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Necrotizing enterocolitis (NEC) is a complex intestinal disease that primarily affects premature neonates. Given its significant mortality and morbidity, there is an urgent need to develop improved prophylactic measures against the disease. One potential preventative strategy for NEC is the use of probiotics. Although there has been significant interest for decades in probiotics in neonatal care, no clear guidelines exist regarding which probiotic to use or for which patients, and no FDA-approved products exist on the market for NEC. In addition, there is lack of agreement regarding the benefits of probiotics in neonates, as well as some concerns about the safety and efficacy of available products. We discuss currently available probiotics as well as next-generation probiotics and novel delivery strategies which may offer an avenue to capitalize on the benefits of probiotics, while minimizing the risks. Thus, probiotics may still prove to be an effective prevention strategy for NEC, although further product development and research is needed to support use in the preterm population.

Mesenchymal stem cells (MSCs) are multipotent adult stem cells which have become popular research targets for their use in cellular therapy for tissue repair. While recent advancements in research have shown the MSCs have immunomodulatory functions which are altered in response to host inflammatory molecules, how these stimuli produce different functional outcomes is not understood. Here, we evaluate research examining how the proinflammatory cytokine interferon-γ (IFN-γ) affects the immunomodulatory functions of MSCs by altering their metabolism. This study indicates that IFN-γ causes an increase in glycolytic activity and uncoupling of glycolysis to tricarboxylic acid cycle and hence, the glycolytic metabolites and intermediates can be funneled toward the production of anti-inflammatory modulators indoleamine-2,3-dioxygenase and PGE2. A complete understanding of how MSCs' cellular metabolism affects their function is necessary for their employment in cellular therapy, as MSCs have been demonstrated to have pro- and anti-inflammatory functions. These findings are a large step forward in the understanding of the regulation of MSCs and toward their eventual use in cellular therapy, specifically for stroke recovery, in which MSCs have been shown to have powerful neuroprotective and neurogenerative effects.

Background The process of obtaining informed consent is an important and complex pursuit, especially within a paediatric setting. Medical governing bodies have stated that the role of the trainee surgeon must be explained to patients and their families during the consent process. Despite this, attitudes and practices of surgeons and their trainees regarding disclosure of the trainee’s participation during the consent process has not been reported in the paediatric setting.Methods Nineteen face-to-face interviews were conducted with surgical trainees and staff surgeons at a tertiary-level paediatric hospital in Toronto, Canada. These were transcribed and subsequently thematically coded by three reviewers.Results Five main themes were identified from the interviews. (1) Surgeons do not consistently disclose the role of surgical trainees to parents. (2) Surgical trainees are purposefully vague in disclosing their role during the consent discussion without being misleading. (3) Surgeons and surgical trainees believe parents do not fully understand the specific role of surgical trainees. (4) Graduated responsibility is an important aspect of training surgeons. (5) Surgeons feel a responsibility towards both their patients and their trainees. Surgeons do not explicitly inform patients about trainees, believing there is a lack of understanding of the training process. Trainees believe families likely underestimate their role and keep information purposely vague to reduce anxiety.Conclusion The majority of surgeons and surgical trainees do not voluntarily disclose the degree of trainee participation in surgery during the informed consent discussion with parents. An open and honest discussion should occur, allowing for parents to make an informed decision regarding their child’s care. Further patient education regarding trainees’ roles would help develop a more thorough and patient-centred informed consent process.

Background Paediatric clavicle fractures are commonly seen in the emergency department (ED), and the current standard of care is to obtain a radiograph for all suspected clavicle fractures. We are yet to determine whether radiographs add valuable information to clinicians’ assessment and therefore if they are necessary in the management of paediatric clavicle fractures.Objective To determine whether clinicians can manage paediatric clavicle fractures without radiographs, first by determining the accuracy of clinicians in identifying the presence of a clavicle fracture, and second by evaluating the level of agreement (kappa (κ)) between the ultimate management of children with suspected clavicle fractures and clinicians’ blinded prediction prior to the radiograph.Methods This prospective study enrolled patients presenting to a paediatric ED with a suspected clavicle fracture. Prior to requesting a radiograph, clinicians completed a standardised form, where they predicted the presence of a fracture and their ultimate management based on their clinical findings, and rated their confidence.Results Of the 50 patients aged 7.2±3.9 years included, 40 (80%) had a radiologically proven clavicle fracture, and clinicians were able to accurately identify them (sensitivity 93%, positive predictive value 88%). There were five (50%) patients without a radiological fracture that were treated with broad arm sling. Clinicians’ prediction of ultimate management had the highest agreement with the ultimate management of the patient on leaving the ED, compared with clinicians’ prediction of the presence of fracture and the final radiograph findings: κ of 0.88 (95% CI 0.64 to 1), 0.67 (95% CI 0.36 to 0.98) and 0.62 (95% CI 0.30 to 0.94), respectively. Thirty-six (72%) of the clinicians felt comfortable treating without radiographs, and this was dependent on their level of training.Conclusions Clinicians can identify the presence of a fracture and tend to be overconservative in their management. Despite negative radiological findings, some patients were treated as though they had a fracture, based on clinical judgement. This adds evidence that radiographs are not routinely required for uncomplicated paediatric clavicle fractures.

Recent translational studies in the fields of tissue regeneration and cell therapy have characterized mesenchymal stem cells (MSCs) as a potentially effective and accessible measure for treating ischemic cerebral and neurodegenerative disorders such as stroke, Parkinson's disease, and amyotrophic lateral sclerosis. Developing more efficient cell tracking techniques bear the potential to optimize MSC transplantation therapies by providing a more accurate picture of the fate and area of effect of implanted cells. Currently, determining the location of transplanted MSCs involves a histological approach, but magnetic resonance imaging (MRI) presents a noninvasive paradigm that permits repeat evaluations. To visualize MSCs using MRI, the implanted cells must be treated with an intracellular contrast agent. These are commonly paramagnetic compounds, many of which are based on superparamagnetic iron oxide (SPIO) nanoparticles. Recent research has set out characterize the effects of SPIO-uptake on the cellular activity of in vitro human MSCs and the resultant influence that respective SPIO concentration has on MRI sensitivity. As these studies reveal, SPIO-uptake has no effect on the cellular processes of proliferation and differentiation while producing high contrast MRI signals. Moreover, transplantation of SPIO-labeled MSCs in animal models encouragingly showed no loss in MRI contrast, suggesting that SPIO labeling may be an appealing regime for lasting MRI detection. This study is a review article. Referred literature in this study has been listed in the reference part. The datasets supporting the conclusions of this article are available online by searching the PubMed. Some original points in this article come from the laboratory practice in our research centers and the authors' experiences.

[This corrects the article DOI: 10.1371/journal.pone.0283643.].

BackgroundLassa fever (LF), a haemorrhagic illness caused by the Lassa fever virus (LASV), is endemic in West Africa and causes 5000 fatalities every year. The true prevalence and incidence rates of LF are unknown as infections are often asymptomatic, clinical presentations are varied, and surveillance systems are not robust. The aim of the Enable Lassa research programme is to estimate the incidences of LASV infection and LF disease in five West African countries. The core protocol described here harmonises key study components, such as eligibility criteria, case definitions, outcome measures, and laboratory tests, which will maximise the comparability of data for between-country analyses.MethodWe are conducting a prospective cohort study in Benin, Guinea, Liberia, Nigeria (three sites), and Sierra Leone from 2020 to 2023, with 24 months of follow-up. Each site will assess the incidence of LASV infection, LF disease, or both. When both incidences are assessed the LASV cohort (nmin = 1000 per site) will be drawn from the LF cohort (nmin = 5000 per site). During recruitment participants will complete questionnaires on household composition, socioeconomic status, demographic characteristics, and LF history, and blood samples will be collected to determine IgG LASV serostatus. LF disease cohort participants will be contacted biweekly to identify acute febrile cases, from whom blood samples will be drawn to test for active LASV infection using RT-PCR. Symptom and treatment data will be abstracted from medical records of LF cases. LF survivors will be followed up after four months to assess sequelae, specifically sensorineural hearing loss. LASV infection cohort participants will be asked for a blood sample every six months to assess LASV serostatus (IgG and IgM).DiscussionData on LASV infection and LF disease incidence in West Africa from this research programme will determine the feasibility of future Phase IIb or III clinical trials for LF vaccine candidates.