The study explores antibacterial, antiinflammatory and cytoprotective capacity of Pelargonium sidoides DC root extract (PSRE) and proanthocyanidin fraction from PSRE (PACN) under conditions characteristic for periodontal disease. Following previous finding that PACN exerts stronger suppression of Porphyromonas gingivalis compared to the effect on commensal Streptococcus salivarius, the current work continues antibacterial investigation on Staphylococcus aureus, Staphylococcus epidermidis, Aggregatibacter actinomycetemcomitans and Escherichia coli. PSRE and PACN are also studied for their ability to prevent gingival fibroblast cell death in the presence of bacteria or bacterial lipopolysaccharide (LPS), to block LPS- or LPS + IFNγ-induced release of inflammatory mediators, gene expression and surface antigen presentation. Both PSRE and PACN were more efficient in suppressing Staphylococcus and Aggregatibacter compared to Escherichia, prevented A. actinomycetemcomitans- and LPS-induced death of fibroblasts, decreased LPS-induced release of interleukin-8 and prostaglandin E2 from fibroblasts and IL-6 from leukocytes, blocked expression of IL-1β, iNOS, and surface presentation of CD80 and CD86 in LPS + IFNγ-treated macrophages, and IL-1β and COX-2 expression in LPS-treated leukocytes. None of the investigated substances affected either the level of secretion or expression of TNFα. In conclusion, PSRE, and especially PACN, possess strong antibacterial, antiinflammatory and gingival tissue protecting properties under periodontitis-mimicking conditions and are suggestable candidates for treatment of the disease.

Although the pig is a model for heart disease, the neuroanatomy of cardiac ventricles (CV) in this species remains undetailed. We aimed to define the innervation pattern of pig CV, combining histochemistry for acetylcholinesterase, immunofluorescent labeling and electron microscopy. Forty nine examined pig hearts show that the major nerves supplying the ventral side of CV descend from the venous part of the heart hilum. Fewer in number and smaller in size, epicardial nerves supply the dorsal half of the CV. Epicardial nerves on the left ventricle are thicker than those on the right. Ventricular ganglia of various sizes distribute at the basal level of both CV. Averagely, we found 3,848 ventricular neuronal somata per heart. The majority of somata were cholinergic, although ganglionic cells of different neurochemical phenotypes (positive for nNOS, ChAT/nNOS, or ChAT/TH) were also observed. Large and most numerous nerves proceeded within the epicardium. Most of endocardium and myocardium contained a network of nerve bundles and nerve fibers (NFs). But, a large number of thin nerves extended along the bundle of His and its branches. The majority of NFs were adrenergic, while cholinergic NFs were scarce yet more abundant than nitrergic ones. Sensory NFs positive for CGRP were the second most abundant phenotype after adrenergic NFs in all layers of the ventricular wall. Electron microscopy elucidated that ultrastructure of nerves varied between different areas of CV. The described structural organization of CV provides an anatomical basis for further functional and pathophysiological studies in the pig heart. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:1756–1780, 2017.

Fever is the most common complaint of children who are attending a pediatric emergency department (PED). Most of the fever cases are of viral origin; however, the most common markers, such as leucocyte, neutrophil count, or C-reactive protein, are not sensitive or specific enough to distinguish the etiology of fever, especially if children present at the early phase of infection. Currently, platelets have been attributed a role as important sentinels in viral and bacterial infection pathogenesis. Thus, our aim was to analyze different platelet indices, such as PNLR (platelet-to-neutrophil/lymphocyte ratio), PNR (platelet-to-neutrophil ratio) as well as specific secreted proteins, such as sP-selectin, CXCL4, CXCL7, and serotonin. We included 68 children who were referred to PED with the early onset of fever (<12 h). All children with comorbidities, older than five years, and psychiatric diseases, who refused to participate were excluded. All the participants were divided into viral, bacterial, or serious bacterial infection (SBI) groups. All the children underwent blood sampling, and an additional sample was collected for protein analysis. Our analysis revealed statistically significant differences between leucocyte, neutrophil, and CRP levels between SBI and other groups. However, leucocyte and neutrophil counts were within the age norms. A higher PNLR value was observed in a bacterial group, PNR-in viral. As we tested CXCL7 and sP-selectin, alone and together those markers were statistically significant to discriminate SBI and sepsis from other causes of infection. Together with tachypnoe and SpO2 < 94%, it improved the prediction value of sepsis as well as SBI. CXCL4 and serotonin did not differ between the groups. Concluding, CXCL7 and sP-selectin showed promising results in early SBI and sepsis diagnosis.

The implementation of structured guidelines, such as the World Health Organisation’s Emergency Triage, Assessment and Treatment has been shown to reduce in-hospital mortality, addressing the high burden of early in-hospital deaths. We evaluated the capacity to provide paediatric emergency care at higher-level health facilities in the Busoga sub-region, Uganda, and explored healthcare workers’ perceptions of quality care. This assessment aimed to inform policy and facilitate the implementation of guidelines. A comprehensive mixed-methods study was conducted, comprising a facility audit, a survey of healthcare providers to assess their knowledge, and focus group discussions with facility staff. The study included all public and private not-for-profit facilities that provide in-patient paediatric care in Busoga. Quantitative data were analysed using descriptive statistics and linear regression, while thematic analysis with the framework method approach was applied to qualitative data. A total of 14 focus group discussions, 14 facility audits, and 100 surveys with healthcare providers were conducted. Essential equipment for paediatric emergencies and staff shortages were identified as primary barriers to quality care and key contributors to worker demotivation. Referrals were one of the main challenges, with only 25% of facilities accessing a fuelled ambulance. Knowledge scores were higher among healthcare professionals who had undergone emergency management training and participated in refresher courses (mean 13.2, 95% CI 11.6–14.8, compared to 9.2, 95% CI 8.0–10.3). Participants who felt well-prepared achieved markedly higher scores on knowledge surveys than those feeling unprepared (mean 12.2, 95% CI 11.2–13.1, versus mean 8.5, 95% CI 7.3–9.7). Qualitative discussions demonstrated positive attitudes of healthcare workers toward ETAT guidelines. Results underscore the importance of focused training with refresher sessions to enhance health workers’ knowledge and confidence in managing paediatric emergency cases. However, substantial limitations in staffing numbers and the availability of necessary equipment need to be addressed for overall quality of care improvement.

Melatonin is a hormone naturally produced by the body that has recently been found to have antiviral properties. However, its antiviral mechanisms are not entirely understood. Using Caco-2 cells, we developed a gastrointestinal organoid model to investigate the impact of melatonin on cellular organoid culture response to Poly I:C-induced viral inflammation in the gastrointestinal tract. Melatonin was found to have different effect when applied as a pretreatment before the induction of viral inflammation or as a treatment after it. Melatonin pretreatment after Poly I:C stimulation did not protect organoids from size reduction but enhanced cell proliferation, especially when lower (1 and 10 µM) melatonin concentrations were used. On the other hand, treatment with melatonin after the induction of viral inflammation helped to maintain the size of the organoids while reducing cell proliferation. In pretreated cells, reduced IFNLR1 expression was found, while melatonin treatment increased IFNLR1 expression and reduced the production of viral cytokines, such as IFNλ1 and STAT1-3, but did not prevent from apoptosis. The findings of this study emphasize the importance of type III IFNs in antiviral defense in epithelial gastrointestinal cells and shed more light on the antiviral properties of melatonin as a potential therapeutic substance.