Lung preservation solution substrate composition affects rat lung oxidative metabolism during hypothermic storage

Lungs harvested for transplantation utilize oxygen after procurement. We investigated the effects of storage solution substrate composition on pulmonary oxidative metabolism and energetics during the preservation interval. Rat lungs were harvested and stored at 10 degrees C in low-potassium dextran (LPD) solution. Groups of lungs were preserved with preservation solution containing 5mM carbon-13 ((13)C) labeled glucose or increasing concentrations of (13)C labeled pyruvate. Additional groups of rat lungs were studied with dichloroacetate (DCA) added to the pyruvate-modified preservation solutions. Oxidative metabolism (measured by (13)C-enrichment of glutamate) and adenine nucleotide levels were quantified. Increasing preservation solution pyruvate concentration augmented glutamate (13)C-enrichment up to a concentration of 32mM pyruvate. DCA further stimulated oxidative metabolism only at lower concentrations of pyruvate (4 and 8mM). ATP and ADP were not different among groups, but AMP levels were higher in the glucose group. These data suggest that altering the substrate composition of the preservation solution influences lung metabolism during allograft preservation for transplantation.     

P2x7 deficiency suppresses development of experimental autoimmune encephalomyelitis

Background  

The purinergic receptor P2x7 is expressed on myeloid cells as well as on CNS glial cells, and P2x7 activation has been shown to increase both glial and T-cell activation. These properties suggest a role in the development of autoimmune disease including multiple sclerosis.     

Antibiotic susceptabilities of Pseudomonas aeruginosa isolates derived from patients with cystic fibrosis under aerobic, anaerobic, and biofilm conditions

Recent studies have determined that Pseudomonas aeruginosa can live in a biofilm mode within hypoxic mucus in the airways of patients with cystic fibrosis (CF). P. aeruginosa grown under anaerobic and biofilm conditions may better approximate in vivo growth conditions in the CF airways, and combination antibiotic susceptibility testing of anaerobically and biofilm-grown isolates may be more relevant than traditional susceptibility testing under planktonic aerobic conditions. We tested 16 multidrug-resistant isolates of P. aeruginosa derived from CF patients using multiple combination bactericidal testing to compare the efficacies of double and triple antibiotic combinations against the isolates grown under traditional aerobic planktonic conditions, in planktonic anaerobic conditions, and in biofilm mode. Both anaerobically grown and biofilm-grown bacteria were significantly less susceptible (P < 0.01) to single and combination antibiotics than corresponding aerobic planktonically grown isolates. Furthermore, the antibiotic combinations that were bactericidal under anaerobic conditions were often different from those that were bactericidal against the same organisms grown as biofilms. The most effective combinations under all conditions were colistin (tested at concentrations suitable for nebulization) either alone or in combination with tobramycin (10 microg ml(-1)), followed by meropenem combined with tobramycin or ciprofloxacin. The findings of this study illustrate that antibiotic sensitivities are dependent on culture conditions and highlight the complexities of choosing appropriate combination therapy for multidrug-resistant P. aeruginosa in the CF lung.     

Effects of age and size in the ears of gekkonomorph lizards: middle-ear morphology with evolutionary implications

The function of the ear depends in part on its absolute size and internal proportions. Thus, in both young individuals and small species, the middle ear is expected to be allometrically enlarged despite its smaller absolute size. Here we aim to compare the ontogenetic allometry of relevant middle-ear structures as observed within gecko (gekkonomorph lizards) species, with the evolutionary allometry observed interspecifically. These observations also provide middle-ear data for future evaluation of variation in auditory sensitivity. The material comprised 84 museum specimens of geckos, representing nine species of three gekkonomorph subfamilies. The results of dissections and measurements show that different reports notwithstanding, the middle-ear ossicular chain is indeed structured as described for geckos by Werner and Wever. Some sexual dimorphism is indicated, but this requires further study. During postnatal ontogeny, the allometric growth in the ratio of the columellar footplate area to body length differed between the intraspecific and interspecific levels, hence species differences in the middle ear do not merely result from animal size. The ratio of the tympanic membrane area to the columellar footplate area increased during ontogeny. In this, geckos resemble birds and probably also mammals. Similarly, when the comparison was among adults representing different species, the ratio of the tympanic membrane area to the columellar footplate area increased with body size. In this, however, the geckos differed from birds and mammals, in which this ratio varied taxonomically, irrespective of body size. It would thus seem that middle-ear proportions have evolved among geckos to produce small interspecific differences, but among amniote tetrapods they have evolved according to different principles in the classes reptiles, birds, and mammals.     

The state of the art

The physician-author traces the physical and mental decline of his 96-year-old mother during the past six years. Despite her stated readiness to die and against the wishes of her family, her medical attendants have aggressively treated all episodes of acute illness. Feinstein deplores the attitudes of his profession, which pursues a "vigorous therapy that benefits no one except its own satisfaction in thwarting death, regardless of the consequences."     

Mitigating disparity in children with acute appendicitis: Impact of patient-driven protocols

PurposePrevious reports in the literature demonstrate racial and ethnic disparities for children diagnosed with acute appendicitis, with minorities experiencing worse outcomes. At our institution, we have developed an evidence based patient driven protocol for children following laparoscopic appendectomy. However, the influence of such protocol on mitigating racial and ethnic disparities in outcomes remains unknown. The purpose of our study is to assess the impact of our protocol by evaluating the influence of race and ethnicity on surgical outcomes among children treated for acute appendicitis.Material and methodsA retrospective review of prospectively collected data was conducted. Children undergoing a laparoscopic appendectomy at our freestanding children's hospital between December 2015 and July 2017 were included. Demographic data, post-operative length of stay, same day discharge rates and hospital readmission rates were abstracted from patient medical records. Patients were classified by their race and ethnic background. Comparative analysis was performed in STATA with a p value < .05 determined as significant.ResultsA total of 786 children were included, with the majority being either White (70%, n = 547), Black (8%, n = 62) or Hispanic (17%, n = 133); 569 patients (72%) were found to have non-perforated appendicitis. There was no statistically significant difference in the rates of same day discharge among White, Black or Hispanic children respectively (88% vs. 77% vs. 86%, p = .126). Of the 217 children with perforated appendicitis, Hispanic children had increased rates of perforation (41%, n = 55) compared to White and Black children respectively (23%, n = 128 and 29%, n = 18, p = .001). However, average post-operative length of stay were similar among White, Black and Hispanic children (96 h vs. 95 h vs. 98 h, p = .015). On multivariate analysis, the only significant risk factor for an elevated post-operative length of stay was the presence of a perforation.ConclusionOur evidence based patient driven protocol effectively mitigates racial and ethnic disparities found in children with acute appendicitis. Further prospective investigation into the role of such patient-driven protocols to mitigate healthcare disparities is warranted.Levels of EvidenceTherapeutic study; Level 3.     

A single institution experience with Laparoscopic Hernia repair in 791 children

IntroductionThere are many described technique to performing laparoscopic inguinal hernia repair in children. We describe our outcomes using a percutaneous internal ring suturing technique.MethodsA retrospective review of patients under 18 years old who underwent repair between January 2014 - March 2019 was performed. A percutaneous internal ring suturing technique, involving hydro-dissection of the peritoneum, percutaneous suture passage, and cauterization of the peritoneum in the sac prior to high ligation, was used. p < 0.05 was considered significant during the analysis.Results791 patients were included. The median age at operation was 1.9 years (IQR 0.37, 5.82). The median operative time for a unilateral repair was 21 min (IQR 16, 28), while the median time for a bilateral repair was 30.5 min (IQR 23, 41).In total, 3 patients required conversion to an open procedure (0.4%), 4 (0.6%) experienced post-operative bleeding, 9 (1.2%) developed a wound infection, and iatrogenic ascent of testis occurred in 10 (1.3%) patients. Twenty patients (2.5%) developed a recurrent hernia. All but two were re-repaired laparoscopically.ConclusionsThe use of percutaneous internal ring suturing for laparoscopic repair of inguinal hernias in the pediatric population is safe and effective with a low rate of complications and recurrence.     

Effects of Sex,Race, and Education on the Timing of Coming Out among Lesbian,Gay, and Bisexual Adults in the U.S.

Sexual identity formation or “coming out” as lesbian, gay, or bisexual (LGB) involves a complex process including both private realization and public disclosure. Private realization refers to the process through which an individual becomes aware of their LGB identity, whereas public disclosure reflects when an individual discloses their identity to another person. Sex, race, and class affect the timing of these processes across the life course. While extant research has identified the bivariate nature of these processes, we took a multivariate approach to understand the timing of these sexual identity milestones from a life-course perspective. Using data from the Pew Research Center’s 2013 Survey of LGBT Adults (n?=?1136), we considered how the timing of private realization and public disclosure of LGB identity is a sexed, racialized, and classed experience. The sample consisted of lesbians (n?=?270), gay males (n?=?396), bisexual females (n?=?342), and bisexual males (n?=?127). Results indicated that females uniformly realized and disclosed their identities at later stages in the life course, whereas individuals with at least some college education came out during their prime college-age years. We also found variation in timing between private realization and public disclosure for Black respondents, but not other racial groups. These findings provide insight into how organizations can develop specific programs that allow LGB individuals to safely explore their sexuality and provide support over the life course.