Characteristics of non-sleep related apneas in children with alternating hemiplegia of childhood.

BACKGROUND: Non-sleep related apnea (NSA) has been observed in alternating hemiplegia of childhood (AHC) but has yet to be characterized. GOALS: Investigate the following hypotheses: 1) AHC patients manifest NSA that is often severe. 2) NSA is usually triggered by precipitating events. 3) NSA is more likely in patients with ATP1A3 mutations. METHODS: Retrospective review of 51 consecutive AHC patients (ages 2-45 years) enrolled in our AHC registry. NSAs were classified as mild (not needing intervention), moderate (needing intervention but not perceived as life threatening), or severe (needing intervention and perceived as life threatening). RESULTS: 19/51 patients (37 %) had 52 NSA events (6 mild, 11 moderate, 35 severe). Mean age of onset of NSA (± Standard Error of the Mean (SEM)): 3.8 ± 1.5 (range 0-24) years, frequency during follow up was higher at younger ages as compared to adulthood (year 1: 2.2/year, adulthood: 0.060/year). NSAs were associated with triggering factors, bradycardia and with younger age (p < 0.008 in all) but not with mutation status (p = 0.360). Triggers, observed in 17 patients, most commonly included epileptic seizures in 9 (47 %), anesthesia, AHC spells and intercurrent, stressful, conditions. Management included use of pulse oximeter at home in nine patients, home oxygen in seven, intubation/ventilatory support in seven, and basic CPR in six. An additional patient required tracheostomy. There were no deaths or permanent sequalae. CONCLUSIONS: AHC patients experience NSAs that are often severe. These events are usually triggered by seizures or other stressful events and can be successfully managed with interventions tailored to the severity of the NSA.

Conus involvement and leptomeningeal enhancement in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder: A case report.

There are a variety of clinical phenotypes and radiological features that continue to make a diagnosis of neuromyelitis optica spectrum disorder (NMOSD) challenging. We present an atypical case of an adult woman who presented with flaccid paralysis of all extremities with unusual neuroimaging features, including extensive enhancing lesions in the upper cervical cord and conus medullaris with associated leptomeningeal enhancement. She was ultimately found to have AQP4 antibody-positive NMOSD. We discuss the factors that complicated a timely diagnosis, including her atypical radiographic features and an initially negative cell-based assay for myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibodies. Despite the rarity of conus medullaris involvement or leptomeningeal enhancement in AQP4 antibody-positive NMOSD, it is important to maintain a high level of clinical suspicion to avoid diagnostic and therapeutic delays. Though cell-based assays have high sensitivities, testing should be repeated on negative values in these scenarios.

Comparing levels of fitness of police Officers between two United States law enforcement agencies.

BACKGROUND: The general physical task demands of law enforcement may suggest that police Officers are of similar fitness levels across cities, states and countries. OBJECTIVE: To investigate whether fitness levels of police Officers from two different United States (U.S.) Law Enforcement Agencies (LEA) are similar. METHODS: Retrospective data were analysed from two LEAs (LEA1 n = 79 and LEA2 n = 319). The data for Officers included: age, mass, 1-minute push-up repetitions, 1-minute sit-up repetitions, vertical jump height, 2.4 km run time (LEA 1) and 20-meter Multi-Stage Fitness Test results (LEA 2). Independent samples t-tests were used to compare anthropometric and fitness data between LEA with significance set at 0.05. RESULTS: Officers from LEA1 weighed significantly less and performed significantly better than Officers from LEA2 on all fitness measures. When comparing male Officers alone, there was no statistical difference in age and mass; nonetheless, Officers from LEA1 significantly outperformed Officers from LEA2 on all fitness measures. CONCLUSION: While similarities / differences in job tasks performed between these two LEA are not known, the results from this study suggest differences in fitness between these two different U.S. LEA. Fitness standards and training protocols need to be developed and contextualized to each LEA's specific population and needs.

The Persistence of Hippocampal-Based Memory Requires Protein Synthesis Mediated by the Prion-like Protein CPEB3.

Consolidation of long-term memories depends on de novo protein synthesis. Several translational regulators have been identified, and their contribution to the formation of memory has been assessed in the mouse hippocampus. None of them, however, has been implicated in the persistence of memory. Although persistence is a key feature of long-term memory, how this occurs, despite the rapid turnover of its molecular substrates, is poorly understood. Here we find that both memory storage and its underlying synaptic plasticity are mediated by the increase in level and in the aggregation of the prion-like translational regulator CPEB3 (cytoplasmic polyadenylation element-binding protein). Genetic ablation of CPEB3 impairs the maintenance of both hippocampal long-term potentiation and hippocampus-dependent spatial memory. We propose a model whereby persistence of long-term memory results from the assembly of CPEB3 into aggregates. These aggregates serve as functional prions and regulate local protein synthesis necessary for the maintenance of long-term memory.

SUMOylation Is an Inhibitory Constraint that Regulates the Prion-like Aggregation and Activity of CPEB3.

Protein synthesis is crucial for the maintenance of long-term-memory-related synaptic plasticity. The prion-like cytoplasmic polyadenylation element-binding protein 3 (CPEB3) regulates the translation of several mRNAs important for long-term synaptic plasticity in the hippocampus. Here, we provide evidence that the prion-like aggregation and activity of CPEB3 is controlled by SUMOylation. In the basal state, CPEB3 is a repressor and is soluble. Under these circumstances, CPEB3 is SUMOylated in hippocampal neurons both in vitro and in vivo. Following neuronal stimulation, CPEB3 is converted into an active form that promotes the translation of target mRNAs, and this is associated with a decrease of SUMOylation and an increase of aggregation. A chimeric CPEB3 protein fused to SUMO cannot form aggregates and cannot activate the translation of target mRNAs. These findings suggest a model whereby SUMO regulates translation of mRNAs and structural synaptic plasticity by modulating the aggregation of the prion-like protein CPEB3.