Gamma knife capsulotomy for intractable OCD: Neuroimage analysis of lesion size, location, and clinical response.

Obsessive-compulsive disorder (OCD) affects 2-3% of the population. One-third of patients are poorly responsive to conventional therapies, and for a subgroup, gamma knife capsulotomy (GKC) is an option. We examined lesion characteristics in patients previously treated with GKC through well-established programs in Providence, RI (Butler Hospital/Rhode Island Hospital/Alpert Medical School of Brown University) and São Paulo, Brazil (University of São Paolo). Lesions were traced on T1 images from 26 patients who had received GKC targeting the ventral half of the anterior limb of the internal capsule (ALIC), and the masks were transformed into MNI space. Voxel-wise lesion-symptom mapping was performed to assess the influence of lesion location on Y-BOCS ratings. General linear models were built to compare the relationship between lesion size/location along different axes of the ALIC and above or below-average change in Y-BOCS ratings. Sixty-nine percent of this sample were full responders (≥35% improvement in OCD). Lesion occurrence anywhere within the targeted region was associated with clinical improvement, but modeling results demonstrated that lesions occurring posteriorly (closer to the anterior commissure) and dorsally (closer to the mid-ALIC) were associated with the greatest Y-BOCS reduction. No association was found between Y-BOCS reduction and overall lesion volume. GKC remains an effective treatment for refractory OCD. Our data suggest that continuing to target the bottom half of the ALIC in the coronal plane is likely to provide the dorsal-ventral height required to achieve optimal outcomes, as it will cover the white matter pathways relevant to change. Further analysis of individual variability will be essential for improving targeting and clinical outcomes, and potentially further reducing the lesion size necessary for beneficial outcomes.

Association between genetic polymorphisms in the promoter region of the defensin beta 1 gene and persistent apical periodontitis.

AIM: To evaluate the association between the promoter region of defensin beta 1 (DEFB1) genetic polymorphisms and persistent apical periodontitis (PAP) in Brazilian patients. METHODOLOGY: Seventy-three patients with post-treatment PAP (PAP group) and 89 patients with root filled teeth with healed and healthy periradicular tissues (healed group) were included (all teeth had apical periodontitis lesions at the beginning of the treatment). Patients who had undergone at least 1 year of follow-up after root canal treatment were recalled, and their genomic DNA was extracted from saliva. Two single nucleotide polymorphisms (SNPs) in DEFB1 at the g. -52G>A (rs1799946) and g. -20G>A (rs11362) positions were analysed using real-time polymerase chain reaction. The chi-squared test was performed, and the odds ratios were calculated using Epi Info 3.5.2. Logistic regression analysis in the codominant model, using the time of follow-up as a variable, was used to evaluate the SNP-SNP interaction. All tests were performed with an established alpha of 0.05 (P = 0.05). RESULTS: For the rs11362 polymorphism in the codominant and recessive models, patients who carried two copies of the T allele had a significantly lower risk of developing PAP (P = 0.040 and P = 0.031, respectively). For the rs1799946 polymorphism in DEFB1 in the codominant and recessive models, carrying one copy of the T allele significantly increased the risk of developing PAP (P = 0.007 and P = 0.031, respectively). In the logistic regression, both polymorphisms were associated with PAP as well as the SNP-SNP interaction (P < 0.0001). CONCLUSIONS: Polymorphisms in DEFB1 genes were associated with the development of post-treatment persistent apical periodontitis.

[Discontinuation of Chromium-51 for clinical use: What are the possible alternatives for radiopharmacies and nuclear medicine departments?] / Arrêt de production du chrome-51 (51Cr) a usage clinique : quelles alternatives possibles pour les services de radiopharmacie et de médecine nucléaire ?

OBJECTIVES: Last October, the nuclear medicine departments were informed of the closure of the chromium-51 production line for clinical use. This radionuclide has different diagnostic indications in nephrology and hematology. It was therefore essential to set up alternative exploration protocols to overcome this production stoppage. METHODS: Chromium-51 EDTA has been replaced by technetium-99m DTPA for the determination of glomerular filtration rates. Sodium chromate was substituted by sodium pertechnetate for the determination of globular volumes. A retrospective analysis of the chromium-51 data was performed followed by a prospective study, from January to December 2019 for technetium tracers. RESULTS: One hundred and forty-four patients were included in the study. Forty-two EDTA-51Cr and 30 DTPA-99mTc exams were conducted and compared. There were no significant differences between the methods used to assess renal function (P=0.355). For the determination of blood cell and plasma volumes, 47 tests with 51Cr and 125I and 25 tests with 99mTc and 125I were performed and compared. There were no significant differences in the determination of total (P=0.325) and globular (P=0.148) volumes. CONCLUSIONS: The study carried out shows that there is no significant difference between the results obtained with chromium-51 and technetium tracers. As a result, clinical activity was maintained in good conditions.

Learning curves of open and endoscopic fetal spina bifida closure: systematic review and meta-analysis.

OBJECTIVE: The Management of Myelomeningocele Study (MOMS) trial demonstrated the safety and efficacy of open fetal surgery for spina bifida aperta (SBA). Recently developed alternative techniques may reduce maternal risks without compromising the fetal neuroprotective effects. The aim of this systematic review was to assess the learning curve (LC) of different fetal SBA closure techniques. METHODS: MEDLINE, Web of Science, EMBASE, Scopus and Cochrane databases and the gray literature were searched to identify relevant articles on fetal surgery for SBA, without language restriction, published between January 1980 and October 2018. Identified studies were reviewed systematically and those reporting all consecutive procedures and with postnatal follow-up ≥ 12 months were selected. Studies were included only if they reported outcome variables necessary to measure the LC, as defined by fetal safety and efficacy. Two authors independently retrieved data, assessed the quality of the studies and categorized observations into blocks of 30 patients. For meta-analysis, data were pooled using a random-effects model when heterogeneous. To measure the LC, we used two complementary methods. In the group-splitting method, competency was defined when the procedure provided results comparable to those in the MOMS trial for 12 outcome variables representing the immediate surgical outcome, short-term neonatal neuroprotection and long-term neuroprotection at ≥ 12 months of age. Then, when raw patient data were available, we performed cumulative sum analysis based on a composite binary outcome defining successful surgery. The composite outcome combined four clinically relevant variables for safety (absence of extreme preterm delivery < 30 weeks, absence of fetal death ≤ 7 days after surgery) and efficacy (reversal of hindbrain herniation and absence of any neonatal treatment of dehiscence or cerebrospinal fluid leakage at the closure site). RESULTS: Of 6024 search results, 17 (0.3%) studies were included, all of which had low, moderate or unclear risk of bias. Fetal SBA closure was performed using standard hysterotomy (11 studies), mini-hysterotomy (one study) or fetoscopy by either exteriorized-uterus single-layer closure (one study), percutaneous single-layer closure (three studies) or percutaneous two-layer closure (one study). Only outcomes for standard hysterotomy could be meta-analyzed. Overall, outcomes improved significantly with experience. Competency was reached after 35 consecutive cases for standard hysterotomy and was predicted to be achieved after ≥ 57 cases for mini-hysterotomy and ≥ 56 for percutaneous two-layer fetoscopy. For percutaneous and exteriorized-uterus single-layer fetoscopy, competency was not reached in the 81 and 28 cases available for analysis, respectively, and LC prediction analysis could not be performed. CONCLUSIONS: The number of cases operated is correlated with the outcome of fetal SBA closure, and the number of operated cases required to reach competency ranges from 35 for standard hysterotomy to ≥ 56-57 for minimally invasive modifications. Our observations provide important information for institutions looking to establish a new fetal center, develop a new fetal surgery technique or train their team, and inform referring clinicians, potential patients and third parties. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Curvas de aprendizaje del cierre de la espina bífida fetal mediante cirugía abierta y endoscópica: revisión sistemática y metaanálisis OBJETIVO: El ensayo del Estudio sobre la Gestión del Mielomeningocele (MOMS, por sus siglas en inglés) demostró la seguridad y eficacia de la cirugía fetal abierta para la espina bífida aperta (EBA). Las técnicas alternativas recientemente desarrolladas pueden reducir los riesgos de la madre sin comprometer los efectos neuroprotectores del feto. El objetivo de esta revisión sistemática fue evaluar la curva de aprendizaje (CA) de diferentes técnicas de cierre de la EBA fetal. MÉTODOS: Se realizaron búsquedas en las bases de datos de MEDLINE, Web of Science, EMBASE, Scopus y Cochrane, así como en la literatura gris, para identificar artículos relevantes sobre cirugía fetal para la EBA, sin restricción de idioma, publicados entre enero de 1980 y octubre de 2018. Se examinaron sistemáticamente los estudios identificados y se seleccionaron los que informaban de todos los procedimientos consecutivos y con seguimiento postnatal ≥12 meses. Los estudios se incluyeron sólo si informaban sobre las variables de resultado necesarias para medir la CA, definidas por la seguridad y la eficacia para el feto. Dos autores recuperaron los datos de forma independiente, evaluaron la calidad de los estudios y clasificaron las observaciones en bloques de 30 pacientes. Para el metaanálisis, los datos se agruparon mediante un modelo de efectos aleatorios cuando fueron heterogéneos. Para medir la CA, se usaron dos métodos complementarios. En el método de división de grupos, la competencia se definió cuando el procedimiento proporcionó resultados comparables a los del ensayo MOMS para 12 variables de resultados que representaban el resultado quirúrgico inmediato, la neuroprotección neonatal a corto plazo y la neuroprotección a largo plazo a ≥12 meses de edad. Luego, cuando se dispuso de los datos brutos de los pacientes, se realizó un análisis de suma acumulada basado en un resultado binario compuesto que definió el éxito de la cirugía. El resultado compuesto combinó cuatro variables clínicamente relevantes en cuanto a la seguridad (ausencia de parto pretérmino extremo <30 semanas; ausencia de muerte fetal a ≤7 días después de la cirugía) y eficacia (reducción de la hernia del rombencéfalo y ausencia de cualquier tratamiento neonatal de dehiscencia o derrame de líquido cefalorraquídeo en el lugar del cierre). RESULTADOS: De los 6024 resultados de la búsqueda, se incluyeron 17 (0,3%) estudios, todos ellos con un riesgo de sesgo bajo, moderado o incierto. El cierre de la EBA fetal se realizó mediante histerotomía estándar (11 estudios), mini histerotomía (un estudio) o fetoscopia, ya fuera mediante el cierre exteriorizado del útero de una sola capa (un estudio), el cierre percutáneo de una sola capa (tres estudios) o el cierre percutáneo de dos capas (un estudio). Sólo se pudieron metaanalizar los resultados de la histerotomía estándar. En general, los resultados mejoraron significativamente con la experiencia. Se alcanzó la competencia después de 35 casos consecutivos para la histerotomía estándar y se predijo que se alcanzaría después de ≥57 casos para la mini histerotomía y ≥56 para la fetoscopia percutánea de dos capas. En el caso de las fetoscopias percutánea y exteriorizada del útero de una sola capa, no se alcanzó la competencia en los 81 y 28 casos disponibles para el análisis, respectivamente, y no se pudo realizar el análisis de predicción de la CA. CONCLUSIONES: El número de casos operados está correlacionado con el resultado del cierre de la EBA fetal, y el número de casos operados necesarios para alcanzar la competencia estuvo entre 35 para la histerotomía estándar y ≥56-57 para las operaciones con mínima agresividad. Las observaciones realizadas proporcionan información importante para las instituciones que buscan establecer un nuevo centro fetal, desarrollar una nueva técnica de cirugía fetal o entrenar a su equipo, e informar a los médicos que remiten a especialistas a los posibles pacientes y a terceros. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Absorption of wireless radiation in the child versus adult brain and eye from cell phone conversation or virtual reality.

Children's brains are more susceptible to hazardous exposures, and are thought to absorb higher doses of radiation from cell phones in some regions of the brain. Globally the numbers and applications of wireless devices are increasing rapidly, but since 1997 safety testing has relied on a large, homogenous, adult male head phantom to simulate exposures; the "Standard Anthropomorphic Mannequin" (SAM) is used to estimate only whether tissue temperature will be increased by more than 1 Celsius degree in the periphery. The present work employs anatomically based modeling currently used to set standards for surgical and medical devices, that incorporates heterogeneous characteristics of age and anatomy. Modeling of a cell phone held to the ear, or of virtual reality devices in front of the eyes, reveals that young eyes and brains absorb substantially higher local radiation doses than adults'. Age-specific simulations indicate the need to apply refined methods for regulatory compliance testing; and for public education regarding manufacturers' advice to keep phones off the body, and prudent use to limit exposures, particularly to protect the young.

A needs assessment of education research topics among surgical educators in the United States.

BACKGROUND: There are currently no courses that focus specifically on surgical education research. A needs assessment of surgical educators is required to best design these courses. METHODS: A cross-sectional survey-based study on all faculty members of the Association for Surgical Education was done to determine their education research needs. RESULTS: The overall response rate was 15% and the majority of the 78 respondents were physicians (63%) in their mid- to late career stage (65%). Participants thought research topics should be taught at an advanced level in a workshop format. Senior educators were less interested than junior educators in learning to create conceptual frameworks (p = 0.038) and presenting their research at national meetings (p = 0.014). CONCLUSIONS: Surgical educators desire more training in education research techniques that are taught in a workshop format at a national surgical education meeting. These workshops may lay the groundwork for a nationally recognized certificate in surgical education research.

Hippocampal dynamics of synaptic NF-kappa B during inhibitory avoidance long-term memory consolidation in mice.

Since the discovery that long-term memory is dependent on protein synthesis, several transcription factors have been found to participate in the transcriptional activity needed for its consolidation. Among them, NF-kappa B is a constitutive transcription factor whose nuclear activity has proven to be necessary for the consolidation of inhibitory avoidance in mice. This transcription factor has a wide distribution in the nervous system, with a well-reported presence in dendrites and synaptic terminals. Here we report changes in synaptosomal NF-kappa B localization and activity, during long-term memory consolidation. Activity comparison of synaptosomal and nuclear NF-kappa B, indicates different dynamics for both localizations. In this study we identify two pools of synaptosomal NF-kappa B, one obtained with the synaptoplasm (free fraction) and the second bound to the synaptosomal membranes. During the early steps of consolidation the first pool is activated, as the membrane associated transcription factor fraction increases and concomitantly the free fraction decreases. These results suggest that the activation of synaptic NF-kappa B and its translocation to membranes are part of the consolidation of long-term memory in mice.

Tooth discolouration and internal bleaching after the use of triple antibiotic paste.

AIM: To assess the discolouration of teeth with closed and open apices after placement of triple antibiotic paste (TAP, ciprofloxacin, metronidazole and minocycline) in the pulp chamber and whether discolouration could be reversed by internal bleaching procedures. METHODOLOGY: Twenty extracted human mandibular premolars were divided into 2 groups (n = 10): teeth with closed apices (CA) and teeth with open apices (OA). After conventional access, the TAP was sealed in the pulp chamber for 3 weeks. The paste was removed by a rinse with sodium hypochlorite (NaOCl) and a mixture of sodium perborate and distilled water was sealed in the pulp chamber for 1, 2 and 3 weeks. The shade was measured by a spectrophotometer at six time periods: baseline (T0), after 3 weeks of placement of TAP (T1), after removal of TAP with a NaOCl rinse (T2) and after 1 (T3), 2 (T4) and 3 (T5) weeks of internal bleaching with sodium perborate paste. Data were collected based on the CIELAB-CIE1976 (L*a*b*) system and analysed using t-tests and anova. RESULTS: A significant decrease in the mean values of L* (lightness) was observed after treatment with TAP (T1, P < 0.05). Considerable increases in these values after bleaching with sodium perborate (T3 < T4 < T5) were found in both groups. The only significant difference in the intergroup analysis was between T1 and T2, in which ΔE values in the OA group were higher (P = 0.04). CONCLUSIONS: TAP discoloured the tooth structure, but discolouration could be reversed with sodium perborate paste. In general, teeth with closed and open apices had the same rates of discolouration and bleaching.

Fusarium keratitis in Brazil: genotyping, in vitro susceptibilities, and clinical outcomes.

BACKGROUND: The purpose of this paper is to describe clinical characteristics and determine correlations between clinical outcomes and antifungal susceptibility among molecularly characterized ocular Fusarium isolates in Brazil. METHODS: Forty-one Fusarium isolates obtained from 41 eyes of 41 patients were retrieved from the ophthalmic microbiology laboratory at São Paulo Federal University and grown in pure culture. These isolates were genotyped and antifungal susceptibilities determined for each isolate using a broth microdilution method. The corresponding medical records were reviewed to determine clinical outcomes. RESULTS: The 41 isolates were genotypically classified as Fusarium solani species complex (36 isolates, 88%), Fusarium oxysporum species complex (two isolates, 5%), Fusarium dimerum species complex (one isolate, 2%) and two isolates that did not group into any of the species complexes. Final best corrected visual acuity varied from 20/20 to light perception and was on average 20/800 (logarithm of the minimum angle of resolution (LogMAR) 1.6). A history of trauma was the most common risk factor, being present in 21 patients (51%). Therapeutic penetrating keratoplasty was necessary in 22 patients (54%). Amphotericin B had the lowest minimum inhibitory concentration for 90% of isolates (MIC90) value (2 µg/mL) and voriconazole had the highest (16 µg/mL). There was an association between a higher natamycin MIC and need for therapeutic penetrating keratoplasty (Mann-Whitney test, P < 0.005). CONCLUSION: Trauma was the main risk factor, and therapeutic penetrating keratoplasty was necessary in 54% of patients. Amphotericin B had the lowest MIC90 (2 µg/mL) of the three antifungal agents tested. There was an association between higher natamycin MIC levels and corneal perforation, emphasizing the need for antifungal susceptibility testing and tailoring of antifungal strategies.

[Hirschsprung's disease and medullary carcinoma of the thyroids: two diseases in a monogenetic disorder]. / La enfermedad de Hirschsprung y el carcinoma medular de tiroides: dos enfermedades en una alteración monogénica.

INTRODUCTION: The most common gene involved in Hirschsprung's disease (HD) is protooncogene RET. More than 100 mutations of this gene have been described associated with HD. The mutations that change a cysteine with another aminoacid (mainly in exons 10 and 11) give a risk of familial medullary thyroid carcinoma (FTMC) and MEN 2A. These mutations are found in 5% of patients with HD and have an autosomal dominant inheritance. The FTMC is aggressive and the prophylactic thyroidectomy is the best treatment. We present our results in screening for RET protooncogene mutations associated with TMC in patients with HD. PATIENTS AND METHODS: We have treated 40 patients with HD in the last 15 years. We have classified the patients into two groups: A) high risk of RET protooncogene mutation associated with FTMC (family history of HD, long-segment and/or associated syndromes) and B) low risk (rectosigmoid involvement). We have identified the exons 7, 8, 9, 10, 11, 13, 14 and 15 of the RET protooncogene in 12 of 15 children from group A and 6 from 25 from group B. RESULTS: We have found the p.Cys620Ser mutation (exon 10) in a girl from group A (long-segment). In the family study, we have found the same mutation in her mother, her oncle and her cousin. CONCLUSION: The comprehensive management of children with HD requires screening for RET protooncogene mutations associated with FTMC. In the first-degree relatives of children with a mutation risk, screening is required.

Clonal monosomy of chromosome 21 in a case of myelodysplastic syndrome.

This study reports on a cytogenetic finding in a bone marrow examination of a 47-year-old male patient treated in the Hematology and Blood Transfusion Service of the Hospital de Base in São José do Rio Preto, São Paulo State, Brazil. The only alteration found at diagnosis of myelodysplastic syndrome (MDS) subtype refractory anemia with excess blasts (RAEB-2) was clonal monosomy of chromosome 21. The patient evolved to acute myeloid leukemia type M2 and died nine months after diagnosis. Clonal monosomy of chromosome 21, as the only cytogenetic abnormality in MDS, has only been reported three times previously. This uncommon cytogenetic abnormality in MDS has been associated with a poor clinical course, although more data will be needed to determine if this prognosis is invariable.

Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer.

Prostate cancer (PCa) is the second leading cause of cancer-associated death in men. Once a tumor is established it may attain further characteristics via mutations or hypoxia, which stimulate new blood vessels. Angiogenesis is a hallmark in the pathogenesis of cancer and inflammatory diseases that may predispose to cancer. Heme oxygenase-1 (HO-1) counteracts oxidative and inflammatory damage and was previously reported to play a key role in prostate carcinogenesis. To gain insight into the anti-tumoral properties of HO-1, we investigated its capability to modulate PCa associated-angiogenesis. In the present study, we identified in PC3 cells a set of inflammatory and pro-angiogenic genes down-regulated in response to HO-1 overexpression, in particular VEGFA, VEGFC, HIF1α and α5ß1 integrin. Our results indicated that HO-1 counteracts oxidative imbalance reducing ROS levels. An in vivo angiogenic assay showed that intradermal inoculation of PC3 cells stable transfected with HO-1 (PC3HO-1) generated tumours less vascularised than controls, with decreased microvessel density and reduced CD34 and MMP9 positive staining. Interestingly, longer term grown PC3HO-1 xenografts displayed reduced neovascularization with the subsequent down-regulation of VEGFR2 expression. Additionally, HO-1 repressed nuclear factor κB (NF-κB)-mediated transcription from an NF-κB responsive luciferase reporter construct, which strongly suggests that HO-1 may regulate angiogenesis through this pathway. Taken together, these data supports a key role of HO-1 as a modulator of the angiogenic switch in prostate carcinogenesis ascertaining it as a logical target for intervention therapy.

Revealing hidden Einstein-Podolsky-Rosen nonlocality.

Steering is a form of quantum nonlocality that is intimately related to the famous Einstein-Podolsky-Rosen (EPR) paradox that ignited the ongoing discussion of quantum correlations. Within the hierarchy of nonlocal correlations appearing in nature, EPR steering occupies an intermediate position between Bell nonlocality and entanglement. In continuous variable systems, EPR steering correlations have been observed by violation of Reid's EPR inequality, which is based on inferred variances of complementary observables. Here we propose and experimentally test a new criterion based on entropy functions, and show that it is more powerful than the variance inequality for identifying EPR steering. Using the entropic criterion our experimental results show EPR steering, while the variance criterion does not. Our results open up the possibility of observing this type of nonlocality in a wider variety of quantum states.

Molecular detection of Hepatozoon spp. in Brazilian and exotic wild carnivores.

Hepatozoon spp. are apicomplexan parasites that infect a wide variety of animals. The infection occurs through the ingestion of a hematophagous arthropod definitive host. Herein, we assessed the presence of Hepatozoon spp. in 165 captive wild felids and 100 captive wild canids using molecular techniques. We found that 6 felids (4 little spotted cats, 1 jaguarondi, and 1 puma) and 5 canids (2 bush dogs, 1 fox, 1 crab-eating fox, and 1 maned wolf) were positive for Hepatozoon spp. Hepatozoon spp. may be a potential pathogen and an opportunistic parasite in immunocompromised animals or if occurring in concomitant infections. Because most Brazilian wild felids and canids are endangered, knowing whether Hepatozoon infection represents a threat for these animals is crucial.

Quantum entanglement beyond Gaussian criteria.

Most of the attention given to continuous variable systems for quantum information processing has traditionally been focused on Gaussian states. However, non-Gaussianity is an essential requirement for universal quantum computation and entanglement distillation, and can improve the efficiency of other quantum information tasks. Here we report the experimental observation of genuine non-Gaussian entanglement using spatially entangled photon pairs. The quantum correlations are invisible to all second-order tests, which identify only Gaussian entanglement, and are revealed only under application of a higher-order entanglement criterion. Thus, the photons exhibit a variety of entanglement that cannot be reproduced by Gaussian states.

Entropic entanglement criteria for continuous variables.

We derive several entanglement criteria for bipartite continuous variable quantum systems based on the Shannon entropy. These criteria are more sensitive than those involving only second-order moments, and are equivalent to well-known variance product tests in the case of Gaussian states. Furthermore, they involve only a pair of quadrature measurements, and will thus prove extremely useful in the experimental identification of entanglement.

[Uveitis masquerade syndrome as a presenting form of diffuse retinoblastoma]. / Síndrome Mascarada por retinoblastoma difuso.

CLINIC REPORT: A 3-year-old boy presented with an intermediate uveitis. Complete ophthalmic exam, ocular ultrasonography, magnetic resonance imaging and computerized tomography of the orbit were inconclusive. Determination of the aqueous humor/serum rate of Lactate dehydrogenase (LDH) was the key for the diagnosis of a diffuse retinoblastoma. DISCUSSION: A masquerade syndrome is the initial presentation in 1-3% of retinoblastomas. Aqueous humor punction is contraindicated in patients with retinoblastoma but it might be the only way to achieve a correct diagnosis in these difficult and very unusual cases: enzymatic assays such as LDH offer a good sensitivity and specificity for the diagnosis of these patients.

Observation of a nonlocal optical vortex.

We report the observation of an optical vortex in the correlations of photons produced from spontaneous parametric down-conversion. The singularity appears in a nonlocal coordinate plane consisting of 1 degree of freedom of each photon.