Uncovering Footprints of Dipolar-Octupolar Quantum Spin Ice from Neutron Scattering Signatures.

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}.

Thermal tuning of a fiber-integrated Fabry-Pérot cavity.

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.

Unraveling Two-Photon Entanglement via the Squeezing Spectrum of Light Traveling through Nanofiber-Coupled Atoms.

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.

Reliability of Emergency Department Diagnosis in Identifying the Etiology of Nontraumatic Undifferentiated Hypotension.

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.

A Clinical Study on the Initial Assessment of Arterial Lactate and Base Deficit as Predictors of Outcome in Trauma Patients.

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.

Mechanism-based combination treatment dramatically increases therapeutic efficacy in murine globoid cell leukodystrophy.

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.

Urinary prevalence, metabolite detection rates, temporal patterns and evaluation of suitable LC-MS/MS targets to document synthetic cannabinoid intake in US military urine specimens.

BACKGROUND: Identifying synthetic cannabinoid designer drug abuse challenges toxicologists and drug testing programs. The best analytical approach for reliably documenting intake of emerging synthetic cannabinoids is unknown. Primarily metabolites are found in urine, but optimal metabolite targets remain unknown, and definitive identification is complicated by converging metabolic pathways. METHODS: We screened 20,017 US military urine specimens collected from service members worldwide for synthetic cannabinoids between July 2011 and June 2012. We confirmed 1432 presumptive positive and 1069 presumptive negative specimens by qualitative liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis including 29 biomarkers for JWH-018, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, RCS-4, AM2201 and MAM2201. Specimen preparation included enzyme hydrolysis and acetonitrile precipitation prior to LC-MS/MS analysis. We evaluated individual synthetic cannabinoid metabolite detection rates, prevalence, temporal patterns and suitable targets for analytical procedures. RESULTS: Prevalence was 1.4% with 290 confirmed positive specimens, 92% JWH-018, 54% AM2201 and 39% JWH-122 metabolites. JWH-073, JWH-210 and JWH-250 also were identified in 37%, 4% and 8% of specimens, respectively. The United States Army Criminal Investigation Command seizure pattern for synthetic cannabinoid compounds matched our urine specimen results over the time frame of the study. Apart from one exception (AM2201), no parent compounds were observed. CONCLUSIONS: Hydroxyalkyl metabolites accounted for most confirmed positive tests, and in many cases, two metabolites were identified, increasing confidence in the results, and improving detection rates. These data also emphasize the need for new designer drug metabolism studies to provide relevant targets for synthetic cannabinoid identification.

Distillation of the two-mode squeezed state.

We experimentally demonstrate entanglement distillation of the two-mode squeezed state obtained by parametric down-conversion. Applying the photon annihilation operator to both modes, we raise the fraction of the photon-pair component in the state, resulting in the increase of both squeezing and entanglement by about 50%. Because of the low amount of initial squeezing, the distilled state does not experience significant loss of Gaussian character.

Metabolism of synthetic cannabinoids PB-22 and its 5-fluoro analog, 5F-PB-22, by human hepatocyte incubation and high-resolution mass spectrometry.

BACKGROUND: PB-22 (1-pentyl-8-quinolinyl ester-1H-indole-3-carboxylic acid) and 5F-PB-22 (1-(5-fluoropentyl)-8-quinolinyl ester-1H-indole-3-carboxylic acid) are new synthetic cannabinoids with a quinoline substructure and the first marketed substances with an ester bond linkage. No human metabolism data are currently available, making it difficult to document PB-22 and 5F-PB-22 intake from urine analysis, and complicating assessment of the drugs' pharmacodynamic and toxicological properties. METHODS: We incubated 10 µmol/l PB-22 and 5F-PB-22 with pooled cryopreserved human hepatocytes up to 3 h and analyzed samples on a TripleTOF 5600+ high-resolution mass spectrometer. Data were acquired via TOF scan, followed by information-dependent acquisition triggered product ion scans with mass defect filtering (MDF). The accurate mass full scan MS and MS/MS metabolite datasets were analyzed with multiple data processing techniques, including MDF, neutral loss and product ion filtering. RESULTS: The predominant metabolic pathway for PB-22 and 5F-PB-22 was ester hydrolysis yielding a wide variety of (5-fluoro)pentylindole-3-carboxylic acid metabolites. Twenty metabolites for PB-22 and 22 metabolites for 5F-PB-22 were identified, with the majority generated by oxidation with or without glucuronidation. For 5F-PB-22, oxidative defluorination occurred forming PB-22 metabolites. Both compounds underwent epoxide formation followed by internal hydrolysis and also produced a cysteine conjugate. CONCLUSION: Human hepatic metabolic profiles were generated for PB-22 and 5F-PB-22. Pentylindole-3-carboxylic acid, hydroxypentyl-PB-22 and PB-22 pentanoic acid for PB-22, and 5'-fluoropentylindole-3-carboxylic acid, PB-22 pentanoic acid and the hydroxy-5F-PB-22 metabolite with oxidation at the quinoline system for 5F-PB-22 are likely the best targets to incorporate into analytical methods for urine to document PB-22 and 5F-PB-22 intake.

Combination therapies for lysosomal storage disease: is the whole greater than the sum of its parts?

Lysosomal storage diseases (LSDs), as a group, are among the most common inherited diseases affecting children. The primary defect is typically a genetic deficiency of one of the lysosomal enzymes, often causing accumulation of undegraded substrates within the lysosome. This accumulation causes numerous secondary effects that contribute to the disease phenotype. Viral-mediated gene therapy (GT) can supply a persistent source of the deficient enzyme. However, with some notable exceptions, GT has been only modestly successful as a single approach. Recently, various therapies have been combined in order to more effectively target the diverse pathogenic mechanisms at work in LSDs. One strategy that has shown promise involves providing a persistent source of the deficient enzyme (GT, stem cell transplantation) while targeting a secondary consequence of disease with a more transient approach (substrate reduction, anti-inflammatories, pharmacological mimetic, etc.). This general strategy has resulted in both additive and synergistic effects. Interestingly, some therapeutic approaches by themselves provide essentially no clinical benefit but contribute greatly to the overall efficacy when used in combination with other treatments. Unfortunately, no therapeutic combination is universally effective. This adds to the difficulty in predicting and identifying combinations that will be most effective for individual LSDs. A better understanding of both pathogenic and therapeutic mechanisms is necessary in order to identify potentially successful combinations. While a single treatment would be ideal, the complex nature of these diseases may unavoidably limit the efficacy of single therapies. In order to more successfully treat LSDs, a shift in focus towards a combination therapy may be necessary.

First metabolic profile of XLR-11, a novel synthetic cannabinoid, obtained by using human hepatocytes and high-resolution mass spectrometry.

BACKGROUND: Since the mid-2000s synthetic cannabinoids have been abused as recreational drugs, prompting scheduling of these substances in many countries. To circumvent legislation, manufacturers constantly market new compounds; [1-(5-fluoropentyl)indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone (XLR-11), the fluorinated UR-144 analog, is one of the most recent and widely abused drugs, and its use is now linked with acute kidney injury. Our goal was to investigate XLR-11 metabolism for identification of major urinary targets in analytical methods and to clarify the origin of metabolites when one or more parent synthetic cannabinoids can be the source. METHODS: We incubated 10 µmol/L XLR-11 with pooled human hepatocytes and sampled after 1 and 3 h. Samples were analyzed by high-resolution mass spectrometry with a TOF scan followed by information-dependent acquisition triggered product ion scans with dynamic background subtraction and mass defect filters. Scans were thoroughly data mined with different data processing algorithms (Metabolite Pilot 1.5). RESULTS: XLR-11 underwent phase I and II metabolism, producing more than 25 metabolites resulting from hydroxylation, carboxylation, hemiketal and hemiacetal formation, internal dehydration, and further glucuronidation of some oxidative metabolites. No sulfate or glutathione conjugation was observed. XLR-11 also was defluorinated, forming UR-144 metabolites. On the basis of mass spectrometry peak areas, we determined that the major metabolites were 2'-carboxy-XLR-11, UR-144 pentanoic acid, 5-hydroxy-UR-144, hydroxy-XLR-11 glucuronides, and 2'-carboxy-UR-144 pentanoic acid. Minor metabolites were combinations of the biotransformations mentioned above, often glucuronidated. CONCLUSIONS: These are the first data defining major urinary targets of XLR-11 metabolism that could document XLR-11 intake in forensic and clinical investigations.

Synergistic effects of central nervous system-directed gene therapy and bone marrow transplantation in the murine model of infantile neuronal ceroid lipofuscinosis.

OBJECTIVE: Infantile neuronal ceroid lipofuscinosis (INCL) is an inherited childhood neurodegenerative disorder caused by the loss of palmitoyl protein thioesterase-1 (PPT1) activity. Affected children suffer from blindness, epilepsy, motor dysfunction, cognitive decline, and premature death. The Ppt1(-/-) mouse shares the histological and clinical features of INCL. Previous single-therapy approaches using small molecule drugs, gene therapy, or neuronal stem cells resulted in partial histological correction, with minimal improvements in motor function or lifespan. Here, we combined central nervous system (CNS)-directed adeno-associated virus (AAV)2/5-mediated gene therapy with bone marrow transplantation (BMT) in the INCL mouse. METHODS: At birth, Ppt1(-/-) and wild-type mice were given either intracranial injections of AAV2/5-PPT1 or bone marrow transplantation, separately as well as in combination. To assess function, we measured rotorod performance monthly as well as lifespan. At terminal time points, we evaluated the therapeutic effects on several INCL-specific parameters, such as cortical thickness, autofluorescent accumulation, and glial activation. Finally, we determined levels of PPT1 enzyme activity and bone marrow engraftment in treated mice. RESULTS: AAV2/5-mediated gene therapy alone resulted in significant histological correction, improved motor function, and increased lifespan. Interestingly, the addition of BMT further increased the lifespan of treated mice and led to dramatic, sustained improvements in motor function. These data are truly striking, given that BMT alone is ineffective, yet it synergizes with CNS-directed gene therapy to dramatically increase efficacy and lifespan. INTERPRETATION: AAV2/5-mediated gene therapy in combination with BMT provides an unprecedented increase in lifespan as well as dramatic improvement on functional and histological parameters.

Enhanced efficiency of water desalination in nanostructured thin-film membranes with polymer grafted nanoparticles.

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.

Bone marrow transplantation augments the effect of brain- and spinal cord-directed adeno-associated virus 2/5 gene therapy by altering inflammation in the murine model of globoid-cell leukodystrophy.

Globoid-cell leukodystrophy (GLD) is an inherited demyelinating disease caused by the deficiency of the lysosomal enzyme galactosylceramidase (GALC). A previous study in the murine model of GLD (twitcher) demonstrated a dramatic synergy between CNS-directed adeno-associated virus 2/5 (AAV2/5) gene therapy and myeloreductive bone marrow transplantation (BMT). However, the mechanism by which these two disparate therapeutic approaches synergize is not clear. In addition, the therapeutic efficacy may have been limited since the CNS-directed gene therapy was restricted to the forebrain and thalamus. In the current study, intrathecal and intracerebellar injections were added to the therapeutic regimen and the mechanism of synergy between BMT and gene therapy was determined. Although AAV2/5 alone provided supraphysiological levels of GALC activity and reduced psychosine levels in both the brain and spinal cord, it significantly increased CNS inflammation. Bone marrow transplantation alone provided essentially no GALC activity to the CNS and did not reduce psychosine levels. When AAV2/5 is combined with BMT, there are sustained improvements in motor function and the median life span is increased to 123 d (range, 92-282 d) compared with 41 d in the untreated twitcher mice. Interestingly, addition of BMT virtually eliminates both the disease and AAV2/5-associated inflammatory response. These data suggest that the efficacy of AAV2/5-mediated gene therapy is limited by the associated inflammatory response and BMT synergizes with AAV2/5 by modulating inflammation.

Bone marrow transplantation increases efficacy of central nervous system-directed enzyme replacement therapy in the murine model of globoid cell leukodystrophy.

Globoid cell leukodystrophy (GLD, Krabbe disease), is an autosomal recessive, neurodegenerative disease caused by the deficiency of the lysosomal enzyme galactocerebrosidase (GALC). In the absence of GALC, the toxic metabolite psychosine accumulates in the brain and causes the death of the myelin-producing cells, oligodendrocytes. Currently, the only therapy for GLD is hematopoietic stem cell transplantation using bone marrow (BMT) or umbilical cord blood. However, this is only partially effective. Previous studies have shown that enzyme replacement therapy (ERT) provides some therapeutic benefit in the murine model of GLD, the Twitcher mouse. Experiments have also shown that two disparate therapies can produce synergistic effects when combined. The current study tests the hypothesis that BMT will increase the therapeutic effects of ERT when these two treatments are combined. Twitcher mice were treated with either ERT alone or both ERT and BMT during the first 2-4 days of life. Recombinant enzyme was delivered by intracerebroventricular (ICV) and intrathecal (IT) injections. Twitcher mice receiving ERT had supraphysiological levels of GALC activity in the brain 24h after injection. At 36 days of age, ERT-treated Twitcher mice had reduced psychosine levels, reduced neuroinflammation, improved motor function, and increased lifespan. Twitcher mice receiving both ERT and BMT had significantly increased lifespan, improved motor function, reduced psychosine levels, and reduced neuroinflammation in certain areas of the brain compared to untreated or ERT-treated Twitcher mice. Together, these results indicate that BMT enhances the efficacy of ERT in GLD.

Traumatic extradural haematoma revealed after contralateral decompressive craniectomy.

Traumatic extradural haematoma following a severe head injury is well documented in neurosurgical literature. We report a case of traumatic extradural haematoma which initially was concealed by the high intracranial pressure (ICP) and revealed after the contralateral decompressive craniectomy. A 21-year-old roofer sustained severe head injury from a fall. The CT brain showed right sided fronto-temporal contusions with small acute subdural haematoma and left orbital roof fracture extending into the temporal bone. ICP was above 45 mmHg even after maximal medical therapy. Decompressive craniectomy was performed on the right side along with contusionectomy. Within an hour, ICP spiked and the CT brain showed left side extradural haematoma. The second surgery demonstrated a bleeding middle meningeal artery associated with the left temporal bone fracture. The clinical sequence of events, radiological and operative findings revealed this to be a traumatic extradural haematoma sustained at the initial trauma. This was revealed after the tamponade effect was released from the initial decompressive craniectomy on the contralateral side.

Class 3 obesity is not associated with same-day admission in obese patients undergoing parathyroidectomy.

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.

A Base-Mediated Approach Towards Dihydrofuro[2,3-b]Benzofurans from 2-Nitrobenzofurans and 1,3-Dicarbonyls.

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.

IDIOPATHIC FULL-THICKNESS MACULAR HOLE IN AN 8-YEAR-OLD BOY.

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.