Changes in Cancer Screening Knowledge Among a Prospective Cohort of Spanish-Speaking Hispanic Community Outreach Event Participants in Florida and Puerto Rico.

The current study examined cancer prevention and early detection awareness (pre-workshop) and changes in knowledge (from pre- to post-workshop) among Hispanic/Latino (H/L) community members who participated in Spanish-language educational outreach events in Puerto Rico (PR) and Florida (FL). Spanish-language educational outreach events were comprised of an educational session lasting approximately 45-60 min and were delivered to groups in rural and urban community settings by a single trained community health educator (CHE). The research team assessed sociodemographic characteristics, personal and familial cancer health history, as well as awareness and knowledge (pre-test) of a range of cancer prevention and screening topics. Following the presentation, participants completed a post-test knowledge survey which also measured likelihood of engaging in cancer screening, cancer preventive behaviors, and cancer research as a result of information presented during the session. Change in the average knowledge score was evaluated using a paired samples t-test. Post-session likelihood of completing cancer screening and preventive behaviors and engaging in cancer research were examined using descriptive statistics and group/site comparisons. The percentage reporting awareness of screening procedures ranged from 33% (PSA test) to 79% (mammogram). H/L in PR reported higher percentage of stool blood test awareness when compared to H/L in FL (χ2(1)= 19.20, p<.001). The average knowledge score increased from 5.97 at pre-test to 7.09 at post-test (Cohen's d=0.69). The increase was significant across all participants (t(315)= 12.4, p<.001), as well as within the FL site (t(124)= 6.66, p<.001, d=0.59) and the PR site (t(190)=10.66, p<.001, d=0.77). Results from this study suggest that educational outreach events delivered to H/L community members by a CHE are valuable strategies to address challenges regarding cancer screening knowledge and engagement in multiple behaviors.

Complementary Effect of Maternal Sildenafil and Fetal Tracheal Occlusion Improves Lung Development in the Rabbit Model of Congenital Diaphragmatic Hernia.

OBJECTIVE: To evaluate the effect of combining antenatal sildenafil with fetal tracheal occlusion (TO) in fetal rabbits with surgically induced congenital diaphragmatic hernia (CDH). BACKGROUND: Although antenatal sildenafil administration rescues vascular abnormalities in lungs of fetal rabbits with CDH, it only partially improves airway morphometry. We hypothesized that we could additionally stimulate lung growth by combining this medical treatment with fetal TO. METHODS: CDH was created on gestational day (GD)23 (n=54). Does were randomized to receive either sildenafil 10 mg/kg/d or placebo by subcutaneous injection from GD24 to GD30. On GD28, fetuses were randomly assigned to TO or sham neck dissection. At term (GD30) fetuses were delivered, ventilated, and finally harvested for histological and molecular analyses. Unoperated littermates served as controls. RESULTS: The lung-to-body-weight ratio was significantly reduced in sham-CDH fetuses either (1.2 ±â€Š0.3% vs 2.3 ±â€Š0.3% in controls, P=0.0003). Sildenafil had no effect on this parameter, while CDH fetuses undergoing TO had a lung-to-body-weight ratio comparable to that of controls (2.5 ±â€Š0.8%, P<0.0001). Sildenafil alone induced an improvement in the mean terminal bronchiolar density (2.5 ±â€Š0.8 br/mm2 vs 3.5 ±â€Š0.9 br/mm2, P=0.043) and lung mechanics (static elastance 61 ±â€Š36 cmH2O /mL vs 113 ±â€Š40 cmH2O/mL, P=0.008), but both effects were more pronounced in fetuses undergoing additional TO (2.1 ±â€Š0.8 br/mm2, P=0.001 and 31 ±â€Š9 cmH2O/mL, P<0.0001 respectively). Both CDH-sham and CDH-TO fetuses treated with placebo had an increased medial wall thickness of peripheral pulmonary vessels (41.9 ±â€Š2.9% and 41.8 ±â€Š3.2%, vs 24.0 ±â€Š2.9% in controls, P<0.0001). CDH fetuses treated with sildenafil, either with or without TO, had a medial thickness in the normal range (29.4% ±â€Š2.6%). Finally, TO reduced gene expression of vascular endothelial growth factor and surfactant protein A and B, but this effect was counteracted by sildenafil. CONCLUSION: In the rabbit model for CDH, the combination of maternal sildenafil and TO has a complementary effect on vascular and parenchymal lung development.

Variable mesh optimization applied to fringe pattern demodulation using a Bézier surface.

We present a parametric method to carry out a demodulation process in complex fringe pattern images with either open or closed fringes; this method is based on the parallel demodulation algorithm and introduces a novel way, to the best of our knowledge, to approximate the phase map using the Bezier surface control points. For this study, a recently developed population meta-heuristic called Variable Mesh Optimization is introduced to implement the optimization process. The results of the proposed method improve the phase error and the run time scores in comparison with other global optimization algorithms, which address this type of problem.

Preterm birth impairs postnatal lung development in the neonatal rabbit model.

BACKGROUND: Bronchopulmonary dysplasia continues to cause important respiratory morbidity throughout life, and new therapies are needed. The common denominator of all BPD cases is preterm birth, however most preclinical research in this area focusses on the effect of hyperoxia or mechanical ventilation. In this study we investigated if and how prematurity affects lung structure and function in neonatal rabbits. METHODS: Pups were delivered on either day 28 or day 31. For each gestational age a group of pups was harvested immediately after birth for lung morphometry and surfactant protein B and C quantification. All other pups were hand raised and harvested on day 4 for the term pups and day 7 for the preterm pups (same corrected age) for lung morphometry, lung function testing and qPCR. A subset of pups underwent microCT and dark field imaging on day 0, 2 and 4 for terms and on day 0, 3, 5 and 7 for preterms. RESULTS: Preterm pups assessed at birth depicted a more rudimentary lung structure (larger alveoli and thicker septations) and a lower expression of surfactant proteins in comparison to term pups. MicroCT and dark field imaging revealed delayed lung aeration in preterm pups, in comparison to term pups. Preterm birth led to smaller pups, with smaller lungs with a lower alveolar surface area on day 7/day 4. Furthermore, preterm birth affected lung function with increased tissue damping, tissue elastance and resistance and decreased dynamic compliance. Expression of vascular endothelial growth factor (VEGFA) was significantly decreased in preterm pups, however in the absence of structural vascular differences. CONCLUSIONS: Preterm birth affects lung structure and function at birth, but also has persistent effects on the developing lung. This supports the use of a preterm animal model, such as the preterm rabbit, for preclinical research on BPD. Future research that focuses on the identification of pathways that are involved in in-utero lung development and disrupted by pre-term birth, could lead to novel therapeutic strategies for BPD.

Simvastatin attenuates lung functional and vascular effects of hyperoxia in preterm rabbits.

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains a frequent complication following preterm birth, affecting respiratory health throughout life. Transcriptome analysis in a preterm rabbit model for BPD revealed dysregulation of key genes for inflammation, vascular growth and lung development in animals exposed to hyperoxia, which could be prevented by simvastatin. METHODS: Preterm rabbits were randomized to either normoxia (21% O2) or hyperoxia (95% O2) and within each condition to treatment with 5 mg/kg simvastatin daily or control. Lung function, structure and mRNA-expression was assessed on day 7. RESULTS: Simvastatin partially prevented the effect of hyperoxia on lung function, without altering alveolar structure or inflammation. A trend towards a less fibrotic phenotype was noted in simvastatin-treated pups, and airways were less muscularized. Most importantly, simvastatin completely prevented hyperoxia-induced arterial remodeling, in association with partial restoration of VEGFA and VEGF receptor 2 (VEGFR2) expression. Simvastatin however decreased survival in pups exposed to normoxia, but not to hyperoxia. CONCLUSION: Repurposing of simvastatin could be an advantageous therapeutic strategy for bronchopulmonary dysplasia and other developmental lung diseases with pulmonary vascular disease. The increased mortality in the treated normoxia group however limits the translational value at this dose and administration route.

Local pulmonary drug delivery in the preterm rabbit: feasibility and efficacy of daily intratracheal injections.

Recent clinical trials in newborns have successfully used surfactant as a drug carrier for an active compound, to minimize systemic exposure. To investigate the translational potential of surfactant-compound mixtures and other local therapeutics, a relevant animal model is required in which intratracheal administration for maximal local deposition is technically possible and well tolerated. Preterm rabbit pups (born at 28 days of gestation) were exposed to either hyperoxia or normoxia and randomized to receive daily intratracheal surfactant, daily intratracheal saline, or no injections for 7 days. At day 7, the overall lung function and morphology were assessed. Efficacy in terms of distribution was assessed by micro-PET-CT on both day 0 and day 7. Lung function as well as parenchymal and vascular structure were altered by hyperoxia, thereby reproducing a phenotype reminiscent of bronchopulmonary dysplasia (BPD). Neither intratracheal surfactant nor saline affected the survival or the hyperoxia-induced BPD phenotype of the pups. Using PET-CT, we demonstrate that 82.5% of the injected radioactive tracer goes and remains in the lungs, with a decrease of only 4% after 150 min. Surfactant and saline can safely and effectively be administered in spontaneously breathing preterm rabbits. The described model and method enable researchers to evaluate intratracheal pharmacological interventions for the treatment of BPD.

Magnetic Surgery: Results From First Prospective Clinical Trial in 50 Patients.

OBJECTIVE: To evaluate a new magnetic surgical system during reduced-port laparoscopic cholecystectomy in a prospective, multicenter clinical trial. BACKGROUND: Laparoscopic instrumentation coupled by magnetic fields may enhance surgeon performance by allowing for shaft-less retraction and mobilization. The movements can be performed under direct visualization, generating different angles of traction and reducing the number of trocars to perform the procedure. This may reduce well-known associated complications of trocars, including incisional pain, scarring, infection, bowel, and vascular injuries, among others. METHODS: A prospective, multicenter, single-arm, open-label study was performed to assess the safety and performance of a magnetic surgical system (Levita Magnetics' Surgical System). The investigational device was used during a 3-port laparoscopic technique. The primary endpoints evaluated were safety and feasibility of the device to adequately mobilize the gallbladder to achieve effective exposure of the targeted surgical site. Patients were followed for 30 days postprocedure. RESULTS: Between January 2014 and March 2015, 50 patients presenting with benign gallbladder disease were recruited. Forty-five women and 5 men with an average age of 39 years (18-59), average body mass index of 27 kg/m (20.4-34.1) and an average abdominal wall thickness of 2.6 cm (1.8-4.6). The procedures were successfully performed in all 50 patients. No device-related serious adverse events were reported. Surgeons rated as "excellent" (90%) or "sufficient" (10%) the exposure of the surgical site. CONCLUSIONS: This clinical trial shows that this new magnetic surgical system is safe and effective in reduced-port laparoscopic cholecystectomy.

Thermal Transport and Phonon Hydrodynamics in Strontium Titanate.

We present a study of thermal conductivity, κ, in undoped and doped strontium titanate in a wide temperature range (2-400 K) and detecting different regimes of heat flow. In undoped SrTiO_{3}, κ evolves faster than cubic with temperature below its peak and in a narrow temperature window. Such behavior, previously observed in a handful of solids, has been attributed to a Poiseuille flow of phonons, expected to arise when momentum-conserving scattering events outweigh momentum-degrading ones. The effect disappears in the presence of dopants. In SrTi_{1-x}Nb_{x}O_{3}, a significant reduction in lattice thermal conductivity starts below the temperature at which the average inter-dopant distance and the thermal wavelength of acoustic phonons become comparable. In the high-temperature regime, thermal diffusivity becomes proportional to the inverse of temperature, with a prefactor set by sound velocity and Planckian time (τ_{p}=(ℏ/k_{B}T)).

Tissuepatch is biocompatible and seals iatrogenic membrane defects in a rabbit model.

OBJECTIVE: To evaluate novel sealing techniques for their biocompatibility and sealing capacity of iatrogenic fetal membrane defects in a pregnant rabbit model. METHOD: At day 23 of gestation (term = d31), a standardized fetoscopy was performed through a 14G cannula. The resulting fetal membrane defect was closed with condensed collagen, collagen with fibrinogen, Tissuepatch, Duraseal, or a conventional collagen plug (Lyostypt) as reference. At d30, the fetuses were harvested and full thickness fetal membrane samples were analyzed. The study consisted of 2 consecutive parts: (1) biocompatibility testing by fetal survival, apoptosis, and infiltration of polymorphonuclear cells in the membranes and (2) the efficacy to seal fetal membrane defects. RESULTS: Three sealants (collagen with fibrinogen, Duraseal, or Lyostypt) were associated with a higher fetal mortality compared to control unmanipulated littermates and hence were excluded from further analysis. Tissuepatch was biocompatible, and amniotic fluid levels were comparable to those of control untouched littermates. Compared to the condensed collagen, Tissuepatch was also easier in surgical handling and induced limited cell proliferation. CONCLUSION: Tissuepatch had the best biocompatibility and efficacy in sealing an iatrogenic fetal membrane defect in the pregnant rabbit compared to other readily available sealants.

[Universal health coverage and the More Doctors physician recruitment program (Programa Mais Médicos) in BrazilCobertura universal de salud y el programa Más Médicos (Programa Máis Médicos) en Brasil]. / Cobertura universal em saúde e o Programa Mais Médicos no Brasil.

Universal health coverage can be understood as a goal encompassing a series of structural measures that allow health care systems to enhance access to health care. Primary health care (PHC) should be seen as an essential component of this process, in charge of re-organizing services according to the health needs of the population. A Brazilian physician recruitment program, Programa Mais Médicos (More Doctors), has introduced a set of measures that strengthen PHC. Based on a conceptual review of universal health coverage and on an analysis of the More Doctor Program from the perspective of the results obtained in terms of strengthening PHC in the public Unified Health System (SUS), the aim of the present article was to discuss the potential contribution of the More Physicians Program to the progress towards universal coverage in the SUS. It is concluded that the More Doctors Programs is a driver of universal coverage in the public health care system in Brazil.

La cobertura universal de salud puede entenderse como una meta que abarca una serie de medidas estructurales que permiten a los sistemas de atención médica mejorar el acceso a la atención médica. La atención primaria de salud (APS) debe ser vista como un componente esencial de este proceso, responsable de la reorganización de los servicios, tomando en cuenta las necesidades de salud de la población. El programa Más Médicos, ha introducido en Brasil un conjunto de medidas que fortalecen la APS. Con base en una revisión conceptual de la cobertura universal de salud y de un análisis del programa Más Médicos desde la perspectiva de los resultados obtenidos en términos de fortalecimiento de la APS en el Sistema Único de Salud público (SUS), el objetivo del presente artículo fue analizar la contribución potencial del programa Más Médicos al progreso hacia la cobertura universal en el SUS. Se concluye que el programa Más Médicos es un motor de cobertura universal en el sistema de salud pública en Brasil.

Community Engagement for Identifying Cancer Education Needs in Puerto Rico.

Cancer is the leading cause of death in Puerto Rico, suggesting a need for improved strategies, programs, and resources devoted to cancer prevention. Enhanced prevention needs in Puerto Rico were initially identified in pilot studies conducted by the Ponce School of Medicine (PSM) in collaboration with the H. Lee Moffitt Cancer Center (MCC). In the current study, we used community engagement to identify specific needs in cancer prevention and education and strategies to create culturally attuned, effective cancer prevention education programs. A total of 37 participants attended a community forum and were assigned to one of three discussion groups: patients/survivors (n = 14); family/caregivers (n = 11); or healthcare providers (n = 12). Most participants were women (73 %), over 35 years of age, and a majority were married (58 %) and had a university education (81 %). The sessions were recorded and transcribed and analyzed for key themes. Participants wanted improved awareness of cancer prevention in Puerto Rico and believed cancer prevention education should start early, ideally in elementary school. Participants also stressed the importance of creating partnerships with private and government agencies to coordinate educational efforts. Suggested strategies included outreach to communities with limited resources, incorporating the testimony of cancer survivors, and utilizing social media to disseminate cancer prevention information.

Comparison of Health Communication Channels for Reaching Hispanics About Biobanking: a Pilot Trial.

Cancer education is essential for improving cancer prevention and biobanking knowledge among racial-ethnic minorities, with the goal of increasing diversity and representativeness of biospecimen collections. However, little is known about the communication modalities for optimal delivery of information. We examined feasibility of recruitment and compared communication modalities for delivering cancer prevention and biobanking education to Hispanics. Communication modalities were evaluated using participation rates and change in knowledge, attitudes, self-efficacy, intention, receptivity, and trust. Enrollment in a biobanking registry was a behavioral outcome. Community members in Ponce, Puerto Rico and Tampa, Florida were recruited. Participants (N = 254) were randomized to one of three communication modalities: standard dissemination (mailed materials); enhanced dissemination (mailed materials plus follow-up call); and 'charla' (face-to-face group discussion). Participants completed questionnaires about their knowledge, attitudes, self-efficacy, intentions, receptivity, and trust regarding biobanking and cancer prevention pre- and post-intervention. Knowledge, attitudes, and self-efficacy were improved among all three modalities. Although the greatest increases in knowledge were observed when the information was delivered via charla, the charla had the lowest participation rate. The standard and enhanced dissemination modalities were more feasible for delivering cancer prevention and biobanking education to Hispanics. Lack of differences among the three modalities suggests culturally tailored education may be sufficient to capture the community's intention to participate in biobanking research, regardless of the delivery method for the education. Results from this study contribute to the limited knowledge regarding Hispanics knowledge and intentions for biospecimen collection, and in the future may improve participation in this underrepresented group.

Balloon removal after fetoscopic endoluminal tracheal occlusion for congenital diaphragmatic hernia.

BACKGROUND: Isolated congenital diaphragmatic hernia defect allows viscera to herniate into the chest, competing for space with the developing lungs. At birth, pulmonary hypoplasia leads to respiratory insufficiency and persistent pulmonary hypertension that is lethal in up to 30% of patients. Antenatal measurement of lung size and liver herniation can predict survival after birth. Prenatal intervention aims at stimulating lung development, clinically achieved by percutaneous fetal endoscopic tracheal occlusion under local anesthesia. This in utero treatment requires a second intervention to reestablish the airway, either before birth or at delivery. OBJECTIVE: To describe our experience with in utero endotracheal balloon removal. MATERIALS AND METHODS: This is a retrospective analysis of prospectively collected data on consecutive patients with congenital diaphragmatic hernia treated in utero by fetal endoscopic tracheal occlusion from 3 centers. Maternal and pregnancy-associated variables were retrieved. Balloon removal attempts were categorized as elective or emergency and by technique (in utero: ultrasound-guided puncture; fetoscopy; ex utero: on placental circulation or postnatal tracheoscopy). RESULTS: We performed 351 balloon insertions during a 144-month period. In 9 cases removal was attempted outside fetal endoscopic tracheal occlusion centers, 3 of which were deemed impossible and led to neonatal death. We attempted 302 in-house balloon removals in 292 fetuses (217 elective [71.8%], 85 emergency [28.2%]) at 33.4 ± 0.1 weeks (range: 28.9-37.1), with a mean interval to delivery of 16.6 ± 0.8 days (0-85). Primary attempt was by fetoscopy in 196 (67.1%), by ultrasound-guided puncture in 62 (21.2%), by tracheoscopy on placental circulation in 30 (10.3%), and postnatal tracheoscopy in 4 cases (1.4%); a second attempt was required in 10 (3.4%) cases. Each center had different preferences for primary technique selection. In elective removals, we found no differences in the interval to delivery between fetoscopic and ultrasound-guided puncture removals. Difficulties during fetoscopic removal led to the development of a stylet to puncture the balloon, leading to shorter operating time and easier reestablishment of airways. CONCLUSION: In these fetal treatment centers, the balloon could always be removed successfully. In 90% this was in utero, with the use of fetoscopy preferred over ultrasound-guided puncture. Ex utero removal was a fall-back procedure. In utero removal does not seem to precipitate immediate membrane rupture, labor, or delivery, although the design of the study did not allow for a formal conclusion. For fetoscopic removals, the introduction of a stylet facilitated retrieval. Successful removal may rely on a permanently prepared team with expertise in all possible techniques.

The amniotic fluid as a source of mesenchymal stem cells with lung-specific characteristics.

The amniotic fluid is a clinically accessible source of mesenchymal stem cells (AF-MSC) during gestation, which enables autologous cellular therapy for perinatal disorders. The origin of AF-MSC remains elusive: renal and neuronal progenitors have been isolated from the AF-MSC pool, yet no cells with pulmonary characteristics. We analyzed gene expression of pulmonary and renal markers of 212 clonal lines of AF-MSC isolated from amniocentesis samples. AF-MSC were cultured on dishes coated with extracellular matrix (ECM) proteins from decellularized fetal rabbit lungs. In vivo differentiation potential of AF-MSC that expressed markers suggestive of lung fate was tested by renal subcapsular injections in immunodeficient mice. Of all the isolated AF-MSC lines, 26% were positive for lung endodermal markers FOXA2 and NKX2.1 and lacked expression of renal markers (KSP). This AF-MSC subpopulation expressed other lung-specific factors, including IRX1, P63, FOXP2, LGR6, SFTC, and PDPN. Pulmonary marker expression decreased over passages when AF-MSC were cultured under conventional conditions, yet remained more stable when culturing the cells on lung ECM-coated dishes. Renal subcapsular injection of AF-MSC expressing lung-specific markers resulted in engrafted cells that were SPTB positive. These data suggest that FOXA2+/NKX2.1+/KSP- AF-MSC lines have lung characteristics which are supported by culture on lung ECM-coated dishes.

Importance of and Satisfaction with Psychosocial Support among Cancer Patients and Survivors in Puerto Rico: Gender, Health Status, and Quality of Life Associations.

OBJECTIVE: To assess needs perceptions regarding the importance of and satisfaction with psychosocial support among cancer patients and survivors in Puerto Rico. METHODS: A cross-sectional study was conducted in 181 participants (70 men and 111 women) who were either undergoing cancer treatment (patients) or had completed cancer treatment (survivors). Participants completed a sociodemographic and clinical characteristics questionnaire, and the Psychosocial Needs Inventory (PNI). RESULTS: The participants reported having or having had prostate (36%) or breast (32%) cancer or some other cancer type (32%). Of the 149 participants reporting cancer type, 130 were classified as having a high perceived level of health and quality of life, and 19 were classified as having a low perceived level of health and quality of life. In terms of perceived needs, the highest level of importance were assigned to the Support Network (e.g. family, friends, neighbors, care professionals; M = 2.88, SD = 0.43) and Health Professional (e.g., patient-health professional relationship, etc.; M = 2.80, SD = 0.50) categories, and the Emotional and Spiritual category was given the lowest importance (e.g., help managing negative emotions and spiritual counseling, etc.; M = 2.62, SD = 0.66). These perceptions varied by gender, perceived health status, and date of diagnosis. Women assigned more importance to the Health Professional and Information categories. CONCLUSION: The results reflect the importance of considering psychosocial needs when providing psychosocial support to cancer patients and survivors. These findings are anticipated to inform services provided by psychosocial oncology support programs in Puerto Rico.

Transplacental sildenafil rescues lung abnormalities in the rabbit model of diaphragmatic hernia.

INTRODUCTION: The management of congenital diaphragmatic hernia (DH) would benefit from an antenatal medical therapy, which addresses both lung hypoplasia and persistent pulmonary hypertension. We aimed at evaluating the pulmonary effects of sildenafil in the fetal rabbit model for DH. METHODS: We performed a dose-finding study to achieve therapeutic fetal plasmatic concentrations without toxicity following maternal sildenafil administration. Subsequently, DH fetuses were randomly exposed to transplacental placebo or sildenafil 10 mg/kg/day from gestational day 24 until examination at term (day 30). Efficacy measures were ipsilateral pulmonary vascular and airway morphometry, micro-CT-based branching analysis, Doppler flow in the main pulmonary artery and postnatal lung mechanics. RESULTS: Fetal sildenafil plasmatic concentration was above the minimal therapeutic level for at least 22 h/day without maternal and fetal side effects. The placebo-exposed DH fetuses had increased wall thickness in peripheral pulmonary vessels and significantly less fifth-order vessels compared with controls (CTR). Sildenafil-exposed DH fetuses, instead, had a medial and adventitial thickness in peripheral pulmonary vessels in the normal range and normal vascular branching. Fetal pulmonary artery Doppler showed a reduction of pulmonary vascular resistances both in DH and in CTR fetuses treated by sildenafil compared with the placebo-treated ones. Sildenafil also reversed the mean terminal bronchiolar density to normal and improved lung mechanics, yet without measurable impact on lung-to-bodyweight ratio. CONCLUSIONS: In the rabbit model for DH, antenatal sildenafil rescues vascular branching and architecture, reduces pulmonary vascular resistances and also improves airway morphometry and respiratory mechanics.

Proton-pump inhibitor omeprazole attenuates hyperoxia induced lung injury.

BACKGROUND: The administration of supplemental oxygen to treat ventilatory insufficiency may lead to the formation of reactive oxygen species and subsequent tissue damage. Cytochrome P4501A1 (CYP1A1) can modulate hyperoxic lung injury by a currently unknown mechanism. Our objective was to evaluate the effect of administration of omeprazole on the induction of CYP1A1 and its influence on hyperoxic lung injury in an established preterm rabbit model. METHODS: Omeprazole was administered either (1) directly to the fetus, (2) to the mother or (3) after birth to the pups in different doses (2-10 or 20 mg/kg). Controls were injected with the same amount of saline. Pups were housed in normoxia (21 %) or hyperoxia (>95 %) for 5 days. Outcome parameters were induction of CYP1A1 measured by real-time polymerase chain reaction (RT-PCR) immediately after delivery, at day 3 and day 5 as well as lung function, morphometry and immunohistochemistry assessed at day 5 of life. Transcriptome analysis was used to define the targeted pathways. RESULTS: Daily neonatal injections demonstrated a dose-dependent increase in CYP1A1. Lung function tests showed a significant improvement in tissue damping, tissue elasticity, total lung capacity, static compliance and elastance. Morphometry revealed a more developed lung architecture with thinned septae in animals treated with the highest dose (20 mg/kg) of omeprazole. Surfactant protein B, vascular endothelial growth factor and its receptor were significantly increased on immunohistochemical stainings after omeprazole treatment. CONCLUSIONS: Neonatal administration of omeprazole induces CYP1A1 in a dose-dependent matter and combined pre- and postnatal administration attenuates hyperoxic lung injury in preterm rabbits, even with the lowest dose of omeprazole without clear CYP1A1 induction.

Transplacental Administration of Rosiglitazone Attenuates Hyperoxic Lung Injury in a Preterm Rabbit Model.

INTRODUCTION: Continuous improvements in perinatal care have allowed the survival of increasingly more prematurely born infants. The establishment of respiration in an extremely immature yet still developing lung results in chronic lung injury with significant mortality and morbidity. We experimentally evaluated a novel medical strategy to prevent hyperoxia-induced lung injury by prenatal rosiglitazone. MATERIALS AND METHODS: Pregnant rabbits were injected with saline or rosiglitazone (3 mg/kg) 48 and 24 h prior to preterm delivery at 28 days of gestation (term = 31 days). The pups were held in normoxia (21% O2) or hyperoxia (>95% O2), and assessment was done at three different time points (1 h, 24 h and 7 days). RESULTS: The administration of rosiglitazone resulted in a significant decrease in tissue damping (resistance) on day 7. Furthermore, significantly increased expression of vascular endothelial growth factor, fetal liver kinase 1 and surfactant protein B immediately after delivery was noted by immunohistochemistery. On day 7, there was a more mature lung parenchymal architecture in rosiglitazone-exposed pups. DISCUSSION: In a preterm rabbit model, prenatal maternal administration of rosiglitazone attenuates neonatal hyperoxic lung injury and results in a more mature pulmonary parenchyma.

The Effect of Transplacental Administration of Glucagon-Like Peptide-1 on Fetal Lung Development in the Rabbit Model of Congenital Diaphragmatic Hernia.

OBJECTIVE: Glucagon-like peptide-1 (GLP-1) increases surfactant protein expression in type 2 pneumocytes. Herein, we determine if transplacental GLP-1 treatment accelerates lung growth in the fetal rabbit model of congenital diaphragmatic hernia (DH). METHODS: Time-mated does had an induction of DH on day 23 followed by daily GLP-1 or placebo injection until term. At that time, the does were weighed, fetal blood was obtained for GLP-1 assay, and the lungs were dissected. Fetal outcome measures were lung-to-body-weight ratio (LBWR), morphometry, and Ki67 and surfactant protein B (SPB) expression. RESULTS: Maternal weight loss in the GLP-1 group was 7.1%. Fetal survival was lower in GLP-1 fetuses compared to placebo controls (27/85, 32% vs. 35/57, 61%; p < 0.05). Fetal GLP-1 levels were increased 3.6-fold. The LBWR of GLP-1 DH fetuses fell within the range of DH placebo fetuses (1.166 ± 0.207% vs. 1.312 ± 0.418%), being significantly lower than that of placebo-exposed unoperated fetuses (2.280 ± 0.522%; p < 0.001). GLP-1 did not improve airway morphometry. GLP-1 DH lungs had a reduced adventitial and medial thickness within the range of controls, and lesser muscularization of vessels measuring 30-60 µm. There were no differences in Ki67 and SPB expression. CONCLUSION: GLP-1 at this dosage improves peripheric pulmonary vessel morphology in intra-acinar vessels with no effect on airway morphometry but with significant maternal and fetal side effects. Thus, it is an unlikely medical strategy.

Fetoscopic versus Open Repair for Spina Bifida Aperta: A Systematic Review of Outcomes.

OBJECTIVE: To compare outcomes of fetoscopic spina bifida aperta repair (FSBAR) with the results of the open approach (OSBAR) as in the Management Of Myelomeningocele Study (MOMS). METHODS: This was a systematic comparison of reports on FSBAR with data from the MOMS (n = 78). Inclusion criteria were studies of spina bifida aperta patients who underwent FSBAR and were followed for ≥12 months. Primary outcome was perinatal mortality. Secondary outcomes included operative, maternal, fetal, neonatal and infant outcomes. RESULTS: Out of 16 reports, we included 5 from 2 centers. Due to bias and heterogeneity, analysis was restricted to two overlapping case series (n = 51 and 71). In those, FSBAR was technically different from OSBAR, had comparable perinatal mortality (7.8 vs. 2.6%, p = 0.212) and shunt rate at 12 months (45 vs. 40%, p = 0.619), longer operation time (223 vs. 105 min, p < 0.001), higher preterm prelabor membrane rupture rate (84 vs. 46%, p < 0.001), earlier gestational age at birth (32.9 vs. 34.1 weeks, p = 0.03), higher postnatal reoperation rate (28 vs. 2.56%, p < 0.001) and absence of uterine thinning or dehiscence (0 vs. 36%, p < 0.001). Functional outcomes were not available. CONCLUSION: FSBAR utilizes a different neurosurgical technique, takes longer to complete, induces more prematurity, requires additional postnatal procedures, yet has a comparable shunt rate and is not associated with uterine thinning or dehiscence. Long-term functional data are awaited.