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Purpose: Inflammation may contribute to the pathogenesis of specific cardiovascular diseases, but it is uncertain if mediators released during the inflammatory process will affect the continued efficacy of drugs used to treat clinical signs of the cardiac disease. We investigated the role of the complement 5a receptor 1 (C5aR1/CD88) in the cardiac response to inflammation or atenolol, and the effect of C5aR1 deletion in control of baseline heart rate in an anesthetized mouse model. Methods: An initial study showed that PMX53, an antagonist of C5aR1 in normal C57BL6/J (wild type, WT) mice reduced heart rate (HR) and appeared to have a protective effect on the heart following induced sepsis. C5aR1 knockout (CD88-/-) mice had a lower HR than wild type mice, even during sham surgery. A model to assess heart rate variability (HRV) in anesthetized mice was developed to assess the effects of inhibiting the β1-adrenoreceptor (β1-AR) in a randomized crossover study design. Results: HR and LF Norm were constitutively lower and SDNN and HF Norm constitutively higher in the CD88-/- compared with WT mice (P< 0.001 for all outcomes). Administration of atenolol (2.5 mg/kg) reduced the HR and increased HRV (P< 0.05, respectively) in the wild type but not in the CD88-/- mice. There was no shift of the sympathovagal balance post-atenolol in either strains of mice (P> 0.05), except for the reduced LF/HF (Lower frequency/High frequency) ratio (P< 0.05) at 60 min post-atenolol, suggesting increased parasympathetic tone of the heart due to the effect of atenolol administration. The HR of the WT mice were lower post atenolol compared to the CD88-/- mice (P = 0.001) but the HRV of CD88-/- mice were significantly increased (P< 0.05), compared with WT mice. Conclusion: Knockout of the C5aR1 attenuated the effect of β1-AR in the heart, suggesting an association between the β1-AR and C5aR1, although further investigation is required to determine if this is a direct or causal association. [ABSTRACT FROM AUTHOR]

The article discusses the case of a twin boy diagnosed with congenital hyperinsulinism of infancy. Topics discussed include hypoglycemia manifestation of congenital hyperinsulinism of infancy, focal lesion in the pancreas revealed by 18 fluoro-dihydroxy phenylalanine positron emission tomography/computed tomography (PET-CT), and laparoscopic resection of the lesion.

Background: Hypertrophic scars in burn victims usually occur after delayed wound healing and the active phase of scar formation can persist substantially even after wound closure. Currently, the pathophysiology of the hypertrophic scar is not completely understood. This study investigated the inflammatory response in scar tissue at week 6 post-burn injury. Methods: A porcine deep dermal partial thickness burn model was used. At week 6 post-burn, a total of 528 scar biopsies from 72 burn scars (7–8 biopsies from each scar) and 174 normal skin biopsies from 18 pigs were collected and examined histologically. Results: Microscopic inflammatory foci were identified in 17% (89/528) of scar biopsies. These microscopic inflammatory foci do not contain any irritant materials, are composed largely of polymorphonuclear cells with other inflammatory cells including multinucleate giant cells and show acute on chronic inflammatory response that has not been described previously in burn scars. Importantly, they are present in a significantly lower number in burns surgically debrided than in burns which have not been debrided. Conclusions: This study identifies microscopic inflammatory foci in the porcine scar tissue layer and recommends thorough cleaning/debriding of burned necrotic tissue in order to minimize the formation of these inflammatory foci in scar tissue. Wang X-Q, Phillips GE, Wilkie I, Greer R, Kimble RM. Microscopic inflammatory foci in burn scars: data from a porcine burn model. [ABSTRACT FROM AUTHOR]

Background: There is considerable evidence supporting the role of vitamin D deficiency in the pathogenesis of type 1 diabetes mellitus (T1DM). Vitamin D deficiency is also associated with impairment of insulin synthesis and secretion. There have been no formal studies looking at the relationship between 25(OH)-vitamin D3 and the severity of diabetic ketoacidosis (DKA) in children at presentation with T1DM. Objective: To determine the relationship between measured 25(OH)-vitamin D3 levels and the degree of acidosis in children at diagnosis with T1DM. Subjects: Children presenting with new-onset T1DM at a tertiary children’s hospital. Methods: 25(OH)-vitamin D3 and bicarbonate levels were measured in children at presentation with newly diagnosed T1DM. Those with suboptimal 25(OH)-vitamin D3 levels (<50 nmol/L) had repeat measurements performed without interim vitamin D supplementation. Results: Fourteen of the 64 children had low 25(OH)-vitamin D3 levels at presentation, and 12 of these had low bicarbonate levels (<18 mmol/L) (p = 0.001). Bicarbonate explained 20% of the variation in vitamin D level at presentation (partial r2 = 0.20, p < 0.001) and ethnic background a further 10% (partial r2 = 0.10, p = 0.002). The levels of 25(OH)-vitamin D3 increased in 10 of the 11 children with resolution of the acidosis. Conclusions: Acid–base status should be considered when interpreting 25(OH)-vitamin D3 levels in patients with recently diagnosed T1DM. Acidosis may alter vitamin D metabolism, or alternatively, low vitamin D may contribute to a child’s risk of presenting with DKA. [ABSTRACT FROM AUTHOR]

Introduction: Cannabidiol (CBD) exhibits multiple therapeutic properties, but its use in advanced cancer patients raises concerns about potential drug-drug interactions (DDIs) due to polypharmacy. This study aims to look for evidence of DDIs between concomitant medications and CBD oil in a randomized placebo-controlled trial of CBD oil for symptom control (MedCan-1 parent study). Materials and Methods: Surrogate measures were used to identify possible drug interactions: (1) the maximum mL of oil self-selected by patients in CBD or placebo groups in relation to opioids, specific drug groups, or individual agents; (2) the occurrence of any new or worse adverse effect in relation to the study arm and the concomitant medication classes/medications of interest. Results: The dose of CBD self-selected by participants was not related to opioid use or medications, including benzodiazepines and antipsychotics. The likelihood of developing an adverse effect while on study or when taking specific medications was not increased by CBD. Participants on paracetamol tolerated a higher dose of CBD. Discussion: Concerns regarding the development of clinically significant drug interactions when taking CBD in the context of anti-cancer and other concomitant medications at least in the short term may be unfounded.

Purpose: Rhinoviruses (RVs) occur more frequently than other viruses and more often in people displaying symptoms than in those without. We sought to estimate the spectrum of RV diversity, RV species seasonality and to analyse RV involvement in respiratory virus co-detections., Methodology: A convenience collection of 1179 airway sample extracts from patients with suspected respiratory infections, collected during 2001, was subjected to comprehensive molecular testing., Results: RVs were the most common virus detected. We were able to genotype ~90 % of RV detections, identifying 70 distinct RVs, spanning all three species. RV-Bs were under-represented. We found RV species co-circulated at times, although one species usually dominated. Each species displayed a bimodal distribution., Conclusion: Notably, RVs and influenza A viruses (IFAV) seldom co-occurred, supporting their roles as primary pathogens of the airway among acutely ill infants. Whether RV circulation has a moderating or controlling effect on the IFAV season or is controlled by it cannot be determined from these data. Despite the frequent perception that RVs commonly co-occur with another virus, our findings indicated this was not always the case. Nearly 80 % of RV detections occurred alone. Understanding more about population-level interference between viruses may allow us to harness aspects of it to generate a non-specific antiviral intervention that mimics a putative protective effect. For routine respiratory virus screening to best serve the patient, RV testing should be a principal component of any acute respiratory illness testing algorithm throughout the year., Competing Interests: The authors declare that there are no conflicts of interest., (© 2020 The Authors.)