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1.
Nanoscale ; 15(28): 11935-11944, 2023 Jul 20.
Article in English | MEDLINE | ID: mdl-37366152

ABSTRACT

Polyamide composite (PA-TFC) membranes are the state-of-the-art ubiquitous platforms to desalinate water at scale. We have developed a novel, transformative platform where the performance of such membranes is significantly and controllably improved by depositing thin films of polymethylacrylate [PMA] grafted silica nanoparticles (PGNPs) through the venerable Langmuir-Blodgett method. Our key practically important finding is that these constructs can have unprecedented selectivity values (i.e., ∼250-3000 bar-1, >99.0% salt rejection) at reduced feed water pressure (i.e., reduced cost) while maintaining acceptable water permeance A (= 2-5 L m-2 h-1 Bar-1) with as little as 5-7 PGNP layers. We also observe that the transport of solvent and solute are governed by different mechanisms, unlike gas transport, leading to independent control of A and selectivity. Since these membranes can be formulated using simple and low cost self-assembly methods, our work opens a new direction towards development of affordable, scalable water desalination methods.

2.
Phys Rev Lett ; 129(9): 097202, 2022 Aug 26.
Article in English | MEDLINE | ID: mdl-36083647

ABSTRACT

Recent experiments on Ce_{2}Zr_{2}O_{7} suggest that this material may host a novel form of quantum spin ice, a three-dimensional quantum spin liquid with an emergent photon. The Ce^{3+} local moments on the pyrochlore lattice are described by pseudospin-1/2 degrees of freedom, whose components transform as dipolar and octupolar moments under symmetry operations. In principle, there exist four possible quantum spin ice regimes, depending on whether the Ising component is in the dipolar or octupolar channel, and two possible flux configurations of the emergent gauge field. In this Letter, using exact diagonalization and molecular dynamics, we investigate the equal-time and dynamical spin structure factors in all four quantum spin ice regimes using quantum and classical calculations. Contrasting the distinct signatures of quantum and classical results for the four possible quantum spin ice regimes and elucidating the role of quantum fluctuations, we show that the quantum structure factor computed for the π-flux octupolar quantum spin ice regime is most compatible with the neutron scattering results on Ce_{2}Zr_{2}O_{7}.

3.
Phys Rev Lett ; 127(12): 123602, 2021 Sep 17.
Article in English | MEDLINE | ID: mdl-34597106

ABSTRACT

We observe that a weak guided light field transmitted through an ensemble of atoms coupled to an optical nanofiber exhibits quadrature squeezing. From the measured squeezing spectrum we gain direct access to the phase and amplitude of the energy-time entangled part of the two-photon wave function which arises from the strongly correlated transport of photons through the ensemble. For small atomic ensembles we observe a spectrum close to the line shape of the atomic transition, while sidebands are observed for sufficiently large ensembles, in agreement with our theoretical predictions. Furthermore, we vary the detuning of the probe light with respect to the atomic resonance and infer the phase of the entangled two-photon wave function. From the amplitude and the phase of the spectrum, we reconstruct the real and imaginary part of the time-domain wave function. Our characterization of the entangled two-photon component constitutes a diagnostic tool for quantum optics devices.

4.
Opt Express ; 29(18): 28778-28786, 2021 Aug 30.
Article in English | MEDLINE | ID: mdl-34615000

ABSTRACT

Here, we present the thermal tuning capability of an alignment-free, fiber-integrated Fabry-Pérot cavity. The two mirrors are made of fiber Bragg gratings that can be individually temperature stabilized and tuned. We show the temperature tuning of the resonance wavelength of the cavity without any degradation of the finesse and the tuning of the individual stop bands of the fiber Bragg gratings. This not only permits for the cavity's finesse to be optimized post-fabrication but also makes this cavity applicable as a narrowband filter with a FWHM spectral width of 0.07 ± 0.02 pm and a suppression of more than -15 dB that can be wavelength tuned. Further, in the field of quantum optics, where strong light-matter interactions are desirable, quantum emitters can be coupled to such a cavity and the cavity effect can be reversibly omitted and re-established. This is particularly useful when working with solid-state quantum emitters where such a reference measurement is often not possible once an emitter has been permanently deposited inside a cavity.

5.
ACS Nano ; 15(8): 13591-13603, 2021 Aug 24.
Article in English | MEDLINE | ID: mdl-34347438

ABSTRACT

Hexagonal boron nitride (hBN) is a promising host material for room-temperature, tunable solid-state quantum emitters. A key technological challenge is deterministic and scalable spatial emitter localization, both laterally and vertically, while maintaining the full advantages of the 2D nature of the material. Here, we demonstrate emitter localization in hBN in all three dimensions via a monolayer (ML) engineering approach. We establish pretreatment processes for hBN MLs to either fully suppress or activate emission, thereby enabling such differently treated MLs to be used as select building blocks to achieve vertical (z) emitter localization at the atomic layer level. We show that emitter bleaching of ML hBN can be suppressed by sandwiching between two protecting hBN MLs, and that such thin stacks retain opportunities for external control of emission. We exploit this to achieve lateral (x-y) emitter localization via the addition of a patterned graphene mask that quenches fluorescence. Such complete emitter site localization is highly versatile, compatible with planar, scalable processing, allowing tailored approaches to addressable emitter array designs for advanced characterization, monolithic device integration, and photonic circuits.

6.
J Clin Anesth ; 75: 110472, 2021 12.
Article in English | MEDLINE | ID: mdl-34332495

ABSTRACT

IMPORTANCE: Rising rates of obesity and outpatient performance of parathyroidectomies are making it increasingly crucial to investigate the association of obesity with post-operative complications. OBJECTIVE: To determine whether Class 3 obesity is associated with increased same-day admission compared to lower obesity classes following outpatient parathyroidectomy. DESIGN: Retrospective cohort study. SETTING: Outpatient surgery. PATIENTS: 12,973 patients ≥18 years old who underwent outpatient parathyroidectomy between 2014 and 2016, per the American College of Surgeons National Surgical Quality Improvement Program registry. INTERVENTIONS: Primary exposure variable: body mass index (BMI), with patients assigned to one of six cohorts. MEASUREMENTS: Primary outcome measure: same-day admission. Secondary outcome measure: 30-day readmission. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). MAIN RESULTS: There was a final sample size of 12,973 adult patients who underwent parathyroidectomy from 2014 to 2016. The admission rate for BMI ≥30 and < 40 kg/m2 (reference cohort) was 42.6%. The admission rates for Class 3 obesity categories were 46.2%, 56.2%, and 52.6% for those in the BMI range of ≥40 kg/m2 and < 50 kg/m2, ≥50 kg/m2 and < 60 kg/m2, and ≥ 60 kg/m2, respectively. On multivariable logistic regression, there were no difference in the odds of 30-day hospital admission or readmission rate with any of the BMI cohorts when compared to the reference group. CONCLUSIONS: There is no significant difference in rates of same-day admission or 30-day readmission between any Class 3 (BMI ≥40 kg/m2) obesity cohort and the Class 1 and 2 (BMI ≥30 and < 40 kg/m2) reference cohort following outpatient parathyroidectomy. This corroborates the notion that BMI classes cannot be used in a vacuum to determine eligibility for outpatient parathyroidectomy - a concept that can guide safe and cost-effective institutional practices.


Subject(s)
Obesity , Parathyroidectomy , Adolescent , Adult , Body Mass Index , Humans , Obesity/complications , Obesity/epidemiology , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Risk Factors
7.
ESC Heart Fail ; 8(4): 3119-3129, 2021 08.
Article in English | MEDLINE | ID: mdl-34137193

ABSTRACT

AIMS: Heart failure in constrictive pericarditis (CP) is attributed to impaired biventricular diastolic filling. However, diseases that cause CP due to myocardial infiltration and fibrosis can also impair biventricular systolic function (sf) and contribute to heart failure. This study of patients with CP examined biventricular sf and the effect of myocardial infiltration by pericardial diseases and the resulting fibrosis on ventricular sf. METHODS AND RESULTS: Histopathologic examinations of right ventricular (RV) and left ventricular (LV) myocardia and pericardia were performed on three autopsied hearts of patients with pericardial diseases. Additionally, in 40 adults with clinical heart failure and 40 healthy adults (controls), sf of both ventricles was examined by echocardiography, including strain measurements, and biventricular diastolic filling and pulmonary artery pressures were assessed by cardiac catheterization. Cardiac histopathology indicated thickening of the pericardium with fibrosis, disease infiltrating the myocardium, greater infiltration of the RV than the LV, and an association of pericardial thickness with myocardial infiltrations. Functional analysis indicated that RVsf was impaired on all echo indices, including strain measurement, but LVsf was preserved. CONCLUSIONS: Diseases causing CP are not restricted to the pericardium but also infiltrate the biventricular myocardium and affect the thin-walled RV more than the thick-walled LV, resulting in depressed RVsf. The present results help explain clinical heart failure in the presence of restricted diastolic filling in CP. Depression of RVsf due to progression of fibrosis in the RV myocardium may increase the risk of delayed pericardiectomy.


Subject(s)
Heart Failure , Pericarditis, Constrictive , Adult , Heart Failure/complications , Heart Failure/diagnosis , Humans , Pericardiectomy , Pericarditis, Constrictive/complications , Pericarditis, Constrictive/diagnosis , Systole , Ventricular Function, Right
8.
Chem Asian J ; 16(10): 1271-1279, 2021 May 17.
Article in English | MEDLINE | ID: mdl-33788982

ABSTRACT

A straight-forward approach for the synthesis of a dihydrofuro[2,3-b]benzofuran derivatives has been achieved through a base-mediated Michael addition of 1,3-dicarbonyls to 2-nitrobenzofurans followed by intramolecular cyclization. A variety of 1,3-dicarbonyls, including cyclic as well as trifluoromethylated ones, have been subjected to react with 2-nitrobenzofurans under optimal conditions, and the respective dihydrofuro[2,3-b]benzofurans could be accessed in moderate to excellent yields.

9.
Retin Cases Brief Rep ; 15(4): 373-375, 2021 Jul 01.
Article in English | MEDLINE | ID: mdl-30308527

ABSTRACT

PURPOSE: To report a case of idiopathic full-thickness macular hole in a young boy, which was managed surgically with good visual and anatomical outcomes. METHOD: Single case report. RESULTS: An 8-year-old boy presented for defective vision in the left eye noticed for the past 2 weeks with best-corrected visual acuity of 6/24. A large full-thickness macular hole was diagnosed clinically and was confirmed on optical coherence tomography. There was no clinical or tomographic findings suggestive of trauma or retinal degeneration. After observation for 8 weeks, the patient underwent macular hole surgery in the left eye including internal limiting membrane peeling and C3F8 gas tamponade. Intraoperatively abnormally tight vitreoretinal adherence was noted during the induction of posterior vitreous detachment. Optical coherence tomography at 1 month after surgery showed decrease in the size of macular hole suggestive of incomplete closure. Repeat optical coherence tomography at 3 months showed closed macular hole with mild foveal thinning and ellipsoid zone discontinuity with best-corrected visual acuity improving to 6/18. The tomographic features and best-corrected visual acuity remained stable at 6-month follow-up. CONCLUSION: We hereby report the first case, to the best of our knowledge, of a truly idiopathic full-thickness macular hole in an 8-year-old boy. Surgical treatment offers the best outcomes in these cases and should be considered at the earliest without waiting for spontaneous closure unlike in the case of traumatic full-thickness macular hole.


Subject(s)
Retinal Perforations , Child , Humans , Male , Retinal Perforations/diagnostic imaging , Retinal Perforations/surgery , Tomography, Optical Coherence , Treatment Outcome
10.
Indian J Crit Care Med ; 24(5): 313-320, 2020 May.
Article in English | MEDLINE | ID: mdl-32728321

ABSTRACT

INTRODUCTION: Nontraumatic undifferentiated hypotension is one of the common and challenging critical presentations in the emergency department (ED) due to the difficulty in diagnosing the etiology of shock. In the present study, an attempt was made to test point-of-care ultrasound (PoCUS) as an early approach to improve the accuracy of diagnosis and to narrow the differentials in cases of nontraumatic undifferentiated hypotension. MATERIALS AND METHODS: This is a prospective explorative study conducted in the ED of a tertiary care hospital over a period of 18 months. A total of 100 patients were included in the study. All patients >18 years of age with systolic blood pressure <90 mm Hg with at least one sign or symptom of hypoperfusion were included in the study. Patients referred from another hospital as shock, history of trauma, and history suggestive of orthostatic hypotension and presented with symptomatic postural hypotension as the only chief complaint were excluded. All the patients who met the inclusion/exclusion criteria underwent detailed clinical and multi-organ PoCUS evaluation by two different observers. Assessment of the lungs, cardia, abdomen, aorta, inferior vena cava (IVC), and leg veins during the PoCUS examination was done. A third observer combined the clinical evaluation and the PoCUS findings. All patients were followed through for their final diagnosis at the time of discharge. First, the diagnosis after clinical evaluation alone was compared to the final diagnosis. Then the diagnoses based on the findings of PoCUS alone were compared with the final diagnosis. Last, the diagnosis obtained on combining the data of clinical evaluation with that of PoCUS was compared to the final diagnosis. The data were analyzed based on their reliability indices, accuracy, and the Cohen's kappa coefficient. RESULTS: Diagnoses based on clinical evaluation alone and POCUS alone were found to be accurate in 45% and 47% of patients, respectively. But on combining the findings of clinical evaluation with PoCUS, the accuracy increased to 89%. The most common etiology of shock was found to be distributive shock present in 38% of patients with sepsis being the most common subtype. In patients with obstructive shock, combined clinical evaluation with PoCUS was in perfect agreement with Cohen's kappa coefficient (κ) = 1 and those with distributive shock were in substantial agreement with Cohen's kappa coefficient (κ) = 0717. The overall kappa correlation of the combined evaluation with PoCUS was 0.89, which shows an almost perfect agreement with the final diagnosis. CONCLUSION: This study demonstrates the accuracy and reliability of PoCUS as an easy and valuable bedside tool when added to the clinical evaluation. It helps in narrowing the differentials and thereby guiding early goal-directed therapy in nontraumatic, undifferentiated hypotension patients presenting to the ED. HOW TO CITE THIS ARTICLE: Javali RH, Loganathan A, Srinivasarangan M, Akkamahadevi P, Ganesha BS, Nisarg S, et al. Reliability of Emergency Department Diagnosis in Identifying the Etiology of Nontraumatic Undifferentiated Hypotension. Indian J Crit Care Med 2020;24(5):313-320.

11.
Nat Commun ; 10(1): 4092, 2019 Sep 09.
Article in English | MEDLINE | ID: mdl-31501429

ABSTRACT

Broken symmetries in solids involving higher order multipolar degrees of freedom are historically referred to as "hidden orders" due to the formidable task of detecting them with conventional probes. In this work, we theoretically propose that magnetostriction provides a powerful and novel tool to directly detect higher-order multipolar symmetry breaking-such as the elusive octupolar order-by examining scaling behaviour of length change with respect to an applied magnetic field h. Employing a symmetry-based Landau theory, we focus on the family of Pr-based cage compounds with strongly correlated f-electrons, Pr(Ti,V,Ir)2(Al,Zn)20, whose low energy degrees of freedom are purely higher-order multipoles: quadrupoles [Formula: see text] and octupole [Formula: see text]. We demonstrate that a magnetic field along the [111] direction induces a distinct linear-in-h length change below the octupolar ordering temperature. The resulting "magnetostriction coefficient" is directly proportional to the octupolar order parameter, thus providing clear access to such subtle order parameters.

12.
Sci Rep ; 8(1): 8052, 2018 May 23.
Article in English | MEDLINE | ID: mdl-29795233

ABSTRACT

We theoretically investigate the mechanism to generate large intrinsic spin Hall effect in iridates or more broadly in 5d transition metal oxides with strong spin-orbit coupling. We demonstrate such a possibility by taking the example of orthorhombic perovskite iridate with nonsymmorphic lattice symmetry, SrIrO3, which is a three-dimensional semimetal with nodal line spectrum. It is shown that large intrinsic spin Hall effect arises in this system via the spin-Berry curvature originating from the nearly degenerate electronic spectra surrounding the nodal line. This effect exists even when the nodal line is gently gapped out, due to the persistent nearly degenerate electronic structure. The magnitude of the spin Hall conductivity is shown to be comparable to the best known example such as doped topological insulators and the biggest in any transition metal oxides. To gain further insight, we compute the intrinsic spin Hall conductivity in both bulk and thin film systems. We find that the geometric confinement in thin films leads to significant modifications of the electronic states, leading to even bigger spin Hall conductivity in certain cases. We compare our findings with the recent experimental report on the discovery of large spin Hall effect in SrIrO3 thin films.

13.
Med Clin North Am ; 102(2): 373-385, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29406065

ABSTRACT

Urologic emergencies can involve the kidneys, ureters, bladder, urethra, penis, scrotum, or testicles. History and physical examination are essential to diagnosis, whereas imaging is increasingly used to confirm diagnoses. Acute urinary retention should be relieved with Foley placement. Penile emergencies include paraphimosis, which can be treated by foreskin reduction, whereas penile fracture and priapism require urologic intervention. Fournier gangrene and testicular torsion are scrotal emergencies requiring emergent surgery. Nephrolithiasis, although painful, is not an emergency unless there is concern for concomitant urinary tract infection, both ureters are obstructed by stones, or there is an obstructing stone in a solitary kidney.


Subject(s)
Urologic Diseases/diagnosis , Urologic Diseases/therapy , Acute Disease , Emergencies , Female , Female Urogenital Diseases/diagnosis , Female Urogenital Diseases/therapy , Fournier Gangrene/diagnosis , Fournier Gangrene/therapy , Humans , Male , Male Urogenital Diseases/diagnosis , Male Urogenital Diseases/therapy , Nephrolithiasis/diagnosis , Nephrolithiasis/microbiology , Nephrolithiasis/therapy , Paraphimosis/diagnosis , Paraphimosis/therapy , Penis/injuries , Priapism/diagnosis , Priapism/therapy , Referral and Consultation , Rupture , Spermatic Cord Torsion/diagnosis , Spermatic Cord Torsion/therapy , Urinary Retention/diagnosis , Urinary Retention/therapy
14.
Indian J Crit Care Med ; 21(11): 719-725, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29279631

ABSTRACT

BACKGROUND: Trauma is a leading cause of mortality in India. Outcomes can be improved by early recognition of hemorrhagic shock and expedited management. At present, we rely on traditional vital signs, which are not sensitive measures. Point of care biochemical markers have been emerging as prognostic markers in trauma, but have not been studied in Indian setting. AIMS: This study aims to study the association between arterial lactate and base deficit (BD) at emergency department (ED) admission and 24 h outcome in trauma patients at risk of hemodynamic compromise. MATERIALS AND METHODS: This was a prospective observational study on 100 trauma patients at risk of hemodynamic compromise in tertiary care center ED. Arterial blood gas analysis at admission and 24 h outcomes were noted and statistically analyzed. RESULTS: Arterial lactate ≥4 mmol/L (sensitivity 100% and specificity 85.9%), BD ≥12 mEq/L (sensitivity 87.5% and specificity 82.6%) had more sensitivity than vital signs for predicting 24 h mortality. Higher lactate and BD were associated with increased blood transfusion requirement. Best cutoff values for predicting transfusion were lactate ≥2.9 mmol/L (sensitivity 65.2% and specificity 90.7%), BD ≥8 mEq/L (sensitivity 78.3% and specificity 75.9%). BD-based classification was comparable to ATLS classification in predicting mortality and determining transfusion requirements. Patients with higher arterial lactate and BD were found to have higher 24 h Intensive Care Unit (ICU) admission. CONCLUSION: Emergency admission arterial lactate and Base Deficit are useful predictors of mortality, need for blood transfusion and ICU admission at 24 h. It can be used to triage, identify shock early, assess transfusion requirement, and prognosticate trauma patients.

16.
Future Sci OA ; 3(1): FSO157, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28344822

ABSTRACT

AIM: Lipids such as prostaglandins, leukotrienes and thromboxanes are released as a result of an inflammatory episode in pain (central and peripheral). METHODOLOGY & RESULTS: To measure these lipids as potential mechanistic biomarkers in neuropathic pain models, we developed a higher-throughput LC-MS/MS-based method with simultaneous detection of PGE2, PGD2, PGF2α, LTB4, TXB2 and 2-arachidonoyl glycerol in brain and spinal cord tissues. We also demonstrate that the LC-MS/MS method was more sensitive and specific in differentiating PGE2 levels in CNS tissues compared with ELISA. CONCLUSION: The ability to modify the LC-MS/MS method to accommodate numerous other lipids in one analysis, demonstrates that the presented method offers a cost-effective and more sensitive alternative to ELISA method useful in drug discovery settings.

17.
Biol Psychiatry ; 81(3): 252-264, 2017 02 01.
Article in English | MEDLINE | ID: mdl-27113499

ABSTRACT

BACKGROUND: Studies in psychiatric genetics have identified >100 loci associated with disease risk, yet many of these loci are distant from protein coding genes. Recent characterization of the transcriptional landscape of cell lines and whole tissues has suggested widespread transcription in both coding and noncoding regions of the genome, including differential expression from loci that produce regulatory noncoding RNAs that function within the nucleus; however, the nuclear transcriptome of specific cell types in the brain has not been previously investigated. METHODS: We defined the nuclear transcriptional landscape of the three major cellular divisions of the nervous system using flow sorting of genetically labeled nuclei from bacTRAP mouse lines. Next, we characterized the unique expression of coding, noncoding, and intergenic RNAs in the mature mouse brain with RNA-Seq and validation with independent methods. RESULTS: We found diverse expression across the cell types of all classes of RNAs, including long noncoding RNAs, several of which were confirmed as highly enriched in the nuclei of specific cell types using anatomic methods. We also discovered several examples of cell type-specific expression of tandem gene fusions, and we report the first cell type-specific expression of circular RNAs-a neuron-specific and nuclear-enriched RNA arising from the gene Hnrnpu. CONCLUSIONS: These data provide an important resource for studies evaluating the function of various noncoding RNAs in the brain, including noncoding RNAs that may play a role in psychiatric disease.


Subject(s)
Brain/metabolism , Neuroglia/metabolism , Neurons/metabolism , RNA, Nuclear/metabolism , Transcriptome , Animals , Female , Heterogeneous-Nuclear Ribonucleoprotein U/metabolism , Male , Mice , Oligodendroglia/metabolism , RNA, Long Noncoding/metabolism , Sequence Analysis, RNA
18.
Assay Drug Dev Technol ; 13(8): 466-75, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26292018

ABSTRACT

Kynurenine 3-monooxygenase (KMO), a pivotal enzyme in the kynurenine pathway, was identified as a potential therapeutic target for treating neurodegenerative and psychiatric disorders. In this article, we describe a surface plasmon resonance (SPR) assay that delivers both kinetics and the mechanism of binding (MoB) data, enabling a detailed characterization of KMO inhibitors for the enzyme in real time. SPR assay development included optimization of the protein construct and the buffer conditions. The stability and inhibitor binding activity of the immobilized KMO were significantly improved when the experiments were performed at 10°C using a buffer containing 0.05% n-dodecyl-ß-d-maltoside (DDM) as the detergent. The KD values of the known KMO inhibitors (UPF648 and RO61-8048) from the SPR assay were in good accordance with the biochemical LC/MS/MS assay. Also, the SPR assay was able to differentiate the binding kinetics (k(a) and k(d)) of the selected unknown KMO inhibitors. For example, the inhibitors that showed comparable IC50 values in the LC/MS/MS assay displayed differences in their residence time (τ = 1/k(d)) in the SPR assay. To better define the MoB of the inhibitors to KMO, an SPR-based competition assay was developed, which demonstrated that both UPF648 and RO61-8048 bound to the substrate-binding site. These results demonstrate the potential of the SPR assay for characterizing the affinity, the kinetics, and the MoB profiles of the KMO inhibitors.


Subject(s)
Kynurenine 3-Monooxygenase/antagonists & inhibitors , Kynurenine 3-Monooxygenase/metabolism , Small Molecule Libraries/metabolism , Small Molecule Libraries/pharmacology , Surface Plasmon Resonance/methods , Animals , Binding Sites/physiology , Enzyme Inhibitors/analysis , Enzyme Inhibitors/metabolism , Enzyme Inhibitors/pharmacology , HEK293 Cells , Humans , Insecta , Kinetics , Kynurenine 3-Monooxygenase/analysis , Small Molecule Libraries/analysis , Tandem Mass Spectrometry/methods
19.
J Neurosci ; 35(16): 6495-505, 2015 Apr 22.
Article in English | MEDLINE | ID: mdl-25904800

ABSTRACT

Globoid cell leukodystrophy (GLD, Krabbe disease) is a lysosomal storage disease (LSD) caused by a deficiency in galactocerebrosidase (GALC) activity. In the absence of GALC activity, the cytotoxic lipid, galactosylsphingosine (psychosine), accumulates in the CNS and peripheral nervous system. Oligodendrocytes and Schwann cells are particularly sensitive to psychosine, thus leading to a demyelinating phenotype. Although hematopoietic stem-cell transplantation provides modest benefit in both presymptomatic children and the murine model (Twitcher), there is no cure for GLD. In addition, GLD has been relatively refractory to virtually every experimental therapy attempted. Here, Twitcher mice were simultaneously treated with CNS-directed gene therapy, substrate reduction therapy, and bone marrow transplantation to target the primary pathogenic mechanism (GALC deficiency) and two secondary consequences of GALC deficiency (psychosine accumulation and neuroinflammation). Simultaneously treating multiple pathogenic targets resulted in an unprecedented increase in life span with improved motor function, persistent GALC expression, nearly normal psychosine levels, and decreased neuroinflammation. Treating the primary pathogenic mechanism and secondary targets will likely improve therapeutic efficacy for other LSDs with complex pathological and clinical presentations.


Subject(s)
Bone Marrow Transplantation , Cycloserine/therapeutic use , Galactosylceramidase/genetics , Genetic Therapy , Leukodystrophy, Globoid Cell/therapy , Animals , Body Weight/drug effects , Body Weight/genetics , Brain/drug effects , Brain/metabolism , Combined Modality Therapy , Cytokines/metabolism , Female , Galactosylceramidase/metabolism , Leukodystrophy, Globoid Cell/drug therapy , Leukodystrophy, Globoid Cell/genetics , Leukodystrophy, Globoid Cell/pathology , Male , Mice , Mice, Inbred Strains , Motor Skills/drug effects , Myelin Sheath/drug effects , Myelin Sheath/physiology , Psychosine/metabolism , Sciatic Nerve/metabolism
20.
Urology ; 85(3): e13-4, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25733307

ABSTRACT

Proximal corporospongiosal shunts are used for the most refractory cases of priapism. Here, we present the case of a 58-year-old man whose priapism was only partially responsive to phenylephrine injections and distal shunting. Proximal shunting was required, and he subsequently developed fistulization of the proximal penile urethra into the skin and the corpora cavernosa. The formation of simultaneous urethrocutaneous and urethrocavernous fistulae is a rare complication of proximal corporospongiosal shunts that can be initially managed with urinary diversion with a suprapubic tube.


Subject(s)
Cutaneous Fistula/etiology , Fistula/etiology , Penile Diseases/etiology , Penis/surgery , Urethral Diseases/etiology , Urinary Fistula/etiology , Anastomosis, Surgical/adverse effects , Humans , Male , Priapism/surgery , Prostheses and Implants , Urologic Surgical Procedures, Male/adverse effects , Urologic Surgical Procedures, Male/methods
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