Cross-Saharan transport of water vapor via recycled cold pool outflows from moist convection.

Very sparse data have previously limited observational studies of meteorological processes in the Sahara. We present an observed case of convectively driven water vapor transport crossing the Sahara over 2.5 days in June 2012, from the Sahel in the south to the Atlas in the north. A daily cycle is observed, with deep convection in the evening generating moist cold pools that fed the next day's convection; the convection then generated new cold pools, providing a vertical recycling of moisture. Trajectories driven by analyses were able to capture the direction of the transport but not its full extent, particularly at night when cold pools are most active, and analyses missed much of the water content of cold pools. The results highlight the importance of cold pools for moisture transport, dust and clouds, and demonstrate the need to include these processes in models in order to improve the representation of Saharan atmosphere.

Impacts on South America moisture transport under Amazon deforestation and 2 °C global warming.

The increase in greenhouse gasses (GHG) anthropogenic emissions and deforestation over the last decades have led to many chemical and physical changes in the climate system, affecting the atmosphere's energy and water balance. A process that could be affected is the Amazonian moisture transport in the South American continent (including La Plata basin), which is crucial to the southeast Brazilian water regime. The focus of our research is on evaluating how local (i.e. Amazon deforestation) and global forcings (increase of atmospheric GHG concentration) may modify this moisture transport under climate change scenarios. We used two coupled land-atmosphere models forced by CMIP6 sea surface temperatures to simulate these processes for two scenarios: i) increase in carbon dioxide (CO2) - RCP8.5 atmospheric levels (00DEF), and ii) total Amazon deforestation simultaneous with atmospheric CO2 levels increased (100DEF). These scenarios were compared with a control simulation, set with a constant CO2 of 388 ppm and present-day Amazon Forest cover. The 30-year Specific Warming Level 2 (SWL2) index evaluated from the simulations is set to be reached 2 years earlier due to Amazon deforestation. A reduction in precipitation was observed in the Amazon basin (-3.1 mm·day-1) as well as in La Plata Basin (-0.5 mm·day-1) due to reductions in the Amazon evapotranspiration (-0.9 mm·day-1) through a stomatal conductance decrease (00DEF) and land cover change (100DEF). In addition, the income moisture transport decreased (22 %) in the northern La Plata basin in both scenarios and model experiments. Our results indicated a worse scenario than previously found in the region. Both Amazon and La Plata hydrological regimes are connected (moisture and energy transport), indicating that a large-scale Amazon deforestation will have additional climate, economic and social implications for South America.

Contrasting impacts of forests on cloud cover based on satellite observations.

Forests play a pivotal role in regulating climate and sustaining the hydrological cycle. The biophysical impacts of forests on clouds, however, remain unclear. Here, we use satellite data to show that forests in different regions have opposite effects on summer cloud cover. We find enhanced clouds over most temperate and boreal forests but inhibited clouds over Amazon, Central Africa, and Southeast US. The spatial variation in the sign of cloud effects is driven by sensible heating, where cloud enhancement is more likely to occur over forests with larger sensible heat, and cloud inhibition over forests with smaller sensible heat. Ongoing forest cover loss has led to cloud increase over forest loss hotspots in the Amazon (+0.78%), Indonesia (+1.19%), and Southeast US (+ 0.09%), but cloud reduction in East Siberia (-0.20%) from 2002-2018. Our data-driven assessment improves mechanistic understanding of forest-cloud interactions, which remain uncertain in Earth system models.

Insights into hemolytic uremic syndrome: segregation of three independent predisposition factors in a large, multiple affected pedigree.

Mutations in the complement regulators factor H, membrane cofactor protein (MCP), and factor I are associated with atypical hemolytic uremic syndrome (aHUS, MIM 235400), suggesting that the disease develops as a consequence of the inefficient protection of the renal endothelium from damage by the complement system. Incomplete penetrance of the disease in individuals carrying these mutations is, however, relatively frequent. Here, we report the identification of a large, multiple affected aHUS pedigree in which there is independent segregation of three different aHUS risk factors: a MCP missense mutation (c.-598C>T; Pro165Ser) that decreases MCP expression on the cell surface, a dinucleotide insertion in the coding sequence of factor I (c.-1610insAT) that introduces a premature stop codon in the factor I protein, and the MCPggaac SNP haplotype block that was previously shown to decrease the transcription activity from the MCP promoter. Interestingly, individuals affected by aHUS in the pedigree are only those who have inherited the three aHUS risk factors. These data show an additive effect for mutations in MCP and factor I and provide definitive support to the conclusion that aHUS results from a defective protection of cellular surfaces from complement activation. Furthermore, they help to explain the incomplete penetrance of the disease, illustrating that concurrence of multiple hits in complement regulatory proteins may be necessary to significantly impair host tissue protection and to confer susceptibility to aHUS.

Goodpasture syndrome during the course of a Schönlein-Henoch purpura.

Two months after surgical resection of a bronchogenic carcinoma, a 69-year-old patient presented with Schönlein-Henoch purpura with kidney involvement followed by pulmonary hemorrhage. The presence of an IgA linear pattern on the kidney biopsy specimen and circulating anti-glomerular basement membrane (GBM) IgA antibodies led to the diagnosis of Goodpasture syndrome, which implies the possibility that the well-known pulmonary involvement during the course of Schönlein-Henoch purpura could be caused by Goodpasture syndrome in certain cases. In cases of glomerulonephropathy with lung involvement, clinicians should not limit their investigations to anti-GBM IgG.

Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome.

Hemolytic uremic syndrome (HUS) is an important cause of acute renal failure in children. Mutations in one or more genes encoding complement-regulatory proteins have been reported in approximately one-third of nondiarrheal, atypical HUS (aHUS) patients, suggesting a defect in the protection of cell surfaces against complement activation in susceptible individuals. Here, we identified a subgroup of aHUS patients showing persistent activation of the complement alternative pathway and found within this subgroup two families with mutations in the gene encoding factor B (BF), a zymogen that carries the catalytic site of the complement alternative pathway convertase (C3bBb). Functional analyses demonstrated that F286L and K323E aHUS-associated BF mutations are gain-of-function mutations that result in enhanced formation of the C3bBb convertase or increased resistance to inactivation by complement regulators. These data expand our understanding of the genetic factors conferring predisposition to aHUS, demonstrate the critical role of the alternative complement pathway in the pathogenesis of aHUS, and provide support for the use of complement-inhibition therapies to prevent or reduce tissue damage caused by dysregulated complement activation.

Nuevas drogas en hematología. Pentasacárido / New drugs in haematology. Pentasaccharide

Algunas de las desventajas de los fármacos actualmente en uso como anticoagulantes, como la heparinano fraccionada o las heparinas de bajo peso molecular, han impulsado el desarrollo de nuevas drogas. Los inhibidores del factor Xa son un ejemplo de estas nuevas medicaciones. El SR90107A/ORG31540 es un nuevo pentasacárico (PS) que representa la secuencia mínima de la cadena de heparina capaz de unirse a la antitrombina III y potenciar la actividad anti-Xa. Se demostró que el PS ejerce un efecto antitrombótico en varios modelos animales de trombosis arterial y venosa. Los estudios de fase I demostraron que tiene una farmacocinética lineal, una vida media de alrededor de 15 horas y una biodisponibilidad luego de la inyección subcutánea del 100 porciento. Varios autores han señalado que el PS no produce activación plaquetaria ni tiene reactividad cruzada con los anticuerpos inducidos por heparina. Los estudios de fase II comprobaron la eficacia y la seguridad del PS en pacientes sometidos a angioplastia, como adyuvante en la terapéutica trombolítica del infarto agudo de miocardio, en la prevención del tromboembolismo venoso (TEV) en pacientes sometidos a reemplazo total de cadera y en el tratamiento inicial de la trombosis venosa profunda. Un extenso programa de fase III en la profilaxis del TEV en cirugía mayor ortopédica comprobó que el PS produjo una reducción del riesgo relativo del TEV del 50 porciento comparado con enoxaparina

Transfusión masiva en pacientes politraumatizados / Massive transfusion in polytraumatized patients

Transfusin masiva (TM) es el reemplazo de la volemia total de un paciente por sangre de banco en menos de 24 hs, o la administración aguda de 1,5 veces la volemia estimada. Esto representa una emergencia con una alta mortalidad. La volemia puede ser reemplazada con soluciones cristaloides o coloides, pero pérdidas mayores al 40 por ciento del volumen sanguíneo total requieren transfundir glóbulos rojos, proteínas y factores de la coagulación. La coagulopatía dilucional puede presentarse luego de una aparentemente correcta reposición hídrica. La capacidad de transporte de O2 está supeditada a niveles adecuados de hemoglobina, pero no necesariamente de un valor dado, sino de las manifestaciones clínicas de la necesidad de transfundir (según tensión arterial, frecuencia cardíaca, presión venosa central, presión Wedge, etc.) La coagulopatía dilucional se manifiesta por sangrado microvascular de las mucosas, heridas y sitios de punción, o petequiado generalizado, complicándose en un 30 por ciento de los pacientes con una coagulación intravascular diseminada, por hipoperfusión y/o liberación de trombolastina tisular durante la cirugía. La hipotermia prolonga los tiempos de coagulación y enlentece las reacciones enzimáticas de las vías intrínseca y extrínseca de la coagulación. En presencia de sangrado, un tiempo de protrombina mayor 1,5 veces al normal justifica administrar plasma fresco o congelado. Un recuento menor de 50.000/mmü aconseja la transfusión de plaquetas (1 U/10 kg de peso). El tratamiento de la CID es el de la causa que la generó, y la terapéutica sustitutiva con PFC y crioprecipitados. El citrato de cada unidad de sangre transfundida se une al calcio iónico, produciendo depresión miocárdica. Sin embargo, hoy en día no se recomienda su uso de rutina, excepto que exista compromiso de la función hepática. La transfusión de sangre almacenada puede dar hiperkalemia transitoria luego de una TM, pero con repercusión sistémica importante. Asimismo los glóbulos rojos producen ácido láctico, que junto con el ácido cítrico del anticoagulante dan una carga ácida de 30-40 mmol/L, los que al degradarse dan bicarbonato, que puede producir una alcalosis postransfusional. El desarrollo del síndrome de dificultad respiratoria del adulto (SDRA) luego de una TM se debería a la formación de microagregados de plaquetas, fibrina y granulocitos...