Depolarization-induced retrograde synaptic inhibition in the mouse cerebellar cortex is mediated by 2-arachidonoylglycerol

Endocannabinoids acting on CB₁ cannabinoid receptors are involved in short- and long-term depression of synaptic transmission. The aim of the present study was to determine which endocannabinoid, anandamide or 2-arachidonoylglycerol (2-AG), is involved in depolarization-induced suppression of inhibition (DSI) in the cerebellar cortex, which is the most widely studied form of short-term depression. Depolarization of Purkinje cells in the mouse cerebellum led to an increase in intracellular calcium concentration and to suppression of the inhibitory input to these neurons (i.e. DSI occurred). Orlistat and RHC80267, two blockers of sn -1-diacylglycerol lipase, the enzyme catalysing 2-AG formation, abolished DSI by acting downstream of calcium influx. In contrast, DSI occurred also in the presence of a phospholipase C inhibitor. Intact operation of the calcium-dependent messengers calmodulin and Ca²⁺–calmodulin-dependent protein kinase II were necessary for DSI. DSI was potentiated by an inhibitor of the main 2-AG-degrading enzyme, monoacylglycerol lipase. Interference with the anandamide metabolizing enzyme, fatty acid amide hydrolase, did not modify DSI. Thus, three kinds of observations identified 2-AG as the endocannabinoid involved in DSI in the mouse cerebellum: DSI was abolished by diacylglycerol lipase inhibitors; DSI was potentiated by a monoglyceride lipase inhibitor; and DSI was not changed by an inhibitor of fatty acid amide hydrolase. Further experiments indicated that 2-AG is the endocannabinoid mediating short-term retrograde signalling also at other synapses: orlistat abolished DSI in the rat cerebellum, DSI in the mouse substantia nigra pars reticulata and depolarization-induced suppression of excitation in the mouse cerebellum.     

Engraftment after autologous hematopoietic stem cell transplantation in patients mobilized with Plerixafor: A retrospective,multicenter study of a large series of patients

Plerixafor (PLX) appears to effectively enhance hematopoietic stem-cell mobilization prior to autologous hematopoietic stem cell transplantation (auto-HCT). However, the quality of engraftment following auto-HCT has been little explored. Here, engraftment following auto-HCT was assessed in patients mobilized with PLX through a retrospective, multicenter study of 285 consecutive patients. Information on early and 100-day post-transplant engraftment was gathered from the 245 patients that underwent auto-HCT. The median number of PLX days to reach the stem cell collection goal (≥2 × 10⁶ CD34⁺ cells/kg) was 1 (range 1–4) and the median PLX administration time before apheresis was 11 h (range 1–18). The median number of apheresis sessions to achieve the collection goal was 2 (range 1–5) and the mean number of CD34⁺ cells collected was 2.95 × 10⁶/kg (range 0–30.5). PLX administration was safe, with only 2 mild and transient gastrointestinal adverse events reported. The median time to achieve an absolute neutrophil count (ANC) >500/μL was 11 days (range 3–31) and the median time to platelet recovery >20 × 10³/μL was 13 days (range 5–69). At 100 days after auto-HCT, the platelet count was 137 × 10⁹/L (range 7–340), the ANC was 2.3 × 10⁹/L (range 0.1–13.0), and the hemoglobin concentration was 123 g/L (range 79–165). PLX use allowed auto-HCT to be performed in a high percentage of poorly mobilized patients, resulting in optimal medium-term engraftment in the majority of patients in whom mobilization failed, in this case mainly due to suboptimal peripheral blood CD34⁺ cell concentration on day +4 or low CD34⁺ cell yield on apheresis.     

Pathobiology of Lomentospora prolificans: could this species serve as a model of primary antifungal resistance?

The number of fungal isolates resistant to antifungal drugs has increased dramatically over the last few years and has become an important concern for clinicians. Among these isolates, fungi showing multidrug resistance are particularly worrying because of the difficulties associated with their treatment. These factors hamper the successful recovery of patients and drastically raise mortality rates. Antifungal resistance is multifactorial and several mechanisms in different fungi have been described. There is a need to study these mechanisms in depth; however, the study of antifungal drug resistance separately for each individual species makes progress in the field very slow and tedious. The selection of a multiresistant microorganism as a model for understanding resistance mechanisms and extrapolating the results to other species could help in the search for a solution. In this mini-review, we describe the pathobiology of Lomentospora (Scedosporium) prolificans, paying special attention to its intrinsic resistance to all currently available antifungal agents. The characteristics of L. prolificans offer several advantages: the possibility of using a single microorganism for the study of resistance to different drugs, even cases of double and triple resistance; it is biologically safe for society in general as no new genetically–modified strains are needed for the experiments; it is homologous with other fungal species, and there is repetitiveness between different strains. In conclusion, we propose L. prolificans as a candidate for consideration as a fungal model for the study of resistance mechanisms against antifungal agents.     

Estimación de la prevalencia de infección diagnosticada y no diagnosticada por el virus de la hepatitis C en Navarra, 2014-2016

Objective

To estimate the prevalence of hepatitis C virus (HCV) infection in Navarra, Spain, as well as to distinguish between diagnosed and undiagnosed infections.

Is advanced esophageal adenocarcinoma a distinct entity from intestinal subtype gastric cancer? Data from the AGAMENON-SEOM Registry

Gastric Cancer - Advanced esophageal adenocarcinoma (EAC) is generally treated similarly to advanced gastroesophageal junction (GEJ-AC) and gastric (GAC) adenocarcinomas, although GAC clinical...     

Androgen levels and anger and impulsivity measures as predictors of physical, verbal and indirect aggression in boys and girls

Previous studies indicate that androgen levels and certain psychological characteristics such as anger and impulsivity are related to the development and maintenance of aggression. Further studies are required to analyze the potential predictor role of the interaction of said factors on aggressive behavior. 90 nine-year-old children (44 boys and 46 girls) were assessed in relation to their levels of physical, verbal and indirect aggression, using a peer-rating technique. Testosterone and androstenedione levels were analyzed using an enzymoimmunoassay technique in saliva samples. Anger (state and trait) and anger control were measured using the STAXI-NA, and impulsivity was measured through the MFF-20. A General Linear Model revealed that sex was the best predictor for aggression measures, with boys scoring higher than girls in physical, verbal and indirect aggression; after sex, testosterone was found to be the best predictor (in a positive sense) of all three types of aggressive behavior studied. In addition to observing a main effect of androstenedione on physical and verbal aggression, a 'state anger*androstenedione' interaction was found to predict these types of aggression, with androstenedione acting as a moderator (inhibitor) of the effects of anger on these behaviors; also, a 'state anger*testosterone' interaction was found to predict verbal aggression. The results support the idea that, after sex, androgens constitute a biological marker to be taken into consideration in relation to individual differences in aggressive behavior. It is possible that at the age of 9, testosterone tends to increase aggression, while androstenedione tends to moderate (inhibit) the effects of anger on aggression.     

Episodios aparentemente letales en las primeras dos horas de vida durante el contacto piel con piel. Incidencia y factores de riesgo

Objective

To evaluate an unexpected increase in the incidence of apparently life threatening events and sudden deaths in neonates during the first 2 hours after birth in our hospital. This increase occurred in the first 2 years after generalized skin-to-skin contact between mother and infant became routine practice.

Methods

Full information on all our patients was collected to evaluate possible risk factors. Differences in incidence in four successive periods comprising the previous 35 years, with 208220 live neonates, were also analyzed.

Results

In the last period, there was a statistically significant increase in the rate of apparently life threatening events and sudden deaths in neonates. Several potential risk factors were detected: skin-to-skin contact, primiparity, an increased incidence in night hours and the invariable occurrence of these events in the second period of neonatal adaptation (30 to 90 minutes of life). Of eight patients with apparently life-threatening events, two had neurological sequelae and another died.

Conclusion

Apparently life threatening events in the first 2 hours of life are uncommon but may have serious consequences. One of the main risk factors may be skin-to-skin contact between mother and infant in the delivery room during the early adaptation period. As such contact has been proven to be beneficial and without apparent risks, this practice should be promoted. However, maternity staff should be vigilant during skin-to-skin contact, especially if the mother is alone with her neonate or other risk factors are present.     

Embarazo ectópico bilateral con embrión vivo en la trompa izquierda

Bilateral ectopic pregnancy with a live embryo is a rare occurrence. We report a case of bilateral ectopic pregnancy with live embryo in one tube and an interrupted gestation in the other tube, in a patient with no risk factors. When there is a unilateral ectopic pregnancy, even without risk factors, the other adnexal area and abdominal cavity should also be examined.