During the current era of the COVID-19 pandemic, the dissemination of Mucorales has been reported globally, with elevated rates of infection in India, and because of the high rate of mortality and morbidity, designing an effective vaccine against mucormycosis is a major health priority, especially for immunocompromised patients. In the current study, we studied shared Mucorales proteins, which have been reported as virulence factors, and after analysis of several virulent proteins for their antigenicity and subcellular localization, we selected spore coat (CotH) and serine protease (SP) proteins as the targets of epitope mapping. The current study proposes a vaccine constructed based on top-ranking cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B cell lymphocyte (BCL) epitopes from filtered proteins. In addition to the selected epitopes, β-defensins adjuvant and PADRE peptide were included in the constructed vaccine to improve the stimulated immune response. Computational tools were used to estimate the physicochemical and immunological features of the proposed vaccine and validate its binding with TLR-2, where the output data of these assessments potentiate the probability of the constructed vaccine to stimulate a specific immune response against mucormycosis. Here, we demonstrate the approach of potential vaccine construction and assessment through computational tools, and to the best of our knowledge, this is the first study of a proposed vaccine against mucormycosis based on the immunoinformatics approach.

Introduction:Klebsiella pneumoniae (K. pneumoniae) and Pseudomonas aeruginosa (P. aeruginosa) are the most common Gram-negative bacteria associated with pneumonia and coinfecting the same patient. Despite their high virulence, there is no effective vaccine against them.Methods: In the current study, the screening of several proteins from both pathogens highlighted FepA and OmpK35 for K. pneumonia in addition to HasR and OprF from P. aeruginosa as promising candidates for epitope mapping. Those four proteins were linked to form a multitope vaccine, that was formulated with a suitable adjuvant, and PADRE peptides to finalize the multitope vaccine construct. The final vaccine’s physicochemical features, antigenicity, toxicity, allergenicity, and solubility were evaluated for use in humans.Results: The output of the computational analysis revealed that the designed multitope construct has passed these assessments with satisfactory scores where, as the last stage, we performed a molecular docking study between the potential vaccine construct and K. pneumonia associated immune receptors, TLR4 and TLR2, showing affinitive to both targets with preferentiality for the TLR4 receptor protein. Validation of the docking studies has proceeded through molecular dynamics simulation, which estimated a strong binding and supported the nomination of the designed vaccine as a putative solution for K. pneumoniae and P. aeruginosa coinfection. Here, we describe the approach for the design and assessment of our potential vaccine.

The NRAS gene is a well-known oncogene that acts as a major player in carcinogenesis. Mutations in the NRAS gene have been linked to multiple types of human tumors. Therefore, the identification of the most deleterious single nucleotide polymorphisms (SNPs) in the NRAS gene is necessary to understand the key factors of tumor pathogenesis and therapy. We aimed to retrieve NRAS missense SNPs and analyze them comprehensively using sequence and structure approaches to determine the most deleterious SNPs that could increase the risk of carcinogenesis. We also adopted structural biology methods and docking tools to investigate the behavior of the filtered SNPs. After retrieving missense SNPs and analyzing them using six in silico tools, 17 mutations were found to be the most deleterious mutations in NRAS. All SNPs except S145L were found to decrease NRAS stability, and all SNPs were found on highly conserved residues and important functional domains, except R164C. In addition, all mutations except G60E and S145L showed a higher binding affinity to GTP, implicating an increase in malignancy tendency. As a consequence, all other 14 mutations were expected to increase the risk of carcinogenesis, with 5 mutations (G13R, G13C, G13V, P34R, and V152F) expected to have the highest risk. Thermodynamic stability was ensured for these SNP models through molecular dynamics simulation based on trajectory analysis. Free binding affinity toward the natural substrate, GTP, was higher for these models as compared to the native NRAS protein. The Gly13 SNP proteins depict a differential conformational state that could favor nucleotide exchange and catalytic potentiality. A further application of experimental methods with all these 14 mutations could reveal new insights into the pathogenesis and management of different types of tumors.

Background: Postoperative pain control in neurosurgical patients particularly after elective craniotomy remains clinically challenging due to the need for early neurological assessment and the adverse effects associated with opioid use. This study aimed to compare the efficacy and safety of an opioid-sparing multimodal analgesia (MMA) protocol versus a conventional opioid-based regimen for managing post-craniotomy pain. Methodology: This prospective, randomized controlled trial was conducted over 12 months at Zagazig University Hospitals and included 60 adult patients (aged 18–65 years, American Society of Anesthesiologists )ASA( physical status I–II) scheduled for elective supratentorial craniotomy with planned postoperative intensive care unit (ICU) admission. Patients were randomly assigned in a 1:1 ratio to either a multimodal opioid-sparing analgesia group (Group M, n = 30) or a conventional opioid-based analgesia group (Group O, n = 30) using simple randomization. The MMA protocol included preoperative oral gabapentin, intraoperative dexmedetomidine infusion, a postoperative scalp block with bupivacaine, and scheduled intravenous (IV) acetaminophen and ketorolac. The opioid group received scheduled IV morphine according to institutional practice. The primary outcome was the Visual Analog Scale (VAS) score at 2 h postoperatively. Secondary outcomes included time to first rescue analgesia, total opioid consumption, sedation scores, oxygen saturation, postoperative nausea and vomiting (PONV), and patient satisfaction. Results: VAS scores were significantly lower in Group M at 1, 2, and 4 h postoperatively ( P = 0.046, 0.039, and 0.045, respectively). A highly significant difference in sedation scores was observed between the groups at 30 min, 1 h, and 4 h ( P < 0.001). Additionally, Group M had a significantly lower frequency of vomiting ( P = 0.034); however, excellent satisfaction scores were more frequently reported in Group O, despite the objectively superior analgesic and safety profile observed in Group M. Conclusion: In this randomized controlled trial, opioid-sparing MMA provided superior postoperative pain control after elective craniotomy, with fewer adverse effects compared to conventional opioid-based regimens. These results support the incorporation of MMA into standard postoperative protocols and align with the principles of Enhanced Recovery After Surgery (ERAS) in neurosurgical care. Trial registration: This trial is registered with ClinicalTrials.gov under the identifier NCT05474040, with the initial registration on 26 July 2022, and retrospective registration available at ClinicalTrials.gov.

Background and Objectives: Ventilator-associated pneumonia (VAP) is a common complication in critically ill patients receiving mechanical ventilation. The incidence rates of VAP vary, and it poses significant challenges due to microbial resistance and the potential for adverse outcomes. This study aims to explore the microbial profile of VAP and evaluate the utility of biomarkers and illness severity scores in predicting survival. Materials and Methods: A retrospective cohort study was conducted involving 130 patients diagnosed with VAP. Microbial analysis of bronchoalveolar lavage (BAL) fluid, as well as measurements of C-reactive protein (CRP) and procalcitonin (PCT) levels, were performed. Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were calculated to assess illness severity. Statistical analyses were conducted to determine correlations and associations. Results: The study revealed that Klebsiella pneumoniae (K. pneumoniae) (50.7%) and Pseudomonas aeruginosa (P. aeruginosa) (27.69%) were the most identified microorganisms in VAP cases. SOFA (p-value < 0.0001) and APACHE II (p-value < 0.0001) scores were effective in assessing the severity of illness and predicting mortality in VAP patients. Additionally, our investigation highlighted the prognostic potential of CRP levels (odds ratio [OR]: 0.980, 95% confidence interval [CI] 0.968 to 0.992, p = 0.001). Elevated levels of CRP were associated with reduced survival probabilities in VAP patients. Conclusion: This study highlights the microbial profile of VAP and the importance of biomarkers and illness severity scores in predicting survival. Conclusions: The findings emphasize the need for appropriate management strategies to combat microbial resistance and improve outcomes in VAP patients.

Background: Paroxysmal sympathetic hyperactivity (PSH) is a serious complication of traumatic brain injury (TBI), characterized by episodic hypertension (HTN), tachycardia, hyperthermia, hyperhidrosis, and dystonia. It is associated with prolonged mechanical ventilation (MV), extended ICU and hospital stays, and worse outcomes. Current guidelines lack prophylactic recommendations. Methodology: This single-center randomized controlled trial (NCT05427474) enrolled 90 adults with moderate-to-severe TBI glasgow coma scale (GCS 3–12). Participants were randomized to: standard care (Group I, n = 30); standard care plus propranolol (40 mg/12 h, Group II, n = 30); or standard care plus propranolol (40 mg/12 h) and gabapentin (100 mg/8 h, Group III, n = 30). The primary endpoint was PSH incidence. Secondary endpoints included ventilator days, ICU and hospital length of stay (LOS), and mortality. Results: PSH incidence was lowest in Group III (10%) vs. Group II (33.3%) and Group I (60%) ( p < 0.001). Group II showed the shortest MV duration (5.92 ± 5.15 days) vs. Group III (9.42 ± 6.99 days, p = 0.047) and Group I (12.92 ± 5.98 days, p < 0.001). ICU LOS was shortest in Group II (9.6 ± 5.32 days) vs. Group III (14.69 ± 8.35 days, p = 0.017) and Group I (19.5 ± 8.19 days, p < 0.001). Mortality and GCS improvement did not differ significantly ( p > 0.05). Conclusion: Prophylactic propranolol significantly reduces PSH incidence, shortens MV duration, and decreases ICU stay in moderate-to-severe TBI. Although adding gabapentin further reduces PSH, it prolongs recovery time, suggesting a trade-off between efficacy and sedative effects. These findings suggest that propranolol monotherapy is a promising prophylactic strategy, with gabapentin potentially reserved for refractory cases. However, given the study's limitations, these results should be considered hypothesis-generating and warrant confirmation in larger, multicenter trials. Mortality and neurological outcomes were comparable across groups. Trial registration: The trial was prospectively registered at ClinicalTrials.gov (NCT05427474) on June 22, 2022.