Dynamics of changes in apical cell area during sex comb rotation in Drosophila melanogaster.

Epithelia are highly dynamic tissues displaying various types of tissue rearrangements (Weliky and Oster, 1990; Taylor and Adler, 2008; Harris and Tepass, 2010; Lee et al. , 2013; Firmino et al. , 2016; Rupprecht et al. , 2017). Here, we describe the dynamics of changes in apical cell area (ACA) in an epithelial system displaying tissue rearrangement resulting in sex comb rotation on the forelegs of male Drosophila melanogaster . The sex comb is a row of leg bristles which rotates during morphogenesis (Atallah, 2008; Atallah et al. , 2009; Malagon, 2013). We quantified the ACA in the region proximal to the developing sex comb by tracing apical cell boundaries using ImageJ in pupal first leg imaginal discs. We found that cells display intricate irregular oscillations in size as the comb rotates. However, the net changes in ACA within most of the cells studied are subtle, only 0 to +/-15%. Our current working hypothesis suggests these irregular oscillations confer flexibility during tissue rearrangement and can be an important mechanism for tissue homeostasis.

Intravenous cannula placement in children for induction of general anesthesia: Prospective audit and identification of success factors.

BACKGROUND: Approaches to pediatric induction of anesthesia vary widely. While oral sedative premedication and inhalational induction are common, total intravenous anesthesia is becoming increasingly popular. Total intravenous anesthesia without anxiolytic premedication, which is the most commonly used technique in our hospital, requires intravenous (IV) cannula placement in an awake child. AIMS: To quantify the success rate of IV cannula placement in 1 or 2 attempts and to identify success factors and barriers. METHODS: With ethical approval and written informed consent from participating anesthesiologists, a prospective audit of IV cannulation was undertaken over a 1-month period. The attending anesthesiologist captured basic demographics, IV insertion characteristics, setting, distraction techniques, the behavior of the child, number of attempts, and success/failure. A logistic regression model for successful IV cannulation was created. Anesthesiologists and procedural suite nurses participated in semi-structured interviews to identify success factors, barriers, and teaching approaches. RESULTS: Data from 984 cases were analyzed. IV induction was planned in 562 cases, and IV cannulation was successful in 90% of these patients. Anxiolytic premedication was given in 6% of cases. Observations indicated that 64% of children were pain- and reaction-free, and 90% experienced minimal or no reaction. Predictors for success included older child's age and child behavior at first encounter. Qualitative interview data from 13 participants suggested success factors included effective distraction, preparing the family for IV induction, parental presence, support of the operating room team, effective use of local analgesic cream, adapting the approach to the individual child, and the anesthesiologist's efficiency. Barriers included needle phobia, uncooperative child, anxious parents, ineffective use of analgesic cream, and unfavorable anatomy. Distraction techniques varied by age and developmental stage of the child. CONCLUSIONS: Cannulation for planned IV induction is feasible for most children, enabling increased use of total intravenous anesthesia as an institutional anesthetic strategy.

Unifying Children's Surgery and Anesthesia Stakeholders Across Institutions and Clinical Disciplines: Challenges and Solutions from Uganda.

BACKGROUND: There is a significant unmet need for children's surgical care in low- and middle-income countries (LMICs). Multidisciplinary collaboration is required to advance the surgical and anesthesia care of children's surgical conditions such as congenital conditions, cancer and injuries. Nonetheless, there are limited examples of this process from LMICs. We describe the development and 3-year outcomes following a 2015 stakeholders' meeting in Uganda to catalyze multidisciplinary and multi-institutional collaboration. METHODS: The stakeholders' meeting was a daylong conference held in Kampala with local, regional and international collaborators in attendance. Multiple clinical specialties including surgical subspecialists, pediatric anesthesia, perioperative nursing, pediatric oncology and neonatology were represented. Key thematic areas including infrastructure, training and workforce retention, service delivery, and research and advocacy were addressed, and short-term objectives were agreed upon. We reported the 3-year outcomes following the meeting by thematic area. RESULTS: The Pediatric Surgical Foundation was developed following the meeting to formalize coordination between institutions. Through international collaborations, operating room capacity has increased. A pediatric general surgery fellowship has expanded at Mulago and Mbarara hospitals supplemented by an international fellowship in multiple disciplines. Coordinated outreach camps have continued to assist with training and service delivery in rural regional hospitals. CONCLUSION: Collaborations between disciplines, both within LMICs and with international partners, are required to advance children's surgery. The unification of stakeholders across clinical disciplines and institutional partnerships can facilitate increased children's surgical capacity. Such a process may prove useful in other LMICs with a wide range of children's surgery stakeholders.

Pediatric surgical camps as one model of global surgical partnership: a way forward.

BACKGROUND/PURPOSE: A uniquely Ugandan method of holding surgical "camps" has been one means to deal with the volume of patients needing surgery and provides opportunities for global partnership. METHODS: We describe an evolved partnership between pediatric surgeons in Uganda and Canada wherein Pediatric Surgical Camps were organized by the Ugandans with team participation from Canadians. The camp goals were to provide pediatric surgical and anesthetic service and education and to foster collaboration as a way forward to assist Ugandan health delivery. RESULTS: Three camps were held in Uganda in 2008, 2011, and 2013. A total of 677 children were served through a range of operations from hernia repair to more complex surgery. The educational mandate was achieved through the involvement of 10 Canadian trainees, 20 Ugandan trainees in surgery and anesthesia, and numerous medical students. Formal educational sessions were held. The collaborative mandate was manifest in relationship building, an understanding of Ugandan health care, research projects completed, agreement on future camps, and a proposal for a Canadian-Ugandan pediatric surgery teaching alliance. CONCLUSION: Pediatric Surgical Camps founded on global partnerships with goals of service, education, and collaboration can be one way forward to improve pediatric surgery access and expertise globally.

Robust closed-loop control of induction and maintenance of propofol anesthesia in children.

BACKGROUND: During closed-loop control, a drug infusion is continually adjusted according to a measure of clinical effect (e.g., an electroencephalographic depth of hypnosis (DoH) index). Inconsistency in population-derived pediatric pharmacokinetic/pharmacodynamic models and the large interpatient variability observed in children suggest a role for closed-loop control in optimizing the administration of intravenous anesthesia. OBJECTIVE: To clinically evaluate a robustly tuned system for closed-loop control of the induction and maintenance of propofol anesthesia in children undergoing gastrointestinal endoscopy. METHODS: One hundred and eight children, aged 6-17, ASA I-II, were enrolled. Prior to induction of anesthesia, NeuroSENSE™ sensors were applied to obtain the WAVCNS DoH index. An intravenous cannula was inserted and lidocaine (0.5 mg·kg(-1) ) administered. Remifentanil was administered as a bolus (0.5 µg·kg(-1) ), followed by continuous infusion (0.03 µg·kg(-1) ·min(-1) ). The propofol infusion was closed-loop controlled throughout induction and maintenance of anesthesia, using WAVCNS as feedback. RESULTS: Anesthesia was closed-loop controlled in 102 cases. The system achieved and maintained an adequate DoH without manual adjustment in 87/102 (85%) cases. Induction of anesthesia (to WAVCNS  ≤ 60) was completed in median 3.8 min (interquartile range (IQR) 3.1-5.0), culminating in a propofol effect-site concentration (Ce ) of median 3.5 µg·ml(-1) (IQR 2.7-4.5). During maintenance of anesthesia, WAVCNS was measured within 10 units of the target for median 89% (IQR 79-96) of the time. Spontaneous breathing required no manual intervention in 91/102 (89%) cases. CONCLUSIONS: A robust closed-loop system can provide effective propofol administration during induction and maintenance of anesthesia in children. Wide variation in the calculated Ce highlights the limitation of open-loop regimes based on pharmacokinetic/pharmacodynamic models.

Slower administration of propofol preserves adequate respiration in children.

BACKGROUND: Propofol is a versatile anesthetic agent used in pediatric practice to facilitate investigational and interventional procedures. Propofol can cause significant respiratory depression, the management of which may require advanced airway management skills. This investigation aimed to increase the safety of propofol administration by developing a dosing schedule that would preserve spontaneous respiration in at least 95% of subjects. METHODS: With Research Ethics Board approval and informed consent, American Society of Anesthesiologists' Status I and II children aged 6-15 years presenting for upper or lower gastrointestinal endoscopy were enrolled. An intravenous loading dose of propofol (4 mg·kg(-1) ) was administered at a rate determined by a randomization schedule in a two-phased study. Following the loading dose, additional propofol was infused at 200 mcg·kg(-1) ·min(-1) for 5 min or until respiratory insufficiency was observed. In Phase I, the infusion rate was modified by 100 mcg·kg(-1) ·min(-1) increments depending upon the respiratory response of the previous subject. In Phase II, the duration of infusion was randomized according to a Biased Coin Design principle to determine the 95% threshold for respiratory insufficiency. RESULTS: Fifty subjects were included in the analysis. Infusion rates ranged from 1000 to 2300 mcg·kg(-1) ·min(-1) . Seven subjects experienced respiratory insufficiency. The mean (sd) time to respiratory insufficiency was 104 (36) s and duration was 93 (51) s. A propofol loading dose administered over 3.0 min (CI = 1.9-3.4 min) maintained spontaneous respiration in 95% of subjects. CONCLUSIONS: The respiratory response to propofol is highly variable in children. Slower infusion of propofol will result in a lower risk of respiratory depression.