Infrared spectroscopy of an endohedral water in fullerene.

An infrared absorption spectroscopy study of the endohedral water molecule in a solid mixture of H2O@C60 and C60 was carried out at liquid helium temperature. From the evolution of the spectra during the ortho-para conversion process, the spectral lines were identified as para-H2O and ortho-H2O transitions. Eight vibrational transitions with rotational side peaks were observed in the mid-infrared: ω1, ω2, ω3, 2ω1, 2ω2, ω1 + ω3, ω2 + ω3, and 2ω2 + ω3. The vibrational frequencies ω2 and 2ω2 are lower by 1.6% and the rest by 2.4%, as compared to those of free H2O. A model consisting of a rovibrational Hamiltonian with the dipole and quadrupole moments of H2O interacting with the crystal field was used to fit the infrared absorption spectra. The electric quadrupole interaction with the crystal field lifts the degeneracy of the rotational levels. The finite amplitudes of the pure v1 and v2 vibrational transitions are consistent with the interaction of the water molecule dipole moment with a lattice-induced electric field. The permanent dipole moment of encapsulated H2O is found to be 0.50 ± 0.05 D as determined from the far-infrared rotational line intensities. The translational mode of the quantized center-of-mass motion of H2O in the molecular cage of C60 was observed at 110 cm-1 (13.6 meV).

Singlet-Contrast Magnetic Resonance Imaging: Unlocking Hyperpolarization with Metabolism*.

Hyperpolarization-enhanced magnetic resonance imaging can be used to study biomolecular processes in the body, but typically requires nuclei such as 13 C, 15 N, or 129 Xe due to their long spin-polarization lifetimes and the absence of a proton-background signal from water and fat in the images. Here we present a novel type of 1 H imaging, in which hyperpolarized spin order is locked in a nonmagnetic long-lived correlated (singlet) state, and is only liberated for imaging by a specific biochemical reaction. In this work we produce hyperpolarized fumarate via chemical reaction of a precursor molecule with para-enriched hydrogen gas, and the proton singlet order in fumarate is released as antiphase NMR signals by enzymatic conversion to malate in D2 O. Using this model system we show two pulse sequences to rephase the NMR signals for imaging and suppress the background signals from water. The hyperpolarization-enhanced 1 H-imaging modality presented here can allow for hyperpolarized imaging without the need for low-abundance, low-sensitivity heteronuclei.

Nuclear singlet relaxation by scalar relaxation of the second kind in the slow-fluctuation regime.

The singlet state of nuclear spin-1/2 pairs is protected against many common relaxation mechanisms. Singlet order, which is defined as the population difference between the nuclear singlet and triplet states, usually decays more slowly than the nuclear magnetization. Nevertheless, some decay mechanisms for nuclear singlet order persist. One such mechanism is called scalar relaxation of the second kind (SR2K) and involves the relaxation of additional nuclei ("third spins") which have scalar couplings to the spin-1/2 pair. This mechanism requires a difference between the couplings of at least one third spin with the two members of the spin-1/2 pair, and depends on the longitudinal relaxation time of the third spin. The SR2K mechanism of nuclear singlet relaxation has previously been examined in the case where the relaxation rate of the additional spins is on the time scale of the nuclear Larmor frequency. In this paper, we consider a different regime, in which the longitudinal relaxation of the third spins is on a similar time scale to the J-coupling between the members of the spin pair. This regime is often encountered when the spin-1/2 pair has scalar couplings to nearby deuterium nuclei. We show that the SR2K mechanism may be suppressed in this regime by applying a radiofrequency field which is resonant either with the members of the spin pair, or with the third spins. These phenomena are analyzed theoretically and by numerical simulations, and demonstrated experimentally on a diester of [13C2, 2H2]-labeled fumarate in solution.

Guidelines for the management of postoperative soiling in children with Hirschsprung disease.

Although most children with Hirschsprung disease ultimately achieve functional and comfortable stooling, some will experience a variety of problems after pull-through surgery. The most common problems include soiling, obstructive symptoms, enterocolitis, and failure to thrive. The purpose of this guideline is to present a rational approach to the management of postoperative soiling in children with Hirschsprung disease. The American Pediatric Surgical Association Hirschsprung Disease Interest Group engaged in a literature review and group discussions. Expert consensus was then used to summarize the current state of knowledge regarding causes, methods of diagnosis, and treatment approaches to children with soiling symptoms following pull-through for Hirschsprung disease. Causes of soiling after pull-through are broadly categorized as abnormalities in sensation, abnormalities in sphincter control, and "pseudo-incontinence." A stepwise algorithm for the diagnosis and management of soiling after a pull-through for Hirschsprung disease is presented; it is our hope that this rational approach will facilitate treatment and optimize outcomes.

Bidirectional band-selective magnetization transfer along the protein backbone doubles the information content of solid-state NMR correlation experiments.

Resonance assignment is the first stage towards solving the structure of a protein. This is normally achieved by the employment of separate inter and intra residue experiments. By utilising the mixed rotation and rotary recoupling (MIRROR) condition it is possible to double the information content through the efficient bidirectional transfer of magnetization from the CO to its adjacent Cα and the Cα of the subsequent amino acid. We have incorporated this into a 3D experiment, a 3D-MIRROR-NCOCA, where correlations present in the 3D spectrum permit the sequential assignment of the protein backbone from a single experiment as we have demonstrated on a microcrystalline preparation of GB3. Furthermore, the low-power requirements of the MIRROR recoupling sequence facilitate the development of a low-power 3D-NCOCA experiment. This has enabled us to realise significant reductions in acquisition times, allowing the acquisition of a single 3D-NCOCA spectrum suitable for a full backbone resonance assignment of GB3 in less than 24 h.

Guidelines for the management of postoperative obstructive symptoms in children with Hirschsprung disease.

Although most children with Hirschsprung disease ultimately do well, many experience a variety of ongoing problems after pull-through surgery. The most common include obstructive symptoms, soiling, enterocolitis and failure to thrive. The purpose of this guideline is to present a rational approach to the management of postoperative obstructive symptoms in children with Hirschsprung disease. The American Pediatric Surgical Association Board of Governors established a Hirschsprung Disease Interest Group. Group discussions, literature review and expert consensus were then used to summarize the current state of knowledge regarding causes, methods of diagnosis, and treatment approaches to children with obstructive symptoms following pull-through for Hirschsprung disease. Causes of obstructive symptoms post-pull-through include mechanical obstruction; persistent or acquired aganglionosis, hypoganglionosis, or transition zone pull-through; internal sphincter achalasia; disordered motility in the proximal intestine that contains ganglion cells; or functional megacolon caused by stool-holding behavior. An algorithm for the diagnosis and management of obstructive symptoms after a pull-through for Hirschsprung disease is presented. A stepwise, logical approach to the diagnosis and management of patients experiencing obstructive symptoms following pull-through for Hirschsprung disease can facilitate treatment. Level of evidence V.

Rectal atresia and anal stenosis: the difference in the operative technique for these two distinct congenital anorectal malformations.

Rectal atresia and anal stenosis are rare forms of anorectal malformations. The aim of the definitive surgical repair in such cases is to preserve the anal canal, the dentate line, and the sphincter complex. We present a case of rectal atresia and anal stenosis to demonstrate the differences in the operative repair. The techniques described leave the anterior wall of the very distal anal canal untouched in both rectal stenosis and anal atresia; however, the dissection of the rectum differs. The atretic rectum in rectal atresia is mobilized and sutured to the anal canal circumferentially. In anal stenosis, the posterior rectum is mobilized in the form of rectal advancement, and the posterior 180° is anastomosed directly to the skin (as in a standard PSARP) with preservation of the anal canal as the anterior 180° of the final anoplasty. These patients have an excellent prognosis for bowel control and fecal continence, and therefore, complete mobilization and resection of the anal canal must be avoided.

Propranolol as first-line treatment in orbital infantile haemangiomas: a case series.

PURPOSE: To highlight the importance of Magnetic Resonance Imaging (MRI) and the use of propranolol as both a final diagnostic tool and adequate treatment for orbital Infantile Haemangiomas (IHs). METHODS: A retrospective study was conducted using a case series of 5 infants diagnosed with orbital IH. All patients presented with progressive unilateral proptosis and were at high risk of developing amblyopia, some had combined swelling of the eyelid, impaired eye movements or exposure keratopathy. Propranolol was administered in an initial dose of 0.6 mg/kg/day orally divided in three daily doses and increased in 4 days to 2.7 mg/kg/day. MRI was performed in all children. RESULTS: Striking MR characteristics of an IH lesion were seen in each of our 5 cases, including the presence of flow voids, high contrast enhancement, hypo-intense T1W signal, iso- to hyper intense T2W signal, and lobulated appearance. All patients showed a quick clinical response to treatment, resulting in significant reduction in tumour size within a range of 1-3 weeks and almost complete regression of the lesion at the end of the treatment schedule. CONCLUSIONS: Our study adds another 5 cases to the growing body of reports confirming the efficacy and safety - under controlled circumstances - of propranolol therapy in orbital IH management, in which we highlight the use of propranolol as both a final diagnostic tool and as an adequate treatment.

Post-prostatectomy adjuvant androgen deprivation therapy- Current opinions and practices of Canadian urologists.

INTRODUCTION: Despite the proven benefit of adjuvant androgen deprivation therapy (ADT) for patients receiving primary radiation, there are few studies evaluating adjuvant ADT after prostatectomy. In the absence of evidence, opinions and practice patterns vary. We surveyed Canadian prostate cancer surgeons about their use of adjuvant ADT and their opinions on the design of a potential adjuvant ADT trial. METHODS: An electronic survey was devised and distributed using a modified Dillman approach. The survey was sent to 38 Canadian urologists that perform radical prostatectomy and representing all 17 major academic institutions in Canada and all 10 Canadian provinces. Reminders were sent three and four weeks following the original request. In addition to demographic information, we asked surgeons about their current use of postoperative adjuvant ADT and their opinion about the need for a clinical trial. To inform trial design, we asked respondents their opinions about which patients should be eligible, what duration of ADT was most appropriate, and which outcomes are clinically meaningful. The survey was sent in February 2020 and all responses were received by March 2020. RESULTS: All 38 (100%) invited urologists completed the survey. Only 3 (7%) respondents currently offer postoperative adjuvant ADT as an option for patients without metastases. 35 (92%) urologists believed that a trial is needed before short-term adjuvant treatment should be offered to prevent recurrence. 15 (45%) urologists believed an adjuvant ADT trial was most appropriate for patients with an estimated PSA recurrence risk of >25% and 16 (42%) believed a recurrence risk of >50% was most appropriate. 25 (66%) respondents believed 12-month was the optimal duration of treatment with adjuvant ADT for a randomized trial. 37 (97%) respondents felt that prolonging the time to PSA recurrence and/or pelvic radiation was a clinically important outcome. The majority (20; 53%) of respondents would recommend 12 months of adjuvant ADT in their practice if a randomized trial showed a 50% relative risk reduction in PSA recurrence at 5-year postoperative. CONCLUSION: The vast majority of Canadian prostate cancer surgeons do not offer adjuvant ADT following prostatectomy in patients without metastases. Based on the results from this survey, a randomized trial was considered warranted and feasible, and would influence patient care.

Measurements of the persistent singlet state of N2O in blood and other solvents--potential as a magnetic tracer.

The development of hyperpolarized tracers has been limited by short nuclear polarization lifetimes. The dominant relaxation mechanism for many hyperpolarized agents in solution arises from intramolecular nuclear dipole-dipole coupling modulated by molecular motion. It has been previously demonstrated that nuclear spin relaxation due to this mechanism can be removed by storing the nuclear polarization in long-lived, singlet-like states. In the case of N(2)O, storing the polarization of the nitrogen nuclei has been shown to substantially increase the polarization lifetime. The feasibility of utilizing N(2)O as a tracer is investigated by measuring the singlet-state lifetime of the N(2)O when dissolved in a variety of solvents including whole blood. Comparison of the singlet lifetime to longitudinal relaxation and between protonated and deuterated solvents is consistent with the dominance of spin-rotation relaxation, except in the case of blood.

Infrared spectroscopy of endohedral HD and D2 in C60.

We report on the dynamics of two hydrogen isotopomers, D(2) and HD, trapped in the molecular cages of a fullerene C(60) molecule. We measured the infrared spectra and analyzed them using a spherical potential for a vibrating rotor. The potential, vibration-rotation Hamiltonian, and dipole moment parameters are compared with previously studied H(2)@C(60) parameters [M. Ge, U. Nagel, D. Hüvonen, T. Rõõm, S. Mamone, M. H. Levitt, M. Carravetta, Y. Murata, K. Komatsu, J. Y.-C. Chen, and N. J. Turro, J. Chem. Phys. 134, 054507 (2011)]. The isotropic part of the potential is similar for all three isotopomers. In HD@C(60), we observe mixing of the rotational states and an interference effect of the dipole moment terms due to the displacement of the HD rotation center from the fullerene cage center.

Interaction potential and infrared absorption of endohedral H2 in C60.

We have measured the temperature dependence of the infrared spectra of a hydrogen molecule trapped inside a C(60) cage, H(2)@C(60), in the temperature range from 6 to 300 K and analyzed the excitation spectrum by using a five-dimensional model of a vibrating rotor in a spherical potential. The electric dipole moment is induced by the translational motion of endohedral H(2) and gives rise to an infrared absorption process where one translational quantum is created or annihilated, ΔN = ±1. Some fundamental transitions, ΔN = 0, are observed as well. The rotation of endohedral H(2) is unhindered but coupled to the translational motion. The isotropic and translation-rotation coupling part of the potential are anharmonic and different in the ground and excited vibrational states of H(2). The vibrational frequency and the rotational constant of endohedral H(2) are smaller than those of H(2) in the gas phase. The assignment of lines to ortho- and para-H(2) is confirmed by measuring spectra of a para enriched sample of H(2)@C(60) and is consistent with the earlier interpretation of the low temperature infrared spectra [Mamone et al., J. Chem. Phys. 130, 081103 (2009)].

Factors influencing pulmonary methane excretion in man. An indirect method of studying the in situ metabolism of the methane-producing colonic bacteria.

Measurements of pulmonary excretion of methane (CH(4)) were used to obtain information on the CH(4)-producing bacteria in man. Preliminary studies indicated that (a) all CH(4) excreted by man is produced by colonic bacteria, (b) there is no appreciable utilization of CH(4) by man, and (c) breath CH(4) can serve as a relatively accurate indicator of CH(4) production in the intestine. The rate of pulmonary CH(4) excretion varied enormously, ranging from undetectable (<5 x 10(-6) ml/min) to 0.66 ml/minute. In general, the CH(4) excretion rate for subjects was consistently very low (nonproducers) or relatively large (producers). 33.6% of the adult population were producers of CH(4). Whereas diet, age over 10 yr, and sex did not influence the rate of CH(4) production, some familial factor appeared to play an important role. 84% of siblings of CH(4) producers also were producers, while only 18% of the siblings of nonproducers were found to be CH(4) producers. This familial tendency appeared to be determined by early environmental rather than genetic factors. These studies of CH(4) excretion demonstrate that the exposure of individuals to intestinal bacterial metabolites may differ markedly and that these differences may be chronic and determined by familial factors.

Minimally invasive treatment of fecal incontinence and constipation in children.

The capacity for voluntary bowel movements and thus fecal incontinence may be limited in children born with anorectal anomalies and Hirschsprung's disease, as well as for many patients with spinal problems. Some of these patients have severe constipation which if not properly managed causes overflow pseudoincontinence and some have true fecal incontinence. For patients with anorectal malformations and those with idiopathic constipation with overflow pseudoincontinence, disimpaction, followed by an aggressive laxative regimen, often makes them continent, i.e. capable of having voluntary bowel movements. Surgical resection of a dilated rectosigmoid can dramatically reduce or eliminate these patients' daily laxative requirement, and improve their quality of life. For patients with true fecal incontinence, a bowel management program with a daily enema allows them to be kept artificially clean. For these patients, a surgical procedure whereby the daily enema is given antegrade is ideal, but it is the enema itself not its route which is the key to success. It is vital for the clinician to distinguish between these groups. Their initial presentations are quite similar, i.e. "fecal incontinence" or soiling but the treatments and surgical options differ dramatically. Much of what we have learned in the care of pediatric fecal incontinence can be extrapolated to adults.

Preserving Access: A Review of Stroke Thrombectomy during the COVID-19 Pandemic.

Thrombectomy for large-vessel-occlusion stroke is a highly impactful treatment. The spread of coronavirus 19 (COVID-19) across the United States and the globe impacts access to this crucial intervention through widespread societal and institutional changes. In this document, we review the implications of COVID-19 on the emergency care of large-vessel occlusion stroke, reviewing specific infection-control recommendations, available literature, existing resources, and expert consensus. As a population, patients with large-vessel occlusion stroke face unique challenges during pandemics. These are broad in scope. Responses to these challenges through adaptation of stroke systems of care and with imaging, thrombectomy, and postprocedural care are detailed. Preservation of access to thrombectomy must be prioritized for its public health impact. While the extent of required changes will vary by region, tiered planning for both escalation and de-escalation of measures must be a part of each practice. In addition, preparations described serve as templates in the event of future pandemics.

Multicenter Postmarket Analysis of the Neuroform Atlas Stent for Stent-Assisted Coil Embolization of Intracranial Aneurysms.

BACKGROUND AND PURPOSE: The Neuroform Atlas is a new microstent to assist coil embolization of intracranial aneurysms that recently gained FDA approval. We present a postmarket multicenter analysis of the Neuroform Atlas stent. MATERIALS AND METHODS: On the basis of retrospective chart review from 11 academic centers, we analyzed patients treated with the Neuroform Atlas after FDA exemption from January 2018 to June 2019. Clinical and radiologic parameters included patient demographics, aneurysm characteristics, stent parameters, complications, and outcomes at discharge and last follow-up. RESULTS: Overall, 128 aneurysms in 128 patients (median age, 62 years) were treated with 138 stents. Risk factors included smoking (59.4%), multiple aneurysms (27.3%), and family history of aneurysms (16.4%). Most patients were treated electively (93.7%), and 8 (6.3%) underwent treatment within 2 weeks of subarachnoid hemorrhage. Previous aneurysm treatment failure was present in 21% of cases. Wide-neck aneurysms (80.5%), small aneurysm size (<7 mm, 76.6%), and bifurcation aneurysm location (basilar apex, 28.9%; anterior communicating artery, 27.3%; and middle cerebral artery bifurcation, 12.5%) were common. A single stent was used in 92.2% of cases, and a single catheter for both stent placement and coiling was used in 59.4% of cases. Technical complications during stent deployment occurred in 4.7% of cases; symptomatic thromboembolic stroke, in 2.3%; and symptomatic hemorrhage, in 0.8%. Favorable Raymond grades (Raymond-Roy occlusion classification) I and II were achieved in 82.9% at discharge and 89.5% at last follow-up. mRS ≤2 was determined in 96.9% of patients at last follow-up. The immediate Raymond-Roy occlusion classification grade correlated with aneurysm location (P < .0001) and rupture status during treatment (P = .03). CONCLUSIONS: This multicenter analysis provides a real-world safety and efficacy profile for the treatment of intracranial aneurysms with the Neuroform Atlas stent.

Periodicity of deoxyribonuclease I digestion of chromatin.

Two methods have been used to measure the single-strand lengths of the DNA fragments produced by deoxyribonuclease I digestion of chromatin. The average lengths obtained are muliples of about 10.4 bases, significantly different from the value of 10 previously reported. This periodicity in fragment lengths is closely related to the periodicity of the DNA double helix in chromatin, but the two values need not be exactly the same.

The predicted structure of immunoglobulin D1.3 and its comparison with the crystal structure.

Predictions of the structures of the antigen-binding domains of an antibody, recorded before its experimental structure determination and tested subsequently, were based on comparative analysis of known antibody structures or on conformational energy calculations. The framework, the relative positions of the hypervariable regions, and the folds of four of the hypervariable loops were predicted correctly. This portion includes all residues in contact with the antigen, in this case hen egg white lysozyme, implying that the main chain conformation of the antibody combining site does not change upon ligation. The conformations of three residues in each of the other two hypervariable loops are different in the predicted models and the experimental structure.

p53: a frequent target for genetic abnormalities in lung cancer.

Allele loss is a hallmark of chromosome regions harboring recessive oncogenes. Lung cancer frequently demonstrates loss of heterozygosity on 17p. Recent evidence suggests that the p53 gene located on 17p13 has many features of such an antioncogene. The p53 gene was frequently mutated or inactivated in all types of human lung cancer. The genetic abnormalities of p53 include gross changes such as homozygous deletions and abnormally sized messenger RNAs along with a variety of point or small mutations, which map to the p53 open reading frame and change amino acid sequence in a region highly conserved between mouse and man. In addition, very low or absent expression of p53 messenger RNA in lung cancer cell lines compared to normal lung was seen. These findings, coupled with the previous demonstration of 17p allele loss in lung cancer, strongly implicate p53 as an anti-oncogene whose disruption is involved in the pathogenesis of human lung cancer.

Determination of membrane protein structure by rotational resonance NMR: bacteriorhodopsin.

Rotationally resonant magnetization exchange, a new nuclear magnetic resonance (NMR) technique for measuring internuclear distances between like spins in solids, was used to determine the distance between the C-8 and C-18 carbons of retinal in two model compounds and in the membrane protein bacteriorhodopsin. Magnetization transfer between inequivalent spins with an isotropic shift separation, delta, is driven by magic angle spinning at a speed omega r that matches the rotational resonance condition delta = n omega r, where n is a small integer. The distances measured in this way for both the 6-s-cis- and 6-s-trans-retinoic acid model compounds agreed well with crystallographically known distances. In bacteriorhodopsin the exchange trajectory between C-8 and C-18 was in good agreement with the internuclear distance for a 6-s-trans configuration [4.2 angstroms (A)] and inconsistent with that for a 6-s-cis configuration (3.1 A). The results illustrate that rotational resonance can be used for structural studies in membrane proteins and in other situations where diffraction and solution NMR techniques yield limited information.