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El priapismo isquémico es una urgencia médica que, de no ser tratada, puede conducir a una disfunción eréctil permanente. Aunque la asociación entre cocaína y priapismo está establecida, todavía se desconocen los datos relativos a las características de los pacientes, el tratamiento y los resultados.

Penile Doppler ultrasound (PDU) is suggested to be an alternative to blood gas analysis (BGA) from the corpora cavernosa in differentiating between high- and low-flow priapisms, with limited supportive evidence.

Inflatable penile prostheses may be a solution for patients with erectile dysfunction. To our knowledge, no data exist regarding the effect of different surgical approaches used during implantation on the site of the corporotomy. The main purpose of this multicentre study was to investigate the influence of different surgical approaches on the corporotomy site.

La phalloplastie par lambeau libre antébrachial permet une reconstruction pénienne après traumatisme, micropenis, amputation du pénis ou pour une chirurgie de réassignation sexuelle. Elle permet d’obtenir un phallus fonctionnel et esthétique.

The utility of rare-earth elements (REEs) as natural geochemical tracers for the analysis of groundwater remediation was examined in several example permeable reactive barriers (PRBs). The PRBs utilize zero-valent iron and organic carbon plus limestone mixtures for contaminant treatment. Zero-valent iron removed REEs from groundwater to below detection levels (2–4 ng/L) and subsequent rebound of REE concentrations in regions down-gradient of the treatment zones was not observed. In addition, REE concentrations within and down-gradient of an organic carbon/limestone PRB were significantly reduced to <1% of influent levels. Thus, REEs are sensitive tracers for evaluating the interaction of groundwater with materials placed in the subsurface for contaminant remediation. Analysis of geochemical tracers for understanding in situ remediation becomes important in situations where down-gradient contaminant concentrations fail to decrease within expected timeframes. The field data indicated that increased solid-phase partitioning of REEs occurred with increasing pH and heavy REEs were preferentially removed compared to light REEs in ZVI systems. In the organic carbon PRB, unexpected negative europium anomalies were observed, revealing new information about redox conditions within the treatment zone. REE concentrations and shale-normalized profiles can be used as natural tracers to better understand in situ technologies for groundwater remediation.

ObjectiveWe explore factors such as the blood sampling site (capillary vs venous), the equipment (HemoCue vs automated haematology analyser) and the model of the HemoCue device (201+ vs 301) that may impact haemoglobin measurements in capillary and venous blood.MethodsEleven studies were identified, and bias, concordance and measures of diagnostic performance were assessed within each study.FindingsOur analysis included 11 studies from seven countries (Cambodia, India, The Gambia, Ghana, Laos, Rwanda and USA). Samples came from children, men, non-pregnant women and pregnant women. Mean bias ranged from −8.7 to 2.5 g/L in Cambodian women, 6.2 g/L in Laotian children, 2.4 g/L in Ghanaian women, 0.8 g/L in Gambian children 6–23 months and 1.4 g/L in Rwandan children 6–59 months when comparing capillary blood on a HemoCue to venous blood on a haematology analyser. Bias was 8.3 g/L in Indian non-pregnant women and 2.6 g/L in Laotian children and women and 1.5 g/L in the US population when comparing capillary to venous blood using a HemoCue. For venous blood measured on the HemoCue compared with the automated haematology analyser, bias was 5.3 g/L in Gambian pregnant women 18–45 years and 11.3 g/L in Laotian children 6–59 months.ConclusionOur analysis found large variability in haemoglobin concentration measured on capillary or venous blood and using HemoCue Hb 201+ or Hb 301 or automated haematology analyser. We cannot ascertain whether the variation is due to differences in the equipment, differences in capillary and venous blood, or factors affecting blood collection techniques.

Both heparanase and syndecan-1 are known to be present and active in disease pathobiology. An important feature of syndecan-1 related to its role in pathologies is that it can be shed from the surface of cells as an intact ectodomain composed of the extracellular core protein and attached heparan sulfate and chondroitin sulfate chains. Shed syndecan-1 remains functional and impacts cell behavior both locally and distally from its cell of origin. Shedding of syndecan-1 is initiated by a variety of stimuli and accomplished predominantly by the action of matrix metalloproteinases. The accessibility of these proteases to the core protein of syndecan-1 is enhanced, and shedding facilitated, when the heparan sulfate chains of syndecan-1 have been shortened by the enzymatic activity of heparanase. Interestingly, heparanase also enhances shedding by upregulating the expression of matrix metalloproteinases. Recent studies have revealed that heparanase-induced syndecan-1 shedding contributes to the pathogenesis and progression of cancer and viral infection, as well as other septic and non-septic inflammatory states. This review discusses the heparanase/shed syndecan-1 axis in disease pathogenesis and progression, the potential of targeting this axis therapeutically, and the possibility that this axis is widespread and of influence in many diseases.

The Forties Field, discovered by BP in 1970, is the largest oilfield on the UK Continental Shelf. It is trapped in a simple four-way dip closure, with a Paleocene turbidite sandstone reservoir. The Forties Field originally contained between 4.2 and 5 billion bbl of oil, with 2.75 billion bbl produced to June 2017. Production has been supported by water injection and the influx of a regional aquifer. The original development contained equally spaced producers with peripheral injectors. As the field matured, production was concentrated in the crestal parts of the field with injectors tending to be moved upflank. With the development of seismic lithology prediction and fluid detection, together with 4D seismic technology, it became possible in the late 1990s to target bypassed oil in unexpected locations throughout the field. In 2003, BP sold the field to Apache who were able to rejuvenate production, adding over 170 MMbbl oil reserves, with an extended drilling campaign targeting bypassed pay identified using seismic technologies. Production at the Forties facility has been further enhanced by the development of four satellite oilfields, Bacchus (Jurassic reservoir), Brimmond, Maule and Tonto (Eocene reservoirs), together with Aviat (Pleistocene reservoir) produced for fuel gas supply.

A large and persistent soil seed bank characterises many important grass weeds, including Nassella trichotoma (Nees) Hack. ex Arechav. (serrated tussock), a major weed in Australia and other countries. In the present study we examined the effects of constant and alternating temperatures in regulating primary and secondary dormancy and the creation and maintenance of its soil seed bank in northern NSW, Australia. One-month-old seeds were stored at 4, 25°C, 40/10°C and 40°C, in a laboratory, and germination tests were conducted every two weeks. Few seeds germinated following storage at 4°C, compared with seeds stored at 25°C, 40/10°C and 40°C. Nylon bags containing freshly harvested seeds were buried among N. trichotoma stands in early summer, and germination tests conducted following exhumation after each season over the next 12 months. Seeds buried over summer and summer plus autumn had higher germination than seeds buried over summer plus autumn plus winter, but germination increased again in the subsequent spring. Seeds stored for zero, three, six and 12 months at laboratory temperatures were placed on a thermogradient plate with 81 temperature combinations, followed by incubation at constant 25°C of un-germinated seeds. Constant high or low temperatures prolonged primary dormancy or induced secondary dormancy whereas alternating temperatures tended to break dormancy. Few temperature combinations resulted in more than 80% germination.

Enhanced recovery pathways (ERPs), when combined with transversus abdominis plane (TAP) blocks, have been proven to reduce the length of stay (LOS) and improve quality outcomes. Nonopioid pain management is an essential component of this pathway, leading to a reduction in immobility, postoperative ileus, and an increase in patient satisfaction. TAP block variations have been studied in general and gynecologic surgery. This study evaluates the effectiveness of laparoscopic TAP blocks in conjunction with the benefit of an ERP. One hundred thirty-seven consecutive laparoscopic and robotic-assisted Colorectal Surgery patients received TAP blocks under laparoscopic guidance while under anesthesia, randomized to a placebo, bupivacaine TAP block, or bupivacaine TAP block with an ERP arm of the trial. Patient demographics, operative techniques, and postoperative outcomes were analyzed using statistical analysis software. Our main objective was to determine short-term benefits of TAP blocks on reducing total narcotic consumption. Secondary objectives included effects of TAP blocks on time to ambulation, time to bowel function, and LOS. To isolate the effect of the TAP blocks, no efforts were made to control nursing or patient education in patients managed without an ERP. Of 137 patients, 14 were withdrawn. All cases were elective, with the main diagnosis colon cancer or dysplastic polyps (47.1%). The median age in each group was comparable (P= 0.12), with female majority in both groups (58.5%). Most procedures were segmental colon resections (74.7%). Thirty-one patients received a placebo, 41 bupivacaine TAP, and 51 bupivacaine TAP plus ERP. In terms of primary endpoints, the bupivacaine plus ERP arm used statistically significant less IV narcotics on postoperative day 1 and in total (P= 0.001, P= 0.008). All patients ambulated on average within the first 24 hours postoperatively, with the TAP plus ERP group approximately 0.5 days sooner (P= 0.001). The TAP plus ERP group also had a return of bowel function and LOS approximately 24 hours early (P= 0.001 and P= 0.001). This study shows that a laparoscopically placed bupivacaine TAP block when used as part of an ERP can reduce LOS, postoperative narcotics, time to ambulation and bowel function, and LOS. Defined pain regimens with auxiliary staff teaching can add to the improvement in quality outcomes in laparoscopic colorectal surgery and, with the addition of the TAP block, can add to patient satisfaction and lower hospital costs.

Revisar la literatura actual sobre implantación de prótesis peneana temprana en pacientes con priapismo isquémico (PI) refractario.

Observations by the Lightning and Airglow Camera on Japan's Venus Climate Orbiter “Akatsuki” over its first 3 years in orbit are reported. Forty‐two opportunities during low‐altitude nightside passes have accumulated 16.8 hr of observation, yielding an area‐time product of 81.6 ×106km2‐hr, by far the largest at Venus itself to date. No flashes attributable to lightning have been detected, whereas similar observations at Earth would yield thousands of detections. A low flash rate of ~0.005 per million km2‐hr indicated in ground‐based observations is not excluded (but would require that there are not many more smaller flashes). The allowable flash rate is incompatible with the much higher rates of bursts recorded by magnetic and electric field sensors at Venus, indicating that electrical discharges at Venus lack optical emission or that the electromagnetic detections have a nonlightning explanation or both. Nondetection in 42 observations by a dedicated flash detector on Akatsuki suggests a Venus lightning rate >~1,000 lower than EarthResult is compatible with zero flashes, with claimed ground‐based detections or with lightning that is highly clustered in space or timeNondetection is incompatible with the rate of whistler mode radio waves, suggesting that their origin is not associated with optical flashes

Like Earth, the atmosphere of Titan, Saturn's largest moon, is affected by the ability of the surface to store and release heat. Modeling efforts have shown that global temperature distributions and wind profiles differ between simulations describing Titan's surface with a uniform thermal inertia. Cassini‐Huygensdemonstrated, however, that a variety of morphologies and compositions make up the Titanian landscape. Using data from CassiniRADAR and the Visible and Infrared Mapping Spectrometer, we classified the surface into five terrain types: dune, lake, hummocky, plains, and labyrinth. We estimated the thermal and physical properties (conductivity, specific heat, and density) for each type, creating a 1° × 1° global map of thermal inertia values. For the lakes, as the depth of convection is not yet known, we considered both still and convective bodies. Four simulations of the Titan Atmospheric Model were run with different surface thermal properties: a low homogeneous thermal inertia, a moderate homogeneous, the heterogeneous map with still lakes, and the heterogeneous map with convective lakes. In dry regimes (i.e., without the hydrological cycle), the differences between the four cases were generally minimal, suggesting that general circulation models can use a single (moderate) value for surface thermal inertia value for large‐scale investigations that do not consider diurnal variations. Given the importance of hydrological processes and regional spatial diversity on Titan, future work should consider the effects of nonuniform thermal inertia on Titan's climate on local and regional scales. Titan's heterogeneous surface morphologies and compositions suggest a diversity of thermal inertia valuesLarge‐scale investigations by general circulation models can use a single‐valued moderate thermal inertiaRegional and diurnal variations probably warrant considering heterogeneous thermal inertia

Robert Bruce, king of Scots, is a significant figure in Scottish history, and his facial appearance will have been key to his status, power and resilience as a leader. This paper is the first in a series that discusses the burial and skeletal remains excavated at Dunfermline in 1819. Parts II and III discuss the evidence relating to whether or not the burial vault and skeleton belong to Robert Bruce, and Part I analyses and interprets the historical records and skeletal structure in order to produce a depiction of the facial appearance of Robert Bruce.

Background/Objectives:: In 2009, the Ministry of Health of Kyrgyzstan launched a national Infant and Young Child Nutrition (IYCN) program which included point-of-use fortification of foods with micronutrient powders (MNP) containing iron, vitamin A, and other micronutrients. Caretakers of children aged 6–23 months were given 30 sachets of MNP every 2 months. Micronutrient surveys were conducted in 2009 and 2013. The objective of the study was to compare the prevalence of anemia and deficiencies of iron and vitamin A among children aged 6–29 months prior to the MNP program (2009) with those after full implementation (2013). Subjects/Methods:: Cross-sectional national surveys were conducted in 2009 (n= 666) and 2013 (n= 2150). Capillary blood samples were collected to measure hemoglobin, iron (ferritin and soluble transferrin receptor [sTfR]) and vitamin A (retinol binding protein [RBP]) status, and inflammation status (C-reactive protein [CRP] and α-1-acid glycoprotein [AGP]). Ferritin, sTfR, and RBP were adjusted for inflammation; hemoglobin was adjusted for altitude. Results:: The prevalence of anemia was non-significantly lower in 2013 compared to 2009 (32.7% vs. 39.0%, p= 0.076). Prevalence of inflammation-adjusted iron deficiency (54.8% vs. 74.2%, p&lt;0.001) and iron deficiency anemia (IDA, 25.5% vs. 35.1%, p= 0.003) were lower and the prevalence of inflammation-adjusted vitamin A deficiency was higher (4.3% vs. 2.0%, p= 0.013) in 2013 compared to 2009. Conclusions:: Four years after the initiation of a national Infant and Young Child Nutrition program including the introduction of point-of-use fortification with MNP, the prevalence of iron deficiency and IDA is lower, but the prevalence of vitamin A deficiency is higher.

Seasonal variations in lake levels of Titan's hydrocarbon seas/lakes are predicted by an ocean circulation model in an effort to understand the observed temporal changes in lake size or lack thereof. Three different ground permeabilities are assumed so as to change the relative importance of precipitation, evaporation, river runoff, and groundwater seepage for the lake methane budget. The lake level generally rises in the rainy season around the summer solstice and falls or stagnates during long dry periods in autumn and winter. The annual lake level range in the northern hemisphere amounts to 50–120 cm depending on geographic location and size of the lakes and ground permeability. If the hydraulic connection between Punga Mare and Kraken Mare is weak, the lake level range of Punga Mare amplifies at the expense of other seas and also establishes a large lake level difference between these two seas, which is not compatible with the observation by the Cassini spacecraft. On‐lake precipitation would cause the lake level of Ontario Lacus to vary seasonally by merely 15 cm, yet river runoff from the huge catchment area can increase the annual lake level range to several meters. The shrinkage of Ontario Lacus observed by Cassini is more likely to be caused by lakebed seepage than by evaporation. The ultimate cause of the difference in the seasonal behavior between northern and southern lakes may be the hemispheric asymmetry in precipitation, be it caused astronomically or topographically. Saturn's moon Titan has many hydrocarbon lakes in the polar region, but only one lake near the south pole has so far shown evidence of lake size change. In order to understand the possible difference in the temporal variation between the northern and southern lakes, we simulated numerically the seasonal lake level change of all major lakes on Titan. The lake level generally rises in spring and summer during the rainy season and falls in dry seasons due to evaporation. However, the magnitude of lake level variation strongly depends on the geographic location and size of the lakes as well as how the ground outside the lakes and lake bottom are made of. Large seas near the north pole experience moderate lake level changes of about 1 m as a response to spatially averaged precipitation and evaporation. Ontario Lacus in the southern hemisphere is located in a dry environment and rapidly grows after sporadic rainfall but also rapidly shrinks by leakage from the lake bottom. This difference ultimately reflects the north‐south asymmetry in Titan's climate. Relative importance of sources and sinks for lake level varies between north and southLake level of northern seas may seasonally vary by about 1 m due to precipitation and evaporationCurrent lake level change of Ontario Lacus is probably dominated by lakebed seepage

Observations with sensitive photodiode detectors on the Perseverance rover (Hueso et al., 2023, https://doi.org/10.1029/2022JE007516; Vicente‐Retortillo et al., 2023, https://doi.org/10.1029/2022je007672) to detect dust devils and track formation, and movies of the Ingenuity helicopter's downwash impingement on the Martian surface (Lemmon et al., 2022a, https://doi.org/10.1029/2022je007605; Lemmon et al., 2022b, https://doi.org/10.1029/2022gl100126), together with in‐situ meteorological data, give new insights into the important problem of dust‐lifting on Mars, a phenomenon which influenced the lifetime of recent rovers and landers. These results, together with new low‐gravity wind tunnel experiments on parabolic flights and interpretation of the large blast pattern from lander retrorockets, indicate that particle motion and visible darkening on Mars can result from aerodynamic pressures of only 1–5 Pa, considerably less than previously thought. Dust is important on Mars, not least in that dust falling on solar panels limits the life of spacecraft. New measurements from the Perseverance rover and Ingenuity helicopter show that dust may be lifted off the ground more easily than had been thought. New data show the dust‐lifting threshold may be lower than had been assumedThe dust‐lifting threshold may help interpret features such as dust devil tracks and impact blast wavesObservation of dust devil tracks from orbit may help diagnose the rate of solar array cleaning New data show the dust‐lifting threshold may be lower than had been assumed The dust‐lifting threshold may help interpret features such as dust devil tracks and impact blast waves Observation of dust devil tracks from orbit may help diagnose the rate of solar array cleaning

ABSTRACTSpecies of tropical tar spot fungi (Phyllachorales, Ascomycota) are obligate biotrophic plant parasitic fungi associated with living leaves of a wide range of families of host plants, mainly in tropical and subtropical regions. In this study, samples of tropical tar spot fungi were collected in forests in Costa Rica and Panamá. To identify taxa, we used morphology and information on host plants and combined multigene phylogeny of four genes: the large subunit nuclear ribosomal DNA (28S rDNA), the small subunit nuclear ribosomal DNA (18S rDNA), the complete internal transcribed spacer region of ribosomal DNA (nuc rDNA ITS1-5.8S-ITS2; ITS), and the translation elongation factor 1-α (tef1). Here we propose one new species in the genus Camarotellaand eight new species in Telimenawith their morphological descriptions, illustrations, and sequence data. The newly described species are Camarotella licaniaeon Licania arborea(Chrysobalanaceae) and in the genus Telimena: T. billiaeon Billia rosea(Sapindaceae), T. drymoniaeon Drymonia multiflora(Gesneriaceae), T. hydrangeaeon Hydrangeasp. (Hydrangeaceae), T. miravallensison Symplocos panamensis(Symplocaceae), T. protiion Protiumsp. (Burseraceae), T. rinoreaeon Rinoreasp. (Violaceae), T. semialariion Semialarium mexicanum(Celastraceae), and T. triseptataon Tapirira mexicana(Anacardiaceae). The new name Telimena nitenson Schlegelia brachyanta(Schlegeliaceae) is presented and 10 species of Phyllachoraare transferred to Telimena, leading to the new combinations T. canarii, T. galavisii, T. insueta, T. ruelliae, T. scutiformis, T. serjaniicola, T. spicatae, T. subrepens, T. symploci, and T. symplocicola. Additionally, revisions of tar spot fungi on host families Burseraceae, Sapindaceae, and Symplocaceae are provided, and four new synonyms are proposed.

Seismic data will be a vital geophysical constraint on internal structure of Europa if we land instruments on the surface. Quantifying expected seismic activity on Europa both in terms of large, recognizable signals and ambient background noise is important for understanding dynamics of the moon, as well as interpretation of potential future data. Seismic energy sources will likely include cracking in the ice shell and turbulent motion in the oceans. We define a range of models of seismic activity in Europa's ice shell by assuming each model follows a Gutenberg‐Richter relationship with varying parameters. A range of cumulative seismic moment release between 1016and 1018Nm/yr is defined by scaling tidal dissipation energy to tectonic events on the Earth's moon. Random catalogs are generated and used to create synthetic continuous noise records through numerical wave propagation in thermodynamically self‐consistent models of the interior structure of Europa. Spectral characteristics of the noise are calculated by determining probabilistic power spectral densities of the synthetic records. While the range of seismicity models predicts noise levels that vary by 80 dB, we show that most noise estimates are below the self‐noise floor of high‐frequency geophones but may be recorded by more sensitive instruments. The largest expected signals exceed background noise by ∼50 dB. Noise records may allow for constraints on interior structure through autocorrelation. Models of seismic noise generated by pressure variations at the base of the ice shell due to turbulent motions in the subsurface ocean may also generate observable seismic noise. In this study, we are looking at sources that vibrate the outer ice shell of Europa and produce energy recorded by a seismometer. We are interested in this because seismology has been the best tool for determining the interior structure of the Earth; therefore, we want to consider how much energy we expect to go into seismic activity on Europa. In this study, we simulate long seismic recordings assuming that icequakes behave statistically similar to earthquakes. This predicts how frequently we expect events of different sizes. By scaling the total energy released observed on the Earth's moon by the much higher tidal energy available to Europa, we predict a range of simulated event catalogs. With those catalogs, we simulate the seismic waves recorded at a seismometer. This lets us determine how large events are likely to be, and also what the more or less continuous background noise from many small events will look like. We also examine a technique that can use an approach called autocorrelation to pull signals out of the noise, which in our simulated records show a clear energy arrival representing energy reflected from the ocean bottom. We conclude that a simple instrument does not have enough sensitivity to reliably record either the large signals or the background noise on Europa's surface, but a more sensitive instrument may record the background noise for periods shorter than 10 s, as well as very likely recording signals from larger events expected to occur a few times per week of observation. Seismic activity level and ambient seismic noise due to tidal cracking in the ice on Europa are estimatedActivity and noise are modeled with a Gutenberg‐Richter relationship using numerical wave propagationAutocorrelation of seismic noise may potentially be used to determine structure in the absence of large events

Seismology was developed on Earth and shaped our model of the Earth's interior over the twentieth century. With the exception of the Philae lander, all in situ extraterrestrial seismological effort to date was limited to other terrestrial planets. All have in common a rigid crust above a solid mantle. The coming years may see the installation of seismometers on Europa, Titan, and Enceladus, so it is necessary to adapt seismological concepts to the setting of worlds with global oceans covered in ice. Here we use waveform analyses to identify and classify wave types, developing a lexicon for icy ocean world seismology intended to be useful to both seismologists and planetary scientists. We use results from spectral‐element simulations of broadband seismic wavefields to adapt seismological concepts to icy ocean worlds. We present a concise naming scheme for seismic waves and an overview of the features of the seismic wavefield on Europa, Titan, Ganymede, and Enceladus. In close connection with geophysical interior models, we analyze simulated seismic measurements of Europa and Titan that might be used to constrain geochemical parameters governing the habitability of a sub‐ice ocean. Icy ocean worlds, like Europa or Titan harbor an ocean below a solid ice layer. This ocean may be habitable but is difficult to study from orbit. We demonstrated that surface‐installed seismometers are able to measure ice thickness and ocean depth directly and help constrain ocean temperature and chemistry, which are both critical for potential habitability. This paper tries to bridge the gap between methods of seismology on Earth and potential icy moon seismology by adapting common concepts to this setting. Using seismic wavefield simulations on high‐performance computers, we showcase a few tests for ice thickness, ocean depth, location of seismic events, and the existence of high‐pressure ice layers below an ocean. The paper focuses on Europa and Titan, with a more general description of Ganymede and Enceladus. The seismic waveform databases are made available to the seismological and planetary community to allow other researchers to build their own studies on icy ocean world seismology. Prepares for icy moon seismology by proposing a phase‐naming schemeObservation of a few magnitude 3 events allows estimates of ice thickness and ocean depthThe existence of high‐pressure ice phases can be inferred from spectral analysis

Fans, landforms that record the storage and transport of sediment from uplands to depositional basins, are found on Saturn's moon Titan, a body of significantly different process rates and material compositions from Earth. Images obtained by the Cassini spacecraft's synthetic aperture radar reveal morphologies, roughness, textural patterns and other properties consistent with fan analogues on Earth also viewed by synthetic aperture radar. The observed fan characteristics on Titan reveal some regions of high relative relief and others with gentle slopes over hundreds of kilometres, exposing topographic variations and influences on fan formation. There is evidence for a range of particle sizes across proximal to distal fan regions, from c.2 cm or more to fine-grained, which can provide details on sedimentary processes. Some features are best described as alluvial fans, which implies their proximity to high-relief source areas, while others are more likely to be fluvial fans, drawing from larger catchment areas and frequently characterized by more prolonged runoff events. The presence of fans corroborates the vast liquid storage capacity of the atmosphere and the resultant episodic behaviour. Fans join the growing list of landforms on Titan derived from atmospheric and fluvial processes similar to those on Earth, strengthening comparisons between these two planetary bodies.

The current treatment options for multiple myeloma (MM) osteolytic lesions are mainly combinations of chemotherapy and other small-molecule inhibitors, but toxic side effects still remain a major concern. Studies have shown that osteoclast activity is enhanced in MM patients through increased expression of receptor activator of nuclear factor ?B ligand (RANKL), triggering RANK signaling on osteoclast precursors, which results in aggressive bone resorption. Furthermore, osteoprotegerin (OPG), a decoy receptor for RANKL, and the osteogenic potential of mesenchymal stem cells (MSCs) are significantly decreased in myeloma patients with multiple bone lesions. Thus, the use of OPG as a therapeutic molecule would greatly decrease osteolytic damage and reduce morbidity. However, in addition to inhibiting osteoclast activation, OPG binds to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), thereby rendering the tumor cells resistant to TRAIL-induced apoptosis and limiting the use of OPG for therapy. The present study developed a bone-disseminated myeloma disease model in mouse and successfully tested a cell therapy approach using MSCs, genetically engineered to express OPG variants that retain the capacity to bind RANKL, but do not bind TRAIL. Our results of skeletal remodeling following this regenerative stem cell therapy with OPG variants indicated a significant protection against myeloma-induced osteolytic bone damage in areas of major myeloma skeletal dissemination, suggesting the potential of this therapy for treating osteolytic damage in myeloma patients.

The current treatment options for multiple myeloma (MM) osteolytic lesions are mainly combinations of chemotherapy and other small-molecule inhibitors, but toxic side effects still remain a major concern. Studies have shown that osteoclast activity is enhanced in MM patients through increased expression of receptor activator of nuclear factor κB ligand (RANKL), triggering RANK signaling on osteoclast precursors, which results in aggressive bone resorption. Furthermore, osteoprotegerin (OPG), a decoy receptor for RANKL, and the osteogenic potential of mesenchymal stem cells (MSCs) are significantly decreased in myeloma patients with multiple bone lesions. Thus, the use of OPG as a therapeutic molecule would greatly decrease osteolytic damage and reduce morbidity. However, in addition to inhibiting osteoclast activation, OPG binds to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), thereby rendering the tumor cells resistant to TRAIL-induced apoptosis and limiting the use of OPG for therapy. The present study developed a bone-disseminated myeloma disease model in mouse and successfully tested a cell therapy approach using MSCs, genetically engineered to express OPG variants that retain the capacity to bind RANKL, but do not bind TRAIL. Our results of skeletal remodeling following this regenerative stem cell therapy with OPG variants indicated a significant protection against myeloma-induced osteolytic bone damage in areas of major myeloma skeletal dissemination, suggesting the potential of this therapy for treating osteolytic damage in myeloma patients.