BackgroundNeonatal sepsis is a major contributor to morbidity and mortality among neonates. There has been considerable geographic variation in causative pathogens and antimicrobial sensitivity profiles over time. This makes the continuous monitoring of patterns of emergence crucial for the effective implementation of antimicrobial therapy guidelines in an attempt to control antimicrobial resistance. MethodsA retrospective study was conducted among neonates with sepsis admitted to King

Vitamin D deficiency and sepsis are both significant global health problems. Insufficient vitamin D is considered to be a pathogenically relevant factor of sepsis-related deaths; however, a causal relationship has not yet been demonstrated. Recently, vitamin D has been an exciting field of research owing to the identification of vitamin D receptors on many extra skeletal tissues and cells, suggesting an unexpected role on body physiology, beyond its effects on bone homeostasis. However, while the role of vitamin D on bone health is widely understood and has been successfully translated into clinical applications and public health policies, recent evidence supporting its role in other physiological and pathological processes has not been fully established. In sepsis, there is an induction of local intracellular vitamin D activity by most immune cells, including lymphocytes, macrophages, neutrophils, and dendritic cells, as well as vascular endothelial cells, to ensure efficient clearance of infective microorganisms and mediate anti-inflammatory and tolerogenic effects. The literature suggests an association between low vitamin D levels and sepsis, but clinical trials have yielded contradictory results. A greater understanding of this role may improve disease management. This article reviews the available knowledge regarding vitamin D in immune function, emerging literature regarding the association between its deficiency and sepsis, as well as presenting its potential effect on platelet leukocyte aggregations (PLAs), a significant pathology in sepsis. It also summarizes clinical trials involving vitamin D supplementation during critical illness and sepsis and addresses the impact of relevant factors of sepsis pathogenesis on the efficacy of vitamin D supplementation, which could contribute to the reported inconsistencies. Looking ahead, further studies are required to uncover the possible modulatory relationship between vitamin D and sepsis to define better cut-offs for its levels, proper timing of its administration, and the optimum dosage for best management.

Septicaemia is an acute inflammatory reaction in the bloodstream to the presence of pathogen-associated molecular patterns. Whole blood stimulation assays capture endotoxin-induced formation of aggregates between platelets and leucocytes using flow cytometry. We wanted to assess extent of spontaneous aggregate formation in whole blood stimulation assays and compare the effects of endotoxin and heat-killed, clinically relevant, bacterial pathogens on aggregate formation and then on adhesion of aggregates to TNFα-stimulated endothelial cells. We found that endotoxin (from Escherichia coli or Salmonella enteritidis ) was not a suitable stimulus to provoke platelet-leucocyte aggregates in vitro, as it did not further increase the extent of aggregates formed spontaneously in stasis of hirudin-anticoagulated blood. Specifically, whole blood samples stimulated with or without LPS produced aggregates with a mean surface area of 140.97 and 117.68 μm 2 , respectively. By contrast, incubation of whole blood with heat-killed Klebsiella pneumoniae or Staphylococcus aureus produced significantly enhanced and complex cellular aggregates (with a mean surface area of 470.61 and 518.39 μm 2 , respectively) which adhered more frequently to TNFα (and free fatty acid)-stimulated endothelial cells. These were reliably captured by scanning electron microscopy. Adhesion of cellular aggregates could be blocked by incubation of endothelial cells with a commercial P-selectin antibody and an angiopoietin-2 ligand trap. In conclusion, we have developed an in vitro method that models the acute inflammatory reaction in whole blood in the presence of sepsis-relevant bacterial pathogen surfaces.

Infections caused by the monkeypox virus (MPXV) have continued to be transmitted significantly in recent years. However, understanding the transmission mechanism, risk factors, and consequences of infection are still limited. Structure-based drug design for MPXV is at an early stage due to the availability of protein structures that have been determined experimentally. However, the structure of the A42R profilin-like protein of MPXV has been solved and submitted to the structure database. This study illustrated an in silico structure-based approach to identify the potential hit compound against A42R of MPXV. Here, 65 Plantago lanceolata compounds were computationally screened against A42R of MPXV. Virtual screening identified top five hits (i) Luteolin 7,3′-Diglucuronide (PubChem ID: 44258091), (ii) Luteolin 7-Glucuronide-3′-Glucoside (PubChem ID: 44258090), (iii) Plantagoside (PubChem ID: 174157), (iv) Narcissoside (PubChem ID: 5481663), and (v) (AlphaE,8S,9R)-N-(3,4-Dihydroxyphenethyl)-8-[(3,4-Dihydroxyphenethyl)Carbamoyl]-9-(1,3-Benzodioxole-5-Yl)-3aalpha,7aalpha-Ethano-1,3-Benzodioxole-5-Acrylamide (PubChem ID: 101131595), with binding energy <−9.0 kcal/mol that was further validated by re-docking and molecular dynamic (MD) simulation. Interaction analysis of re-docked poses confirmed the binding of these top hits to the A42R protein as reported in the reference compound, including active residues ARG114, ARG115, and ARG119. Further, MD simulation and post-simulation analysis support Plantagoside and Narcissoside for substantial stability in the binding pocket of viral protein contributed by hydrogen and hydrophobic interactions. The compounds can be considered for further optimisation and in vitro experimental validation for anti-monkeypox drug development.

Evidence from the literature suggests an association between the microbiome and asthma development. Here, we aimed to identify the current evidence for the association between asthma and the upper airway, lower airway and/or the gut microbiome. An electronic systemic search of PubMed, EBSCO, Science Direct and Web of Science was conducted until February 2022 to identify the eligible studies. The Newcastle–Ottawa Scale and the Systematic Review Centre for Laboratory Animal Experimentation risk of the bias tools were used to assess quality of included studies. Twenty-five studies met the inclusion criteria. Proteobacteria and Firmicutes were identified as being significantly higher in the asthmatic children compared with the healthy controls. The high relative abundance of Veillonella, Prevotella and Haemophilus in the microbiome of the upper airway in early infancy was associated with a higher risk of asthma development later in life. The gut microbiome analyses indicated that a high relative abundance of Clostridium in early childhood might be associated with asthma development later in life. The findings reported here serve as potential microbiome signatures associated with the increased risk of asthma development. There is a need for large longitudinal studies to further identify high-risk infants, which will help in design strategies and prevention mechanisms to avoid asthma early in life.

Background and objects: In systemic lupus erythematosus, circulating immune complexes activate complement and, when trapped in renal capillaries, cause glomerulonephritis. Mouse models have been used in the preclinical assessment of targeting complement activation pathways to manage chronic inflammation in lupus. Properdin is the only known positive regulator of complement activation, but its role in the severity of lupus nephritis has not been studied yet. Materials and Methods: Fully characterized properdin-deficient mice were crossed with lupus prone MRL/lpr mice on C57Bl/6 background. Results: Compared to MRL/lpr properdin wildtype mice, MRL/lpr properdin-deficient mice had significantly lower anti-DNA antibody titres, TNFα and BAFF levels in serum. The qualitative glomerulonephritic score was less severe and there was significantly less serum creatinine in MRL/lpr properdin-deficient mice compared to MRL/lpr properdin wildtype littermate mice. Conclusion: Properdin plays a significant role in the severity of lupus overall and specifically in the extent of glomerulonephritis observed in MRL/lpr mice. Because MRL/lpr properdin-deficient mice had lower levels of anti-DNA antibodies, inflammatory mediators and markers of renal impairment, the study implies that properdin could constitute a novel therapy target in lupus disease.

comprising data related to demographic, microbial profile and antibiotic sensitivity pattern of wound infection-suspected cases.Results: A total of 305 wound swabs were collected; of which 56.1% showed microbial growth. Among 187 microbial isolates, 62% were gram-negative bacteria, 30.5% were gram-positive bacteria and 7.5% were fungi. Staphylococcus aureus was the prevailing isolates 17.1%, Original Articlefollowed by Klebsiella pneumoniae and Pseudomonas aeruginosa, each with 13.9% and Escherichia coli with 12.8 %. Providencia sp with 0.1% was the least isolated bacteria. Out of 173 bacterial isolates, 46.8% were sensitive to antimicrobial agents tested, while 53.2% were resistant to one and more drug tested. Of these isolates, 22% were found to be the MDR bacteria. The highest MDR percentages was noted among Acinetobacter baumannii (70%) followed by Klebsiella pneumoniae (53.9%), Escherichia coli (25%) and Pseudomonas aeruginosa (19.2%) and the least by (12.5%) by Staphylococcus aureus. Conclusion:The microbial isolation rates from wound infection was high, with Staphylococcus aureus being the most prevalent. Considerable antimicrobial resistance rate to the commonly used antibiotics was discovered. Thus, regular monitoring of microbial profile and their antimicrobial sensitivity pattern in the study region in attempt to contain antimicrobial resistance is highly recommended.

Background: In addition to developing effective therapeutic approaches, the maintenance of health also constitutes lifestyle and behavioral aspects related to being more resilient in the event of future illness. Reduced immune health has been linked to reports of more frequent and severe infections as well as a variety of non-communicable diseases, both of which may eventually place a significant burden on the healthcare system. Several lifestyles and behaviors can influence immune health, both positively and negatively. Accordingly, this study aimed to evaluate the immune health status and investigate its relationship with widely practiced lifestyle behaviors that are thought to affect immunological functioning.Design and method: Saudi Arabian citizens and international residents of the Western Province were invited to participate in this cross-sectional web-based survey through an online advertisement. The integrated questionnaire on lifestyle (Arab Teens Lifestyle Study) and immune health status (Immune Status Questionnaire (ISQ)) was completed in November 2022 by 1230 participants. Descriptive analysis, Mann-Whitney U test, chi-square, or Fisher's exact test was utilized to investigate the relationships between study variables and immune health status groups. Spearman's or Pearson's correlation coefficients were used to determine correlations between the overall ISQ scores and study variables.Results: Of the 925 study participants, 34.7% scored below 6 on the ISQ. Of the respondents, 50% had a body mass index of 25 or higher, and 46.3% reported sleeping less than four hours each night. Of the participants, 62-82% did not engage in any form of physical activity. The associations between the ISQ score and weight (p = 0.006), total sleep time per night (p = 0.001), duration of household activities (p < 0.001), and smoking status (p = 0.001) were statistically significant.Conclusions: According to the data presented here, reduced immune health as measured by ISQ < 6 was prevalent among residents of Saudi Arabia's Western Province and correlated significantly with obesity, sleep duration, and smoking status. Various measures to mitigate the negative impact of an unhealthy lifestyle on public health and to reverse the observed poor immune health and their economic consequences are highly required.