A dense ring of the trans-Neptunian object Quaoar outside its Roche limit.

Planetary rings are observed not only around giant planets1, but also around small bodies such as the Centaur Chariklo2 and the dwarf planet Haumea3. Up to now, all known dense rings were located close enough to their parent bodies, being inside the Roche limit, where tidal forces prevent material with reasonable densities from aggregating into a satellite. Here we report observations of an inhomogeneous ring around the trans-Neptunian body (50000) Quaoar. This trans-Neptunian object has an estimated radius4 of 555 km and possesses a roughly 80-km satellite5 (Weywot) that orbits at 24 Quaoar radii6,7. The detected ring orbits at 7.4 radii from the central body, which is well outside Quaoar's classical Roche limit, thus indicating that this limit does not always determine where ring material can survive. Our local collisional simulations show that elastic collisions, based on laboratory experiments8, can maintain a ring far away from the body. Moreover, Quaoar's ring orbits close to the 1/3 spin-orbit resonance9 with Quaoar, a property shared by Chariklo's2,10,11 and Haumea's3 rings, suggesting that this resonance plays a key role in ring confinement for small bodies.

P-Rex1 is a novel substrate of the E3 ubiquitin ligase Malin associated with Lafora disease.

Laforin and Malin are two proteins that are encoded by the genes EPM2A and EPM2B, respectively. Laforin is a glucan phosphatase and Malin is an E3-ubiquitin ligase, and these two proteins function as a complex. Mutations occurring at the level of one of the two genes lead to the accumulation of an aberrant form of glycogen meant to cluster in polyglucosans that go under the name of Lafora bodies. Individuals affected by the appearance of these polyglucosans, especially at the cerebral level, experience progressive neurodegeneration and several episodes of epilepsy leading to the manifestation of a fatal form of a rare disease called Lafora disease (LD), for which, to date, no treatment is available. Despite the different dysfunctions described for this disease, many molecular aspects still demand elucidation. An effective way to unknot some of the nodes that prevent the achievement of better knowledge of LD is to focus on the substrates that are ubiquitinated by the E3-ubiquitin ligase Malin. Some substrates have already been provided by previous studies based on protein-protein interaction techniques and have been associated with some alterations that mark the disease. In this work, we have used an unbiased alternative approach based on the activity of Malin as an E3-ubiquitin ligase. We report the discovery of novel bonafide substrates of Malin and have characterized one of them more deeply, namely PIP3-dependent Rac exchanger 1 (P-Rex1). The analysis conducted upon this substrate sets the genesis of the delineation of a molecular pathway that leads to altered glucose uptake, which could be one of the origin of the accumulation of the polyglucosans present in the disease.

The size, shape, density and ring of the dwarf planet Haumea from a stellar occultation.

Haumea-one of the four known trans-Neptunian dwarf planets-is a very elongated and rapidly rotating body. In contrast to other dwarf planets, its size, shape, albedo and density are not well constrained. The Centaur Chariklo was the first body other than a giant planet known to have a ring system, and the Centaur Chiron was later found to possess something similar to Chariklo's rings. Here we report observations from multiple Earth-based observatories of Haumea passing in front of a distant star (a multi-chord stellar occultation). Secondary events observed around the main body of Haumea are consistent with the presence of a ring with an opacity of 0.5, width of 70 kilometres and radius of about 2,287 kilometres. The ring is coplanar with both Haumea's equator and the orbit of its satellite Hi'iaka. The radius of the ring places it close to the 3:1 mean-motion resonance with Haumea's spin period-that is, Haumea rotates three times on its axis in the time that a ring particle completes one revolution. The occultation by the main body provides an instantaneous elliptical projected shape with axes of about 1,704 kilometres and 1,138 kilometres. Combined with rotational light curves, the occultation constrains the three-dimensional orientation of Haumea and its triaxial shape, which is inconsistent with a homogeneous body in hydrostatic equilibrium. Haumea's largest axis is at least 2,322 kilometres, larger than previously thought, implying an upper limit for its density of 1,885 kilograms per cubic metre and a geometric albedo of 0.51, both smaller than previous estimates. In addition, this estimate of the density of Haumea is closer to that of Pluto than are previous estimates, in line with expectations. No global nitrogen- or methane-dominated atmosphere was detected.

Craniofacial morphology/phenotypes influence on mandibular range of movement in the design of a mandibular advancement device.

BACKGROUND: The mandibular opening path movements have different directions according to the craniofacial morphology of the patient but always downward and backward, therefore increasing the collapse of the upper airway. The aim of this work is to determine if there is a relationship between the craniofacial morphology and the mandibular movement to help understand the impact on the mandibular position. METHODS: 52 students with full permanent dentition aged 19 to 23 years (mean 21.3 SD 1.7; 29 females and 23 males), participated in the study. Each subject had a lateral cephalometric radiograph taken. The opening angle was determined for two levels of vertical openings at 5 and 10 mm. RESULTS: The opening angle showed a greater variability between subjects ranging from 63.15 to 77.08 for 5 mm angle and from for 61.65 to 75.72 for the 10 mm angle. Differences of facial phenotypes was evident when comparing the individual dissoccluding angle of the low angle horizontal pattern and high angle vertical pattern. CONCLUSIONS: The opening angle is related to craniofacial morphology with higher vertical anterior and shorter anteroposterior faces having a more horizontal path of mandibular movement than shorter vertical anterior and longer anteroposterior subjects who have a more vertical path.

Synergistic activation of AMPK prevents from polyglutamine-induced toxicity in Caenorhabditis elegans.

Expression of abnormally long polyglutamine (polyQ) tracks is the source of a range of dominant neurodegenerative diseases, such as Huntington disease. Currently, there is no treatment for this devastating disease, although some chemicals, e.g., metformin, have been proposed as therapeutic solutions. In this work, we show that metformin, together with salicylate, can synergistically reduce the number of aggregates produced after polyQ expression in Caenorhabditis elegans. Moreover, we demonstrate that incubation polyQ-stressed worms with low doses of both chemicals restores neuronal functionality. Both substances are pleitotropic and may activate a range of different targets. However, we demonstrate in this report that the beneficial effect induced by the combination of these drugs depends entirely on the catalytic action of AMPK, since loss of function mutants of aak-2/AMPKα2 do not respond to the treatment. To further investigate the mechanism of the synergetic activity of metformin/salicylate, we used CRISPR to generate mutant alleles of the scaffolding subunit of AMPK, aakb-1/AMPKß1. In addition, we used an RNAi strategy to silence the expression of the second AMPKß subunit in worms, namely aakb-2/AMPKß2. In this work, we demonstrated that both regulatory subunits of AMPK are modulators of protein homeostasis. Interestingly, only aakb-2/AMPKß2 is required for the synergistic action of metformin/salicylate to reduce polyQ aggregation. Finally, we showed that autophagy acts downstream of metformin/salicylate-related AMPK activation to promote healthy protein homeostasis in worms.

PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p.

MicroRNAs (miRNAs), small noncoding RNAs modulating messenger RNA (mRNA) and protein expression, have emerged as key regulatory molecules in chronic liver diseases, whose end stage is hepatic fibrosis, a major global health burden. Pharmacological strategies for prevention or treatment of hepatic fibrosis are still limited, what makes it necessary to establish a better understanding of the molecular mechanisms underlying its pathogenesis. In this context, we have recently shown that cyclooxygenase-2 (COX-2) expression in hepatocytes restricts activation of hepatic stellate cells (HSCs), a pivotal event in the initiation and progression of hepatic fibrosis. Here, we evaluated the role of COX-2 in the regulation of a specific set of miRNAs on a mouse model of CCl4 and bile duct ligation (BDL)-induced liver fibrosis. Our results provide evidence that COX-2 represses miR-23a-5p and miR-28-5p expression in HSC. The decrease of miR-23a-5p and miR-28-5p expression promotes protection against fibrosis by decreasing the levels of pro-fibrogenic markers α-SMA and COL1A1 and increasing apoptosis of HSC. Moreover, we demonstrate that serum levels of miR-28-5p are decreased in patients with chronic liver disease. These results suggest a protective effect exerted by COX-2-derived prostanoids in the process of hepatofibrogenesis.

Albedo and atmospheric constraints of dwarf planet Makemake from a stellar occultation.

Pluto and Eris are icy dwarf planets with nearly identical sizes, comparable densities and similar surface compositions as revealed by spectroscopic studies. Pluto possesses an atmosphere whereas Eris does not; the difference probably arises from their differing distances from the Sun, and explains their different albedos. Makemake is another icy dwarf planet with a spectrum similar to Eris and Pluto, and is currently at a distance to the Sun intermediate between the two. Although Makemake's size (1,420 ± 60 km) and albedo are roughly known, there has been no constraint on its density and there were expectations that it could have a Pluto-like atmosphere. Here we report the results from a stellar occultation by Makemake on 2011 April 23. Our preferred solution that fits the occultation chords corresponds to a body with projected axes of 1,430 ± 9 km (1σ) and 1,502 ± 45 km, implying a V-band geometric albedo p(V) = 0.77 ± 0.03. This albedo is larger than that of Pluto, but smaller than that of Eris. The disappearances and reappearances of the star were abrupt, showing that Makemake has no global Pluto-like atmosphere at an upper limit of 4-12 nanobar (1σ) for the surface pressure, although a localized atmosphere is possible. A density of 1.7 ± 0.3 g cm(-3) is inferred from the data.

A Pluto-like radius and a high albedo for the dwarf planet Eris from an occultation.

The dwarf planet Eris is a trans-Neptunian object with an orbital eccentricity of 0.44, an inclination of 44 degrees and a surface composition very similar to that of Pluto. It resides at present at 95.7 astronomical units (1 AU is the Earth-Sun distance) from Earth, near its aphelion and more than three times farther than Pluto. Owing to this great distance, measuring its size or detecting a putative atmosphere is difficult. Here we report the observation of a multi-chord stellar occultation by Eris on 6 November 2010 UT. The event is consistent with a spherical shape for Eris, with radius 1,163 ± 6 kilometres, density 2.52 ± 0.05 grams per cm(3) and a high visible geometric albedo, Pv = 0.96(+0.09)(-0.04). No nitrogen, argon or methane atmospheres are detected with surface pressure larger than ∼1 nanobar, about 10,000 times more tenuous than Pluto's present atmosphere. As Pluto's radius is estimated to be between 1,150 and 1,200 kilometres, Eris appears as a Pluto twin, with a bright surface possibly caused by a collapsed atmosphere, owing to its cold environment. We anticipate that this atmosphere may periodically sublimate as Eris approaches its perihelion, at 37.8 astronomical units from the Sun.

Implementation of a hybrid healthcare model in rheumatic musculoskeletal diseases: 6-months results of the multicenter Digireuma study.

OBJECTIVES: Rheumatic and musculoskeletal diseases (RMDs) require a tailored follow-up that can be enhanced by the implementation of innovative tools. The Digireuma study aimed to test the feasibility of a hybrid follow-up utilizing an electronic patient reported outcomes (ePROs)-based monitoring strategy in patients with RMDs. METHODS: Adult patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) were recruited for a 6-month bicentric prospective follow-up consisting of face-to-face and digital assessments. Patients were asked to report disease-specific ePROs on a pre-established basis, and could also report flares, medication changes, and recent infections at any time. Four rheumatologists monitored these outcomes and contacted patients for interventions when deemed necessary. Results from face-to-face and digital assessments were described. RESULTS: Of 56 recruited patients, 47 (84%) submitted any ePROs to the digital platform. Most patients with RA were female (74%, median age of 47 years), while 48% of patients with SpA were female (median age 40.4 years). A total of 3,800 platform visits were completed, with a median of 57 and 29 visits in patients with RA and SpA, respectively. Among 52 reported alerts, 47 (90%) needed contact, of which 36 (77%) were managed remotely. Adherence rates declined throughout the study, with around half of patients dropping out during the 6 months follow-up. CONCLUSION: The implementation of a hybrid follow-up in clinical practice is feasible. Digital health solutions can provide granular knowledge of disease evolution and enable more informed clinical decision making, leading to improved patient outcomes. Further research is needed to identify target patient populations and engagement strategies.

Dechlorane-related compounds in franciscana dolphin (Pontoporia blainvillei) from southeastern and southern coast of Brazil.

Concentrations of Dechlorane (Dec) 603 (0.75 ng/g lipid weight (lw); mean) and Dec 602 (0.38 ng/g lw; mean) were quantified in more than 95% of the franciscana (Pontoporia blainvillei) dolphin samples, whereas the frequency of detection decreased to 75% for Dechlorane Plus (DP) (1.53 ng/g lw, mean). The presence of Chlordene Plus (CP) was also observed (0.13 ng/g lw, mean) in half of the samples. On the contrary, Dec 604, decachloropentacyclooctadecadiene (aCl(10)DP), and undecachloropentacyclooctadecadiene (aCl(11)DP) concentrations were below the limit of quantifications in all cases. To the best of our knowledge, this is the first article reporting the presence of Dec 603, Dec 602, and CP in mammals. For comparative purposes, levels of Mirex, polybrominated diphenyl ethers (PBDEs), and decabromodiphenylethane (DBDPE) are also reported. Considering geographic distribution evaluation together with the strong positive correlations found between DP and PBDEs (r(s) = 0.63; p < 0.01), highly anthropogenic areas were identified as potential sources of these chemicals in this dolphin species. However, local sources for Dec 602, 603, Mirex, CP, and DBDPE were not found indicating that in this case historical use and/or atmospheric transport and deposition may play an important role in their fate.

Chronic inflammatory demyelinating polyradiculoneuropathy in a patient with systemic lupus erythematosus and good outcome with rituximab treatment.

A patient with chronic inflammatory demyelinating polyradiculoneuropathy and systemic lupus erythematosus arising after rubella vaccination was initially treated with plasmapheresis, corticosteroids and intravenous immunoglobulins, with partial response. After shift to rituximab, most clinical symptoms improved markedly, emphasizing the possible role of this monoclonal antibody in conventional therapy-resistant cases.

Ewing-like sarcoma bladder primary tumour: A case report and literature review.

Bladder primitive neuroectodermal tumors are extremely rare but are most frequent in older adult. 59-year-old man that complained of hematuria for the previous 24 h, urethral syndrome, and pain in the right renal fossa over the previous two weeks. No definitive management or treatment guidelines have been established. Hematuria is the most frequent symptom. Advanced age, metastasis, and incomplete tumor resection are determinants of a poor prognosis. Ewing-like bladder primary tumor is a rare entity with a poor prognosis, hence an aggressive treatment combining surgery and chemotherapy must be considered from the beginning.

Reliability and agreement analysis among 5 subjective methods of ocular torsion measurement.

OBJECTIVE: To evaluate the reliability in the measurement of ocular torsion and the agreement of the following subjective methods: double Maddox test, synoptophore, Gracis torsionometer, Harms screen and Awaya cyclodeviation test. METHOD: Patients with vertical strabismus acquired in adulthood were recruited and ocular torsion was measured with the 5 methods described on three occasions. As a gold standard test does not exist, the one that obtained the best repeatability data was chosen as the reference test. RESULTS: 25 patients were included in the study. The repeatability of each test was studied: double Maddox test (ICC = 0.783, CV = 29.33%), synoptophore (ICC = 0.976, CV = 6.71%), Gracis torsionometer (ICC = 0.937, CV = 20.10%), Harms screen (ICC = 0.962, CV = 11.86%) and Awaya test (ICC = 0.987, CV = 52.58%). The reference test to compare the agreement was the synoptophore. Statistically significant differences were found when comparing the ocular torsion ranges between the synoptophore and the Gracis torsionometer (p = 0.008) and between the synoptophore and the Awaya test (p = 0.02). CONCLUSIONS: The double Maddox test, the synoptophore, the Gracis torsionometer, and the Harms screen are reliable methods with good reproducibility indices. Among them, the synoptophore is the most consistent method. The Awaya test did not show good reliability. The bilateral Maddox test, the Gracis torsionometer, and the Harms screen were methods with good agreement with the synoptophore, which was determined as the reference test. The Awaya test did not show good agreement with the synoptophore.

Efficacy and complications of transposition surgery in Duane esotropia syndrome. / Eficacia y complicaciones de las transposiciones musculares en el síndrome de Duane con esotropía.

OBJECTIVE: To study the long-term efficacy and the complications of several transposition techniques for the treatment of Duane syndrome. These included, full vertical rectus transposition, partial vertical rectus transposition, transposition without muscle disinsertion, and superior rectus transposition. MATERIAL AND METHODS: A retrospective study of the patients diagnosed with Duane syndrome, and who underwent any of the different transposition techniques associated or not to the medial rectus recession with a follow-up longer than 12 months. A good result was considered a final deviation≤10 prism dioptres (pd) in primary position, anomalous head posture<10°, and an improvement of the abduction without diplopia. RESULTS: Seven cases were included (6 women, 6 unilateral), and a mean age of 37.71 years. Pre-operative central gaze esotropia of 28±11.68pd decreased to 6±4.62pd at the final visit (P=.009). The anomalous head posture decreased in 6 patients, and the abduction improved one degree from -3.14 to -2.14 (mean). An induced vertical deviation≤8pd was observed in 4 cases. None experienced diplopia at the final visit. The percentage of reoperations was 71.42%. Only 28.57% had a favourable outcome with a single surgery, which increased to 71.42% with further surgeries at the final follow-up. Mean evolution time was 52±31.65 months. CONCLUSIONS: Vertical rectus transpositions in Duane syndrome with moderate or severe clinical signs have only been effective in a small percentage of the cases. Most of them required further surgeries to resolve the complications or the under-corrections.

High-flow priapism in pediatric population: Case series and review of the literature.

INTRODUCTION: Priapism is a prolonged erection that lasts longer than four hours. It is a rare pathology in the pediatric population, with an estimation of 0.3-1.5 per 100,000 children per year. The diagnostic sequence includes clinical history, physical examination and penile Doppler ultrasound (PDUS). Puncture of corpora cavernosa is not always necessary to establish the differential diagnosis between high-flow and low-flow priapism. The treatment of choice in pediatric age is not well defined. PATIENTS AND METHODS: Multicentric, retrospective and descriptive study including patients under 14 years with high-flow priapism between 2010 and 2020. RESULTS: A total of seven patients were diagnosed with high-flow priapism. None of them required puncture of the corpora cavernosa. Patients were treated with a conservative management, two patients required superselective arterial embolization due to persistent symptoms. CONCLUSIONS: High-flow priapism is a very rare entity in pediatric age; therefore, knowing the proper diagnosis and management is crucial. Currently, penile doppler ultrasound is enough for diagnosis in most cases and allows obviating the use of blood gas analysis. Children should be initially treated with a conservative management, reserving embolization for refractory cases.

High-flow Priapism in Pediatric Population: Case Series and Review of the Literature. / Priapismo de alto flujo en población pediátrica: serie de casos y revisión de la literatura.

INTRODUCTION: Priapism is a prolonged erection that lasts longer than four hours. It is a rare pathology in the pediatric population, with an estimation of 0.3-1.5 per 100,000 children per year. The diagnostic sequence includes clinical history, physical examination and penile Doppler ultrasound (PDUS). Puncture of corpora cavernosa is not always necessary to establish the differential diagnosis between high-flow and low-flow priapism. The treatment of choice in pediatric age is not well defined. PATIENTS AND METHODS: Multicentric, retrospective and descriptive study including patients under 14 years with high-flow priapism between 2010 and 2020. RESULTS: A total of seven patients were diagnosed with high-flow priapism. None of them required puncture of the corpora cavernosa. Patients were treated with a conservative management, two patients required superselective arterial embolization due to persistent symptoms. CONCLUSIONS: High-flow priapism is a very rare entity in pediatric age; therefore, knowing the proper diagnosis and management is crucial. Currently, penile doppler ultrasound is enough for diagnosis in most cases and allows obviating the use of blood gas analysis. Children should be initially treated with a conservative management, reserving embolization for refractory cases.

Modeling thermophysical properties of food under high pressure.

A set of well-known generic models to predict the thermophysical properties of food from its composition at atmospheric conditions was adapted to work at any pressure. The suitability of the models was assessed using data from the literature for four different food products, namely tomato paste, potato, pork, and cod. When the composition of the product considered was not known, an alternative was proposed if some thermal data at atmospheric conditions were available. Since knowledge on the initial freezing point and ice content of food are essential for the correct prediction of its thermal properties, models for obtaining these properties under pressure were also included. Our results showed that good predictions under pressure, accurate enough for most engineering calculations can be made, either from composition data or using known thermal data of the food considered at atmospheric conditions. All the equations and coefficients needed to construct the models are given throughout the text, thus readers can compose their own routines. However, these routines can also be downloaded free at http://www.if.csic.es/programas/ifiform.htm as executable programs running in Windows.