Optimizing Reversal of Muscle Relaxation with Sugammadex to Accelerate Discharge Readiness in Operative Laryngoscopy: A Randomized Clinical Trial.

IMPORTANCE: Operative laryngoscopy is a commonly performed ambulatory procedure in patients with significant co-morbidity. Optimal anesthetics for surgical exposure with rapid return to baseline after the procedure enhances postoperative patient safety. OBJECTIVE: To determine whether sugammadex hastens recovery in patients undergoing operative laryngoscopy under general anesthesia with rocuronium-induced paralysis. DESIGN: Prospective clinical intervention randomized single-blinded, single-center study in an academic tertiary care center. Approved by the institutional review board and registered with ClinicalTrials.gov. SETTINGS: Single center tertiary care academic institution. PARTICIPANTS: 18 years or older, American Society of Anesthesiology physical status I-III with ability to give written informed consent undergoing operative laryngoscopy. INTERVENTION: Participants were randomized into two groups. Both groups received inhaled anesthetic: sevoflurane, remifentanil, and rocuronium at 0.6-1.2 mg/kg for intubation and anti-nausea prophylaxis. Group 1 received reversal with neostigmine (0.04 mg/kg) and glycopyrrolate (0.01 mg/kg). Group 2 received reversal with sugammadex (4 mg/kg). Vital signs were maintained at 20% of baseline in both groups. Post anesthesia care unit nurses were blinded to the reversal agent and were the evaluators of the discharge criteria and times. Primary end point was time to extubation after the procedures and secondary end points were: Subjective interpretation of surgical conditions by the surgeon, hemodynamic, respiratory parameters, anesthetics, and opioids used, operative time, and duration to achieve discharge readiness. RESULTS: A total of eighty-four participants, who were similar in age, sex, and weight in both groups. The primary end point and secondary end points were similar except time to meet discharge criteria in the two groups. 65% in the sugammadex versus 35% in the neostigmine group met Aldrete criteria of 18 or higher on arrival at the post anesthesia care unit. CONCLUSIONS: Optimizing the anesthetic regimen, along with stable intraoperative hemodynamics and reversal with sugammadex improves discharge readiness in patients undergoing operative laryngoscopy.

Rectus femoris transfers with and without a hamstring lengthening will not change hip kinematics in children with cerebral palsy.

BACKGROUND: A rectus femoris transfer (RFT) surgery with and without a hamstring lengthening (HSL) is used to treat stiff-knee gait in children with cerebral palsy (CP). While current literature has reported that a RFT surgery improves the kinematics at the knee, little is known about the kinematic changes at the hip. RESEARCH QUESTION: Does a RFT surgery change hip joint kinematics in children with CP? METHODS: This retrospective study included children (<18 years old) diagnosed with CP, who underwent a RFT procedure, and who were seen at our institution's accredited clinical motion laboratory. Patients with both pre- and post-operative gait analysis were identified and comparison between those analyses were performed to identify kinematic differences at the hip and knee. A total of 66 legs from 46 children (mean age: 11.1 ± 3.6) met the inclusion criteria. RESULTS: Overall results revealed that a RFT did not change kinematics at the hip [p > 0.05], however, a RFT did increase the maximum knee flexion during the swing period [Mean Difference Post - Pre: 8.3°, 95% CI: 4.9-11.8, p < 0.0001]. Additionally, it was found that changes in hip extension during the terminal stance phase were significantly different between the combined RFT and HSL compared to solely an RFT. The results of this study also revealed that children whose stiff-knee gait did not improve, tended to have increased hip external rotation during terminal stance and swing and greater hip extension during terminal stance, compared to children whose stiff-knee gait did improve. SIGNIFICANCE: Overall, a RFT with and without a HSL surgery improves hip and knee kinematics in the sagittal plane, however, improvements at the hip were not clinically significant. As a result, a RFT or a combined RFT with HSL should not be used to change hip kinematics in children with CP.

A parent-led, patient-centered medical home model instruction for interprofessional undergraduate and graduate learning opportunities.

INTRODUCTION: Despite national efforts to establish patient-centered medical homes (PCMH), 57.3% of children with special health care needs are receiving care that does not meet medical home criteria. Project DOCC, a national curriculum designed by parents of children with disabilities or chronic disease, has shown documented strengths in medical resident learner education of children with special health care needs from the parent perspectives for over a decade. Because of the importance of PCMH and the need to provide compassionate care, our team adapted the curriculum to incorporate team-based learning in the rural setting. MATERIALS AND METHODS: Reading materials were distributed to learners prior to an in-person workshop at which time, learners reviewed a video and discussed PCMH materials to identify elements of the PCMH. Learners then engaged with parent mentors across three breakout sessions. A final group reflection was completed to review and discuss efforts providers would take to establish and maintain the PCMH in their own practice. Baseline and post-workshop PCMH perceptions and parent mentor reflections were collected and compared using t-test comparisons. RESULTS: Learner knowledge, perceptions, and comfort significantly increased after the workshop. Parent mentor comments also highlighted an increased understanding for the provider. Discussion: The adapted PCMH curriculum significantly impacted learner outcomes using a feasible approach that fit nicely within health professional curricula and limited resources of the rural setting. Parents enjoyed the opportunity to serve as mentors and valued the instruction format.

Incidence, Prevalence, and Outcomes of Pediatric Trauma in Rural Appalachia (West Virginia) From 2017 to 2019.

Background Appalachian rural pediatric trauma has its unique incidence, presentation, and distribution due to the mechanisms of injury, geographic location, access to care, and social issues.  Purpose To review, analyze, and understand pediatric trauma in West Virginia during the period 2017-2019. Materials and methods After institutional review board approval, the statewide trauma database was queried and analyzed in a retrospective cohort study for all pediatric trauma ages zero to 18 from 2017-2019 in the Appalachian regions one through four in West Virginia. The following were analyzed: gender, injury mechanism, Glasgow Coma Scale Score (GCS) at admission, injury severity score (ISS), toxicology screen results, hospital length of stay, duration of ventilatory support, number of procedures performed during admission, presence of non-accidental trauma, cardiac arrest, patient discharge disposition, and mortality. Results One-thousand eighty-two (1182) patients between the ages of zero to 18 were admitted to the trauma center. An average of 37% was female and 63% male. In the 11-18 age group, 24% were female and 76% were male. Most injuries were due to blunt force (89%), followed by penetrating injuries (7.2%) and burns (1.4%). The majority had minor or moderate injuries with 95% receiving a Glasgow Coma Scale (GCS) >13 and 72% listed as minor on the injury severity score (ISS). Children in ages 0-2 years had the highest proportion of poor (0-8) GCS scores, high ISS (>14) scores, most hospital admission days, most days on a ventilator, highest mortality, most pre-hospital cardiac arrests, child abuse, burns, and placement with child protective services. An average of 31% of children tested, and 17% in the age group of 0-2 had a positive toxicology screen. There were 3670 procedures done in total and the most common procedure performed was an ultrasound of the abdomen. Procedures were performed in 90% of the patients. Conclusions and relevance Based on our study, the zero to two-year-old pediatric trauma patients are most vulnerable to poor outcomes and may need targeted preventative interventions. Toxicology screens may need to be more widely implemented in pediatric trauma in the Appalachian region. Rural trauma in Appalachia has endemic issues related to substance abuse, poverty, and a lower degree of social support as compared to urban areas. Although the distribution of injury may follow a national distribution, mechanism, management, and outcomes can vary.

Acyclic Stereocontrol in the Additions of Nucleophilic Alkenes to α-Chiral N-Sulfonyl Imines.

Diastereoselective Lewis acid-mediated additions of nucleophilic alkenes to N-sulfonyl imines are reported. The canonical polar Felkin-Anh model describing additions to carbonyls does not adequately describe analogous additions to N-sulfonyl imines. Herein, we describe the development of conditions to produce both syn and anti products with high diastereoselectivity and good yields. A stereoelectronic model consistent with experimental outcomes is also proposed.

Diastereoselective Base-Catalyzed Formal [4 + 2] Cycloadditions of N-Sulfonyl Imines and Cyclic Anhydrides.

A diastereoselective base-catalyzed Mannich reaction of cyclic, enolizable anhydrides and N-sulfonyl imines for the synthesis of δ-lactams is reported. This anhydride Mannich reaction tolerates imines derived from aryl and enolizable aldehydes. A base-catalyzed product epimerization pathway ensures high anti diastereoselectivity in aryl and achiral enolizable imines.

Targeting quinolone- and aminocoumarin-resistant bacteria with new gyramide analogs that inhibit DNA gyrase.

Bacterial DNA gyrase is an essential type II topoisomerase that enables cells to overcome topological barriers encountered during replication, transcription, recombination, and repair. This enzyme is ubiquitous in bacteria and represents an important clinical target for antibacterial therapy. In this paper we report the characterization of three exciting new gyramide analogs-from a library of 183 derivatives-that are potent inhibitors of DNA gyrase and are active against clinical strains of gram-negative bacteria (Escherichia coli, Shigella flexneri, and Salmonella enterica; 3 of 10 wild-type strains tested) and gram-positive bacteria (Bacillus spp., Enterococcus spp., Staphylococcus spp., and Streptococcus spp.; all 9 of the wild-type strains tested). E. coli strains resistant to the DNA gyrase inhibitors ciprofloxacin and novobiocin display very little cross-resistance to these new gyramides. In vitro studies demonstrate that the new analogs are potent inhibitors of the DNA supercoiling activity of DNA gyrase (IC50s of 47-170 nM) but do not alter the enzyme's ATPase activity. Although mutations that confer bacterial cells resistant to these new gyramides map to the genes encoding the subunits of the DNA gyrase (gyrA and gyrB genes), overexpression of GyrA, GyrB, or GyrA and GyrB together does not suppress the inhibitory effect of the gyramides. These observations support the hypothesis that the gyramides inhibit DNA gyrase using a mechanism that is unique from other known inhibitors.

How active are rural children and adolescents during PE class? An examination of light physical activity.

BACKGROUND: Few studies have examined non-exercise activity thermogenesis (NEAT) or light physical activity among a group of rural youth, particularly during physical education (PE) class. The purpose of this study was to determine whether the percent of PE class time spent in NEAT is related to school level (elementary versus high school) in a group of rural youth. METHODS: Accelerometer data from 357 students (192 elementary, 165 high school) were included in the analysis. Mixed model linear regression was performed to examine the effect of school level on the percent of PE class time spent in NEAT. Covariates included gender, PE teacher, and the duration of the PE class. RESULTS: School level was a significant predictor of the percent of PE class time spent in NEAT. Specifically, elementary school students spent more of their PE class time in NEAT than high school students (p < .001). No other significant predictors were identified. CONCLUSIONS: The results of this study suggest an association between lower levels of light (NEAT) physical activity among high school versus elementary school students during PE class.

Overweight and obesity among low-income women in rural West Virginia and urban Los Angeles County.

We described the prevalence of overweight and obesity among low-income women in rural West Virginia (WV) and urban Los Angeles County (LA County). Both communities participated in the national Communities Putting Prevention to Work program during 2010-2012. In each community, we completed health assessments on adult women recruited from public-sector clinics serving low-income populations. All participants answered survey questions regarding socio-demographics and diets. In both jurisdictions, we assessed obesity using objectively measured height and weight (calculated BMI). As part of each community case study, we performed multivariable regression analyses to describe the relationships between overweight and obesity and selected covariates (e.g., dietary behaviors). Overweight and obesity were prevalent among low-income women from WV (73%, combined) and LA County (67%, combined). In both communities, race and ethnicity appeared to predict the two conditions; however, the associations were not robust. In LA County, for example, African American and Hispanic women were 1.4 times (95% CI=1.12, 1.81) more likely than white women to be overweight and obese. Collectively, these subpopulation health data served as an important guide for further planning of obesity prevention efforts in both communities. These efforts became a part of the subsequent Community Transformation Grants portfolio.

Rural Student Voices to Improve Educational Attainment Oriented Programs.

The Health Sciences and Technology Academy (HSTA) strives to increase college-going and completion rates for students in West Virginia (USA), a state with low educational attainment and the second most rural state in the country. The positive impact of HSTA on student academic trajectories has been documented, but student voices have not been represented. This qualitative study using Bronfenbrenner's ecological perspective explores student experiences through HSTA, with an eye toward how similar programs serving rural populations might improve while understanding student participant perspectives. Participants were 706 incoming 9th -12th graders from rural West Virginia who provided survey responses across two years. We address the organizational and individual considerations that were instrumental in creating a supportive learning environment for rural youth.

Assessing moderate to vigorous physical activity in rural West Virginia elementary school physical education classes.

BACKGROUND: Physical education (PE) provides a natural opportunity for students to be physically active during the school day; however, the amount and intensity of this activity varies. The Centers for Disease Control and Prevention recommends that students engage in MVPA for at least 50% of their PE class period. The purpose of the present study was to quantify the amount of MVPA that occurs during elementary school PE. METHODS: Accelerometer data were collected from 203 students (100 2nd grade; 103 5th grade) in 10 West Virginia elementary schools. At each school, PE teachers identified three 2nd grade classes and three 5th grade classes in which to collect the physical activity data. For each selected class, the teachers identified the first 4 students on their alphabetic roll to wear the accelerometers. PE teachers recorded the date and time of the class and the gender of the students wearing the accelerometers. RESULTS: Using 5-second epochs and Puyau's cut-offs, results indicated that, on average, students engaged in MVPA for 27% of their PE class. No significant differences were observed in MVPA between 2nd and 5th grade students or between males and females. Male and female students spent equal amounts of PE class in MVPA. CONCLUSION: Findings support policy to increase the required minimum amount of MVPA during each PE class.

Unliganded HIV-1 gp120 core structures assume the CD4-bound conformation with regulation by quaternary interactions and variable loops.

The HIV-1 envelope (Env) spike (gp120(3)/gp41(3)) undergoes considerable structural rearrangements to mediate virus entry into cells and to evade the host immune response. Engagement of CD4, the primary human receptor, fixes a particular conformation and primes Env for entry. The CD4-bound state, however, is prone to spontaneous inactivation and susceptible to antibody neutralization. How does unliganded HIV-1 maintain CD4-binding capacity and regulate transitions to the CD4-bound state? To define this mechanistically, we determined crystal structures of unliganded core gp120 from HIV-1 clades B, C, and E. Notably, all of these unliganded HIV-1 structures resembled the CD4-bound state. Conformational fixation with ligand selection and thermodynamic analysis of full-length and core gp120 interactions revealed that the tendency of HIV-1 gp120 to adopt the CD4-bound conformation was restrained by the V1/V2- and V3-variable loops. In parallel, we determined the structure of core gp120 in complex with the small molecule, NBD-556, which specifically recognizes the CD4-bound conformation of gp120. Neutralization by NBD-556 indicated that Env spikes on primary isolates rarely assume the CD4-bound conformation spontaneously, although they could do so when quaternary restraints were loosened. Together, the results suggest that the CD4-bound conformation represents a "ground state" for the gp120 core, with variable loop and quaternary interactions restraining unliganded gp120 from "snapping" into this conformation. A mechanism of control involving deformations in unliganded structure from a functionally critical state (e.g., the CD4-bound state) provides advantages in terms of HIV-1 Env structural diversity and resistance to antibodies and inhibitors, while maintaining elements essential for entry.

Exploring the relationship between parental concern and the management of childhood obesity.

Parental concern about child weight has been identified as a factor in parental monitoring and regulation of child diet. However, little is known about factors that influence parental concern or about how concern may influence parent management of child physical activity. The objectives of the current study were to identify the factors associated with parental concern about child weight and determine if parental concern is associated with specific actions to improve diet and increase physical activity. A stratified random sample of 1,500 parents of children in kindergarten, 2nd, 4th, 5th, 7th, and 9th grade were interviewed. Interviews addressed: (a) child and parent physical activity, (b) child and family nutrition, (c) child and parent BMI weight category, (d) interactions with health care providers, (e) parent obesity knowledge, (f) school assessment of BMI, and (g) parent perception of and concern about child weight. Child gender, weight status, and parent perception of child weight were significant predictors of parental concern. Parents were significantly more likely to report concern if their child was female, they believed their child to be overweight/obese, or their child was overweight/obese as indicated by BMI percentile. Concerned parents were significantly more likely to limit child screen time, take steps to improve child diet, and increase child physical activity than were parents who reported no concern. Treatment and prevention efforts should emphasize parental concern and awareness about child weight by providing accurate feedback on child weight status and education regarding the health risks associated with childhood overweight and obesity. Schools can play an important role in this process through the incorporation of BMI screenings.

A heterogeneous-catalyst-based, microwave-assisted protocol for the synthesis of 2,2'-bipyridines.

A new method of preparing 2,2'-bipyridines with short reaction times by using microwave assistance and heterogeneous catalysts has been developed. With a Negishi-like protocol, it was found that Ni/Al(2)O(3)-SiO(2) afforded 2,2'-bipyridine products in up to 86% yield in 1 h. Palladium supported on alumina also provided yields of 2,2'-bipyridines comparable to those seen for homogeneous PEPPSI (1,3-diisopropylimidazol-2-ylidene)(3-chloropyridyl)palladium(II)dichloride) and tetrakis(triphenylphosphanyl)palladium complexes.

Bulky alkylphosphines with neopentyl substituents as ligands in the amination of aryl bromides and chlorides.

Di(tert-butyl)neopentylphosphine (DTBNpP) in combination with palladium sources provided catalysts with comparable or better activity for the Hartwig-Buchwald amination of aryl bromides than tri(tert-butyl)phosphine (TTBP) under mild conditions. DTBNpP also provided effective catalysts for amination reactions of aryl chlorides at elevated temperatures. Further replacement of tert-butyl groups with neopentyl substituents resulted in less effective ligands for amination reactions. Computationally derived cone angles showed that replacement of a tert-butyl group with a neopentyl group significantly increased the cone angle of the phosphine. The larger cone angle of DTBNpP than TTBP appears to correlate with the higher activity of catalysts derived from DTBNpP in the amination of aryl bromides. TTBP is a stronger electron donor than DTBNpP, which may explain the higher activity for TTBP-derived catalysts toward aryl chlorides.

Aqueous-phase, palladium-catalyzed cross-coupling of aryl bromides under mild conditions, using water-soluble, sterically demanding alkylphosphines.

Sterically demanding, water-soluble alkylphosphines have been used in combination with various palladium salts in Suzuki, Sonogashira, and Heck couplings of aryl bromides under mild conditions in aqueous solvents. The tert-butyl-substituted ligands 2-(di-tert-butylphosphino)ethyltrimethylammonium chloride (t-Bu-Amphos) and 4-(di-tert-butylphosphino)-N,N-dimethylpiperidinium chloride (t-Bu-Pip-phos) in combination with palladium(II) salts were found to give catalysts that were significantly more active than catalysts derived from tri(3-sulfonatophenyl)phosphine trisodium (TPPTS). Suzuki couplings of unactivated aryl bromides occurred efficiently at room temperature in water/acetonitrile and water/toluene biphasic mixtures or in neat water. Notably, Suzuki couplings of hydrophilic aryl bromides gave high yields without using organic solvents for the reaction or purification. This methodology has been applied to a highly efficient synthesis of diflunisal. The catalyst derived from t-Bu-Amphos was recycled three times in Suzuki couplings in water/toluene before catalyst activity began to significantly drop. The average yield of four cycles was >80% per cycle. Heck and Sonogashira couplings were carried out under mild conditions (50 and 80 degrees C, respectively) with unactivated aryl bromides to give coupled products in high yield.

Efficient aqueous-phase Heck and Suzuki couplings of aryl bromides using tri(4,6-dimethyl-3- sulfonatophenyl)phosphine trisodium salt (TXPTS).

[reaction: see text] Sterically demanding, sulfonated arylphosphines TXPTS and TMAPTS have been applied to the aqueous-phase Heck and Suzuki coupling of aryl bromides. TXPTS provides good yields of Heck coupling products from aryl bromides at 80 degrees C, while both TMAPTS and TPPTS gave significantly less active catalysts. TXPTS is the first ligand to promote the aqueous-phase Heck coupling under such mild conditions. Both TXPTS and TMAPTS provide active catalysts for Suzuki couplings of aryl bromides at 50 degrees C.