The Safety of Direct Oral Anticoagulants Compared to Warfarin in Patients Hospitalized With Acute Kidney Injury.

BACKGROUND: Direct oral anticoagulants (DOACs) are preferred over warfarin for many indications, though their safety has not been well established in patients with acute renal impairment. OBJECTIVE: The purpose of this study was to evaluate the frequency of bleeding complications associated with DOACs compared with warfarin in patients admitted to the hospital with acute kidney injury (AKI). METHODS: This was a retrospective cohort study evaluating patients admitted to the Penn Medicine Lancaster General Hospital with a diagnosis of AKI from October 2017 through September 2021 and receiving therapy with oral anticoagulants. Comparing DOACs with warfarin, the primary endpoint was the percent frequency of composite major and minor bleeding during the admission and within 30 days of discharge. RESULTS: There were 112 hospitalization encounters included in the study. Of these, 42 (37.5%) patients were receiving warfarin and 70 (62.5%) patients were receiving DOAC therapy before admission. There was a higher frequency of the primary endpoint of bleeding in patients receiving DOACs as compared with warfarin, though this was not statistically significant (18.5% vs. 11.9%, respectively, P = 0.432). There were no differences between groups in the frequency of major bleeding, minor bleeding, or transfusions. Patients receiving DOAC therapy were more likely to experience anticoagulation-related readmissions or emergency department visits compared with patients on warfarin therapy (11.4% vs. 0%, P = 0.024). CONCLUSION AND RELEVANCE: Direct oral anticoagulants and warfarin were associated with statistically similar rates of bleeding in patients presenting with AKI. Further research is necessary to elucidate if DOACs are safer than warfarin in this patient population.

Pluripotent stem cell-derived interneuron progenitors mature and restore memory deficits but do not suppress seizures in the epileptic mouse brain.

GABAergic interneuron dysfunction has been implicated in temporal lobe epilepsy (TLE), autism, and schizophrenia. Inhibitory interneuron progenitors transplanted into the hippocampus of rodents with TLE provide varying degrees of seizure suppression. We investigated whether human embryonic stem cell (hESC)-derived interneuron progenitors (hESNPs) could differentiate, correct hippocampal-dependent spatial memory deficits, and suppress seizures in a pilocarpine-induced TLE mouse model. We found that transplanted ventralized hESNPs differentiated into mature GABAergic interneurons and became electrophysiologically active with mature firing patterns. Some mice developed hESNP-derived tumor-like NSC clusters. Mice with transplants showed significant improvement in the Morris water maze test, but transplants did not suppress seizures. The limited effects of the human GABAergic interneuron progenitor grafts may be due to cell type heterogeneity within the transplants.

Natural aversive learning in Tetramorium ants reveals ability to form a generalizable memory of predators' pit traps.

Many species of ants fall prey to pit-digging larval antlions (Myrmeleon spp.), extremely sedentary predators that wait, nearly motionless at the bottom of their pit traps, for prey to stumble inside. Previous research, both in the field and laboratory, has demonstrated a remarkable ability of these ants to rescue trapped nestmates, thus sabotaging antlions' attempts to capture them. Here we show that pavement ants, Tetramorium sp. E, an invasive species and a major threat to biodiversity, possess yet another, more effective, antipredator strategy, namely the ability to learn to avoid antlion traps following a single successful escape from a pit. More importantly, we show that this learned antipredator behavior, an example of natural aversive learning in insects, is more complicated than a single cue-to-consequence form of associative learning. That is, pavement ants were able to generalize, after one experience, from the learned characteristics of the pit and its specific location, to other pits and other contexts that differed in many features. Such generalization, often described as a lack of precise stimulus control, nonetheless would be especially adaptive in nature, enabling ants to negotiate antlions' pit fields, which contain a hundred or more pits within a few centimetres of one another. Indeed, the ability to generalize in exactly this way almost certainly is responsible for the sudden, and heretofore inexplicable, behavioural modifications of ants in response to an invasion of antlions in the vicinity of an ant colony.

Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement.

Focal cortical dysplasia (FCD), a local malformation of cortical development, is the most common cause of pharmacoresistant epilepsy associated with life-long neurocognitive impairments. It remains unclear whether neuronal misplacement is required for seizure activity. Here we show that dyslamination and white matter heterotopia are not necessary for seizure generation in a murine model of type II FCDs. These experimental FCDs generated by increasing mTOR activity in layer 2/3 neurons of the medial prefrontal cortex are associated with tonic-clonic seizures and a normal survival rate. Preventing all FCD-related defects, including neuronal misplacement and dysmorphogenesis, with rapamycin treatments from birth eliminates seizures, but seizures recur after rapamycin withdrawal. In addition, bypassing neuronal misplacement and heterotopia using inducible vectors do not prevent seizure occurrence. Collectively, data obtained using our new experimental FCD-associated epilepsy suggest that life-long treatment to reduce neuronal dysmorphogenesis is required to suppress seizures in individuals with FCD.