employed advanced computational drug design methods such as molecular docking, pharmacokinetics, drug-likeness, and molecular dynamics simulation to investigate evodiamine derivatives as potential LASV inhibitors. The results revealed remarkable binding affinities, with many outperforming standard compounds. Additionally, molecular active simulation data suggest stability when bound to target receptors. These promising findings indicate that evodiamine derivatives may offer superior pharmacokinetics and drug-likeness properties, serving as a valuable resource for professionals developing synthetic drugs to combat the Lassa virus.

The Bioactive Value of Tamarix gallica Honey from Different Geographical Origins.

This study was conducted to assess the bioactive value of Tamarix gallica honey samples collected from three countries. In total, 150 Tamarix gallica honey samples from Saudi Arabia (50), Libya (50), and Egypt (50) were collected and compared, based on the results of the melissopalynological analysis, their physicochemical attributes, antioxidant and antimicrobial activities, and biochemical properties, together with their total phenolic and total flavonoid contents. Depending on the geographical origin, we observed different levels of growth suppression for six resistant bacterial strains. The pathogenic microorganisms tested in this study were Staphylococcus aureus, Streptococcus mutans, Klebsiella pneumoniae, Escherichia coli, Proteus vulgaris, and Pseudomonas aeruginosa. There was a strong correlation between the polyphenol and flavonoid contents, as well as significant (p < 0.05) radical scavenging activities. The melissopalynological analysis and physicochemical properties complied with the recommendation of the Gulf and Egyptian Technical Regulations on honey, as well as the Codex Alimentarius of the World Health Organization and the European Union Normative related to honey quality. It was concluded that Tamarix gallica honey from the three countries has the capacity to suppress pathogenic bacterial growth and has significant radical scavenging activities. Moreover, these findings suggest that Tamarix gallica honey may be considered as an interesting source of antimicrobial compounds and antioxidants for therapeutical and nutraceutical industries or for food manufacturers.

Exploring the cardioprotective effects of canagliflozin against cisplatin-induced cardiotoxicity: Role of iNOS/NF-κB, Nrf2, and Bax/cytochrome C/Bcl-2 signals.

Cardiotoxicity is a severe considerable side effect of cisplatin (CDDP) that requires much medical attention. The current study investigates the cardioprotective effects of canagliflozin (CA) against CDDP-induced heart toxicity. Rats were allocated to the control group; the CA group was administered CA 10 mg/kg/day orally for 10 days; the CDDP group was injected with 7 mg/kg, intraperitoneal as a single dose on the 5th day, and the CDDP + CA group. Compared to the CDDP-treated group, CA effectively attenuated CDDP-induced heart injury as evidenced by a decrease of serum aspartate aminotransferase, alkaline phosphatase, creatine kinase-MB, and lactate dehydrogenase enzymes and supported by the alleviation of histopathological changes in cardiac tissues. Biochemically, CA attenuated cardiac oxidative injury through upregulation of the nuclear factor-erythroid 2 related factor 2 (Nrf2) signal. CA suppressed inflammation by decreasing cardiac NO2 - , MPO, iNOS, nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha, and interleukin 1-beta levels. Besides, CA significantly upregulated cardiac levels of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and p-AKT proteins. Moreover, CA remarkably mitigated CDDP-induced apoptosis via modulation of Bax, cytochrome C, and Bcl-2 protein levels. Together, the present study revealed that CA could be a good candidate for preventing CDDP-induced cardiac injury by modulating iNOS/NF-κB, Nrf2, PI3K/AKT, and Bax/cytochrome C/Bcl-2 signals.

Current Insights into Diagnosis, Prevention Strategies, Treatment, Therapeutic Targets, and Challenges of Monkeypox (Mpox) Infections in Human Populations.

In the wake of the emergence and worldwide respread of a viral infection called Monkeypox (Mpox), there is a serious threat to the health and safety of the global population. This viral infection was endemic to the western and central parts of Africa, but has recently spread out of this endemic area to various countries, including the United Kingdom (UK), Portugal, Spain, the United States of America (USA), Canada, Sweden, Belgium, Italy, Australia, Germany, France, the Netherlands, Israel, and Mexico. This is a timely review focusing on recent findings and developments in the epidemiology, clinical features, therapeutic targets, diagnosis, prevention mechanisms, research challenges and possible treatment for Mpox. To date (29 November 2022), there have been around 81,225 reported cases of Mpox. In most cases, this illness is mild; however, there is a fatality rate ranging from 1 to 10%, which might be increased due to associated complications and/or secondary infections. There is a real challenge in the diagnosis of Mpox, since its symptoms are very similar to those of other infections, including smallpox and chickenpox. Generally, to prevent/limit the risk and transmission of Mpox, the detection and isolation of infected individuals, as well as hand hygiene and cleanliness, are essential and effective approaches to control/combat this viral infection. Nevertheless, updated information about Mpox from different angles is lacking. Thus, this review provides updated and comprehensive information about the Mpox illness, which should highlight the global burden, pathogenicity, symptoms, diagnosis, prevention measures and possible treatment of this emerging disease.

Neuroprotective effect of canagliflozin against cisplatin-induced cerebral cortex injury is mediated by regulation of HO-1/PPAR-γ, SIRT1/FOXO-3, JNK/AP-1, TLR4/iNOS, and Ang II/Ang 1-7 signals.

OBJECTIVES: Canagliflozin (CAN), a sodium-glucose co-transporter 2 inhibitor, is an anti-hyperglycemic drug that has been approved to treat diabetes. This study evaluated the beneficial effects of CAN on cerebral cortex intoxication induced by cisplatin (CIS). MATERIALS AND METHODS: Rats were allocated into four groups: normal control, CAN (10 mg/kg, P.O.) for 10 days, CIS (8 mg/kg, i.p.) as a single dose on the 5th day of the experiment, and CAN + CIS group. RESULTS: In comparison with CIS control rats, CAN significantly mitigated CIS-induced cortical changes in rats' behavior in the open field and forced swimming assessment as well as histological structure. Biochemically, CAN administration efficiently decreased lipid peroxidation biomarkers MDA and boosted the antioxidant status via a remarkable increase in the cortical reduced glutathione (GSH) content as well as enzymatic activities of antioxidant enzymes superoxide dismutase (SOD), glutathione-S-transferase (GST), catalase (CAT), and glutathione peroxidase (GPx) mediated by up-regulation of heme oxygenase-1 (HO-1), peroxisome proliferator-activated receptors (PPARγ), and silent information regulator (SIRT1)/forkhead box-O3 (FOXO-3) signals. Additionally, pretreatment with CAN significantly decreased cortical myeloperoxidase (MPO), nitrite (NO2-), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels. At the same time, it elevated the IL-10 level associated with the downregulation of Jun N-terminal kinase (JNK)/activator protein 1 (AP-1), TLR4/inducible nitric oxide synthase (iNOS)/nitric oxide (NO), and Ang II/Ang 1-7 signals. CONCLUSIONS: Due to the potent antioxidant and anti-inflammatory properties of CAN, our findings showed that CAN could be a good candidate for the protection against CIS-induced cortical intoxication in the patient receiving CIS.

Tackling strong biofilm and multi-virulent vancomycin-resistant Staphylococcus aureus via natural alkaloid-based porous nanoparticles: perspective towards near future eradication.

Introduction: As a growing direction, nano-based therapy has become a successful paradigm used to address the phytogenic delivery-related problems in overcoming multivirulent vancomycin-resistant Staphylococcus aureus (VRSA) infection. Methods: Hence, our aim was to develop and assess a novel nanocarrier system (mesoporous silica nanoparticles, MPS-NPs) for free berberine (Free-BR) as an antimicrobial alkaloid against strong biofilm-producing and multi-virulent VRSA strains using in vitro and in vivo mouse model. Results and discussion: Our outcomes demonstrated vancomycin resistance in 13.7% of Staphylococcus aureus (S. aureus) strains categorized as VRSA. Notably, strong biofilm formation was observed in 69.2% of VRSA strains that were all positive for icaA gene. All strong biofilm-producing VRSA strains harbored a minimum of two virulence genes comprising clfA and icaA with 44.4% of them possessing all five virulence genes (icaA, tst, clfA, hla, and pvl), and 88.9% being multi-virulent. The study findings affirmed excellent in vitro antimicrobial and antibiofilm properties of BR-loaded MPS-NPs. Real-time quantitative reverse transcription PCR (qRT-PCR) assay displayed the downregulating role of BR-loaded MPS-NPs on strong biofilm-producing and multi-virulent VRSA strains virulence and agr genes in both in vitro and in vivo mice models. Additionally, BR-loaded MPS-NPs supplementation has a promising role in attenuating the upregulated expression of pro-inflammatory cytokines' genes in VRSA-infected mice with attenuation in pro-apoptotic genes expression resulting in reduced VRSA-induced apoptosis. In essence, the current study recommends the future scope of using BR-loaded MPS-NPs as auspicious alternatives for antimicrobials with tremendous antimicrobial, antibiofilm, anti-quorum sensing (QS), and anti-virulence effectiveness against problematic strong biofilm-producing and multi-virulent VRSA-associated infections.

Ultrastructural analysis of zinc oxide nanospheres enhances anti-tumor efficacy against Hepatoma.

Zinc oxide nanomaterial is a potential material in the field of cancer therapy. In this study, zinc oxide nanospheres (ZnO-NS) were synthesized by Sol-gel method using yeast extract as a non-toxic bio-template and investigated their physicochemical properties through various techniques such as FTIR, XR, DLS, and TEM. Furthermore, free zinc ions released from the zinc oxide nanosphere suspended medium were evaluated by using the ICP-AS technique. Therefore, the cytotoxicity of ZnO nanospheres and released Zn ions on both HuH7 and Vero cells was studied using the MTT assay. The data demonstrated that the effectiveness of ZnO nanospheres on HuH7 was better than free Zn ions. Similarly, ZnO-Ns were significantly more toxic to HuH7 cell lines than Vero cells in a concentration-dependent manner. The cell cycle of ZnO-Ns against Huh7 and Vero cell lines was arrested at G2/M. Also, the apoptosis assay using Annexin-V/PI showed that apoptosis of HuH7 and Vero cell lines by ZnO nanospheres was concentration and time-dependent. Caspase 3 assay results showed that the apoptosis mechanism may be intrinsic and extrinsic pathways. The mechanism of apoptosis was determined by applying the RT-PCR technique. The results revealed significantly up-regulated Bax, P53, and Cytochrome C, while the Bcl2 results displayed significant down-regulation and the western blot data confirmed the RT-PCR data. There is oxidative stress of the ZnO nanospheres and free Zn+2 ions. Results indicated that the ZnO nanospheres and free Zn+2 ions induced oxidative stress through increasing reactive oxygen species (ROS) and lipid peroxidation. The morphology of the HuH7 cell line after exposure to ZnO nanospheres at different time intervals revealed the presence of the chromatin condensation of the nuclear periphery fragmentation. Interestingly, the appearance of canonical ultrastructure features of apoptotic morphology of Huh7, Furthermore, many vacuoles existed in the cytoplasm, the majority of which were lipid droplets, which were like foamy cells. Also, there are vesicles intact with membranes that are recognized as swollen mitochondria.

Research on acute phase proteins and inflammatory cytokines biomarkers in dromedary camels (Camelus dromedarius) with clinical endometritis.

Uterine diseases are prevalent in camels and lead to economic losses because of decreased fertility. The aim of this study is to look into the expression patterns of acute-phase proteins (APPs) and inflammatory cytokines in dromedary camels with clinical endometritis (CE) to highlight their role in the immune pathogenesis of the disease. Moreover, to identify the use of these parameters as a complementary tool for CE screening as well as investigate the efficacy of ceftiofur antibiotic, APPs and inflammatory cytokines were estimated in camels with CE. Values of APPs (Hp, SAA, and Fg), pro-inflammatory (IFN-γ, TNF-α, IL-1α, IL-1ß, and IL-6), and anti-inflammatory cytokines (IL-10) were higher in camels with CE than in healthy controls (P < 0.05). The strongest correlations were observed between HP and IFN-γ (r = 0.73) and IL-1ß and IL-6 (r = 0.73), while the weakest correlations were observed between Fg and IFN-γ (r = 0.25). Corynebacterium pyogenes and Arcanobacterium pyogenes were the most common pathogens involved in the etiology of CE. All investigated biomarkers demonstrated a high degree of recognition between CE camel and healthy controls (AUC was > 0.90). A higher proportion of camels with CE that were treated with ceftiofur (90%, P < 0.0001) scored clinical cures after the first dose, while 10% required a second dose. In conclusion, CE causes increased APPs and inflammatory cytokine biomarkers, indicating a significant acute phase response in diseased camels with CE. These changes in biomarkers could be beneficial for understanding the immune pathogenesis of CE in dromedary camels, clinical practice, and basic clinical research.

The Adverse Reactions of Pfizer BioNTech COVID-19 Vaccine Booster Dose are Mild and Similar to the Second Dose Responses: A Retrospective Cross-Sectional Study.

Background: Like other vaccines, Pfizer BioNTech's COVID-19 vaccine efficacy against SARS-CoV-2 virus infections begins to decline within a few months after the 2nd dose. On August 12, 2021, the FDA allowed additional Pfizer BioNTch's COVID-19 vaccine dose (3rd or booster dose) for individuals with weakened immunity. This study aimed to evaluate the short-term adverse reactions (ADRs) of the 2nd and the 3rd doses of the Pfizer BioNTech COVID-19 vaccine. Methods: Information for this study was collected by Google Form questionnaire (online survey). The results included responses from 442 people, the majority from Saudi Arabia. Results: The most common local ADRs following the 3rd dose were injection site pain, injection site hypersensitivity, and axillary lymph node swelling. The most common systemic ADRs were fatigue, muscle pain, bone pain, headache, and fever less than 38ºC. Less common systemic ADRs were shivering, fever more than 38ºC, nasal congestion and rhinorrhea, arrhythmia, cough, abdominal pain, chest tightness, nausea, diarrhea, vomiting, and tachypnea. Rare systemic ADRs were constipation, dizziness and vertigo, lack of concentration, sore throat, excessive hair loss, dysmenorrhea and heavy menstruation, and Bell's palsy. Severe allergic reactions were reported by 2.6% of participants after the 2nd dose, compared with none after the 3rd dose. Nasal congestion and runny nose are more frequent after the 3rd dose. The ADRs of the 2nd and 3rd doses were significantly more prevalent in females. 12% of participants reported ADRs lasting more than one week after the 3rd dose compared to 5% after the 2nd dose. People ≤ 60 years were more affected by the vaccine ADRs. Conclusion: Most of the ADRs reported after the 3rd vaccine dose were consistent with the Pfizer vaccine information sheet and similar to the 2nd dose ADRs.

A Pituitary Abscess Caused by Morganella morganii: A Case Report.

BACKGROUND Pituitary abscess (PA) is a rare pituitary lesion accounting for less than 1% of all pituitary diseases and is associated with high mortality rates. The non-specific clinical symptoms and radiological features preclude accurate diagnosis of the disease. Hence, surgical intervention is still considered the criterion standard method for PA diagnosis. Most PAs occur as a primary disease or due to complications such as surgery, sepsis, and adjacent inflamed lesions. CASE REPORT A 53-year-old man presented to the Emergency Department with a headache associated with nausea, vomiting, and constipation. The patient had no visual disturbances, polyuria, polydipsia, nocturia, or abnormal discharges. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a large suprasellar mass. The patient underwent left-side trans-nasal transsphenoidal microscopic surgery for mass removal. An abscess with discharge was noticed and sent for microbiological evaluation, revealing an infection with a commensal enteric bacterium that rarely causes nosocomial infection, known as Morganella morganii. The patient was discharged after completing the intravenous antibiotic course and was given oral antibiotics. CONCLUSIONS Pituitary abscess is a rare pituitary lesion. However, taking the history of recent meningitis, sinusitis, and/or surgery may help to reach an early diagnosis, prompt surgical intervention, and vital therapeutic steps to reduce mortality rates and improve patient's outcomes. PA should always be considered when patients demonstrate signs of pituitary dysfunction associated with signs of infection. Furthermore, antibiotics should be administered immediately once the PA case is confirmed and should last for at least 6 weeks postoperatively.

Accelerating Effect of Cucurbita pepo L. Fruit Extract on Excisional Wound Healing in Depressed Rats Is Mediated through Its Anti-Inflammatory and Antioxidant Effects.

Background: Chronic stress can hinder wound healing as it suppresses both the cellular and innate immune responses. Objectives: The study aims to assess the effectiveness of the administration of topical and oral Cucurbita pepo L. (CP) ethanolic extract in prompting excisional wound healing in rats exposed to chronic stress, and to explain how it works. Materials and methods: Fifty albino rats assigned to five groups (n = 10) were utilized in this study. The chronic unpredictable mild stress (CUMS) model was used for 4 weeks to induce depressive-like behavior in rats, and a forced swim test and corticosterone were assessed to confirm its occurrence. During the experiment, an excisional wound was induced in the rats and followed. Oxidant/antioxidants status and pro-inflammatory cytokines levels were measured in the serum and wound area. Gene expression of pro-inflammatory cytokines was also assessed using RT-PCR. Wound closure histopathological changes and immunohistochemical expression of CD68, CD3, and CD4 at the wound area was assessed. Results: The administration of CP, both orally and topically, significantly reduced (p < 0.001) the depressive-like behavior and corticosterone and pro-inflammatory cytokines levels, while it significantly up-regulated the antioxidant activity compared to the untreated and topically CP-treated groups. Both topically CP-treated and combined CP-treated groups showed complete re-epithelialization, reduced inflammatory cells infiltration, collagen fibers deposition, and significantly increased CD3, CD4 positive T cells count, with a superior effect in the combined CP-treated groups. Conclusion: Cucurbita pepo L., administrated both topically and orally, can enhance the wound healing process in rats with depressive-like behavior mostly through the antioxidant, anti-inflammatory, and antidepressant activities observed in this study.

Prevalence and Molecular Characterization of Metallo ß-Lactamase Producing Gram-Negative Pathogens Causing Eye Infections.

Purpose: Metallo ß-lactamases (MßL) production is a worldwide problem, particularly in gram-negative bacteria. As scanty data is available on the prevalence of MBL, the present study is being undertaken to determine the prevalence, antibacterial sensitivity patterns, and molecular characterization of MßL associated resistant genes in gram-negative bacteria isolated from ocular infections. Material and Methods: At a tertiary eye care center in south India, 359 gram-negative pathogens, 200 isolates from eye infections, and 159 isolates from normal flora of the eye were studied. A gold standard microbiology method was used to identify the isolates. An antibiotic double disc synergy test and a combination disc test were used to detect MßL production. Multiplex PCR was used to investigate the molecular characteristics of the MßL encoding genes blaVIM, blaIMP, and blaNDM. Results: Of the 359 gram-negative bacterial pathogens, Pseudomonas aeruginosa 108 (30.1%) and Enterobacter agglomerans 46 (12.8%) were commonly isolated. High prevalence of P. aeruginosa 81% (17 strains) was detected as an MßL producer and it shows 100% resistance to 2nd and 3rd generation cephalosporins and meropenem. Multiplex PCR detected only the blaVIM gene in 56 (28%) of various eye infections and 27 (17%) of normal flora of the gram-negative bacteria (GNB). The blaVIM gene is detected predominantly in 51.8% of keratitis and 21.4% of postoperative endophthalmitis. High prevalence of the gene was detected in P. aeruginosa 42.9% (24 of 56) and Alcaligens denitrificans 10.7% (6 of 56) from eye infections. Whereas, in the control group, P. aeruginosa and E. coli each had 14.8% (4 of 27) that were shown positive. Conclusion: The emerging MßLs mediated resistance among P. aeruginosa is a challenging task for ophthalmologists, especially in patients with endophthalmitis and bacterial keratitis. This local knowledge will aid in advising appropriate antibiotic use and avoiding unnecessary antibiotic prescriptions, which are highly warranted.