Epidemiologic trends of multiple sclerosis in Puerto Rico (2013-2020).

BACKGROUND: Previous studies have demonstrated higher multiple sclerosis (MS) incidence and prevalence in Puerto Rico (PR) than in other Caribbean and Latin American countries. Our objectives are to update the epidemiologic trends in MS incidence and prevalence rates for PR from 2017 through 2020 and compare them to prior rate data from 2013 to 2016. METHODS: We used the Puerto Rico MS Foundation's registry (PRMS Registry) data to identify all newly diagnosed MS cases between January 2017 and December 2020. The study population included 568 MS patients, 406 women and 162 men living in PR. All individuals were 18 years and older and met the 2017 revised McDonald criteria for MS diagnosis. In addition, age- and sex-standardized incidence rates were estimated. RESULTS: A total of 568 new MS cases were diagnosed in Puerto Rico between 2017 and 2020. The 2020 MS cumulative prevalence for Puerto Rico was 95.3/100,000 (95% CI: 91.6, 99.1), higher than previously reported. The age- and sex-standardized MS incidence rate for Puerto Rico decreased from 6.5/100,000 (2017) to 6.3/100,000 (2020). The annual age-standardized MS incidence rates declined for females: from 9.5/100,000 (2017) to 8.2/100,000 (2020) but increased for males from 3.6/100,000 to 4.6/100,000 during the same period. CONCLUSION: These incidence and prevalence rates are among the highest reported among Caribbean and Latin American countries. A peak in the age- and sex-standardized MS incidence rate was observed after hurricane María (2018) and a decline during the first year of the COVID-19 pandemic (2020). Further investigation is needed to determine whether there was a causal relationship between the fluctuations observed and those natural events.

Maternal immune activation in mice disrupts proteostasis in the fetal brain.

Maternal infection and inflammation during pregnancy are associated with neurodevelopmental disorders in offspring, but little is understood about the molecular mechanisms underlying this epidemiologic phenomenon. Here, we leveraged single-cell RNA sequencing to profile transcriptional changes in the mouse fetal brain in response to maternal immune activation (MIA) and identified perturbations in cellular pathways associated with mRNA translation, ribosome biogenesis and stress signaling. We found that MIA activates the integrated stress response (ISR) in male, but not female, MIA offspring in an interleukin-17a-dependent manner, which reduced global mRNA translation and altered nascent proteome synthesis. Moreover, blockade of ISR activation prevented the behavioral abnormalities as well as increased cortical neural activity in MIA male offspring. Our data suggest that sex-specific activation of the ISR leads to maternal inflammation-associated neurodevelopmental disorders.

Computational simulations establish a novel transducer array placement arrangement that extends delivery of therapeutic TTFields to the infratentorium of patients with brainstem gliomas.

BACKGROUND AND PURPOSE: Tumor treating fields (TTFields) are a non-invasive, efficacious treatment modality currently approved for supratentorial glioblastomas. Despite their ability to improve overall survival in supratentorial tumors, the current placement of arrays is limited to the supratentorial head, precluding its use in infratentorial tumors. Infratentorial malignancies are in need of new therapy modalities given their poor prognoses in both children and adults. The aim of this research is to determine whether rearrangement of TTFields may allow for management of infratentorial tumors. MATERIALS AND METHODS: Delivery of TTFields using Novocure's prototype Optune™ device human male head model was simulated based on brain MRIs from patients with brainstem gliomas to develop a novel array layout designed to extend adequate infratentorial coverage. RESULTS: Array placement on the vertex, bilateral posterolateral occiput, and superior-posterior neck achieved intensities above 1.1 V/cm (average 1.7 V/cm; maximum 2.3 V/cm) in the vertical field direction and above 1 V/cm (average 2 V/cm; maximum 2.8 V/cm) in the horizontal field direction of the infratentorium. The calculated field intensity within the simulated tumors were in the therapeutic range and demonstrated the effective delivery of TTFields to the infratentorial brain. CONCLUSIONS: Our findings suggest that rearrangement of the TTFields standard array with placement of electrodes on the vertex, bilateral posterolateral occiput, and superior-posterior neck allows for adequate electric field distribution in the infratentorium that is within the therapeutic range.

A splicing isoform of GPR56 mediates microglial synaptic refinement via phosphatidylserine binding.

Developmental synaptic remodeling is important for the formation of precise neural circuitry, and its disruption has been linked to neurodevelopmental disorders such as autism and schizophrenia. Microglia prune synapses, but integration of this synapse pruning with overlapping and concurrent neurodevelopmental processes, remains elusive. Adhesion G protein-coupled receptor ADGRG1/GPR56 controls multiple aspects of brain development in a cell type-specific manner: In neural progenitor cells, GPR56 regulates cortical lamination, whereas in oligodendrocyte progenitor cells, GPR56 controls developmental myelination and myelin repair. Here, we show that microglial GPR56 maintains appropriate synaptic numbers in several brain regions in a time- and circuit-dependent fashion. Phosphatidylserine (PS) on presynaptic elements binds GPR56 in a domain-specific manner, and microglia-specific deletion of Gpr56 leads to increased synapses as a result of reduced microglial engulfment of PS+ presynaptic inputs. Remarkably, a particular alternatively spliced isoform of GPR56 is selectively required for microglia-mediated synaptic pruning. Our present data provide a ligand- and isoform-specific mechanism underlying microglial GPR56-mediated synapse pruning in the context of complex neurodevelopmental processes.

Dietary supplementation with the polyphenol-rich açaí pulps (Euterpe oleracea Mart. and Euterpe precatoria Mart.) improves cognition in aged rats and attenuates inflammatory signaling in BV-2 microglial cells.

OBJECTIVES: The present study was carried out to determine if lyophilized açaí fruit pulp (genus, Euterpe), rich in polyphenols and other bioactive antioxidant and anti-inflammatory phytochemicals, is efficacious in reversing age-related cognitive deficits in aged rats. METHODS: The diets of 19-month-old Fischer 344 rats were supplemented for 8 weeks with 2% Euterpe oleracea (EO), Euterpe precatoria (EP), or a control diet. Rats were tested in the Morris water maze and then blood serum from the rats was used to assess inflammatory responses of BV-2 microglial cells. RESULTS: After 8 weeks of dietary supplementation with 2% EO or EP, rats demonstrated improved working memory in the Morris water maze, relative to controls; however, only the EO diet improved reference memory. BV-2 microglial cells treated with blood serum collected from EO-fed rats produced less nitric oxide (NO) than control-fed rats. Serum from both EO- and EP-fed rats reduced tumor necrosis factor-alpha (TNF-α). There is a relationship between performance in the water maze and the production of NO and TNF-α by serum-treated BV-2 cells, such that serum from rats with better performance was more protective against inflammatory signaling. DISCUSSION: Protection of memory during aging by supplementation of lyophilized açaí fruit pulp added to the diet may result from its ability to influence antioxidant and anti-inflammatory signaling.