Upstream kinases of plant SnRKs are involved in salt stress tolerance.

Sucrose non-fermenting 1-related protein kinases (SnRKs) are important for plant growth and stress responses. This family has three clades: SnRK1, SnRK2 and SnRK3. Although plant SnRKs are thought to be activated by upstream kinases, the overall mechanism remains obscure. Geminivirus Rep-Interacting Kinase (GRIK)1 and GRIK2 phosphorylate SnRK1s, which are involved in sugar/energy sensing, and the grik1-1 grik2-1 double mutant shows growth retardation under regular growth conditions. In this study, we established another Arabidopsis mutant line harbouring a different allele of gene GRIK1 (grik1-2 grik2-1) that grows similarly to the wild-type, enabling us to evaluate the function of GRIKs under stress conditions. In the grik1-2 grik2-1 double mutant, phosphorylation of SnRK1.1 was reduced, but not eliminated, suggesting that the grik1-2 mutation is a weak allele. In addition to high sensitivity to glucose, the grik1-2 grik2-1 mutant was sensitive to high salt, indicating that GRIKs are also involved in salinity signalling pathways. Salt Overly Sensitive (SOS)2, a member of the SnRK3 subfamily, is a critical mediator of the response to salinity. GRIK1 phosphorylated SOS2 in vitro, resulting in elevated kinase activity of SOS2. The salt tolerance of sos2 was restored to normal levels by wild-type SOS2, but not by a mutated form of SOS2 lacking the T168 residue phosphorylated by GRIK1. Activation of SOS2 by GRIK1 was also demonstrated in a reconstituted system in yeast. Our results indicate that GRIKs phosphorylate and activate SnRK1 and other members of the SnRK3 family, and that they play important roles in multiple signalling pathways in vivo.

Germ line variants in patients with acute myeloid leukemia without a suspicion of hereditary hematologic malignancy syndrome.

Germ line predisposition in acute myeloid leukemia (AML) has gained attention in recent years because of a nonnegligible frequency and an impact on management of patients and their relatives. Risk alleles for AML development may be present in patients without a clinical suspicion of hereditary hematologic malignancy syndrome. In this study we investigated the presence of germ line variants (GVs) in 288 genes related to cancer predisposition in 47 patients with available paired, tumor-normal material, namely bone marrow stroma cells (n = 29), postremission bone marrow (n = 17), and saliva (n = 1). These patients correspond to 2 broad AML categories with heterogeneous genetic background (AML myelodysplasia related and AML defined by differentiation) and none of them had phenotypic abnormalities, previous history of cytopenia, or strong cancer aggregation. We found 11 pathogenic or likely pathogenic variants, 6 affecting genes related to autosomal dominant cancer predisposition syndromes (ATM, DDX41, and CHEK2) and 5 related to autosomal recessive bone marrow failure syndromes (FANCA, FANCM, SBDS, DNAJC21, and CSF3R). We did not find differences in clinical characteristics nor outcome between carriers of GVs vs noncarriers. Further studies in unselected AML cohorts are needed to determine GV incidence and penetrance and, in particular, to clarify the role of ATM nonsense mutations in AML predisposition.

Cardiopulmonary resuscitation skill maintenance for primary care staff: brief training sessions with feedback. / Sesiones breves con retroalimentación: una oportunidad para mantener las habilidades en reanimación cardiopulmonar en profesionales de atención primaria

OBJECTIVES: Cardiopulmonary resuscitation (CPR) feedback applications can facilitate learning in brief training sessions, but they have never been tested in primary care settings. We aimed to see if brief CPR training sessions that include feedback improve the skills of primary care staff. MATERIAL AND METHODS: Randomized trial with a control group and 2 intervention groups (G) using the feedback app and a control group: in G1, the instructor gave spoken feedback to the trainee and both could see the app; in G2, only the instructor giving feedback could see the app; and in G3, the control group, neither the instructor nor the trainee could see the app. All trainees received 10 minutes of instruction on theory followed by 6 minutes of practical instruction according to group assignment. The trainees used a high-quality CPR manikin connected to the Skillreporter feedback app (Laerdal Medical). CPR results were measured immediately before and after training and 6 months later. The main outcome measure was the overall CPR quality score. Secondary outcomes were 6 measures related to compressions and 5 related to ventilation. RESULTS: The main outcome improved with statistical significance in the two intervention groups (G1 and G2) respect to controls (G3). Most secondary outcome measures also improved after training. Trainees in the intervention groups scored better than trainees in G3 on the compression score (G1, P = .012), mean compression depth (G1, P = .001; G2, P = .022), number of compressions with adequate depth (G1, P = .026; G2, P = .019), and number of ventilations at adequate volume (G1, P = .033). The 2 intervention groups achieved statistically similar results. At 6 months, all outcome measures remained slightly improved over baseline levels, there were no between-group differences. CONCLUSION: Brief retraining sessions with feedback are useful for maintaining CPR skills in primary care, but skill improvement is not long lasting.

OBJETIVO: Los dispositivos de retroalimentación en sesiones breves facilitan el aprendizaje en reanimación cardiopulmonar (RCP), pero nunca se han probado para formación en atención primaria (AP). El objetivo fue determinar si estas sesiones mejoran las habilidades de RCP en formación continuada en profesionales de AP. METODO: Estudio prospectivo aleatorizado con 2 grupos de intervención (G1 y G2) y 1 grupo control (G3) en función de las personas que recibían la retroalimentación: G1: instructor y alumno, G2: solamente instructor, G3: ni instructor ni alumno. Todos recibieron 10 minutos de formación teórica común y 6 minutos de formación práctica según grupo, utilizando maniquí Annie QCPR® (Laerdal) conectado al programa de retroalimentación Skillreporter® (Laerdal). Se midieron los resultados, antes y después de la instrucción y a los 6 meses. La variable de resultado principal fue la puntuación total RCP y las variables secundarias fueron 6 relacionadas con compresión y 5 con ventilación. RESULTADOS: La variable de resultado principal mejoró en ambos grupos (G1 y G2) respecto al control (G3). La mayoría de las variables secundarias mejoraron después de la formación. Los grupos de intervención fueron superiores al de control en la puntuación en compresión (G1: p = 0,012), la profundidad media compresiones (G1: p = 0,001, y G2: p = 0,022), el número compresiones con profundidad adecuada (G1: p = 0,026 y G2: p = 0,019) y el número ventilaciones con volumen adecuado (G1: p = 0,033). No hubo diferencias entre grupos intervención en ninguna variable. A los 6 meses, los valores de todas las variables fueron ligeramente superiores a los basales, sin diferencias entre grupos. CONCLUSIONES: Las sesiones breves con retroalimentación son útiles para formación en RCP en AP, pero su validez no es duradera.