Providing care to children from low and middle-income countries with complex surgical problems: An 18 year review.

PURPOSE: The burden of surgical disease in children from low and middle-income countries (LMICs) is becoming more recognized as significant and undertreated.  We recently reviewed our health system's experience with providing quaternary-level surgical care to children from LMICs through a partnership with World Pediatric Project (WPP), a not-for-profit organization. METHODS: A retrospective review was performed of all WPP-sponsored patients who received surgical care at our children's hospital from LMICs in the Caribbean and Central America from July 2000 to August 2018. RESULTS: Two hundred and fifty-five patients (average age: 5.9 ± 5.3 years; range: <1-18 years) from 14 countries received a total of 371 moderately to significantly complex operations from 10 pediatric surgical subspecialties, with cardiac, neurosurgery, craniofacial and general/thoracic surgical subspecialties being the most common. The average length of hospital stay was 10.7 ± 18.9 days.  All patients had the opportunity to follow-up with local providers and/or visiting WPP-sponsored surgical teams. 227 patients (93.8%) were seen by WPP providers or released to an in-country physician partnering with WPP. There were 21 (8.2%) total, minor and major, postoperative complications.  Five deaths (2.0%) occurred at our institution and 7 from disease progression, after returning to their home country. CONCLUSIONS: Providing complex surgical care to LMIC children in the US may help address a significant global burden.  This care can be provided by multiple subspecialists with excellent outcomes, good follow-up, and low complication and mortality rates.  Having a supportive health care system, volunteer surgeons, and an organization that manages logistics and provides financial support is essential. TYPE OF STUDY: Clinical research, retrospective review LEVEL OF EVIDENCE: Level IV.

Sex-specific effects of psychedelics on prepulse inhibition of startle in 129S6/SvEv mice.

BACKGROUND: Prepulse inhibition (PPI) of startle is a sensorimotor gating phenomenon perturbed in a variety of neuropsychiatric conditions. Psychedelics disrupt PPI in rats and humans, but their effects and involvement of the serotonin 5-HT2A receptor (5-HT2AR) in mice remain unexplored. METHODS: We tested the effect of the psychedelic 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.5 mg/kg, i.p.) on startle amplitude and %PPI in response to acoustic stimuli under up to four different experimental conditions that included changes in background and stimulus intensity, prepulse and pulse duration, and interstimulus interval in male and female 129S6/SvEv mice. We also evaluated the effect of the 5-HT2AR antagonist M100,907 (1 mg/kg, i.p.) on DOI-induced startle amplitude and %PPI, as well as the effect of the psychedelic LSD (0.24 mg/kg, i.p.) and the dopamine agonists apomorphine (5 mg/kg, s.c.) and SKF-82,958 (0.5 mg/kg, i.p.) in male 129S6/SvEv mice. RESULTS: DOI altered startle amplitude with either pulse alone or prepulse + pulse presentations in all PPI conditions, and increased %PPI in three out of four PPI conditions in male mice - an effect that was prevented by M100,907. In female mice, DOI increased %PPI without affecting startle amplitude. %PPI was positively correlated with startle amplitude in males while being negatively correlated in female mice. In male mice, LSD also increased %PPI, although it did not affect startle amplitude, whereas apomorphine and SKF-82,958 induced decreases in %PPI. CONCLUSION: Our findings highlight a distinct effect of the psychedelic DOI on PPI in 129S6/SvEv mice, suggesting 5-HT2AR-dependent PPI improvement in a paradigm-dependent and sex-dependent manner.

Automated quantification of head-twitch response in mice via ear tag reporter coupled with biphasic detection.

BACKGROUND: Head-twitch response (HTR) is a manifestation of the serotonergic system behavioral pharmacology commonly used as a proxy of psychedelic drug action in rodents. NEW METHOD: We developed a minimally invasive magnetic ear tag reporter and designed a detection system that performs a comprehensive characterization of each potential HTR event on an electromagnetic readout. RESULTS: Magnetic ear tags were easy to install and generally well tolerated by the animals. On the low-threshold first phase of detection, the tags' signal recorded in a magnetometer was filtered and screened for potential HTR events. On the second phase, the detector performed a comprehensive spectral analysis evaluation of each event and identified the HTR characteristic distribution of power density. Our system delivered satisfactory performance in the identification of pharmacologically-induced HTR and discrimination power against common non-HTR behaviors. COMPARISON WITH EXISTING METHODS: Our system offers a high-throughput solution for studying HTR in mice employing minimally invasive procedures and superior standalone discriminative power compared to our previously reported fully-automated approach. CONCLUSIONS: High-throughput identification of HTR utilizing magnetic ear-tagging and biphasic detection delivers satisfactory detection and discrimination power employing less invasive procedures.

Fully automated head-twitch detection system for the study of 5-HT2A receptor pharmacology in vivo.

Head-twitch behavior (HTR) is the behavioral signature of psychedelic drugs upon stimulation of the serotonin 5-HT2A receptor (5-HT2AR) in rodents. Following the previous report of a semi-automated detection of HTR based on the dynamics of mouse's head movement, here we present a system for the identification of individual HTR events in a fully automated fashion. The validity of this fully automated HTR detection system was tested with the psychedelic drug DOI in 5-HT2AR-KO mice, and via evaluation of potential sources of false-positive and false-negative HTR events. The increased throughput in data processing achieved via automation afforded the possibility of conducting otherwise time consuming HTR time-course studies. To further assess the versatility of our system, we also explored the pharmacological interactions between 5-HT2AR and the metabotropic glutamate receptor 2 (mGluR2). Our data demonstrate the potentiation effect of the mGluR2/3 antagonist LY341495 on DOI-induced HTR, as well as the HTR-blocking effect of the mGluR2/3 agonist and antipsychotic drug in development LY404039. This fully automated system can contribute to speed up our understanding of 5-HT2AR's pharmacology and its characteristic behavioral outputs in rodents.