Proteomics-Based Mapping of Bronchopulmonary Dysplasia-Associated Changes in Noninvasively Accessible Oral Secretions.

OBJECTIVE: To determine if oral secretions (OS) can be used as a noninvasively collected body fluid, in lieu of tracheal aspirates (TA), to track respiratory status and predict bronchopulmonary dysplasia (BPD) development in infants born <32 weeks. STUDY DESIGN: This was a retrospective, single center cohort study that included data and convenience samples from week-of-life (WoL) 3 from 2 independent preterm infant cohorts. Using previously banked samples, we applied our sample-sparing, high-throughput proteomics technology to compare OS and TA proteomes in infants born <32 weeks admitted to the Neonatal Intensive Care Unit (NICU) (Cohort 1; n = 23 infants). In a separate similar cohort, we mapped the BPD-associated changes in the OS proteome (Cohort 2; n = 17 infants including 8 with BPD). RESULTS: In samples collected during the first month of life, we identified 607 proteins unique to OS, 327 proteins unique to TA, and 687 overlapping proteins belonging to pathways involved in immune effector processes, neutrophil degranulation, leukocyte mediated immunity, and metabolic processes. Furthermore, we identified 37 OS proteins that showed significantly differential abundance between BPD cases and controls: 13 were associated with metabolic and immune dysregulation, 10 of which (eg, SERPINC1, CSTA, BPI) have been linked to BPD or other prematurity-related lung disease based on blood or TA investigations, but not OS. CONCLUSIONS: OS are a noninvasive, easily accessible alternative to TA and amenable to high-throughput proteomic analysis in preterm newborns. OS samples hold promise to yield actionable biomarkers of BPD development, particularly for prospective categorization and timely tailored treatment of at-risk infants with novel therapies.

Labels Affect Food Choices, but in What Ways?

To reduce obesity and thus promote healthy food choices, front-of-pack (FOP) labels have been introduced. Though FOP labels help identify healthy foods, their impact on actual food choices is rather small. A newly developed so-called swipe task was used to investigate whether the type of label used (summary vs. nutrient-specific) had differential effects on different operationalizations of the "healthier choice" measure (e.g., calories and sugar). After learning about the product offerings of a small online store, observers (N = 354) could, by means of a swipe gesture, purchase the products they needed for a weekend with six people. Observers were randomly assigned to one of five conditions, two summary label conditions (Nutri-Score and HFL), two nutrient (sugar)-specific label conditions (manga and comic), or a control condition without a label. Unexpectedly, more products (+7.3 products)-albeit mostly healthy ones-and thus more calories (+1732 kcal) were purchased in the label conditions than in the control condition. Furthermore, the tested labels had different effects with respect to the different operationalizations (e.g., manga reduced sugar purchase). We argue that the additional green-labeled healthy products purchased (in label conditions) "compensate" for the purchase of red-labeled unhealthy products (see averaging bias and licensing effect).

Deficiency of the Lysosomal Protein CLN5 Alters Lysosomal Function and Movement.

Batten disease is a devastating, childhood, rare neurodegenerative disease characterised by the rapid deterioration of cognition and movement, leading to death within ten to thirty years of age. One of the thirteen Batten disease forms, CLN5 Batten disease, is caused by mutations in the CLN5 gene, leading to motor deficits, mental deterioration, cognitive impairment, visual impairment, and epileptic seizures in children. A characteristic pathology in CLN5 Batten disease is the defects in lysosomes, leading to neuronal dysfunction. In this study, we aimed to investigate the lysosomal changes in CLN5-deficient human neurons. We used an induced pluripotent stem cell system, which generates pure human cortical-like glutamatergic neurons. Using CRISPRi, we inhibited the expression of CLN5 in human neurons. The CLN5-deficient human neurons showed reduced acidic organelles and reduced lysosomal enzyme activity measured by microscopy and flow cytometry. Furthermore, the CLN5-deficient human neurons also showed impaired lysosomal movement-a phenotype that has never been reported in CLN5 Batten disease. Lysosomal trafficking is key to maintain local degradation of cellular wastes, especially in long neuronal projections, and our results from the human neuronal model present a key finding to understand the underlying lysosomal pathology in neurodegenerative diseases.

Long-term outcomes up to 25 years following balloon pulmonary valvuloplasty: A multicenter study.

OBJECTIVE: Evaluate long-term outcomes following balloon pulmonary valvuloplasty (BPV) for pulmonary stenosis (PS). BACKGROUND: Long-term data following BPV is limited to small, single center studies. METHODS: BPV from April 12, 1985 to January 7, 2015 from three centers were included. Outcomes studied were ≥ moderate PI by echocardiogram and residual PS ≥ 40 mm Hg. Risk factors for ≥ moderate PI, residual PS, and repeat intervention were assessed by univariate and multivariate analysis. RESULTS: Among 254 patients, mean age at BPV was 3.8 years (range 1 day-67 years), initial PS catheter gradient was 56 mm Hg (IQR 40-70), 19% had critical PS, and 9% had genetic syndromes. Mean follow-up duration was 7.5 years (maximum 25 years). Sixty-nine (29%) had ≥ moderate PI, 41 patients (17%) had residual PS > 40 mm Hg, and 31 (13%) had re-intervention. In univariate analysis, younger age, lower weight, greater initial PS gradient, greater initial RV/systemic pressure ratio, critical PS, and longer follow-up duration were associated with ≥ moderate PI. Greater initial PS gradient was associated with long-term residual PS or repeat intervention. In multivariate analysis, greater initial gradient and lower weight were independently associated with > moderate PI and greater initial PS gradient and genetic abnormality were independently associated with residual PS and repeat intervention. CONCLUSION: Smaller patients with greater initial PS were more likely to develop significant long-term PI. Patients with greater initial PS and genetic abnormalities were more likely to have residual PS or require repeat intervention following BPV.

Advances in acetabular reconstruction in revision total hip arthroplasty: maximizing function and outcomes after treatment of periacetabular osteolysis around the well-fixed shell.

As the incidence of primary and revision hip arthroplasty increases, the need for a comprehensive approach to acetabular revision cannot be overstated. In the presence of osteolysis, there is a substantial population of patients with a well-fixed acetabular shell. It will be helpful to orthopaedic surgeons to review the classification of acetabular defects, techniques for exposing an acetabular component when the femoral component will be retained, methods of facilitating access to osteolytic lesions, the principles of bone grafting, options for liner fixation, and when removal of a well-fixed shell is necessary.

Fecal near infrared spectroscopy to discriminate physiological status in giant pandas.

Giant panda (Ailuropoda melanoleuca) monitoring and research often require accurate estimates of population size and density. However, obtaining these estimates has been challenging. Innovative technologies, such as fecal near infrared reflectance spectroscopy (FNIRS), may be used to differentiate between sex, age class, and reproductive status as has been shown for several other species. The objective of this study was to determine if FNIRS could be similarly used for giant panda physiological discriminations. Based on samples from captive animals in four U.S. zoos, FNIRS calibrations correctly identified 78% of samples from adult males, 81% from adult females, 85% from adults, 89% from juveniles, 75% from pregnant and 70% from non-pregnant females. However, diet had an impact on the success of the calibrations. When diet was controlled for plant part such that "leaf only" feces were evaluated, FNIRS calibrations correctly identified 93% of samples from adult males and 95% from adult females. These data show that FNIRS has the potential to differentiate between the sex, age class, and reproductive status in the giant panda and may be applicable for surveying wild populations.

Seasonal shifts in giant panda feeding behavior: relationships to bamboo plant part consumption.

The giant panda (Ailuropoda melanoleuca) is classified as a carnivore, yet subsists on a diet comprised almost exclusively of bamboo. Wild and captive giant pandas use highly selective foraging behaviors for processing and consuming bamboo. These behaviors are for the first time quantified in captive giant pandas over a 5-year period of time showing highly specific seasonal trends. Giant panda feeding behavior was recorded using live video observations of two giant pandas housed at the Memphis Zoo from November 2003 to June 2008. Leaf was the primary plant part consumed from June to December, whereas culm was consumed primarily from February to May, with both bears displaying similar seasonal shifts in plant part consumption. From May to June, leaf consumption increased significantly (P-values<0.001); from June to August, leaf consumption remained high and stable. From December to March, leaf consumption decreased significantly (P-values<0.001). Specific behaviors for bamboo leaf and culm consumption were also observed. Both bears formed wads of leaves before ingestion while feeding on leaf, but the male employed this feeding behavior more often than the female (54 and 33%, respectively). Both bears used similar culm-stripping behavior (26 and 25%), used to remove the outer layer and isolate the pith for consumption. This study indicates that unique seasonal foraging behaviors observed in wild pandas are also apparent in captive animals in relation to plant part selectivity and feeding behaviors.