Progressive reduction in circulating levels of carotenoids and other micronutrients in patients with chronic pancreatitis.

BACKGROUND: Although micronutrients modulate immunity and inflammation, it remains elusive whether they are implicated in the development and progression of chronic pancreatitis (CP). This study aimed to investigate differences in the circulating levels of selected carotenoids and vitamins between CP and controls and trends in the levels of these micronutrients across controls, early CP, and definite CP. METHODS: Demographic and lifestyle data were extracted from medical records for 53 patients with CP (13 early and 38 definite) and obtained using a questionnaire for 52 controls. Plasma ß-carotene, lycopene, cryptoxanthin, zeaxanthin, and α-tocopherol and serum 25(OH)D, folate, IL-6, TNF-α, and MCP-1 were measured with state-of-the-art methods. RESULTS: The levels of all micronutrients (except folate) were significantly lower in CP than in controls. There was a progressive decrease in the levels of these micronutrients across controls, early CP, and definite CP (all p values for trend: ≤0.0012); e.g., plasma lycopene was 36.6, 21.5, and 14.5 µg/dL for controls, early CP, and definite CP, respectively. After adjustment for confounders, there were strong, inverse associations between the levels of all micronutrients (except folate) and CP (e.g., OR (95% CI) for ≥ median vs.

Telementoring initiative for newborn care providers in Kenya, Pakistan and Tanzania.

OBJECTIVES: To support governments' efforts at neonatal mortality reduction, UNICEF and the American Academy of Pediatrics launched a telementoring project in Kenya, Pakistan and Tanzania. METHODS: In Fall 2019, an individualised 12-session telementoring curriculum was created for East Africa and Pakistan after site visits that included care assessment, patient data review and discussion with faculty and staff. After the programme, participants, administrators and UNICEF staff were surveyed and participated in focus group discussions. RESULTS: Participants felt the programme improved knowledge and newborn care. Qualitative analysis found three common themes of successful telementoring: local buy-in, use of existing training or clinical improvement structures, and consideration of technology needs. CONCLUSIONS: Telementoring has potential as a powerful tool in newborn education. It offers more flexibility and easier access than in-person sessions. This project has the potential for scale-up, particularly when physical distancing and travel restrictions are the norm.

Dietary and supplemental long-chain omega-3 fatty acids as moderators of cognitive impairment and Alzheimer's disease.

PURPOSE: There is an ever-growing body of literature examining the relationship between dietary omega-3 polyunsaturated fatty acids (ω3 PUFAs) and cerebral structure and function throughout life. In light of this, the use of ω3 PUFAs, namely, long-chain (LC) ω3 PUFAs (i.e., eicosapentaenoic acid and docosahexaenoic acid), as a therapeutic strategy to mitigate cognitive impairment, and progression to Alzheimer's disease is an attractive prospect. This review aims to summarise evidence reported by observational studies and clinical trials that investigated the role of LC ω3 PUFAs against cognition impairment and future risk of Alzheimer's disease. METHODS: Studies were identified in PubMed and Scopus using the search terms "omega-3 fatty acids", "Alzheimer's disease" and "cognition", along with common variants. Inclusion criteria included observational or randomised controlled trials (RCTs) with all participants aged ≥ 50 years that reported on the association between LC ω3 PUFAs and cognitive function or biological markers indicative of cognitive function linked to Alzheimer's disease. RESULTS: Evidence from 33 studies suggests that dietary and supplemental LC ω3 PUFAs have a protective effect against cognitive impairment. Synaptic plasticity, neuronal membrane fluidity, neuroinflammation, and changes in expression of genes linked to cognitive decline have been identified as potential targets of LC ω3 PUFAs. The protective effects LC ω3 PUFAs on cognitive function and reduced risk of Alzheimer's disease were supported by both observational studies and RCTs, with RCTs suggesting a more pronounced effect in individuals with early and mild cognitive impairment. CONCLUSION: The findings of this review suggest that individuals consuming higher amounts of LC ω3 PUFAs are less likely to develop cognitive impairment and that, as a preventative strategy against Alzheimer's disease, it is most effective when dietary LC ω3 PUFAs are consumed prior to or in the early stages of cognitive decline.

Taking the Pulse on Pediatric Simulation: A National Survey of Pediatric Residency Programs' Simulation Practices and Challenges.

OBJECTIVES: There is abundant literature on simulation use in individual pediatric residency programs but limited overall data on simulation in US pediatric residency programs. This study sought to determine how US pediatric residency programs use simulation for teaching and assessment and the challenges programs face in their use of simulation. METHODS: The Association of Pediatric Program Director's Healthcare Simulation in Pediatrics Learning Community members developed a 15-multipart question survey on the use of simulation in US pediatric residency programs using best practices in survey design. The survey was distributed electronically to US pediatric residency program directors. Qualitative questions were analyzed by content analysis and quantitative questions using descriptive statistics. RESULTS: The survey response rate was 21%; respondents were disproportionately from large academic medical centers. Qualitative analysis found that respondents use simulation to teach pediatric residents in the areas of urgent/emergent situations, procedures, and communication, and common challenges to simulation implementation are time, physical resources, expertise, competing priorities, logistics, and buy-in. Quantitative analysis demonstrated that, although respondents are largely confident that their simulation programs improve resident preparedness and competence, few objectively evaluate their simulation programs. CONCLUSIONS: Pediatric residency programs use simulation for similar purposes and face similar challenges. By collaborating, the resources of the national pediatric simulation community can be leveraged to collect evidence for best practices for simulation use in pediatric residency training.

Amyloid Aggregation of Bacillus circulans Xylanase under Native Conditions and its Modulation by ß-Amyloid-Derived Peptide Fragments.

The aggregation of intrinsically disordered proteins into fibrils is implicated in many neurodegenerative diseases. Amyloid aggregation is a generic property of proteins as evidenced by globular proteins that often form amyloid aggregates under partially denaturing conditions. Recently, multiple lines of evidence have suggested that the amyloid aggregation of globular proteins can also occur under native conditions. Unfortunately, amyloid aggregation under native conditions has been demonstrated in only a handful of cases. Engineering a globular protein's amyloid aggregation might benefit from its fusion to an amyloid-derived fragment with reduced aggregation propensity. Unfortunately, the impacts of such fragments on the amyloid aggregation under native conditions have yet to be examined. In this study, we show that a globular protein, Bacillus circulans xylanase (BCX), can aggregate to form amyloid fibrils under native conditions. When BCX was mixed with or fused to the non-self-aggregating fragments, KLVFWAK and ELVFWAE-which were derived from ß-amyloid (Aß)-they modulated the BCX amyloid aggregation to differing extents. This study also provides insight into a correlation between the kinetic stability and amyloid aggregation of BCX, and supports a view that Aß-derived fragments can be useful for the modulating amyloid aggregation of some, though not all, proteins.

Real-Time Reporting of Complications in Hospitalized Surgical Patients by Surgical Team Members Using a Smartphone Application.

BACKGROUND: The surgical morbidity and mortality (M&M) conference is a vital part of a resident's surgical education, but methods to collect and store M&M data are often rudimentary and unreliable. The authors propose a Health Insurance Portability and Accountability Act (HIPAA)-compliant, electronic health record (EHR)-connected application and database to report and store complication data. METHODS: The app is linked to the patient's EHR, and as a result, basic data on each surgical case-including diagnosis, surgery type, and surgeon-are automatically uploaded to the app. In addition, all data are stored in a secure SQL database-with communications between the app and the database end-to-end encrypted for HIPAA compliance. The full surgical team has access to the app, democratizing complications reporting and allowing for reporting in both the inpatient and outpatient settings. This complication information can then be automatically pulled from the app with a premade presentation for the M&M conference. The data can also be accessed by a Power BI dashboard, allowing for easy quality improvement analyses. RESULTS: When implemented, the app improved data collection for the M&M conference while providing a database for institutional quality improvement use. The authors also identified additional utility of the app, including ensuring appropriate revenue capture. The general appearance of the app and the dashboard can be found in the article. CONCLUSION: The app developed in this project significantly improves on more common methods for M&M conference complication reporting-transforming M&M data into a valuable resource for resident education and quality improvement.

Caregiver Burden and Its Relationship to Health-Related Quality of Life in Craniopharyngioma Survivors.

CONTEXT: Craniopharyngioma (CP) is a rare brain tumor associated with severe comorbidities that reduce survivor health-related quality of life (HRQOL). However, CP impact on caregivers is unknown. OBJECTIVE: To measure caregiver burden and examine its relationship to survivor HRQOL and other determinants in CP. METHODS: Eighty-two participants who self-identified as caregivers of CP survivors responded to an online survey including caregiver-reported Pediatric Quality of Life Inventory (PedsQL), and the Zarit Burden Interview (ZBI). RESULTS: Caregivers reported an average of 13 out of 29 health conditions in survivors following tumor treatment, including excess weight, hypopituitarism, fatigue, mood, cognition, social issues, temperature dysregulation, visual impairment, and sleep problems. Strikingly, 70% of survivors who experienced obesity also experienced hyperphagia. ZBI scores were moderate with a median of 37. PedsQL total scores were poor with a median of 46.2. ZBI scores were independent of caregiver level of education and care duration. Both scores were independent of income, survivor age, gender, age at diagnosis, or tumor recurrence. In contrast, both scores depended on the number (P < .001) and the type of survivor health problems, with significantly worse scores for caregivers or survivors with symptoms of hypothalamic dysfunction (P < .001) including hyperphagia but not obesity. PedsQL total scores significantly predicted ZBI scores (P < .001). CONCLUSION: Survivor poly-symptomatology predicted and incurred significant caregiver burden. Our study separated hyperphagia and obesity and identified hyperphagia and other hypothalamic dysfunction symptoms as understudied issues. Altogether, these findings draw particular attention to the unmet needs of CP survivors and their caregivers.

Pretreatment Health-Related Quality-of-Life Status and Survival in Pancreatobiliary Surgical Patients.

BACKGROUND: Pancreatobiliary (PB) disorders, especially cancer, negatively affect patients' health-related quality of life (HRQoL). However, the influence of baseline, preintervention HRQoL on perioperative and oncologic outcomes has not been well defined. We hypothesized that low baseline HRQoL is associated with worse perioperative and long-term survival outcomes for PB surgical patients. STUDY DESIGN: Pretreatment Functional Assessment of Cancer Therapy - Hepatobiliary Survey results and clinical data from PB patients (2008 to 2016) from a single center's prospective database were analyzed. Survey responses were aggregated into composite scores and divided into quintiles. Patients in the highest quintile of HRQoL were compared to patients in the bottom four quintiles combined. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method. Logistic and Cox regressions were used to determine associations between quintiles of HRQoL scores and 30-day complications and long-term survival, respectively. RESULTS: Of 162 patients evaluated, 99 had malignancy, and 63 had benign disease. Median follow-up was 31 months. Baseline HRQoL scores were similar for benign and malignant disease (p = 0.42) and were not associated with the development of any (p = 0.08) or major complications (p = 0.64). Patients with highest quintile HRQoL scores had improved 3-year OS (84.6 vs 61.7%, p = 0.03) compared to patients in the lowest four quintiles of HRQoL. Among cancer patients only, those with the highest quintile scores had improved 3-year OS (81.6 vs 47.4%, p = 0.02). On multivariable analysis, highest quintile HRQoL scores were associated with longer OS and DFS for patients with malignancy. CONCLUSIONS: Pretreatment HRQoL was associated with both OS and DFS among PB patients and might have prognostic utility. Future studies are necessary to determine whether patients with poorer HRQoL may benefit from targeted psychosocial interventions.

The Impact of Improved Treatments on Survival of Adult U.S. Leukemia Patients: 1990-2018.

INTRODUCTION: Molecularly targeted therapies such as tyrosine kinase inhibitors (TKI) are effective treatments for B-cell receptor (BCR)-ABL-bearing leukemias. We evaluated the impact of TKIs on historical chronic myeloid leukemia (CML) mortality trends compared with acute lymphoblastic leukemia (ALL) and chronic lymphoblastic leukemia (CLL). METHODS: Because mortality trends reflect combined effects of leukemia incidence and survival, we also evaluated the contribution of incidence and survival trends to mortality trends by subtypes. We used data from 13 U.S. (SEER) registries (1992-2017) among U.S. adults. We utilized histology codes to identify cases of CML, ALL, and CLL and death certificate data to calculate mortality. We used Joinpoint to characterize incidence (1992-2017) and mortality (1992-2018) trends by subtype and diagnosis year. RESULTS: For CML, mortality rates started declining in 1998 at an average rate of 12% annually. Imatinib was approved by the FDA for treating CML and ALL in 2001, leading to clear benefits for patients with CML. Five-year CML survival increased dramatically over time, especially between 1996 to 2011, 2.3% per year on average. ALL incidence increased 1.5% annually from 1992 to 2017. ALL mortality decreased 0.6% annually during 1992 to 2012 and then stopped declining. CLL incidence fluctuated during 1992 to 2017 while mortality decreased 1.1% annually during 1992 to 2011 and at a faster rate of 3.6% per year from 2011. Five-year survival increased 0.7% per year on average during 1992 to 2016. CONCLUSIONS: Survival benefit from TKIs and other novel therapies for treating leukemia subtypes has been demonstrated in clinical trials. IMPACT: Our study highlights the impact of molecularly targeted therapies at the population level.

A risk-adjusted analysis of drain use in pancreaticoduodenectomy: Some is good, but more may not be better.

BACKGROUND: Intraperitoneal drain placement decreases morbidity and mortality in patients who develop a clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). It is unknown whether multiple drains mitigate CR-POPF better than a single drain. We hypothesized that multiple drains decrease the complication burden more than a single drain in cases at greater risk for CR-POPF. METHODS: The Fistula Risk Score (FRS), mitigation strategies (including number of drains placed), and clinical outcomes were obtained from a multi-institutional database of PDs performed from 2003 to 2020. Outcomes were compared between cases utilizing 0, 1, or 2 intraperitoneal drains. Multivariable regression analysis was used to evaluate the optimal drainage approach. RESULTS: A total of 4,292 PDs used 0 (7.3%), 1 (45.2%), or 2 (47.5%) drains with an observed CR-POPF rate of 9.6%, which was higher in intermediate/high FRS zone cases compared with negligible/low FRS zone cases (13% vs 2.4%, P < .001). The number of drains placed also correlated with FRS zone (median of 2 in intermediate/high vs 1 in negligible/low risk cases). In intermediate/high risk cases, the use of 2 drains instead of 1 was not associated with a reduced rate of CR-POPF, average complication burden attributed to a CR-POPF, reoperations, or mortality. Obviation of drains was associated with significant increases in complication burden and mortality - regardless of the FRS zone. CONCLUSION: In intermediate/high risk zone cases, placement of a single drain or multiple drains appears to mitigate the complication burden while use of no drains is associated with inferior outcomes.

Cyclophilin D binds to the acidic C-terminus region of α-Synuclein and affects its aggregation characteristics.

Cyclophilin D (CypD) is a peptidyl-prolyl isomerase expressed in the nucleus and transported into the mitochondria where it is best associated with the regulation of the mitochondrial permeability transition pore (MPTP). There are, however, other possible roles of CypD in the mitochondria which may or may not be linked with the MPTP. Alpha synuclein (αSyn) is shown here to interact directly with CypD via its acidic proline-rich C-terminus region and binding at the putative ligand binding pocket of CypD. The study shows that CypD binding with soluble αSyn prevents its aggregation. Furthermore, the addition of CypD to preformed αSyn fibrils leads to the disassembly of these fibrils. Enzymatically-compromised mutants of CypD show reduced abilities to dissociate αSyn aggregates, suggesting that fibril disassembly is linked to the increased rate of peptidyl-prolyl isomerisation catalysed by CypD. Protein aggregation in the mitochondria is increasingly seen as the cause of neurodegeneration. However, protein aggregation is a reversible process but disaggregation requires help from other proteins such as isomerases and chaperones. The results here demonstrate a possible mechanism by which CypD achieves this and suggest that disaggregation could be one of the many functions of this protein.

A KLVFFAE-Derived Peptide Probe for Detection of Alpha-Synuclein Fibrils.

Aggregation of an amyloid protein, α-synuclein (αS), is a critical step in the neurodegenerative pathway of Parkinson's diseases (PD). Specific detection of amyloid conformers (i.e., monomers, oligomers, and fibrils) produced during αS aggregation is critical in better understanding a molecular basis of PD and developing a diagnostic tool. While various molecular probes are available for detection of αS fibrils, which may serve as a reservoir of toxic αS aggregate forms, these probes suffer from limited conformer-specificity and operational flexibility. In the present study, we explored the potential of non-self-aggregating peptides derived from the highly aggregation-prone KLVFFAE region of an amyloid protein, ß-amyloid, as molecular probes for αS aggregates. We show that of the four peptides tested (KLVFWAK, ELVFWAE, and their C-terminal capping variants, all of which were attached with fluorescein isothiocyanate at their respective N-termini), KLVFWAK with C-terminal capping was selectively bound to αS fibrils over monomers and oligomers and readily used for monitoring αS fibrilization. Our analyses suggest that binding of the peptide to αS fibrils is mediated by both electrostatic and hydrophobic interactions. We anticipate that our peptide can readily be optimized for conformer-specificity and operational flexibility. Overall, this study presents the creation of a KLVFFAE-based molecular probe for αS fibrils and demonstrates fine-tuning of its conformer-specificity by terminal mutations and capping.

Atrial septal interventions in patients with hypoplastic left heart syndrome.

OBJECTIVES: To report an institutional experience performing percutaneous atrial septal interventions in patients with hypoplastic left heart syndrome (HLHS). BACKGROUND: The success of the Hybrid approach in palliating patients with HLHS is crucially dependant on relieving any significant interatrial restriction. Data on transcatheter interventions to relieve atrial septal restrictions in patients with HLHS are limited. METHODS: We retrospectively reviewed 67 transcatheter atrial septal interventions that were performed between July 2002 and September 2007 in 56 patients with HLHS. The median weight was 3.35 kg. About 10.7% of patients had an intact atrial septum. Balloon atrial septostomy (BAS) was used in 77.6% of procedures, additional techniques in 35.8% of procedures. Patients were divided into those with standard atrial septal anatomy (group A, n = 33) and those with complex atrial septal anatomy (group B, n = 23). RESULTS: The mean trans-septal gradient was reduced significantly from 7 mm Hg to 1 mm Hg with the median time to discharge being 3.5 days. Major adverse events were seen in 8.9% of procedures, whereas minor adverse events occurred in 26.8% of procedures. Adverse events were significantly less common in patients with standard atrial septal anatomy, compared to those with complex atrial septal anatomy (25.6% versus 50.0%). About 19.6% patients required repeated atrial septal interventions. Survival up to and including Comprehensive stage II palliation was 73% group A, and 57% in group B. CONCLUSIONS: With utilization of appropriate techniques and equipment, atrial septal interventions in HLHS can be performed successfully in virtually all patients. Complex atrial septal anatomy is technically challenging and has a higher incidence of procedural adverse events. In the majority of patients, standard BAS can be performed safely, and is usually the only intervention required to achieve adequate relief of atrial septal restriction until Comprehensive stage II palliation.

Evaluating the effectiveness of a consumer-provided mental health recovery education presentation.

The current study investigated the effectiveness of the In Our Own Voice (IOOV) mental health education program in improving knowledge and attitudes about mental illnesses. Undergraduate participants (N = 114) completed three pre-test measures of knowledge and attitudes, attended either an In Our Own Voice presentation or a control presentation about psychology careers, and repeated the three measures following the presentation. Results indicated that the IOOV group showed significant positive change across time, as well as significantly greater improvement than a control group in their knowledge and attitude scores on all measures. These findings support the effectiveness of the IOOV program.

Structure of the Epigenetic Oncogene MMSET and Inhibition by N-Alkyl Sinefungin Derivatives.

The members of the NSD subfamily of lysine methyl transferases are compelling oncology targets due to the recent characterization of gain-of-function mutations and translocations in several hematological cancers. To date, these proteins have proven intractable to small molecule inhibition. Here, we present initial efforts to identify inhibitors of MMSET (aka NSD2 or WHSC1) using solution phase and crystal structural methods. On the basis of 2D NMR experiments comparing NSD1 and MMSET structural mobility, we designed an MMSET construct with five point mutations in the N-terminal helix of its SET domain for crystallization experiments and elucidated the structure of the mutant MMSET SET domain at 2.1 Å resolution. Both NSD1 and MMSET crystal systems proved resistant to soaking or cocrystallography with inhibitors. However, use of the close homologue SETD2 as a structural surrogate supported the design and characterization of N-alkyl sinefungin derivatives, which showed low micromolar inhibition against both SETD2 and MMSET.

Naturally Occurring Mutations in the MPS1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance.

Acquired resistance to therapy is perhaps the greatest challenge to effective clinical management of cancer. With several inhibitors of the mitotic checkpoint kinase MPS1 in preclinical development, we sought to investigate how resistance against these inhibitors may arise so that mitigation or bypass strategies could be addressed as early as possible. Toward this end, we modeled acquired resistance to the MPS1 inhibitors AZ3146, NMS-P715, and CCT251455, identifying five point mutations in the kinase domain of MPS1 that confer resistance against multiple inhibitors. Structural studies showed how the MPS1 mutants conferred resistance by causing steric hindrance to inhibitor binding. Notably, we show that these mutations occur in nontreated cancer cell lines and primary tumor specimens, and that they also preexist in normal lymphoblast and breast tissues. In a parallel piece of work, we also show that the EGFR p.T790M mutation, the most common mutation conferring resistance to the EGFR inhibitor gefitinib, also preexists in cancer cells and normal tissue. Our results therefore suggest that mutations conferring resistance to targeted therapy occur naturally in normal and malignant cells and these mutations do not arise as a result of the increased mutagenic plasticity of cancer cells.

Structure-based design of orally bioavailable 1H-pyrrolo[3,2-c]pyridine inhibitors of mitotic kinase monopolar spindle 1 (MPS1).

The protein kinase MPS1 is a crucial component of the spindle assembly checkpoint signal and is aberrantly overexpressed in many human cancers. MPS1 is one of the top 25 genes overexpressed in tumors with chromosomal instability and aneuploidy. PTEN-deficient breast tumor cells are particularly dependent upon MPS1 for their survival, making it a target of significant interest in oncology. We report the discovery and optimization of potent and selective MPS1 inhibitors based on the 1H-pyrrolo[3,2-c]pyridine scaffold, guided by structure-based design and cellular characterization of MPS1 inhibition, leading to 65 (CCT251455). This potent and selective chemical tool stabilizes an inactive conformation of MPS1 with the activation loop ordered in a manner incompatible with ATP and substrate-peptide binding; it displays a favorable oral pharmacokinetic profile, shows dose-dependent inhibition of MPS1 in an HCT116 human tumor xenograft model, and is an attractive tool compound to elucidate further the therapeutic potential of MPS1 inhibition.

Neonatal resuscitation skills among pediatricians and family physicians: is residency training preparing for postresidency practice?

BACKGROUND: Pediatricians and family physicians are responsible for providing newborn resuscitation, yet Accreditation Council for Graduate Medical Education requirements for training in this area during residency differ markedly for the two specialties. Our objectives were to determine (1) the extent to which neonatal resuscitation training differs for pediatric and family medicine residents; (2) the extent to which general pediatricians and family physicians engage in newborn resuscitation in their practice; and (3) whether use of resuscitation skills differs between urban/suburban and rural providers. METHODS: We surveyed a national cohort of pediatricians and family physicians who obtained board certification between 2001 and 2005. Data were analyzed based on type of physician and setting of current practice. RESULTS: Survey response rate was 22% (382 of 1736). Compared with family medicine physicians, pediatricians received more neonatal resuscitation training during residency. Most members of both groups had attended no deliveries in the year prior to the survey (75% [111 of 148] versus 74% [114 of 154]). In their current practice, the groups were equally likely to have provided a newborn bag and mask ventilation, chest compressions, and resuscitation medications. Pediatricians were more likely than family physicians to have attempted to either intubate a newborn (20% [28 of 148] versus 10% [16 of 153]; P  =  .0495) or insert umbilical catheters (15% [22 of 148] versus 5% [8 of 153]; P  =  .005). Regardless of specialty, rural physicians were much more likely to report that they attended deliveries (61% [41 of 67] versus 15% [36 of 234]; P < .001). Among rural pediatricians attending deliveries, 44% (7 of 16) reported feeling inadequately prepared for at least one delivery in the past year. CONCLUSIONS: Few primary care pediatricians and family physicians provide newborn resuscitation after residency. For those who do attend deliveries, current training 5 provide insufficient preparation. Flexible, individualized residency curricula could target intensive resuscitation training to individuals who plan to practice in rural areas and/or attend deliveries after graduation.

Transcatheter elimination of left-to-right shunts in infants with bronchopulmonary dysplasia is feasible and safe.

OBJECTIVE: To test the hypothesis that transcatheter elimination of left-to-right (L-R) cardiac shunts in former premature infants with bronchopulmonary dysplasia (BPD) is feasible, safe, and is associated with an improvement in respiratory status. DESIGN: Retrospective case review. PATIENTS: Twelve patients with BPD who underwent an attempt at transcatheter closure of an L-R shunt lesion within the first year of life at a single center. Median weight was 5.4 kg and median age was 6 months. Fifteen L-R shunt lesions included patent ductus arteriosus (n = 1), atrial septal defect (ASD) (n = 9), and aortopulmonary collaterals (n = 5). OUTCOME MEASURES: Echocardiographic and clinical markers were collected before and after intervention as well as procedural variables including successful elimination of the shunt and procedural complications. RESULTS: The L-R shunts were successfully occluded in 11/12 (91.6%) patients without any significant procedural adverse event. The ASD closure group demonstrated a decrease in right heart size after the procedure. All patients required respiratory support prior to, and 1 month after, the procedure while only 5/10 (50%) required respiratory support at 12 months of age (P = .0129). There was no change in the median weight percentile over time. CONCLUSION: Transcatheter occlusion of L-R shunts can be performed safely and effectively in children with BPD. Further studies may clarify the role of such therapy in improvement in respiratory physiology over time.

Use of a novel induced spawning technique for the first reported captive spawning of Tetraodon nigroviridis.

The spotted green pufferfish (Tetraodon nigroviridis) is an important genetics model animal due to its small, well-mapped genome. However, only wild-caught juveniles and adults are available to researchers. A lack of gametes, fertilized eggs, developing embryos, and other early life stages hampers development of the full potential of T. nigroviridis as a model research species. We report on successful spawning trials using a novel induced spawning technique, ovarian lavage. Chorulon(®) (human chorionic gonadotropin, hCG) was injected into a catheter inserted into the oviduct at a rate of 3 µl/g body weight. In one trial, a female paired with a male spawned in an aquarium at about 72 h post-treatment. In other trials, females were hand-stripped of eggs at 36 h post-treatment. There were 3680 eggs/g of eggs and females produced up to 24% of their body weight in eggs. Hatch resulted from all trials on the 4th day post-fertilization. Ovarian lavage is a simple method for administering spawning hormones, uses a catheter technique similar to that frequently performed to determine egg maturity in broodstock, and eliminates the need for injection.