Comparing survival and outcomes in isolated versus polytrauma-associated TBI: a retrospective cohort study.

Background: One in four patients with moderate to severe traumatic brain injury (TBI) also has other body district injuries (OBD). The impact of OBD on mortality and disability is debated. This study compared outcomes of TBI patients with polytrauma (p-TBI) versus isolated TBI (alone-TBI) and identified outcome determinants, focusing on survival time and prognosis.

Corroborating written history with ancient DNA: The case of the Well-man described in an Old Norse .

The potential of ancient DNA analyses to provide independent sources of information about events in the historical record remains to be demonstrated. Here we apply palaeogenomic analysis to human remains excavated from a medieval well at the ruins of Sverresborg Castle in central Norway. In , the Old Norse of King Sverre Sigurdsson, one passage details a 1197-CE raid on the castle and mentions a dead man thrown into the well.

Big data research is everyone's research-Making epilepsy data science accessible to the global community: Report of the ILAE big data commission.

Epilepsy care generates multiple sources of high-dimensional data, including clinical, imaging, electroencephalographic, genomic, and neuropsychological information, that are collected routinely to establish the diagnosis and guide management. Thanks to high-performance computing, sophisticated graphics processing units, and advanced analytics, we are now on the cusp of being able to use these data to significantly improve individualized care for people with epilepsy. Despite this, many clinicians, health care providers, and people with epilepsy are apprehensive about implementing Big Data and accompanying technologies such as artificial intelligence (AI).

Similarity of Phenotype in Three Male Patients With the c.320A>G Variant in ALG13: Possible Genotype-Phenotype Correlation.

Background: Congenital disorders of glycosylation (CDG) are a group of neurometabolic diseases that result from genetic defects in the glycosylation of proteins and/or lipids. Multiple pathogenic genes contribute to the varying reported phenotypes of individuals with CDG-1 syndromes, most of which are inherited as autosomal recessive traits, although X-linked inheritance has also been reported. Pathogenic variants in the asparagine-linked glycosylation 13 homolog (ALG13) gene have been implicated in the aetiology of developmental and epileptic encephalopathy (DEE) 36 (OMIM:*300776, DEE36).

All hands on deck during the COVID-19 pandemic. Maintaining face-to-face medical education and clinical placements.

Medical students must have robust educational experiences, graduate and commence timely employment. Here, we describe how the Royal College of Surgeons in Ireland (RCSI) delivered clinical placements in medical programmes over the first three waves of the COVID-19 pandemic in Ireland, including a student-centred, holistic approach to students' educational, social and health needs with strong student involvement, re-organising the university's primary care team, developing COVID-19 PCR testing on site and re-focusing communications and student services. This resulted in re-arranging the students into learning communities, and students and staff electronically recorded their COVID-19 symptom status daily.

Donor genetic burden for cerebrovascular risk and kidney transplant outcome.

Background And Hypothesis: Kidney grafts from donors who died of stroke and related traits have worse outcomes relative to grafts from both living donors and those who died of other causes. We hypothesise that deceased donors, particularly those who died of stroke, have elevated polygenic burden for cerebrovascular traits. We further hypothesise that this donor polygenic burden is associated with inferior graft outcomes in the recipient.

A WORLDWIDE ENIGMA STUDY ON EPILEPSY-RELATED GRAY AND WHITE MATTER COMPROMISE ACROSS THE ADULT LIFESPAN.

Objectives: Temporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of grey and white matter structures. Evidence supports a progressive condition although the temporal evolution of TLE is poorly defined. This ENIGMA-Epilepsy study utilized multimodal magnetic resonance imaging (MRI) data to investigate structural alterations in TLE patients across the adult lifespan.

Somatic variants as a cause of drug-resistant epilepsy including mesial temporal lobe epilepsy with hippocampal sclerosis.

Objective: The contribution of somatic variants to epilepsy has recently been demonstrated, particularly in the etiology of malformations of cortical development. The aim of this study was to determine the diagnostic yield of somatic variants in genes that have been previously associated with a somatic or germline epilepsy model, ascertained from resected brain tissue from patients with multidrug-resistant focal epilepsy.

Methods: Forty-two patients were recruited across three categories: (1) malformations of cortical development, (2) mesial temporal lobe epilepsy with hippocampal sclerosis, and (3) nonlesional focal epilepsy.

Familial Variability of Disease Severity in Adult Patients With ADPKD.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic nephropathy and has striking familial variability of disease severity.

Methods: To better comprehend familial phenotypic variability, we analyzed clinical and pedigree data on 92 unrelated ADPKD kindreds with ≥2 affected individuals ( = 292) from an Irish population. All probands underwent genetic sequencing.

Functional / missense variant is associated with hematocrit in Andean highlanders.

Hypoxia-inducible factor pathway genes are linked to adaptation in both human and nonhuman highland species. , a notable target of hypoxia adaptation, is associated with relatively lower hemoglobin concentration in Tibetans. We provide evidence for an association between an adaptive variant (rs570553380) and the same phenotype of relatively low hematocrit in Andean highlanders.

Cerebral autoregulation in traumatic brain injury: ultra-low-frequency pressure reactivity index and intracranial pressure across age groups.

Background: The ultra-low-frequency pressure reactivity index (UL-PRx) has been established as a surrogate method for bedside estimation of cerebral autoregulation (CA). Although this index has been shown to be a predictor of outcome in adult and pediatric patients with traumatic brain injury (TBI), a comprehensive evaluation of low sampling rate data collection (0.0033 Hz averaged over 5 min) on cerebrovascular reactivity has never been performed.

Testing for pharmacogenomic predictors of ppRNFL thinning in individuals exposed to vigabatrin.

Background: The anti-seizure medication vigabatrin (VGB) is effective for controlling seizures, especially infantile spasms. However, use is limited by VGB-associated visual field loss (VAVFL). The mechanisms by which VGB causes VAVFL remains unknown.

Everolimus precision therapy for the GATOR1-related epilepsies: A case series.

Background: Pathogenic variants in the GAP activity towards RAGs 1 (GATOR1) complex genes (DEPDC5, NPRL2, NPRL3) cause focal epilepsy through hyperactivation of the mechanistic target of rapamycin pathway. We report our experience using everolimus in patients with refractory GATOR1-related epilepsy.

Methods: We performed an open-label observational study of everolimus for drug-resistant epilepsy caused by variants in DEPDC5, NPRL2 and NPRL3.

The Newfoundland and Labrador mosaic founder population descends from an Irish and British diaspora from 300 years ago.

The founder population of Newfoundland and Labrador (NL) is a unique genetic resource, in part due to its geographic and cultural isolation, where historical records describe a migration of European settlers, primarily from Ireland and England, to NL in the 18th and 19th centuries. Whilst its historical isolation, and increased prevalence of certain monogenic disorders are well appreciated, details of the fine-scale genetic structure and ancestry of the population are lacking. Understanding the genetic origins and background of functional, disease causing, genetic variants would aid genetic mapping efforts in the Province.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance.

Differential diagnosis of familial adult myoclonic epilepsy.

Objective: Familial adult myoclonic epilepsy (FAME) is an under-recognized disorder characterized by cortical myoclonus, generalized tonic-clonic seizures, and additional clinical symptoms, which vary depending on the FAME subtype. FAME is caused by pentanucleotide repeat expansions of intronic TTTCA/TTTTA in different genes. FAME should be distinguished from a range of differential diagnoses.

The genetic history of Scandinavia from the Roman Iron Age to the present.

We investigate a 2,000-year genetic transect through Scandinavia spanning the Iron Age to the present, based on 48 new and 249 published ancient genomes and genotypes from 16,638 modern individuals. We find regional variation in the timing and magnitude of gene flow from three sources: the eastern Baltic, the British-Irish Isles, and southern Europe. British-Irish ancestry was widespread in Scandinavia from the Viking period, whereas eastern Baltic ancestry is more localized to Gotland and central Sweden.

Rare Genetic Variation and Outcome of Surgery for Mesial Temporal Lobe Epilepsy.

Objective: Genetic factors have long been debated as a cause of failure of surgery for mesial temporal lobe epilepsy (MTLE). We investigated whether rare genetic variation influences seizure outcomes of MTLE surgery.

Methods: We performed an international, multicenter, whole exome sequencing study of patients who underwent surgery for drug-resistant, unilateral MTLE with normal magnetic resonance imaging (MRI) or MRI evidence of hippocampal sclerosis and ≥2-year postsurgical follow-up.

Germline mosaicism in a family with haploinsufficiency.

Haploinsufficiency of the methyl-CpG-binding domain protein 5 () gene causes a neurodevelopmental disorder that includes intellectual disability, developmental delay, speech impairment, seizures, sleep disturbances, and behavioral difficulties. Microdeletion of 2q23.1 is the most common cause of haploinsufficiency, although haploinsufficiency may also cause this genetic disorder.

The population genomic legacy of the second plague pandemic.

Human populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%-40%.