Bacterial adhesins attach their hosts to surfaces that the bacteria will colonize. This surface adhesion occurs through specific ligand-binding domains located towards the distal end of the long adhesin molecules. However, recognizing which of the many adhesin domains are structural and which are ligand binding has been difficult up to now. Here we have used the protein structure modeling program AlphaFold2 to predict structures for these giant 0.2- to 1.5-megadalton proteins. Crystal structures previously solved for several adhesin regions are in good agreement with the models. Whereas most adhesin domains are linked in a linear fashion through their N- and C-terminal ends, ligand-binding domains can be recognized by budding out from a companion core domain so that their ligand-binding sites are projected away from the axis of the adhesin for maximal exposure to their targets. These companion domains are "split" in their continuity by projecting the ligand-binding domain outwards. The "split domains" are mostly β-sandwich extender modules, but other domains like a β-solenoid can serve the same function. Bioinformatic analyses of Gram-negative bacterial sequences revealed wide variety ligand-binding domains are used in their Repeats-in-Toxin adhesins. The ligands for many of these domains have yet to be identified but known ligands include various cell-surface glycans, proteins, and even ice. Recognizing the ligands to which the adhesins bind could lead to ways of blocking colonization by bacterial pathogens. Engineering different ligand-binding domains into an adhesin has the potential to change the surfaces to which bacteria bind.

The ability to accurately record the temperature at which ice nucleation occurs is critical for studying biological ice nucleators. Several instruments have been designed and custom built to make such measurements, but they are not yet on the market. Here we reproducibly measure ice nucleation temperatures down close to the homogeneous nucleation temperature of-38 degrees C with a commercially available nanoliter osmometer, which we routinely use to assay the thermal hysteresis activity of antifreeze proteins. This instrument has both a wide operating temperature range and fine temperature control, while the oil immersion format on 12-well grids prevents droplet evaporation and surface nucleation events. The results obtained are consistent with those reported on other instruments in common use.

In nature, frost can form at a few degrees below 0 °C. However, this process requires the assembly of tens of thousands of ice-like water molecules that align together to initiate freezing at these relatively high temperatures. Water ordering on this scale is mediated by the ice nucleation proteins (INPs) of common environmental bacteria like Pseudomonas syringae and Pseudomonas borealis. However, individually, these 100 kDa proteins are too small to organize enough water molecules for frost formation, and it is not known how giant, megadalton-sized multimers, which are crucial for ice nucleation at high sub-zero temperatures, form. The ability of multimers to self-assemble was suggested when the transfer of an INP gene into Escherichia coli led to efficient ice nucleation. Here, we demonstrate that a positively charged subdomain at the C-terminal end of the central β-solenoid of the INP is crucial for multimerization. Truncation, relocation, or change of the charge of this subdomain caused a catastrophic loss of ice nucleation ability. Cryo-electron tomography of the recombinant E. coli showed that the INP multimers form fibres that are ~5 nm across and up to 200 nm long. A model of these fibres as an overlapping series of antiparallel dimers can account for all their known properties and suggests a route to making cell-free ice nucleators for biotechnological applications.

Bacterial ice nucleation proteins (INPs) can cause frost damage to plants by nucleating ice formation at high sub-zero temperatures. Modeling of Pseudomonas borealis INP by AlphaFold suggests that the central domain of 65 tandem sixteen-residue repeats forms a beta-solenoid with arrays of outward-pointing threonines and tyrosines, which may organize water molecules into an ice-like pattern. Here we report that mutating some of these residues in a central segment of P. borealis INP, expressed in Escherichia coli , decreases ice nucleation activity more than the section’s deletion. Insertion of a bulky domain has the same effect, indicating that the continuity of the water-organizing repeats is critical for optimal activity. The ~10 C-terminal coils differ from the other 55 coils in being more basic and lacking water-organizing motifs; deletion of this region eliminates INP activity. We show through sequence modifications how arrays of conserved motifs form the large ice-nucleating surface required for potency.

Objective To test the hypothesis that infants born <30 weeks’ gestation supported by Seattle-PAP will have lower rates of continuous positive airway pressure (CPAP) failure than infants supported with conventional, Fisher&Paykel-CPAP (FP-CPAP). Study design Randomized trial (3/2017-01/2019) at 5 NICUs. The primary outcome was CPAP failure; subgroup analyses (gestational age, receipt antenatal corticosteroids) were performed. Results A total of 232 infants were randomized. Infants in the Seattle-PAP and FP-CPAP groups had mean gestational ages of 27.0 and 27.2 weeks, respectively. We observed no differences in rates of treatment failure between Seattle-PAP (40/112, 35.7%) and FP-CPAP (38/120, 31.7%; risk difference, 4.1%; 95% CI, −8.1–16.2; P = 0.51). Subgroup analysis indicated no differences in rates of CPAP failure. We observed no differences between the two groups in frequencies of adverse events or duration of respiratory support. Conclusions Among infants born <30 weeks’ gestation, rates of CPAP failure did not differ between Seattle-PAP and FP-CPAP.

BackgroundAt birth, the majority of neonates born at <30weeks of gestation require respiratory support to facilitate transition and ensure adequate gas exchange. Although the optimal approach to the initial respiratory management is uncertain, the American Academy of Pediatrics endorses noninvasive respiratory support with nasal continuous positive airway pressure (nCPAP) for premature neonates with respiratory insufficiency. Despite evidence for its use, nCPAP failure, requiring intubation and mechanical ventilation, is common. Recently, investigators have described a novel method to deliver bubble nCPAP, termed Seattle-PAP. While preclinical and pilot studies are encouraging regarding the potential value of Seattle-PAP, a large trial is needed to compare Seattle-PAP directly with the current standard of care for bubble nCPAP (Fisher & Paykel CPAP or FP-CPAP).Methods/designWe designed a multicenter, non-blinded, randomized controlled trial that will enroll 230 premature infants (22(0/7) to 29(6/7) weeks of gestation). Infants will be randomized to receive Seattle-PAP or FP-CPAP. The primary outcome is respiratory failure requiring intubation and mechanical ventilation. Secondary outcomes include measures of short- and long-term respiratory morbidity and cost-effectiveness.DiscussionThis trial will assess whether Seattle-PAP is more efficacious and cost-effective than FP-CPAP in real-world practice among premature neonates.Trial registrationClinicalTrials.gov, NCT03085329. Registered on 21 March 2017.

Background Almost one million prematurely born infants die annually from respiratory insufficiency, predominantly in countries with limited access to respiratory support for neonates. The primary hypothesis tested in the present study was that a modified device for bubble nasal continuous positive airway pressure (Bn-CPAP) would provide lower work of spontaneous breathing, estimated by esophageal pressure-rate products. Methods Infants born <32 weeks gestation and stable on Bn-CPAP with FiO2 <0.30 were studied within 72 h following delivery. Esophageal pressures during spontaneous breathing were measured during 2 h on standard Bn-CPAP, then 2 h with Bn-CPAP using a modified bubble device presently termed Seattle-PAP, which produces a different pattern of pressure fluctuations and which provided greater respiratory support in preclinical studies, then 2 h on standard Bn-CPAP. Results All 40 infants enrolled completed the study and follow-up through 36 wks post menstrual age or hospital discharge, whichever came first. No infants were on supplemental oxygen at completion of follow-up. No infants developed pneumothoraces or nasal trauma, and no adverse events attributed to the study were observed. Pressure-rate products on the two devices were not different, but effort of breathing, assessed by areas under esophageal pressure-time curves, was lower with Seattle-PAP than with standard Bn-CPAP. Conclusion Use of Seattle-PAP to implement Bn-CPAP lowers the effort of breathing exerted even by relatively healthy spontaneously breathing premature neonates. Whether the lower effort of breathing observed with Seattle-PAP translates to improvements in neonatal mortality or morbidity will need to be determined by studies in appropriate patient populations.

Background: At birth, the majority of neonates born at <30 weeks of gestation require respiratory support to facilitate transition and ensure adequate gas exchange. Although the optimal approach to the initial respiratory management is uncertain, the American Academy of Pediatrics endorses noninvasive respiratory support with nasal continuous positive airway pressure (nCPAP) for premature neonates with respiratory insufficiency. Despite evidence for its use, nCPAP failure, requiring intubation and mechanical ventilation is common. Recently, investigators have described a novel method to deliver bubble nCPAP, termed Seattle-PAP. While preclinical and pilot studies are encouraging with regard to the potential value of Seattle-PAP, a large trial is needed to compare Seattle-PAP directly with the current standard of care for bubble nCPAP (Fisher Paykel-CPAP; FP-CPAP).Methods: We designed a multicenter, non-blinded, randomized controlled trial that will enroll 230 premature infants (220/7 to 296/7 weeks of gestation). Infants will be randomized to receive Seattle-PAP or FP-CPAP. The primary outcome is respiratory failure requiring intubation and mechanical ventilation. Secondary outcomes include measures of short and long-term respiratory morbidity and cost effectiveness.Discussion: This trial will assess whether Seattle-PAP is more efficacious and cost effective than FP-CPAP in real-world practice among premature neonates.

Curent topics in neonatology number1 , Curent topics in neonatology number1 , کتابخانه مرکزی دانشگاه علوم پزشکی تهران

INVASIVE PULMONARY INFECTIONS caused by the opportunistic fungus Aspergillus fumigatus are common in immunocompromised patients and are notoriously difficult to treat successfully. 1 Patterson J.E. Epidemiology of fungal infections in solid organ transplant patients. Transpl Infect Dis. 1999; 1: 229-236 Crossref PubMed Scopus (127) Google Scholar , 2 Doffman S.R. Agarwal S.G. Brown J.S. Invasive pulmonary aspergillosis. Expert Rev Anti Infect Ther. 2005; 3: 613-627 Crossref PubMed Scopus (12) Google Scholar , 3 Maschmeyer G. Haas A. Cornely O.A. Invasive aspergillosis: Epidemiology, diagnosis and management in immunocompromised patients. Drugs. 2007; 67: 1567-1601 Crossref PubMed Scopus (294) Google Scholar , 4 Gallien S. Fournier S. Porcher R. et al. Therapeutic outcome and prognostic factors of invasive aspergillosis in an infectious disease department: A review of 34 cases. Infection. 2008; 36: 533-538 Crossref PubMed Scopus (35) Google Scholar Such infections frequently are encountered after solid organ or bone marrow transplantation 5 Dictar M.O. Maiolo E. Alexander B. et al. Mycoses in the transplanted patient. Med Mycol. 2000; 38: 251-258 Crossref PubMed Scopus (35) Google Scholar , 6 Marik P.E. Fungal infections in solid organ transplantation. Expert Opin Pharmacother. 2006; 7: 297-305 Crossref PubMed Scopus (59) Google Scholar and may also occur in patients with severe acquired immunodeficiency syndrome 7 Xie L. Gebre W. Szabo K. et al. Cardiac aspergillosis in patients with acquired immunodeficiency syndrome: A case report and review of the literature. Arch Pathol Lab Med. 2005; 129: 511-515 PubMed Google Scholar or those receiving chronic corticosteroid therapy for other indications. 8 Shibuya K. Ando T. Hasegawa C. et al. Pathophysiology of pulmonary aspergillosis. J Infect Chemother. 2004; 10: 138-145 Abstract Full Text PDF PubMed Scopus (54) Google Scholar Primary cardiac aspergillosis or the spread of invasive pulmonary A fumigatus to the mediastinum, pericardium, or heart is exceedingly rare in the absence of previous cardiac surgery and carries a very high mortality rate. 9 El-Hamamsy I. Durrleman N. Stevens L.M. et al. Aspergillus endocarditis after cardiac surgery. Ann Thorac Surg. 2005; 80: 359-364 Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar Long-term antifungal therapy combined with aggressive surgical management appear to afford patients with pulmonary or cardiac A fumigatus with the optimal chance for survival. 9 El-Hamamsy I. Durrleman N. Stevens L.M. et al. Aspergillus endocarditis after cardiac surgery. Ann Thorac Surg. 2005; 80: 359-364 Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar , 10 Le Moing V. Lortholary O. Timsit J.F. et al. Aspergillus pericarditis with tamponade: Report of a successfully treated case and review. Clin Infect Dis. 1998; 26: 451-460 Crossref PubMed Scopus (35) Google Scholar , 11 Reis L.J. Barton T.D. Pochettino A. et al. Successful treatment of Aspergillus prosthetic valve endocarditis with oral voriconazole. Clin Infect Dis. 2005; 41: 752-753 Crossref PubMed Scopus (21) Google Scholar , 12 Saxena P. Clarke B. Dunning J. Aspergillus endocarditis of the mitral valve in a lung-transplanted patient. Tex Heart Inst J. 2007; 34: 95-97 PubMed Google Scholar , 13 Danner B.C. Didilis V. Dorge H. et al. Surgical treatment of pulmonary aspergillosis/myocosis in immunocompromised patients. Interact Cardiovasc Thorac Surg. 2008; 7: 771-776 Crossref PubMed Scopus (19) Google Scholar In the current report, the authors describe their perioperative management of a debilitated, immunocompromised patient with a large anterior mediastinal Aspergillus abscess that invaded the right atrium and caused dynamic partial obstruction of the tricuspid valve inlet. The mediastinal abscess was debrided, the intracardiac fungal mass was excised, and the right atrium was repaired using femoral cardiopulmonary bypass (CPB) without the need for deep hypothermic circulatory arrest. The pathophysiology and management of disseminated pulmonary and cardiac aspergillosis are also discussed.

INTRODUCTION:Interventions directed toward mothers before and during pregnancy and childbirth may help reduce preterm births and stillbirths. Survival of preterm newborns may also be improved with interventions given during these times or soon after birth. This comprehensive review assesses existing interventions for low- and middle-income countries (LMICs). METHODS:Approximately 2,000 intervention studies were systematically evaluated through December 31, 2008. They addressed preterm birth or low birth weight; stillbirth or perinatal mortality; and management of preterm newborns. Out of 82 identified interventions, 49 were relevant to LMICs and had reasonable amounts of evidence, and therefore selected for in-depth reviews. Each was classified and assessed by the quality of available evidence and its potential to treat or prevent preterm birth and stillbirth. Impacts on other maternal, fetal, newborn or child health outcomes were also considered. Assessments were based on an adaptation of the Grades of Recommendation Assessment, Development and Evaluation criteria. RESULTS:Most interventions require additional research to improve the quality of evidence. Others had little evidence of benefit and should be discontinued. The following are supported by moderate- to high-quality evidence and strongly recommended for LMICs: Two interventions prevent preterm births--smoking cessation and progesterone. Eight interventions prevent stillbirths--balanced protein energy supplementation, screening and treatment of syphilis, intermittant presumptive treatment for malaria during pregnancy, insecticide-treated mosquito nets, birth preparedness, emergency obstetric care, cesarean section for breech presentation, and elective induction for post-term delivery. Eleven interventions improve survival of preterm newborns--prophylactic steroids in preterm labor, antibiotics for PROM, vitamin K supplementation at delivery, case management of neonatal sepsis and pneumonia, delayed cord clamping, room air (vs. 100% oxygen) for resuscitation, hospital-based kangaroo mother care, early breastfeeding, thermal care, and surfactant therapy and application of continued distending pressure to the lungs for respiratory distress syndrome CONCLUSION:The research paradigm for discovery science and intervention development must be balanced to address prevention as well as improve morbidity and mortality in all settings. This review also reveals significant gaps in current knowledge of interventions spanning the continuum of maternal and fetal outcomes, and the critical need to generate further high-quality evidence for promising interventions.

Bubble continuous positive airway pressure (B-CPAP) applies small-amplitude, high-frequency oscillations in airway pressure (ΔPaw) that may improve gas exchange in infants with respiratory disease. We developed a device, high-amplitude B-CPAP (HAB-CPAP), which provides greater ΔPaw than B-CPAP provides. We studied the effects of different operational parameters on ΔPaw and volumes of gas delivered to a mechanical infant lung model. I n vivo studies tested the hypothesis that HAB-CPAP provides noninvasive respiratory support greater than that provided by B-CPAP. Lavaged juvenile rabbits were stabilized on ventilator nasal CPAP. The animals were then supported at the same mean airway pressure, bias flow, and fraction of inspired oxygen (FiO2) required for stabilization, whereas the bubbler angle was varied in a randomized crossover design at exit angles, relative to vertical, of 0 (HAB-CPAP0; equivalent to conventional B-CPAP), 90 (HAB-CPAP90), and 135° (HAB-CPAP135). Arterial blood gases and pressure-rate product (PRP) were measured after 15 min at each bubbler angle. Pao2 levels were higher (p < 0.007) with HAB-CPAP135 than with conventional B-CPAP. PaCO2 levels did not differ (p = 0.073) among the three bubbler configurations. PRP with HAB-CPAP135 were half of the PRP with HAB-CPAP0 or HAB-CPAP90 (p = 0.001). These results indicate that HAB-CPAP135 provides greater respiratory support than conventional B-CPAP does.

We have developed two devices: a high-amplitude bubble continuous positive airway pressure (HAB-CPAP) and an inexpensive bubble intermittent mandatory ventilator (B-IMV) to test the hypotheses that simple, inexpensive devices can provide gas exchange similar to that of bubble CPAP (B-CPAP) and conventional mechanical ventilation (CMV). Twelve paralyzed juvenile rabbits were intubated, stabilized on CMV, and then switched to CPAP. On identical mean airway pressures (MAPs), animals were unable to maintain pulse oximeter oxygen saturation (SpO2) >80% on conventional B-CPAP, but all animals oxygenated well (97.3 ± 2.1%) on HAB-CPAP. In fact, arterial partial pressures of O2 (Pao2) were higher during HAB-CPAP than during CMV (p = 0.01). After repeated lung lavages, arterial partial pressures of CO2 (Paco2) were lower with B-IMV than with CMV (p < 0.0001), despite identical ventilator settings. In lavaged animals, when HAB-CPAP was compared with CMV at the same MAP and 100% O2, no differences were observed in Pao2, but Paco2 levels were higher with HAB-CPAP (70 ± 7 versus 50 ± 5 mm Hg; p < 0.05). Arterial blood pressures were not impaired by HAB-CPAP or B-IMV. The results confirm that simple inexpensive devices can provide respiratory support in the face of severe lung disease and could extend the use of respiratory support for preterm infants into severely resource-limited settings.

REEXPANSION PULMONARY EDEMA (REPE) is a well-known but rare complication of lung reinflation after pathologic collapse or intentional deflation. The presentation of REPE may be highly variable, ranging from a clinically asymptomatic, incidental radiologic finding to acute respiratory failure accompanied by severe, life-threatening hypoxemia. 1 Mahajan V.K. Simon M. Guber G.L. Reexpansion pulmonary edema. Chest. 1979; 75: 192-194 Crossref PubMed Scopus (55) Google Scholar , 2 Mahfood S. Hix W.R. Aaron B.L. et al. Reexpansion pulmonary edema. Ann Thorac Surg. 1988; 45: 340-345 Abstract Full Text PDF PubMed Scopus (273) Google Scholar , 3 Trachiotis G.D. Vricella L.A. Aaron B.L. et al. As originally published in 1988: Reexpansion pulmonary edema Updated in 1997. Ann Thorac Surg. 1997; 63: 1206-1207 Abstract Full Text PDF PubMed Scopus (61) Google Scholar , 4 Neustein S.M. Reexpansion pulmonary edema. J Cardiothorac Vasc Anesth. 2007; 21: 887-891 Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar Early reviews of REPE 1 Mahajan V.K. Simon M. Guber G.L. Reexpansion pulmonary edema. Chest. 1979; 75: 192-194 Crossref PubMed Scopus (55) Google Scholar , 2 Mahfood S. Hix W.R. Aaron B.L. et al. Reexpansion pulmonary edema. Ann Thorac Surg. 1988; 45: 340-345 Abstract Full Text PDF PubMed Scopus (273) Google Scholar reported that fatalities occur in as many as 20% of afflicted patients, but more recent data suggest that the knowledge of major risk factors, early clinical recognition, and improvements in supportive management may substantially limit mortality. 4 Neustein S.M. Reexpansion pulmonary edema. J Cardiothorac Vasc Anesth. 2007; 21: 887-891 Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar The estimated incidence of REPE was reported as 0.9% and 14% in 2 investigations of patients receiving treatment for spontaneous pneumothorax. 5 Rozenman J. Yellin A. Simansky D.A. et al. Re-expansion pulmonary oedema following spontaneous pneumothorax. Respir Med. 1996; 90: 235-238 Abstract Full Text PDF PubMed Scopus (63) Google Scholar , 6 Matsuura Y. Nomimura T. Murakami H. et al. Clinical analysis of reexpansion pulmonary edema. Chest. 1991; 100: 1562-1566 Crossref PubMed Scopus (142) Google Scholar The true incidence of this disorder is probably much lower because other studies described no cases of REPE in a similar patient cohort. 7 Mills M. Balsch B.F. Spontaneous pneumothorax: A series of 400 cases. Ann Thorac Surg. 1965; 22: 286-297 Abstract Full Text PDF Scopus (37) Google Scholar , 8 Brooks J.W. Open thoracotomy in the management of spontaneous pneumothorax. Ann Surg. 1973; 177: 798-805 Crossref PubMed Scopus (41) Google Scholar REPE is most often described in patients with a persistently collapsed lung (eg, pneumothorax, pleural effusion, and extrinsic compression by an intrathoracic mass) concomitant with rapid reexpansion of the lung and application of negative pressure to the affected pleural space. 2 Mahfood S. Hix W.R. Aaron B.L. et al. Reexpansion pulmonary edema. Ann Thorac Surg. 1988; 45: 340-345 Abstract Full Text PDF PubMed Scopus (273) Google Scholar , 6 Matsuura Y. Nomimura T. Murakami H. et al. Clinical analysis of reexpansion pulmonary edema. Chest. 1991; 100: 1562-1566 Crossref PubMed Scopus (142) Google Scholar Patients who are less than 40 years of age and those with large, subacute pneumothoraces (air occupying greater than 30% of hemithorax volume for more than 3 days) appear to be at the greatest risk of developing REPE after rapid lung reinflation. 2 Mahfood S. Hix W.R. Aaron B.L. et al. Reexpansion pulmonary edema. Ann Thorac Surg. 1988; 45: 340-345 Abstract Full Text PDF PubMed Scopus (273) Google Scholar , 6 Matsuura Y. Nomimura T. Murakami H. et al. Clinical analysis of reexpansion pulmonary edema. Chest. 1991; 100: 1562-1566 Crossref PubMed Scopus (142) Google Scholar , 9 Tan H.C. Mak K.H. Johan A. Cardiac output increases prior to development of pulmonary edema after re-expansion of spontaneous pneumothorax. Respir Med. 2002; 96: 461-465 Abstract Full Text PDF PubMed Scopus (24) Google Scholar REPE may also occur after relatively brief periods of atelectasis or lung deflation during surgical procedures. 10 Humphreys R.L. Berne A.S. Rapid re-expansion of pneumothorax A cause of unilateral pulmonary edema. Radiology. 1970; 96: 509-512 PubMed Google Scholar , 11 Ravin C.E. Dahmash N.S. Re-expansion pulmonary edema. Chest. 1980; 77: 709-710 Crossref PubMed Scopus (20) Google Scholar , 12 Yanagidate F. Dohi S. Hamaya Y. et al. Reexpansion pulmonary edema after thoracoscopic mediastinal tumor resection. Anesth Analg. 2001; 92: 1416-1417 Crossref PubMed Scopus (20) Google Scholar , 13 Her C. Mandy S. Acute respiratory distress syndrome of the contralateral lung after reexpansion pulmonary edema of a collapse lung. J Clin Anesth. 2004; 16: 244-250 Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar In the current report, the authors describe the development of REPE concomitant with severe, persistent hypoxemia in a patient with aortic stenosis undergoing minimally invasive aortic valve replacement. Conventional supportive care, including mechanical ventilation using positive end-expiratory pressure (PEEP), diuretics, steroids, and inotropic drugs, was ineffective. Instead, temporary support of arterial oxygenation using extracorporeal membrane oxygenation (ECMO) was required for the successful management of the patient.

To recruit and train the next generations of pediatric clinician-scientists, the American Pediatric Society and Society for Pediatric Research initiated a program in 1991 to support medical students with interests in research and pediatrics to conduct research at institutions other than their respective medical schools. Since 1991, the American Pediatric Society-Society for Pediatric Research Medical Student Research Program (MSRP) has funded 732 of 2209 applicants from 132 US or Canadian medical schools for 8–12 wk of research under the direction of experienced investigators. PubMed-attributable publications tabulated in 2001 for MSRP applicants through 2000 indicated that participants had published more actively than had nonparticipant applicants. Male nonparticipants exhibited greater publication activities than did female nonparticipants, but female and male participants published equally. Of all MSRP participants between 1991 and 1996, as of 2008, 36% were in pediatrics, and a remarkable 29% were in academic pediatrics.

A 55-YEAR-OLD, 122-kg, 178-cm man was admitted to the authors' institution for the evaluation of fever, weight loss, fatigue, and progressive dyspnea on exertion of 8 weeks' duration. The patient had undergone an uncomplicated minimally invasive aortic valve replacement with a 25-mm St Jude BioCor Epic bioprosthesis (St Jude Medical, Minneapolis, MN) for severe aortic stenosis 6 months before the current admission. Dental extractions were performed 3 months after this operation with appropriate antibiotic prophylaxis following established guidelines, 1 Wilson W. Taubert K.A. Gewitz M. et al. Prevention of infective endocarditis: Guidelines from the American Heart Association: A guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2007; 116: 1736-1754 Crossref PubMed Scopus (1986) Google Scholar but several dental caries extending into the tooth pulp and severe, generalized periodontal disease remained to be treated. The past medical history was also notable for poorly controlled diabetes mellitus (glycosylated hemoglobin = 10.1%), essential hypertension, hyperlipidemia, and chronic renal insufficiency (serum creatinine concentration = 1.6 mg/dL). The physical examination was significant for a coarse III of VI systolic murmur heard best at the right upper sternal border. A leukocytosis was observed (white blood cell count = 11.6 K/μL), 3 sets of blood cultures grew gram-positive cocci in chains, and antimicrobial therapy (consisting of vancomycin and ceftriaxone) was initiated. Transesophageal echocardiography (TEE) was performed as part of the evaluation and revealed the following images (Fig 1, Fig 2, Fig 3). What is the diagnosis? Fig 2A color-flow Doppler map obtained during LV ejection in the midesophageal aortic valve long-axis plane showing blood flow within the cavitated mass and moderate mitral regurgitation. View Large Image Figure Viewer Download Hi-res image Fig 3A midesophageal aortic valve long-axis image obtained during diastole showing apparent “disappearance” of the cavitated mass from the distal LV outflow tract. View Large Image Figure Viewer Download Hi-res image