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IMPORTANCE: This study represents up-to-date information on the current status of and future projections for the pediatric otolaryngology workforce. OBJECTIVE: To provide an update on the practice patterns of and projections for the US pediatric otolaryngology workforce. DESIGN, SETTING, AND PARTICIPANTS: An online survey was sent to all 172 members of the American Academy of Pediatrics Section on Otolaryngology–Head and Neck Surgery and fielded from May 29, 2014, to September 17, 2014. MAIN OUTCOMES AND MEASURES: Current status of and perceived trends in the pediatric otolaryngology workforce RESULTS: Eighty-four (48.8%) of the 172 members responded to the survey. Not all respondents answered all questions, and so totals and percentages might not reflect a total of 84 for any given response. The demographics and practice characteristics of the responding pediatric otolaryngologists were similar to those noted in a 1997 workforce survey. Fifty-four percent of respondents (n = 38) planned to continue full-time work over the next 5 years, and 47% (n = 31) believed that the number of patients in their practice was increasing. The proportion of those who believed that the need for pediatric otolaryngologists in their community was increasing (31%; n = 21) or decreasing (13%; n = 9) remained relatively constant from the 1997 survey (34% and 12%, respectively). Forty-nine percent (n = 35) reported believing that the number of pediatric otolaryngologists being trained was appropriate and that the need in their community was stable. Eighty-three percent (n = 55) reported believing that employment opportunities for pediatric otolaryngologists in the United States would be plentiful in the near future. CONCLUSIONS AND RELEVANCE: The overall state of the pediatric otolaryngology workforce appears stable. The perceived current and future needs for pediatric otolaryngologists appear to be met by the current number of trainees. Employment opportunities appear promising for future pediatric otolaryngologists based on our respondents’ opinions. This represents up-to-date information on the current status of and future projections for the pediatric otolaryngology workforce.

The development and thorough characterization of nonviral delivery agents for nucleic acid and genome editing therapies are of high interest to the field of nanomedicine. Indeed, this vehicle class offers the ability to tune chemical architecture/biological activity and readily package nucleic acids of various sizes and morphologies for a variety of applications. Herein, we present the synthesis and characterization of a class of trehalose-based block copolycations designed to stabilize polyplex formulations for lyophilization and in vivo administration. A 6-methacrylamido-6-deoxy trehalose (MAT) monomer was synthesized from trehalose and polymerized via reversible addition–fragmentation chain transfer (RAFT) polymerization to yield pMAT43. The pMAT43macro-chain transfer agent was then chain-extended with aminoethylmethacrylamide (AEMA) to yield three different pMAT-b-AEMA cationic-block copolymers, pMAT-b-AEMA-1 (21 AEMA repeats), -2 (44 AEMA repeats), and -3 (57 AEMA repeats). These polymers along with a series of controls were used to form polyplexes with plasmids encoding firefly luciferase behind a strong ubiquitous promoter. The trehalose-coated polyplexes were characterized in detail and found to be resistant to colloidal aggregation in culture media containing salt and serum. The trehalose-polyplexes also retained colloidal stability and promoted high gene expression following lyophilization and reconstitution. Cytotoxicity, cellular uptake, and transfection ability were assessed in vitro using both human glioblastoma (U87) and human liver carcinoma (HepG2) cell lines wherein pMAT-b-AEMA-2 was found to have the optimal combination of high gene expression and low toxicity. pMAT-b-AEMA-2 polyplexes were evaluated in mice via slow tail vein infusion. The vehicle displayed minimal toxicity and discouraged nonspecific internalization in the liver, kidney, spleen, and lungs as determined by quantitative polymerase chain reaction (qPCR) and fluorescence imaging experiments. Hydrodynamic infusion of the polyplexes, however, led to very specific localization of the polyplexes to the mouse liver and promoted excellent gene expression in vivo.

ABSTRACTPrevious research suggests a role for rumination on eating, shape and weight in the maintenance of eating disorder symptoms. The Ruminative Response Scale for Eating Disorders (RRS-ED) measures this type of rumination. To date, no research has verified the two-factor structure of the RRS-ED. Nor has research investigated the association between rumination on eating, shape and weight and the eating disorder behaviours of binge eating and dietary restriction in young adult females. To test these hypotheses, a sample of 119 females (aged 17–24) completed a battery of self-report measures. A confirmatory factor analysis confirmed that the RRS-ED consists of two dimensions, namely reflection and brooding. Furthermore, brooding was found to be uniquely associated with general eating disorder symptoms, over and above mood and body mass index (BMI). Finally, results provided novel evidence for the association between brooding and clinically significant levels of binge eating and dietary restriction, while controlling for mood and BMI. The current study highlights the association between ruminative brooding and eating disorder symptoms in a sample of young adult females. The findings may have implications for prevention and treatment strategies given that binge eating and dietary restraint are primary risk factors for, and also serve to maintain, eating disorders.

ObjectivesThe diagnosis and treatment of Chlamydia trachomatisinfection is important in preventing persistent or recurrent infection. Expedited partner therapy (EPT) is the favoured and supported method for STI treatment of the Centers for Disease Control and Prevention when the provider cannot be assured that all recent sexual partner(s) will seek therapy. EPT is legally permissible in 38 states and is endorsed by healthcare organisations to decrease the rates of chlamydia and gonorrhoea infection. Our study investigated the impact of EPT legal status (permissible, potentially allowable or prohibited) on C. trachomatisinfection rates for each state.MethodsOur ecological study modelled the number of reported chlamydia cases from 2000 to 2013 as a function of year, legal status and the interaction between year and legality. We used a negative binomial regression model that included state fixed effects (including the District of Columbia) to account for both the repeated measures per state and state-specific characteristics that could not be measured for inclusion in this study. The lagged number of C. trachomatiscases was included as a covariate and each state's total population for a given year was included in the model as an exposure parameter. States were designated Y(EPT permissible), N(EPT prohibited) and M(EPT potentially allowable), and the legal status of each state could vary over time.ResultsEach legal category saw an increase in the incidence rate of C. trachomatisinfection, but on average, the incidence rate for states with prohibitive EPT legislation grew significantly faster over time compared with the rate for the states where EPT was permissible. The average increase in predicted incidence rates per year for states with Y, Nand Mlegal status were 14.1 (95% CI (12.0 to 16.2)), 17.5 (95% CI (15.9 to 19.2)) and 16.8 (95% CI (15.0 to 18.6)) cases per 100 000 persons per year, respectively, when controlling for state-specific effects.ConclusionsOur model suggests that a lack of EPT legislation is associated with an increase in STI rates. States with potentially allowable EPT legislation as of 2013 (n=8) should consider permitting EPT as a component of a multipronged strategy for treatment of sexual partners to prevent C. trachomatisinfection.

We conducted a retrospective study to reexamine the value of single-photon emission computed tomography (SPECT) in the evaluation of patients with neurotologic complaints, and to assess the intra- and inter-radiologist variability of SPECT readings. Our study population was made up of 63 patients—23 men and 40 women, aged 34 to 91 years (mean: 59)—who had presented to a tertiary care otolaryngology practice and university hospital for evaluation of head trauma, sensorineural hearing loss, tinnitus, and/or vertigo. All patients had undergone brain scanning with SPECT during their evaluation, and almost all had also undergone magnetic resonance imaging (MRI) and standard computed tomography (CT). We compared the findings of all three imaging modalities in terms of their ability to detect neurotologic abnormalities. We found that detection rates were very similar among the three modalities; abnormalities were found in 24% of SPECT scans, 26% of MRIs, and 23% of CTs. Nevertheless, we did find that among 60 patients who underwent all three types of imaging, 13 (22%) exhibited areas of cerebral hypoperfusion on SPECT while their MRIs and CTs were read as either normal or nonspecific. In all, 18 of these 60 patients (30%) exhibited normal or nonspecific findings on all three types of imaging. In addition, when SPECT scans were read by the same radiologist at different times, different results were reported for 17 of the 63 scans (27%). Likewise, when SPECT scans were read by different radiologists, different results were reported for 21 of 63 scans (33%). We conclude that SPECT may be a valuable complementary diagnostic modality for making a comprehensive neurotologic evaluation and that it may detect abnormalities in some patients whose other imaging is read as normal. However, we did not find that SPECT was the most sensitive of the three modalities in neurotologic evaluation, as we had previously found in a preliminary study that the senior author (R.T.S.) published in 1996. In addition, with respect to our radiologists, both their intra- and inter-reader reliability was low, and we recommend additional study on this matter.

Sleeping Beauty (SB) transposons have been effective in delivering therapeutic genes to treat certain diseases in mice. Hydrodynamic gene delivery of integrating transposons to 5-20 of the hepatocytes in a mouse results in persistent elevated expression of the therapeutic polypeptides that can be secreted into the blood for activity throughout the animal. An alternative route of delivery is ex vivo transformation with SB transposons of hematopoietic cells, which then can be reintroduced into the animal for treatment of cancer. We discuss issues associated with the scale-up of hydrodynamic delivery to the liver of larger animals as well as ex vivo delivery. Based on our and others experience with inefficient delivery to larger animals, we hypothesize that impulse, rather than pressure, is a critical determinant of the effectiveness of hydrodynamic delivery. Accordingly, we propose some alterations in delivery strategies that may yield efficacious levels of gene delivery in dogs and swine that will be applicable to humans. To ready hydrodynamic delivery for human application we address a second issue facing transposons used for gene delivery regarding their potential to “re-hop” from one site to another and thereby destabilize the genome. The ability to correct genetic diseases through the infusion of DNA plasmids remains an appealing goal.

The study's objective was to develop a tool that would characterize and compare resident training in female sexual dysfunction (FSD).

The formation and maintenance of single-stranded DNA (ssDNA) are essential parts of many processes involving DNA. For example, strand separation of double-stranded DNA (dsDNA) is catalyzed by helicases, and this exposure of the bases on the DNA allows further processing, such as replication, recombination, or repair. Assays of helicase activity and probes for their mechanism are essential for understanding related biological processes. Here we describe the development and use of a fluorescent probe to measure ssDNA formation specifically and in real time, with high sensitivity and time resolution. The reagentless biosensor is based on the ssDNA binding protein (SSB) from Escherichia coli, labeled at a specific site with a coumarin fluorophore. Its use in the study of DNA manipulations involving ssDNA intermediates is demonstrated in assays for DNA unwinding, catalyzed by DNA helicases.

Nonviral, DNA-mediated gene transfer is an alternative to viral delivery systems for expressing new genes in cells and tissues. The Sleeping Beauty (SB) transposon system combines the advantages of viruses and naked DNA molecules for gene therapy purposes; however, efficacious delivery of DNA molecules to animal tissues can still be problematic. Here we describe the hydrodynamic delivery procedure for the SB transposon system that allows efficient delivery to the liver in the mouse. The procedure involves rapid, high-pressure injection of a DNA solution into the tail vein. The overall procedure takes <1 h although the delivery into one mouse requires only a few seconds. Successful injections result in expression of the transgene in 5–40% of hepatocytes 1 d after injection. Several weeks after injection, transgene expression stabilizes at ∼1% of the level at 24 h, presumably owing to integration of the transposons into chromosomes.

Serine β-lactamases are inhibited by phosphonate monoester monoanions. These compounds phosphonylate the active site serine hydroxyl group to form inert, covalent complexes. Since spontaneous hydrolysis of these phosphonates is generally quite slow, the β-lactamase active site must have considerable affinity for the (presumably) pentacoordinated phosphonyl transfer transition state. Structural analogs of such a transition state might well therefore be effective and novel β-lactamase inhibitors. Complexes of vanadate with hydroxamic acids may be able to achieve such a structure. Indeed, mixtures of these two components, but neither one alone, were found to inhibit a typical class C β-lactamase. A Job plot of the inhibition by vanadate/benzohydroxamic acid mixtures indicated that the inhibitor was a 1:1 complex for which an inhibition constant of 4.2 μM could be calculated. A bacterial DD-peptidase, structurally similar to the β-lactamase, was also inhibited (Ki = 22 μM) by this complex. A similar rationale would suggest that other serine hydrolases might also be inhibited by these mixtures. In fact, chymotrypsin was inhibited by a complex of vanadate with benzohydroxamic acid (Ki = 10 μM) and elastase by a complex with acetohydroxamic acid (Ki = 90 μM).

Deuterium nuclear magnetic resonance (NMR) spectra and spin-lattice relaxation times (T1) are used to investigate the dynamics of the guest molecule, acetone, in tris(5-acetyl-3-thienyl)methane (TATM) and cyclotriveratrylene (CTV) inclusion compounds. 13C CPMAS powder NMR spectra were obtained for each clathrate, to verify inclusion. In acetone: TATM, the guest molecule is undergoing twofold reorientation about the CO bond, exchanging the two methyl groups. An activation energy of 20 (± 1.4) kJ/mol, for the two-site jump motion, was found, independently, from deuterium NMR spectra an T1measurements. Acetone in CTV performs the same type of motion as acetone in TATM. Activation energies of 25.0 (± 3.2) kJ/mol and 24.1 (± 0.5) kJ/mol were determined using the same two techniques. both inclusion compounds, the rate of methyl rotation within the acetone molecule is greater than 108 Hz even at the lowest temperature measured (84 K). Analytical expressions for the spin-lattice relaxation time (T1), for a twofold jump, were derived. Calculated values of the effective quadrupolar coupling constant and T1minfor the guests agree very well with the experimental data. The 84 K spectrum of acetone:TATM unexpectedly shows some asymmetry, the origin of which is discussed. Finally, these two clathrates are compared to the recently examined acetone: tri-ortho-thymotide inclusion compound. Key words: inclusion compounds, deuterium NMR, solid state NMR spectroscopy, molecular dynamics.

Deuterium nuclear magnetic resonance (NMR) spectra and spin-lattice relaxation times (T1) are used to investigate the guest molecular dynamics of tris(5-acetyl-3-thienyl) methane (TATM) inclusion compounds. The seven guests: acetonitrile, nitromethane, dimethyl sulfoxide, benzene, mesitylene, ortho-xylene, and para-xylene show a wide variety of motional behaviour. The reorientation of acetonitrile in TATM and nitromethane in TATM were both modelled as precession on a cone, the base of which is more elliptical in shape for nitromethane, as would be expected considering their molecular symmetries. DMSO in TATM does not undergo any reorientation other than methyl rotation at the temperatures investigated. At low temperatures, the 2H lineshape and the deuterium spin-lattice relaxation time both depend on the rate of methyl rotation. Activation barriers of 11.7 (±0.4) kJ/mol and 11.2 (±0.5) kJ/mol were found from the two techniques, respectively. Benzene undergoes sixfold reorientation about the principal molecular axis; however, the rate is still greater than 108 Hz down to 113 K. The spin-lattice relaxation time profile does not reach a minimum on decreasing temperature to 112 K, while the slope of this plot provides an activation energy of 4.1 (±0.4) kJ/mol for the sixfold reorientation. The deuterium NMR spectra of mesitylene-d9in TATM can be simulated using a model where the guest occupies two different sites in the TATM lattice, with the guest molecules performing in-plane C3rotation either very rapidly (k > 108 Hz) or very slowly (k < 103 Hz), with the relative populations of each changing with temperature. Another model proposed suggests the possibility that there is a continuous distribution of motional rates, the median of which is increasing with temperature. This second model is more realistic; however, too many parameters are present to consider a detailed fit. Finally, both o-xylene and p-xylene are rigidly held in the TATM clathrate, while rotation of the methyl groups is rapid. Keywords: inclusion compounds, solid state deuterium NMR spectroscopy, molecular dynamics.

Profiles music performers Morcheeba, while referring to the performance of `Who Can You Trust?' the band's music recording. Background information on Morcheeba; Pregnancy of Skye, a member of Morcheeba; Reference to the release of the music recording `Big Calm'. INSET: Ten mellow Morcheeba facts.

RNA is a fundamental component of chromatin. Noncoding RNAs (ncRNAs) can associate with chromatin to influence gene expression and chromatin state; many also act at long distances from their transcriptional origin. Yet we know almost nothing about the functions or sites of action for most ncRNAs. Current methods to identify sites of RNA interaction with the genome are limited to the study of a single RNA at a time. Here we describe a protocol for ChAR‐seq, a strategy to identify all chromatin‐associated RNAs and map their DNA contacts genome‐wide. In ChAR‐seq, proximity ligation of RNA and DNA to a linker molecule is used to construct a chimeric RNA‐DNA molecule that is converted to DNA for sequencing. In a single assay, ChAR‐seq can discover de novochromatin interactions of distinct RNAs, including nascent transcripts, splicing RNAs, and long noncoding RNAs (lncRNAs). Resulting “maps” of genome‐bound RNAs should provide new insights into RNA biology. © 2019 by John Wiley & Sons, Inc.