Targeting of 3D oral cancer spheroids by αVß6 integrin using near-infrared peptide-conjugated IRDye 680.

BACKGROUND: In the treatment of oral cavity cancer, margin status is one of the most critical prognostic factors. Positive margins are associated with higher local recurrence and lower survival rates. Therefore, the universal goal of oral surgical oncology is to achieve microscopically clear margins. Near-infrared fluorescence guided surgery (FGS) could improve surgical resection using fluorescent probes. αVß6 integrin has shown great potential for cancer targeting due to its overexpression in oral cancers. Red fluorescent contrast agent IRDye 680 coupled with anti-αVß6 peptide (IRDye-A20) represents an asset to improve FGS of oral cancer. This study investigates the potential of IRDye-A20 as a selective imaging agent in 3D three-dimensional tongue cancer cells. METHODS: αVß6 integrin expression was evaluated by RT-qPCR and Western Blotting in 2D HSC-3 human tongue cancer cells and MRC-5 human fibroblasts. Targeting ability of IRDye-A20 was studied in both cell lines by flow cytometry technique. 3D tumor spheroid models, homotypic (HSC-3) and stroma-enriched heterotypic (HSC-3/MRC-5) spheroids were produced by liquid overlay procedure and further characterized using (immuno)histological and fluorescence-based techniques. IRDye-A20 selectivity was evaluated in each type of spheroids and each cell population. RESULTS: αVß6 integrin was overexpressed in 2D HSC-3 cancer cells but not in MRC-5 fibroblasts and consistently, only HSC-3 were labelled with IRDye-A20. Round shaped spheroids with an average diameter of 400 µm were produced with a final ratio of 55%/45% between HSC-3 and MRC-5 cells, respectively. Immunofluorescence experiments demonstrated an uniform expression of αVß6 integrin in homotypic spheroid, while its expression was restricted to cancer cells only in heterotypic spheroid. In stroma-enriched 3D model, Cytokeratin 19 and E-cadherin were expressed only by cancer cells while vimentin and fibronectin were expressed by fibroblasts. Using flow cytometry, we demonstrated that IRDye-A20 labeled the whole homotypic spheroid, while in the heterotypic model all cancer cells were highly fluorescent, with a negligible fluorescence in fibroblasts. CONCLUSIONS: The present study demonstrated an efficient selective targeting of A20FMDV2-conjugated IRDye 680 in 3D tongue cancer cells stroma-enriched spheroids. Thus, IRDye-A20 could be a promising candidate for the future development of the fluorescence-guided surgery of oral cancers.

Auroral emissions from Uranus and Neptune.

Uranus and Neptune possess highly tilted/offset magnetic fields whose interaction with the solar wind shapes unique twin asymmetric, highly dynamical, magnetospheres. These radiate complex auroral emissions, both reminiscent of those observed at the other planets and unique to the ice giants, which have been detected at radio and ultraviolet (UV) wavelengths to date. Our current knowledge of these radiations, which probe fundamental planetary properties (magnetic field, rotation period, magnetospheric processes, etc.), still mostly relies on Voyager 2 radio, UV and in situ measurements, when the spacecraft flew by each planet in the 1980s. These pioneering observations were, however, limited in time and sampled specific solar wind/magnetosphere configurations, which significantly vary at various timescales down to a fraction of a planetary rotation. Since then, despite repeated Earth-based observations at similar and other wavelengths, only the Uranian UV aurorae have been re-observed at scarce occasions by the Hubble Space Telescope. These observations revealed auroral features radically different from those seen by Voyager 2, diagnosing yet another solar wind/magnetosphere configuration. Perspectives for the in-depth study of the Uranian and Neptunian auroral processes, with implications for exoplanets, include follow-up remote Earth-based observations and future orbital exploration of one or both ice giant planetary systems. This article is part of a discussion meeting issue 'Future exploration of ice giant systems'.

The H3+ ionosphere of Uranus: decades-long cooling and local-time morphology.

The upper atmosphere of Uranus has been observed to be slowly cooling between 1993 and 2011. New analysis of near-infrared observations of emission from H3+ obtained between 2012 and 2018 reveals that this cooling trend has continued, showing that the upper atmosphere has cooled for 27 years, longer than the length of a nominal season of 21 years. The new observations have offered greater spatial resolution and higher sensitivity than previous ones, enabling the characterization of the H3+ intensity as a function of local time. These profiles peak between 13 and 15 h local time, later than models suggest. The NASA Infrared Telescope Facility iSHELL instrument also provides the detection of a bright H3+ signal on 16 October 2016, rotating into view from the dawn sector. This feature is consistent with an auroral signal, but is the only of its kind present in this comprehensive dataset. This article is part of a discussion meeting issue 'Advances in hydrogen molecular ions: H3+, H5+ and beyond'.

Cusp observation at Saturn's high-latitude magnetosphere by the Cassini spacecraft.

We report on the first analysis of magnetospheric cusp observations at Saturn by multiple in situ instruments onboard the Cassini spacecraft. Using this we infer the process of reconnection was occurring at Saturn's magnetopause. This agrees with remote observations that showed the associated auroral signatures of reconnection. Cassini crossed the northern cusp around noon local time along a poleward trajectory. The spacecraft observed ion energy-latitude dispersions-a characteristic signature of the terrestrial cusp. This ion dispersion is "stepped," which shows that the reconnection is pulsed. The ion energy-pitch angle dispersions suggest that the field-aligned distance from the cusp to the reconnection site varies between ∼27 and 51 RS . An intensification of lower frequencies of the Saturn kilometric radiation emissions suggests the prior arrival of a solar wind shock front, compressing the magnetosphere and providing more favorable conditions for magnetopause reconnection. KEY POINTS: We observe evidence for reconnection in the cusp plasma at SaturnWe present evidence that the reconnection process can be pulsed at SaturnSaturn's cusp shows similar characteristics to the terrestrial cusp.

A Perspective on Substorm Dynamics Using 10 Years of Auroral Kilometric Radiation Observations From Wind.

We study 10 years (1995-2004 inclusive) of auroral kilometric radiation (AKR) radio emission data from the Wind spacecraft to examine the link between AKR and terrestrial substorms. We use substorm lists based on parameters including ground magnetometer signatures and geosynchronous particle injections as a basis for superposed epoch analyses of the AKR data. The results for each list show a similar, clear response of the AKR power around substorm onset. For nearly all event lists, the average response shows that the AKR power begins to increase around 20 min prior to expansion phase onset, as defined by the respective lists. The analysis of the spectral parameters of AKR bursts show that this increase in power is due to an extension of the source region to higher altitudes, which also precedes expansion phase onset by 20 min. Our observations show that the minimum frequency channel that observes AKR at this time, on average, is 60 kHz. AKR visibility is highly sensitive to observing spacecraft location, and the biggest radio response to substorm onset is seen in the 21:00-03:00 hr local time sector.

Magnetosphere-Ionosphere-Thermosphere Coupling Study at Jupiter Based on Juno's First 30 Orbits and Modeling Tools.

The dynamics of the Jovian magnetosphere is controlled by the interplay of the planet's fast rotation, its solar-wind interaction and its main plasma source at the Io torus, mediated by coupling processes involving its magnetosphere, ionosphere, and thermosphere. At the ionospheric level, these processes can be characterized by a set of parameters including conductances, field-aligned currents, horizontal currents, electric fields, transport of charged particles along field lines including the fluxes of electrons precipitating into the upper atmosphere which trigger auroral emissions, and the particle and Joule heating power dissipation rates into the upper atmosphere. Determination of these key parameters makes it possible to estimate the net transfer of momentum and energy between Jovian upper atmosphere and equatorial magnetosphere. A method based on a combined use of Juno multi-instrument data and three modeling tools was developed by Wang et al. (2021, https://doi.org/10.1029/2021ja029469) and applied to an analysis of the first nine orbits to retrieve these parameters along Juno's magnetic footprint. We extend this method to the first 30 Juno science orbits and to both hemispheres. Our results reveal a large variability of these parameters from orbit to orbit and between the two hemispheres. They also show dominant trends. Southern current systems are consistent with the generation of a region of sub-corotating ionospheric plasma flows, while both super-corotating and sub-corotating plasma flows are found in the north. These results are discussed in light of the previous space and ground-based observations and currently available models of plasma convection and current systems, and their implications are assessed.

The low-frequency source of Saturn's kilometric radiation.

Understanding how auroral radio emissions are produced by magnetized bodies requires in situ measurements within their source region. Saturn's kilometric radiation (SKR) has been widely used as a remote proxy of Saturn's magnetosphere. We present wave and plasma measurements from the Cassini spacecraft during its ring-grazing high-inclination orbits, which passed three times through the high-altitude SKR emission region. Northern dawn-side, narrow-banded radio sources were encountered at frequencies of 10 to 20 kilohertz, within regions of upward currents mapping to the ultraviolet auroral oval. The kilometric waves were produced on the extraordinary mode by the cyclotron maser instability from 6- to 12-kilo-electron volt electron beams and radiated quasi-perpendicularly to the auroral magnetic field lines. The SKR low-frequency sources appear to be strongly controlled by time-variable magnetospheric electron densities.

Modulation of egg-white lysozyme activity by viscosity intensifier additives.

The activity of egg-white lysozyme was measured in the presence of carbohydrate additives in the reaction medium. These additives show a significant affinity for water. They depress water activity and increase the viscosity of the medium. Solute-solvent interactions in aqueous solutions of the additives are characterized by properties such as the intrinsic viscosity, Huggins constant apparent molar volume and hydration number. It was found that, despite the lowering of enzyme activity when the concentration of additive is increased, the behavior remains Michaelian and neither modification of Km nor inhibition by excess substrate is observed. On the other hand, the effect of the viscosity of the medium on enzyme activity was determined. This effect is independent of the nature of the additive at high viscosities (greater than 4 mPa s-1) for which enzyme activity is very low and appears to vary according to the kind of additive in dilute solution at low viscosities (less than 2 mPa s-1).

[Isolated vasculitis of the central nervous system and involvement of the 8th cranial nerve: rare manifestations of acquired immunodeficiency syndrome]. / Vasculite isolada do sistema nervoso central e acometimento do VIII nervo craniano. Manifestações raras da síndrome de imunodeficiência adquirida.

The authors report the case of an AIDS patient with rare neurologic manifestations: primary vasculitis of the central nervous system and VIII cranial nerve dysfunction. The authors make a review on the subject, and call special attention for the differential diagnosis. In fact, the patient, a 36 year old woman, with promiscuous life, presented with dizziness, gait ataxia, nausea, headache and hypoacusia. Seven days after the admission, she noted blurred vision in both eyes and soon she became blind. The physical examination showed bilateral optic neuritis and vestibulocochlear dysfunction, stiff neck and fever. No abnormalities were detected on CT scan. CSF showed 40 mononuclear cells/mm3, 79 mg/dl of proteins and normal glucose content. Microbiological research was negative. Serum anti-HIV test was positive. The hypothesis of primary CNS vasculitis was made, and pulse methylprednisolone therapy was introduced with good recovery of neurological syndrome except for persistent amaurosis.

Propylthiouracil and peripheral neuropathy.

Peripheral neuropathy is a rare manifestation in hyperthyroidism. We describe the neurological manifestations of a 38 year old female with Graves' disease who developed peripheral neuropathy in the course of her treatment with propylthiouracil. After the drug was tapered off, the neurological signs disappeared. Therefore, we call attention for a possible toxic effect on peripheral nervous system caused by this drug.

Priorities in adolescent health care: the teenager's viewpoint.

The purpose of this study was to determine what issues teenagers want discussed or covered when they visit primary care physicians and to assess to what extent such discussion takes place. A questionnaire was administered to 1,564 students aged between 13 and 18 years in six high schools. Mean participant age was 15.3 years; 801 were male and 763 were female. Questions were drawn from both physical and psychosocial aspects of teenage life. The teenagers answered as to whether they would like to discuss the suggested topics on visits to physicians, and whether in fact such a discussion had taken place. The three topics of most interest to teenagers were physical fitness, nutrition, and growth. Teenagers wanted to discuss these topics in over 80 percent of the visits, and they indicated that actual discussion took place in just under 50 percent of the visits. Discussion of sexually transmitted disease was desired by teenagers 70 percent of the time, with a discussion rate of only 18 percent; contraception at 66 percent with a physician discussion rate of only 22 percent. If physicians discuss exercise, nutrition, and growth with teenage patients, in over 80 percent of cases they will be providing the patient with valued information. This initial dialogue will establish a base of communication that may allow for the discussion of issues teenagers often find more difficult (such as contraception, sexually transmitted disease, depression, drugs, and drinking).

Inhibition of respiration and of respiratory development by different doses of chloramphenicol in frog embryos (Rana pipiens).

High doses of chloramphenicol (4.5 and 9 mM) directly inhibited respiration in conjunction with an unusual cleavage anomaly (blastomere refusion) in embryos of the frog, Rana pipiens. Lower doses (2.1-3 mM) did not affect respiration or cleavage and, when added later, did not directly affect respiration or development at any tested stage. Continuous incubation in the latter doses, however, did eventually, by day 6 or 7, produce a parallel retardation of embryonic development and of respiratory development relative to controls, suggestive of impaired mitochondrial biogenesis. A lower continuous dose (0.9 mM) affected neither respiration nor development at any stage.

[Resection-suture of the posterior urethra for post-traumatic stenosis. Study of 29 patients operated upon between 1964 and 1976]. / Résection-suture de l'urètre postérieur pour sténose post-traumatique. Etude de 29 malades opérés de 1964 à 1976.

The authors report their experience of resection-suture of post-traumatic stenoses of the posterior urethra. Their series includes 27 patients suffering pelvic or perineal trauma (26 fractures, including 12 severe with crushing of the pelvis or symphisieal dysjunction). In 9 cases there had been an attempt at emergency repair of the urethral rupture via a perineal approach and in 5 a secondary local repair (4 urethral resection-sutures and 1 insertion of an arterial graft). Twelve patients in this series had additional lesions : 5 false channels, 3 urethroperineal fistulae, 3 urethrorectal fistulae and one periprostatic leak. The authors emphasise the principles which guided their technique : total excision of fibrous callus, excision of the entire length of pathological urethra including the membranous urethra and the prostatic apex if necessary, sufficient mobilisation of healthy zones to permit urethral suture without traction (dissection of the lower end of the prostatic urethra separated from the pubis and rectum, extensive dissection of the spongious urethra, separation of the corpora cavernosa.) Suture using non-absorbable material. Drainage of urine via an indwelling urethral catheter for 12 to 20 days. The postoperative period of follow up is longer than 1 year in 22 patients, more than 2 years in 20 and 4 years in 19. In the latter 19, results were perfect for 16 (87%) and fairly good in two. No late failures! Four of the patients had to undergo a number of secondary urethral dilatations but these dilatations could be completely stopped in three of them without any subsequent worsening. No case of persistent sexual impotence imputable to urethral resection-suture, since problems of virility recovered in periods of 4 to 18 months.

Microsurgery for haemodialysis distal arteriovenous fistulae in children weighing less than 10kg.

Between 1977 and 1981, 30 distal arteriovenous fistulae have been created in 22 children weighing less than 10kg. With microsurgical techniques the rate of immediate patency was 90%. Fifteen fistulae had a maturation sufficient for haemodialysis, sometimes after secondary superficialisation of the vein. The evolution of six fistulae could not be evaluated either because of the death of the child shortly after operation or because the anastomosis was too recent. Nine fistulae failed because of immediate or secondary thrombosis and lack of maturation.

[Spiramycin]. / La spiramycine.

Chemotherapeutic agents appear to offer a great potential in the treatment of periodontal disease in conjunction with root planning and/or surgical approach. One of these chemotherapeutic agents is spiramycin. The aim of this paper is to review some data about the spiramycin in vitro, in vivo, the effects of spiramycin on plaque control and some interesting hypothesis on action of spiramycin.

The hemagglutinating adhesin HA-Ag2 of Bacteroides gingivalis is distinct from fimbrilin.

We carried out a series of immunoblots with antigenic preparations from the periodontal pathogen Bacteroides gingivalis using antisera of restricted specificity for the hemagglutinating adhesin HA-Ag2, and for the major structural subunit of the fimbriae (fimbrilin). We have been able to show that these 2 antigens are distinct. The fimbrilin subunit had an apparent molecular weight of 42 kDa in all of the bacterial preparations tested. HA-Ag2 occurred as a pair of bands at 43 and 49 kDa in outer membranes prepared as extracellular vesicles, and at 33 and 38 kDa in glass-bead-EDTA extracted antigens and in sheared-cell outer membranes prepared in the presence of EDTA. No HA-Ag2 was found in an enriched fimbrial preparation. The 2 antigens could thus be distinguished on the basis of their behaviour when subjected to different extraction techniques. The lower apparent molecular weight of HA-Ag2 (a pair of bands at 33 and 38 kDa) was invariably associated with the presence of EDTA in the buffers used to prepare the extracts, and the effect could be partially prevented by adding MgCl2 to the extraction buffer. The difference in apparent molecular weight of HA-Ag2 in the different extracts can thus be attributed either to an EDTA-sensitive tertiary conformation of its component polypeptides, or to an EDTA-sensitive linkage of each of these polypeptides to an unknown component of approximately 10 kDa.

Lysozyme kinetics in low water activity media. A possible hydration memory.

The influence of water activity on initial lysozyme kinetics is studied. Enzyme catalytic capacity exponentially increases with thermodynamical water activity of the reactant medium; this relation seems independent of the chemical structure of the water activity depressors but dependent on the structuration of water molecules they induce. This influence of water organization on initial enzyme activity is immediate and may be preserved even after a large dilution, thus lysozyme presents a "hydration memory" phenomenon. This effect is in accordance with sorption/desorption isotherms, an hysteresis loop being observed.

[Ectopic ureter ending in the seminal vesicle in adults. Apropos of a case and review of the literature]. / Abouchement ectopique de l'uretère dans la vésicule seminale chez l'adulte. A propos d'un cas et revue de la littérature.

The authors report a 38 years old patient in whom an intravenous pyelogram was performed for moderate arterial hypertension. This showed a large filling defect in the right lower part of the bladder without renal function on that side. Endoscopic separation of the jet coming from the right half of the trigone showed a liquid containing numerous spermatozoa. A cystogram opacified by reflux a cavity in the genital system via this, the right ureter. With the diagnosis of ectopic ureter ending in the genital system, a nephro-ureterectomy demonstrated the attachment of the ureter into a pouch which communicated with the bladder and the seminal vesicle. A view of the normal embryology insists on the fact that contrary to the classic view, the pronephros disappears entirely and that the metanephros is at the origin of the Woffian canal which opens on the posterior wall of the urogenital sinus at the 28th day when the ureter springs from a ureteral bud. Since 1960 this would be the 34th case in the literature, seminal ectopia (24%) coming after ectopia in the prostatic urethra (54%). Epididymitis is a frequent presenting symptom (44%). The workup shows: absence of renal function (100%), raising of the ipsilateral trigone by a cystic swelling (76%), absence of the meatus on that side on endoscopy, presence of an ipsilateral mass above the prostate on rectal examination (30%). The diagnosis is confirmed by vasography where the ureter is opacified by the seminal vesicle or by systography after endoscopic incision of the mass. Excision of the seminal vesicle was done in conjunction with total nephroureterectomy in 17% of cases.