Fatal diffuse pulmonary fat microemboli following reperfusion in liver transplantation with the use of marginal steatotic allografts.

Organ shortage is a major cause of delayed liver transplantation and increased waitlist time. The level of donor steatosis is a significant determinant in organ selection. Scarcity of organs has led some programs to expand their acceptable criteria for the percentage of steatosis. We report two cases of liver transplantation of steatotic donor organs that resulted in mortality within hours from transplantation. Postmortem analysis showed evidence of diffuse pulmonary fat microemboli likely originating from the donor organ, with marked preservation reperfusion injury. The mechanism of diffuse fat microemboli in this setting and possible relationship to other perioperative syndromes (transfusion-related lung injury, acute kidney injury, and postreperfusion syndrome) is discussed.

Heavy Physics Contributions to Neutrinoless Double Beta Decay from QCD.

Observation of neutrinoless double beta decay, a lepton number violating process that has been proposed to clarify the nature of neutrino masses, has spawned an enormous world-wide experimental effort. Relating nuclear decay rates to high-energy, beyond the standard model (BSM) physics requires detailed knowledge of nonperturbative QCD effects. Using lattice QCD, we compute the necessary matrix elements of short-range operators, which arise due to heavy BSM mediators, that contribute to this decay via the leading order π^{-}→π^{+} exchange diagrams. Utilizing our result and taking advantage of effective field theory methods will allow for model-independent calculations of the relevant two-nucleon decay, which may then be used as input for nuclear many-body calculations of the relevant experimental decays. Contributions from short-range operators may prove to be equally important to, or even more important than, those from long-range Majorana neutrino exchange.

A per-cent-level determination of the nucleon axial coupling from quantum chromodynamics.

The axial coupling of the nucleon, gA, is the strength of its coupling to the weak axial current of the standard model of particle physics, in much the same way as the electric charge is the strength of the coupling to the electromagnetic current. This axial coupling dictates the rate at which neutrons decay to protons, the strength of the attractive long-range force between nucleons and other features of nuclear physics. Precision tests of the standard model in nuclear environments require a quantitative understanding of nuclear physics that is rooted in quantum chromodynamics, a pillar of the standard model. The importance of gA makes it a benchmark quantity to determine theoretically-a difficult task because quantum chromodynamics is non-perturbative, precluding known analytical methods. Lattice quantum chromodynamics provides a rigorous, non-perturbative definition of quantum chromodynamics that can be implemented numerically. It has been estimated that a precision of two per cent would be possible by 2020 if two challenges are overcome1,2: contamination of gA from excited states must be controlled in the calculations and statistical precision must be improved markedly2-10. Here we use an unconventional method 11 inspired by the Feynman-Hellmann theorem that overcomes these challenges. We calculate a gA value of 1.271 ± 0.013, which has a precision of about one per cent.

Effects of Pectus Excavatum Repair on Right and Left Ventricular Strain.

BACKGROUND: The cardiopulmonary benefits of pectus excavatum repair have been debated. Echocardiographic speckle-tracking strain and strain rate have been used to evaluate and detect subclinical myocardial dysfunction in patients receiving cardiotoxic chemotherapy, and patients with valvular heart disease. This technology was applied to evaluate the effects of pectus excavatum surgery on left ventricular (LV) and right ventricular (RV) function. METHODS: Speckle tracing strain evaluation was performed on intraoperative transesophageal echocardiographic images acquired immediately before and after Nuss repair in adult patients (aged 18 years or more) from 2011 to 2014. Standard severity and compression indices were measured on chest imaging performed before pectus excavatum repair. RESULTS: In total, 165 patients with transesophageal echocardiographic images during repair were reviewed (71.5% male; mean age 33.0 years; range, 18 to 71; Haller index 5.7; range, 2.3 to 24.3). Significant improvement after repair was seen in global RV longitudinal strain (-13.5% ± 4.1% to -16.7% ± 4.4%, p < 0.0001) and strain rate (-1.3 ± 0.4 s-1 to -1.4 ± 0.4 s-1, p = 0.0102); LV global circumferential strain (-18.7% ± 5.7% to -23.5% ± 5.8%, p < 0.0001) and strain rate (-1.5 ± 0.5 s-1 to -1.9 ± 0.8 s-1, p = 0.0003); and LV radial strain (24.1% ± 13.5% to 31.1% ± 16.4%, p = 0.0050). There was a strong correlation between preoperative right atrial compression on transesophageal echocardiogram and improvement in RV global longitudinal strain rate immediately after pectus repair. CONCLUSIONS: Mechanical compression and impaired RV and LV strain is improved by Nuss surgical repair of pectus deformity.

Randomized trial of epidural vs. subcutaneous catheters for managing pain after modified Nuss in adults.

BACKGROUND: Minimally invasive repair of pectus excavatum (MIRPE) is now performed in adults. Managing adult patients' pain postoperatively has been challenging due to increased chest wall rigidity and the pressure required for supporting the elevated sternum. The optimal pain management regimen has not been determined. We designed this prospective, randomized trial to compare postoperative pain management and outcomes between thoracic epidural analgesia (TEA) and bilateral subcutaneous infusion pump catheters (On-Q). METHODS: Patients undergoing MIRPE (modified Nuss) underwent random assignment to TEA or On-Q group. Both groups received intravenous, patient-controlled opioid analgesia, with concomitant delivery of local anesthetic. Primary outcomes were length of stay (LOS), opioid use, and pain scores. RESULTS: Of 85 randomly assigned patients, 68 completed the study [52 men, 76.5%; mean (range) age, 32.2 (20.0-58.0) years; Haller index, 5.9 (range, 3.0-26.7)]. The groups were equally matched for preoperative variables; however, the On-Q arm had more patients (60.3%). No significant differences were found between groups in mean daily pain scores (P=0.52), morphine-equivalent opioid usage (P=0.28), or hospital stay 3.5 vs. 3.3 days (TEA vs. On-Q; P=0.55). Thirteen patients randomized to TEA refused the epidural and withdrew from the study because they perceived greater benefit of the On-Q system. CONCLUSIONS: Postoperative pain management in adults after MIRPE can be difficult. Both continuous local anesthetic delivery by TEA and On-Q catheters with concomitant, intravenous, patient-controlled anesthesia maintained acceptable analgesia with a reasonable LOS. In our cohort, there was preference for the On-Q system for pain management.

Evolutionary Conservation of a GPCR-Independent Mechanism of Trimeric G Protein Activation.

Trimeric G protein signaling is a fundamental mechanism of cellular communication in eukaryotes. The core of this mechanism consists of activation of G proteins by the guanine-nucleotide exchange factor (GEF) activity of G protein coupled receptors. However, the duration and amplitude of G protein-mediated signaling are controlled by a complex network of accessory proteins that appeared and diversified during evolution. Among them, nonreceptor proteins with GEF activity are the least characterized. We recently found that proteins of the ccdc88 family possess a Gα-binding and activating (GBA) motif that confers GEF activity and regulates mammalian cell behavior. A sequence similarity-based search revealed that ccdc88 genes are highly conserved across metazoa but the GBA motif is absent in most invertebrates. This prompted us to investigate whether the GBA motif is present in other nonreceptor proteins in invertebrates. An unbiased bioinformatics search in Caenorhabditis elegans identified GBAS-1 (GBA and SPK domain containing-1) as a GBA motif-containing protein with homologs only in closely related worm species. We demonstrate that GBAS-1 has GEF activity for the nematode G protein GOA-1 and that the two proteins are coexpressed in many cells of living worms. Furthermore, we show that GBAS-1 can activate mammalian Gα-subunits and provide structural insights into the evolutionarily conserved determinants of the GBA-G protein interface. These results demonstrate that the GBA motif is a functional GEF module conserved among highly divergent proteins across evolution, indicating that the GBA-Gα binding mode is strongly constrained under selective pressure to mediate receptor-independent G protein activation in metazoans.

Revision of failed, recurrent or complicated pectus excavatum after Nuss, Ravitch or cardiac surgery.

Pectus excavatum (PE) can recur after both open and minimally invasive repair of pectus excavatum (MIRPE) techniques. The cause of recurrence may differ based on the initial repair procedure performed. Recurrence risks for the open repair are due to factors which include incomplete previous repair, repair at too young of age, excessive dissection, early removal or lack of support structures, and incomplete healing of the chest wall. For patients presenting after failed or recurrent primary MIRPE repair, issues with support bars including placement, number, migration, and premature removal can all be associated with failure. Connective tissue disorders can complicate and increase recurrence risk in both types of PE repairs. Identifying the factors that contributed to the previous procedure's failure is critical for prevention of another recurrence. A combination of surgical techniques may be necessary to successfully repair some patients.

Surface plasmon resonance modulation in nanopatterned Au gratings by the insulator-metal transition in vanadium dioxide films.

Correlated experimental and simulation studies on the modulation of Surface Plasmon Polaritons (SPP) in Au/VO2 bilayers are presented. The modification of the SPP wave vector by the thermally-induced insulator-to-metal phase transition (IMT) in VO2 was investigated by measuring the optical reflectivity of the sample. Reflectivity changes are observed for VO2 when transitioning between the insulating and metallic states, enabling modulation of the SPP in the Au layer by the thermally induced IMT in the VO2 layer. Since the IMT can also be optically induced using ultrafast laser pulses, we postulate the viability of SPP ultrafast modulation for sensing or control.

NF-kappaB mediates FGF signal regulation of msx-1 expression.

The nuclear factor-kappaB (NF-kappaB) family of transcription factors is involved in proliferation, differentiation, and apoptosis in a stage- and cell-dependent manner. Recent evidence has shown that NF-kappaB activity is necessary for both chicken and mouse limb development. We report here that the NF-kappaB family member c-rel and the homeodomain gene msx-1 have partially overlapping expression patterns in the developing chick limb. In addition, inhibition of NF-kappaB activity resulted in a decrease in msx-1 mRNA expression. Sequence analysis of the msx-1 promoter revealed three potential kappaB-binding sites similar to the interferon-gamma (IFN-gamma) kappaB-binding site. These sites bound to c-Rel, as shown by electrophoretic mobility shift assay (EMSA). Furthermore, inhibition of NF-kappaB activity significantly reduced transactivation of the msx-1 promoter in response to FGF-2/-4, known stimulators of msx-1 expression. These results suggest that NF-kappaB mediates the FGF-2/-4 signal regulation of msx-1 gene expression.

Nuclear factor-kappaB (NF-kappaB) regulates proliferation and branching in mouse mammary epithelium.

The nuclear factor-kappaB (NF-kappaB) family of transcription factors has been shown to regulate proliferation in several cell types. Although recent studies have demonstrated aberrant expression or activity of NF-kappaB in human breast cancer cell lines and tumors, little is known regarding the precise role of NF-kappaB in normal proliferation and development of the mammary epithelium. We investigated the function of NF-kappaB during murine early postnatal mammary gland development by observing the consequences of increased NF-kappaB activity in mouse mammary epithelium lacking the gene encoding IkappaBalpha, a major inhibitor of NF-kappaB. Mammary tissue containing epithelium from inhibitor kappaBalpha (IkappaBalpha)-deficient female donors was transplanted into the gland-free mammary stroma of wild-type mice, resulting in an increase in lateral ductal branching and pervasive intraductal hyperplasia. A two- to threefold increase in epithelial cell number was observed in IkappaBalpha-deficient epithelium compared with controls. Epithelial cell proliferation was strikingly increased in IkappaBalpha-deficient epithelium, and no alteration in apoptosis was detected. The extracellular matrix adjacent to IkappaBalpha-deficient epithelium was reduced. Consistent with in vivo data, a fourfold increase in epithelial branching was also observed in purified IkappaBalpha-deficient primary epithelial cells in three-dimensional culture. These data demonstrate that NF-kappaB positively regulates mammary epithelial proliferation, branching, and functions in maintenance of normal epithelial architecture during early postnatal development.

Cyclin-dependent kinase inhibitor p27(Kip1) is required for mouse mammary gland morphogenesis and function.

We have studied the role of the cyclin-dependent kinase (Cdk) inhibitor p27(Kip1) in postnatal mammary gland morphogenesis. Based on its ability to negatively regulate cyclin/Cdk function, loss of p27 may result in unrestrained cellular proliferation. However, recent evidence about the stabilizing effect of p27 on cyclin D1-Cdk4 complexes suggests that p27 deficiency might recapitulate the hypoplastic mammary phenotype of cyclin D1-deficient animals. These hypotheses were investigated in postnatal p27-deficient (p27(-/-)), hemizygous (p27(+/)-), or wild-type (p27(+/+)) mammary glands. Mammary glands from p27(+/)- mice displayed increased ductal branching and proliferation with delayed postlactational involution. In contrast, p27(-/-) mammary glands or wild-type mammary fat pads reconstituted with p27(-/-) epithelium produced the opposite phenotype: hypoplasia, low proliferation, decreased ductal branching, impaired lobuloalveolar differentiation, and inability to lactate. The association of cyclin D1 with Cdk4, the kinase activity of Cdk4 against pRb in vitro, the nuclear localization of cyclin D1, and the stability of cyclin D1 were all severely impaired in p27(-/-) mammary epithelial cells compared with p27(+/+) and p27(+/-) mammary epithelial cells. Therefore, p27 is required for mammary gland development in a dose-dependent fashion and positively regulates cyclin D-Cdk4 function in the mammary gland.

Bleaching primary teeth with 10% carbamide peroxide.

Bleaching teeth with 10% carbamide peroxide in a custom-fitted tray has been popular for more than 10 years. However, primary teeth are seldom considered for bleaching due to the need for compliance by the child and the natural whiteness of the primary teeth. This report describes an indication-teeth darkened from trauma-as well as the technique and outcome for bleaching discolored primary teeth.

Dynamic expression and activity of NF-kappaB during post-natal mammary gland morphogenesis.

The Rel/NF-kappaB family of transcription factors has been implicated in such diverse cellular processes as proliferation, differentiation, and apoptosis. As each of these processes occurs during post-natal mammary gland morphogenesis, the expression and activity of NF-kappaB factors in the murine mammary gland were examined. Immunohistochemical and immunoblot analyses revealed expression of the p105/p50 and RelA subunits of NF-kappaB, as well as the major inhibitor, IkappaBalpha, in the mammary epithelium during pregnancy, lactation, and involution. Electrophoretic mobility shift assay (EMSA) demonstrated that DNA-binding complexes containing p50 and RelA were abundant during pregnancy and involution, but not during lactation. Activity of an NF-kappaB-dependent luciferase reporter in transgenic mice was highest during pregnancy, decreased to near undetectable levels during lactation, and was elevated during involution. This highly regulated pattern of activity was consistent with the modulated expression of p105/p50, RelA, and IkappaBalpha.

Mesenchymal expression of nuclear factor-kappaB inhibits epithelial growth and branching in the embryonic chick lung.

It is becoming increasingly recognized that the ubiquitous, inducible transcription factor nuclear factor-kappaB (NF-kappaB) is involved in developmental processes. For example, NF-kappaB acts as a mediator of epithelial-mesenchymal interactions in the developing chick limb. We investigated the role of NF-kappaB in directing the branching morphogenesis of the developing chick lung, a process which relies on epithelial-mesenchymal communication. High level expression of relA was found in the mesenchyme surrounding the nonbranching structures of the lung but was not detected either in the mesenchyme surrounding the branching structures of the distal lung or in the developing lung epithelium. Specific inhibition of mesenchymal NF-kappaB in lung cultures resulted in increased epithelial budding. Conversely, expression of a trans-dominant activator of NF-kappaB in the lung mesenchyme repressed budding. Ectopic expression of RelA was sufficient to inhibit the ability of the distal mesenchyme to induce epithelial bud formation. Cellular proliferation in the mesenchyme was inhibited by hyperactivation of NF-kappaB in the mesenchyme of lung cultures. Interestingly, increased NF-kappaB activity in the mesenchyme also decreased the proliferation of the associated epithelium, while inhibition of NF-kappaB activity increased cellular proliferation in lung cultures. Expression patterns of several genes which are known to influence lung branching morphogenesis were altered in response to changes in mesenchymal NF-kappaB activity, including fgf10, bmp-4, and tgf-beta1. Thus NF-kappaB represents the first transcription factor reported to function within the lung mesenchyme to limit growth and branching of the adjacent epithelium.

Early repolarization: an electrocardiographic predictor of enhanced aerobic fitness.

The presence or absence of early repolarization on the electrocardiogram at rest was correlated with aerobic exercise capacity in healthy volunteers from the Baltimore Longitudinal Study of Aging. Patients with early repolarization had both longer treadmill exercise duration and higher peak oxygen consumption than age-and gender-matched control subjects.

Inhibition of NF-kappaB activity results in disruption of the apical ectodermal ridge and aberrant limb morphogenesis.

In Drosophila, the Dorsal protein establishes the embryonic dorso-ventral axis during development. Here we show that the vertebrate homologue of Dorsal, nuclear factor-kappa B (NF-kappaB), is vital for the formation of the proximo-distal organizer of the developing limb bud, the apical ectodermal ridge (AER). Transcription of the NF-kappaB proto-oncogene c-rel is regulated, in part, during morphogenesis of the limb bud by AER-derived signals such as fibroblast growth factors. Interruption of NF-kappaB activity using viral-mediated delivery of an inhibitor results in a highly dysmorphic AER, reduction in overall limb size, loss of distal elements and reversal in the direction of limb outgrowth. Furthermore, inhibition of NF-kappaB activity in limb mesenchyme leads to a reduction in expression of Sonic hedgehog and Twist but derepresses expression of the bone morphogenetic protein-4 gene. These results are the first evidence that vertebrate NF-kappaB proteins act to transmit growth factor signals between the ectoderm and the underlying mesenchyme during embryonic limb formation.

Gonoccocal endocarditis.

In the postantibiotic era, systemic complications from a gonococcal infection are rare. Females tend to have a higher frequency of gonococcal sepsis than males. In contrast, males have a higher rate of gonococcal endocarditis. This article describes a case of a previously healthy young male who presented with aortic insufficiency and blood cultures positive for Neisseria gonorrhoeae. Despite adequate antibiotic coverage, the patient's aortic insufficiency worsened, requiring aortic value replacement before discharge from the hospital. The patient's recovery was uneventful.

Elephantiasis nostras verrucosa.

Elephantiasis is an uncommon disease in the United States. We present a case of nonfilarial elephantiasis nostras verrucosa in a 14-year-old girl. Most commonly, the upper and lower extremities are affected; the disease, in this patient, was confined to the buttock. The patient has done well after excision and primary closure. The patient is currently undergoing pressure therapy 1 year after surgery. She has no evidence of recurrence. We present this case and review the literature.

Fatal mishap report: first SPH-4B flight helmet recovered from a U.S. Army helicopter mishap.

The most common cause of death in helicopter accidents is head injury. Flight helmets can be designed to distribute and attenuate crash forces to the head. Experience derived from crashes using the U.S. Army SPH-4 flight helmet has led to modifications to improve protection. Within the past year, the Army has introduced the SPH-4B flight helmet which includes several new features to reduce injury in future mishaps. The first SPH-4B flight helmet recovered from a fatal mishap is described and correlated with the injuries to the wearer. The new shell and liner reduced the impact forces to the head. There were no side impacts to determine the performance of the crushable earcups in the helmet. The new SPH-4B flight helmet has several new and distinctive features that should improve survival in future helicopter crashes. Careful study of life support equipment retrieved from crashes is important to understand how the equipment performs in the crash environment.

Human excretion patterns following occupational uptake of 3H-, 14C- and 35S-labeled compounds.

Graphs of excretion patterns following occupational uptake of 3H, 14C and 35S labeled compounds in humans are presented. A brief description of New England Nuclear's bioassay program and analytical methods is given. One or two exponential regression curves are found to fit most sets of data. Exceptions where exponentials do not closely fit the data are discussed. Characteristic rate constants are estimated and used to establish retention equations. When groups of workers were exposed to the same source excretion parameters were not found to strongly correlate with weight or sex. Variations in individual excretion patterns following low level group exposure did not significantly effect individual dose commitment estimates. Excretion rates following uptake of 14C and 3H labeled compounds were found to span three orders of magnitude. This indicates that health physicists may tend to dissipate resources in unnecessary investigations if conservative ICRP recommendations are assumed.