Pediatric anesthesia in North America.

BACKGROUND AND OBJECTIVES: This educational review outlines the current landscape of pediatric anesthesia training, care delivery, and challenges across Canada, Barbados, and the United States. DESCRIPTIONS AND CONCLUSIONS: Approximately 5% of Canadian children undergo general anesthesia annually, administered by fellowship-trained pediatric anesthesiologists in children's hospitals, general anesthesiologists in community hospitals, or family practice anesthesiologists in underserved regions. In Canada, the focus is on national-level evaluation and accreditation of pediatric anesthesia fellowship training, addressing challenges arising from workforce shortages, particularly in remote areas. Barbados, a Caribbean nation, lacks dedicated pediatric hospitals but has provided pediatric anesthesia since 1972 through anesthetists with additional training. Challenges in its development, common to low-middle-income countries, include inadequate infrastructure and workforce shortages. Increased awareness of pediatric anesthesia as a sub-specialty could enhance perioperative care for Barbadian children. Pediatric anesthesia encompasses various specialties in the United States, with pediatric anesthesiologists playing a foundational role. Challenges faced include recruitment and retention difficulties, supply-chain shortages, and the proliferation of anesthesia sites, all impacting the delivery of modern, high-quality, and cost-effective patient care. Collaborative efforts at national and organizational levels strive to improve the quality and safety of pediatric anesthesia care in the United States.

Professorial Advancement Initiative: A Cross-Institutional Collaboration to Increase Faculty Diversity in STEM.

In this paper, we describe the model for faculty diversity developed as part of the Professorial Advancement Initiative (PAI) funded under the NSF AGEP program. The PAI, consisting of 12 of the 14 Big Ten Academic Alliance universities, had the goal of doubling the rate at which the universities hired tenure-track minoritized faculty, defined by National Science Foundation as African Americans, Hispanic/Latinx, Native Americans, and Pacific Islanders. This paper reviews the key programmatic elements of the PAI and discusses lessons learned and the practices developed that helped the Alliance achieve its faculty diversity goal.

Effect of Hypoxia on the Lethal Mortality Time of Adult Sitophilus oryzae L.

Sitophilus oryzae is one of the most destructive pests of stored grains. It leads to significant quantitative and qualitative losses, resulting in food and income insecurity among farmers. Chemical pesticides are the most common methods used by farmers and other grain value chain actors to manage this pest. However, pesticides are increasingly becoming unattractive for pest control due to health hazards posed to applicators, consumers, the environment, and insect resistance. Modified atmospheres have the potential to manage stored insect pests as an alternative to pesticides. There is limited understanding of when insect pests die when grain is stored in airtight containers. This experiment was conducted to assess the time required to reach mortality of adult S. oryzae when exposed to 1, 3, and 5% oxygen levels. Results revealed that the LT50 for 1, 3, and 5% of oxygen were reached after 69.7 h, 187.8 h, and 386.6 h of exposure, respectively. No adult emergence was observed on infested grains following exposure to 1 and 3% oxygen levels. This result provides vital rationale for storing grain in hermetic storage conditions for at least 39 days to achieve adult S. oryzae mortality and minimize grain reinfestation.

Determining baseline toxicity of ozone against an insecticide-susceptible strain of the common bed bug, Cimex lectularius L. under laboratory conditions.

BACKGROUND: Ozone gas is commercially used for deodorization and microbial control. Its efficacy against stored product insect pests is well documented. In the midst of the common bed bug (Cimex lectularius L.) outbreak, claims were made that ozone gas was effective for their control. This study was conducted to determine baseline ozone concentrations and exposure times required for the control of an insecticide-susceptible C. lectularius strain under laboratory conditions. Dichlorvos (DDVP), an organophosphate class fumigant insecticide was used as a positive control. RESULTS: Nymphs and adults were more susceptible to ozone than eggs. Complete (100%) nymph and adult mortality was achieved at an ozone concentration (C) of 1500 ppm and exposure time (T) of 180 min, or concentration × time product (CT) of 270 000 ppm-min, whereas eggs required an eightfold higher CT (2 040 000 ppm-min). DDVP vapor was 2070-, 2542- and 450-fold more potent than ozone, against nymphs, adults and eggs, respectively. CONCLUSIONS: Baseline ozone toxicity data provide insights on the practicality of using this gas for the management of common bed bugs. High ozone CT products required for C. lectularius control, particularly eggs, suggest that its use for treating infested human dwellings is not feasible due to logistic, safety and monetary concerns. © 2020 Society of Chemical Industry.

A time-saving method for sealing Purdue Improved Crop Storage (PICS) bags.

Purdue Improved Crop Storage (PICS) bags were designed to reduce grain storage losses on smallholder farms. The bag consists of three layers: two high-density polyethylene liners fitted inside a woven polypropylene bag. Recently, farmer groups, development relief programs, and government food security agencies have shown interest in PICS bags for large-scale use. PICS bags are conventionally closed by a twist-tie (TT) method, which involves twisting, folding, and tying the lip of each layer individually with a cord. This is not only time and labor intensive, but also may affect the integrity of the liners. We evaluated three new bag closure methods: i) inner liner rolled onto itself and middle liner fold-tied (IR), ii) both liners folded together and tied (FT), and iii) both liners folded and tied separately (FS), along with the conventional twist tie (TT) method. The time to close partially or fully filled 50 kg-capacity PICS bags filled with maize grain was assessed. Results showed that FT was the most time-saving method, reducing bag sealing time by >34% versus the usual TT method. The average internal oxygen levels reached <2% within a week in bags containing grain highly infested with Sitophilus zeamais, while it remained >5% levels for less-infested bags. In both cases, insect population growth was suppressed. Oxygen depletion rates among tying methods remained the same regardless of the closure method used. When large numbers of bags need to be closed, the time-saving FT method is a good alternative PICS sealing method over the conventional twist-tie approach.

Essential role for CCR6 in certain inflammatory diseases demonstrated using specific antagonist and knockin mice.

The chemokine receptor CCR6 marks subsets of T cells and innate lymphoid cells that produce IL-17 and IL-22, and as such may play a role in the recruitment of these cells to certain inflammatory sites. However, the precise role of CCR6 has been controversial, in part because no effective monoclonal antibody (mAb) inhibitors against this receptor exist for use in mouse models of inflammation. We circumvented this problem using transgenic mice expressing human CCR6 (hCCR6) under control of its native promoter (hCCR6-Tg/mCCR6-/-). We also developed a fully humanized mAb against hCCR6 with antagonistic activity. The expression pattern of hCCR6 in hCCR6-Tg/mCCR6-/- mice was consistent with the pattern observed in humans. In mouse models of experimental autoimmune encephalomyelitis (EAE) and psoriasis, treatment with anti-hCCR6 mAb was remarkably effective in both preventive and therapeutic regimens. For instance, in the imiquimod model of psoriasis, anti-CCR6 completely abolished all signs of inflammation. Moreover, anti-hCCR6 attenuated clinical symptoms of myelin oligodendrocyte glycoprotein-induced (MOG-induced) EAE and reduced infiltration of inflammatory cells in the central nervous system. CCR6 plays a critical role in Th17 type inflammatory reactions, and CCR6 inhibition may offer an alternative approach for the treatment of these lesions.

Translocation and dissemination of commensal bacteria in post-stroke infection.

Bacterial infection is highly prevalent in patients who have had a stroke. Despite the potential contribution of micro-aspiration in post-stroke pneumonia, we found that the majority of the microorganisms detected in the patients who developed infections after having a stroke were common commensal bacteria that normally reside in the intestinal tracts. In a mouse model of ischemic stroke, post-stroke infection was only observed in mice that were born and raised in specific-pathogen-free facilities; this was not seen in mice that were born and raised in germ-free facilities. Using high-throughput 16S rRNA gene amplicon sequencing and bioinformatics analyses, we provide evidence demonstrating that the source of the bacteria forming the microbial community in the lungs of post-stroke mice was indeed the host small intestine. Additionally, stroke-induced gut barrier permeability and dysfunction preceded the dissemination of orally inoculated bacteria to peripheral tissues. This study identifies a novel pathway in which stroke promotes the translocation and dissemination of selective strains of bacteria that originated from the host gut microbiota.

G Protein-Coupled Receptor 43 Modulates Neutrophil Recruitment during Acute Inflammation.

Fermentation of dietary fibre in the gut yields large amounts of short chain fatty acids (SCFAs). SCFAs can impart biological responses in cells through their engagement of 'metabolite-sensing' G protein-coupled receptors (GPCRs). One of the main SCFA receptors, GPR43, is highly expressed by neutrophils, which suggests that the actions of GPR43 and dietary fibre intake may affect neutrophil recruitment during inflammatory responses in vivo. Using intravital imaging of the small intestine, we found greater intravascular neutrophil rolling and adhesion in Gpr43-/-mice in response to LPS at 1 h. After 4 h of LPS challenge, the intravascular rolling velocity of GPR43-deficient neutrophils was reduced significantly and increased numbers of neutrophils were found in the lamina propria of Gpr43-/-mice. Additionally, GPR43-deficient leukocytes demonstrated exacerbated migration into the peritoneal cavity following fMLP challenge. The fMLP-induced neutrophil migration was significantly suppressed in wildtype mice that were treated with acetate, but not in Gpr43-/-mice, strongly suggesting a role for SCFAs in modulating neutrophil migration via GPR43. Indeed, neutrophils of no fibre-fed wildtype mice exhibited elevated migratory behaviour compared to normal chow-fed wildtype mice. Interestingly, this elevated migration could also be reproduced through simple transfer of a no fibre microbiota into germ-free mice, suggesting that the composition and function of microbiota stemming from a no fibre diet mediated the changes in neutrophil migration. Therefore, GPR43 and a microbiota composition that allows for SCFA production function to modulate neutrophil recruitment during inflammatory responses.

Avenues to autoimmune arthritis triggered by diverse remote inflammatory challenges.

Environmental factors contribute to development of autoimmune diseases. For instance, human autoimmune arthritis can associate with intestinal inflammation, cigarette smoking, periodontal disease, and various infections. The cellular and, molecular pathways whereby such remote challenges might precipitate arthritis or flares remain unclear. Here, we used a transfer model of self-reactive arthritis-inducing CD4(+) cells from KRNtg mice that, upon transfer, induce a very mild form of autoinflammatory arthritis in recipient animals. This model enabled us to identify external factors that greatly aggravated disease. We show that several distinct challenges precipitated full-blown arthritis, including intestinal inflammation through DSS-induced colitis, and bronchial stress through Influenza infection. Both triggers induced strong IL-17 expression primarily in self-reactive CD4(+) cells in lymph nodes draining the site of inflammation. Moreover, treatment of mice with IL-1ß greatly exacerbated arthritis, while transfer of KRNtg CD4(+) cells lacking IL-1R significantly reduced disease and IL-17 expression. Thus, IL-1ß enhances the autoaggressive potential of self-reactive CD4(+) cells, through increased Th17 differentiation, and this influences inflammatory events in the joints. We propose that diverse challenges that cause remote inflammation (lung infection or colitis, etc.) result in IL-1ß-driven Th17 differentiation, and this precipitates arthritis in genetically susceptible individuals. Thus the etiology of autoimmune inflammatory arthritis likely relates to diverse triggers that converge to a common pathway involving IL-1ß production and Th17 cell distribution.

The Role of Follicular Helper T Cell Molecules and Environmental Influences in Autoantibody Production and Progression to Inflammatory Arthritis in Mice.

OBJECTIVE: Antibody-mediated autoimmunity involves cognate interactions between self-reactive T cells and B cells during germinal center (GC) reactions. The aim of this study was to determine the role of essential follicular helper T (Tfh) cell molecules (CXCR5, signaling lymphocytic activation molecule-associated protein) on autoreactive CD4+ cells and the role of certain environmental influences that may determine GC-driven autoantibody production and arthritis development. METHODS: We transferred self-reactive CD4+ cells from KRN-Tg mice into recipient mice, which induced autoantibodies and autoinflammatory arthritis. This model allowed manipulation of environmental effects, such as inflammation, and use of transferred cells that were genetically deficient in important Tfh cell-associated molecules. RESULTS: A deficiency of signaling lymphocytic activation molecule-associated protein (SAP) in CD4+ cells from KRN-Tg mice completely protected against arthritis, indicating that stable T cell-B cell interactions are required for GC formation, autoantibody production, and arthritis induction. In contrast, a CXCR5 deficiency in CD4+ cells from KRN-Tg mice still induced disease when these cells were transferred into wild-type mice, suggesting that T cell help for B cells could rely on other migration mechanisms. However, various manipulations influenced this system, including elimination of bystander effects through use of CD28(-/-) recipient mice (reduced disease) or use of inflammation-inducing Freund's complete adjuvant (progression to arthritis). We also examined the capacity of preexisting GCs with a nonautoimmune specificity to co-opt autoimmune T cells and observed no evidence for any influence. CONCLUSION: In addition to the quality and quantity of cognate CD4+ cell help, external factors such as inflammation and noncognate CD4+ cell bystander activation trigger autoimmunity by shaping events within autoimmune GC responses. SAP is an essential molecule for autoimmune antibody production, whereas the importance of CXCR5 varies depending on the circumstances.

Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites.

Asthma is prevalent in Western countries, and recent explanations have evoked the actions of the gut microbiota. Here we show that feeding mice a high-fibre diet yields a distinctive gut microbiota, which increases the levels of the short-chain fatty acid, acetate. High-fibre or acetate-feeding led to marked suppression of allergic airways disease (AAD, a model for human asthma), by enhancing T-regulatory cell numbers and function. Acetate increases acetylation at the Foxp3 promoter, likely through HDAC9 inhibition. Epigenetic effects of fibre/acetate in adult mice led us to examine the influence of maternal intake of fibre/acetate. High-fibre/acetate feeding of pregnant mice imparts on their adult offspring an inability to develop robust AAD. High fibre/acetate suppresses expression of certain genes in the mouse fetal lung linked to both human asthma and mouse AAD. Thus, diet acting on the gut microbiota profoundly influences airway responses, and may represent an approach to prevent asthma, including during pregnancy.

Challenges in paediatric ambulatory anesthesia.

PURPOSE OF REVIEW: Clinical studies and new guidelines are frequently being published in the area of preoperative fasting. A growing population of patients with obstructive sleep apnea is being referred for outpatient procedures including adenotonsillectomy. RECENT FINDINGS: Recently published preoperative fasting guidelines for pediatric patients are covered along with studies comparing gastric volume following different fasting intervals. Pediatric obstructive sleep apnea is discussed. Clinical presentation, severity, perioperative risks, and controversies as whether outpatient procedures are suitable for these patients are presented. New data covering different perioperative aspects are presented. SUMMARY: A more liberal preoperative intake is encouraged with fasting for 2 h for clear liquids, 4  h for breast milk, 6  h for formula and light meals, and 8  h for heavy meals is widely accepted. Interpersonal variation in residual gastric volume exists. Children with obstructive sleep apnea under 3 years of age and those with severe obstructive sleep apnea and comorbidities are not candidates for ambulatory surgery. Polysomnography has specific preoperative indications. Dexmedetomidine can decrease emergence agitation and has an opioid-sparing effect. Intravenous acetaminophen is presented as an opioid-sparing analgesic. Dexamethasone is effective in preventing postoperative nausea without increased risk of bleeding. Surgical techniques may affect postoperative pain.

Airway management in two of newborns with Pierre Robin Sequence: the use of disposable vs multiple use LMA for fiberoptic intubation.

In this article, we discuss the use of LMAs as a conduit to intubate the trachea of two Pierre Robin Sequence infants. Multiple use LMAs will admit larger diameter tracheal tubes (TT) than their disposable counterparts. Increased friction with the surface of the TT makes passing even small diameter tubes through the lumen of the disposable LMA difficult.