Developing, Characterizing, and Modeling CRISPR-Based Point-of-Use Pathogen Diagnostics.

Recent years have seen intense interest in the development of point-of-care nucleic acid diagnostic technologies to address the scaling limitations of laboratory-based approaches. Chief among these are combinations of isothermal amplification approaches with CRISPR-based detection and readouts of target products. Here, we contribute to the growing body of rapid, programmable point-of-care pathogen tests by developing and optimizing a one-pot NASBA-Cas13a nucleic acid detection assay.

Developing, characterizing and modeling CRISPR-based point-of-use pathogen diagnostics.

Recent years have seen intense interest in the development of point-of-care nucleic acid diagnostic technologies to address the scaling limitations of laboratory-based approaches. Chief among these are combinations of isothermal amplification approaches with CRISPR-based detection and readouts of target products. Here, we contribute to the growing body of rapid, programmable point-of-care pathogen tests by developing and optimizing a one-pot NASBA-Cas13a nucleic acid detection assay.

The contributions of neonatal inhalation of copper to air pollution-induced neurodevelopmental outcomes in mice.

Exposures to ambient ultrafine particle (UFP) air pollution (AP) during the early postnatal period in mice (equivalent to human third trimester brain development) produce male-biased changes in brain structure, including ventriculomegaly, reduced brain myelination, alterations in neurotransmitters and glial activation, as well as impulsive-like behavioral characteristics, all of which are also features characteristic of male-biased neurodevelopmental disorders (NDDs). The purpose of this study was to ascertain the extent to which inhaled Cu, a common contaminant of AP that is also dysregulated across multiple NDDs, might contribute to these phenotypes. For this purpose, C57BL/6J mice were exposed from postnatal days 4-7 and 10-13 for 4 hr/day to inhaled copper oxide (CuO) nanoparticles at an environmentally relevant concentration averaging 171.

Recurrence of Cryptogenic (ESUS) Strokes in the First Year: Predictors and Outcome-A South Indian Study.

Introduction: Around 9-25% of ischemic strokes are embolic stroke of undetermined source (ESUS) with an annual recurrence risk of 4.5-5%. Regarding ESUS, studies from India are limited.

Isolated Myelitis and Intramedullary Spinal Cord Abscess in Melioidosis-A Case Report.

Neuromelioidosis is a severe tropical infection with high morbidity and mortality. Isolated myelitis is an extremely rare manifestation of melioidosis which may evade diagnosis. We report a 69-year-old diabetic male patient who presented with acute flaccid paraplegia and longitudinally extensive myelitis and no systemic symptoms.

Attention deficit hyperactivity disorder: a rare clinical presentation of L-2-hydroxyglutaric aciduria.

L-2-hydroxyglutaric aciduria (L2HGA) is a rare autosomal recessive neurometabolic disorder caused by the deficiency of L-2-hydroxyglutarate dehydrogenase (L2HGDH) enzyme. Dystonia, ataxia, pyramidal involvement and seizures are the common clinical manifestations. Coexisting behavioural problems and intellectual disability are also seen, however attention deficit hyperactivity disorder (ADHD) as the presenting clinical feature in L2HGA is rarely described.

Binasal congruous hemianopia secondary to functional visual loss: A case report.

Introduction: To describe an unusual case of binasal congruous hemianopia secondary to functional visual loss (FVL).

Patient Concerns: A 24 year-old male was referred originally by his optician at the Emergency Eye Department of the Leicester Royal Infirmary in October 2018 with visual field changes affecting the nasal field of vision in both eyes on routine eye examination. The patient reported ongoing headaches over the last 6 weeks to 8 weeks associated with simultaneous peripheral visual field changes.

Pregnancy outcomes in aquaporin-4-positive neuromyelitis optica spectrum disorder.

Objective: To investigate the association between neuromyelitis optica spectrum disorder (NMOSD) and pregnancy outcome.

Methods: An international cohort of women with aquaporin-4 antibody-positive NMOSD and ≥1 pregnancy was studied retrospectively. Multivariate logistic regression was used to investigate whether pregnancy after NMOSD onset was associated with an increased risk of miscarriage (cohort of 40 women) or preeclampsia (cohort of 57 women).

Olfactory Pathology in Central Nervous System Demyelinating Diseases.

Olfactory dysfunction is common in multiple sclerosis (MS). Olfactory bulb and tract pathology in MS and other demyelinating diseases remain unexplored. A human autopsy cohort of pathologically confirmed cases encompassing the spectrum of demyelinating disease (MS; n = 17), neuromyelitis optica [(NMO); n = 3] and acute disseminated encephalomyelitis [(ADEM); n = 7] was compared to neuroinflammatory [herpes simplex virus encephalitis (HSE); n = 3], neurodegenerative [Alzheimer's disease (AD); n = 4] and non-neurologic (n = 8) controls.

Opportunistic infections of the retina in patients with aquaporin-4 antibody disease.

Importance: Patients with neuromyelitis optica who have aquaporin-4 antibodies are being identified and receiving immunosuppressant treatment earlier and more aggressively as a result of increasing awareness of the importance of preventing relapses responsible for the high morbidity and mortality associated with the disease. To our knowledge, opportunistic retinal infection in patients with aquaporin-4 antibodies who are receiving immunosuppressants has not been reported to date.

Observations: We describe 2 patients with aquaporin-4 antibodies who were receiving conventional doses of first-line immunosuppressive therapy.

Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: a comparative study.

Importance: Most patients with neuromyelitis optica (NMO) and many with NMO spectrum disorder have autoantibodies against aquaporin-4 (AQP4-Abs), but recently, myelin-oligodendrocyte glycoprotein antibodies (MOG-Abs) have been found in some patients. Here, we showed that patients with NMO/NMOSD with MOG-Abs demonstrate differences when compared with patients with AQP4-Abs.

Objective: To characterize the features of patients with NMO/NMOSD with MOG-Abs and compare them with patients with AQP4-Ab-positive NMO/NMOSD.

Longitudinally extensive transverse myelitis with and without aquaporin 4 antibodies.

Importance: Aquaporin 4 antibody (AQP4-Ab)-negative patients with longitudinally extensive transverse myelitis (LETM) behave differently from those with AQP4-Ab. Aquaporin 4 antibody-negative neuromyelitis optica (NMO) is rare when good assays are used.

Objective: To assess if AQP4-Ab-negative patients with LETM share similar disease characteristics with AQP4-Ab-positive patients or whether they have distinct features and alternative diagnoses.

Methotrexate is an alternative to azathioprine in neuromyelitis optica spectrum disorders with aquaporin-4 antibodies.

Background: Neuromyelitis optica (NMO) is a severe autoimmune inflammatory disorder associated with considerable relapse-related disability. Immunosuppression is the mainstay of treatment but many patients do not tolerate first-line immunosuppressive agents, or experience ongoing relapses.

Objective: To evaluate the effectiveness and tolerability of methotrexate in aquaporin-4 antibody seropositive NMO spectrum disorders.

Reduced EDSS progression in multiple sclerosis patients treated with modafinil for three years or more compared to matched untreated subjects.

Background: Modafinil is a wakefulness-promoting drug used to treat narcolepsy, obstructive sleep apnoea, and shift-work sleep disorder. Modafinil has also been used for the treatment of fatigue and excessive sleepiness in other neurological disorders including multiple sclerosis, psychiatric disorders, and for cognitive enhancement. Recent preclinical studies suggest a potential neuroprotective effect of modafinil in neurodegenerative diseases.

Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan.

Neuromyelitis optica and neuromyelitis optica spectrum disorders have been recently associated with the disease-specific autoantibody aquaporin-4, thought to be pathogenic. Identifying this antibody has allowed the clinical phenotype to be broadened. It is clear that some patients with similar clinical features do not have this antibody and may have a different condition with different outcomes and prognosis.