Successes and shortfalls of community Plusoptix photoscreening: results from the iSee study in Southwestern Ontario

ObjectiveThe purpose of this work is to provide the final results from a community-wide photoscreening program in Southwestern Ontario for children aged 18 to 72 months, and to estimate the prevalence of amblyogenic risk factors in this population.Study DesignProspective, multisite photoscreening program.Participants5959 children aged 18–72 months were recruited and screened in Southwestern Ontario at 210 locations over a period of 3 years and 4 months.MethodsOphthalmic screening examinations were performed with the Plusoptix S12 photoscreener. The threshold for the referral criteria used was the manufacturer's criteria on receiver operating characteristics 4.ResultsThe screening was negative in 5386 children (90.4%), positive in 403 (6.8%), and unreadable in 170 (2.9%); 42% of all screened children were ≤36 months old. The estimated amblyogenic risk factor prevalence of anisometropia was 4.0%, astigmatism was 3.1%, hyperopia was 1.1%, myopia was 0.4%, and strabismus was 0.4%. Of the 403 referred children, 99 (24.5%) completed a formal eye examination based on the responses returned to the study site.ConclusionsThis is the first Canadian study that provides data on amblyogenic risk factors based on a volunteer-led photoscreening program. Photoscreening is an effective screening tool, particularly for pre-school-aged children; however, the lack of mandatory follow-up to ensure that children receive proper treatment based on cycloplegic refraction reduces the efficacy of screening.     

Electrophysiological findings in immune checkpoint inhibitor-related peripheral neuropathy

ObjectiveTo report the electrodiagnostic features of immune checkpoint inhibitor (ICI)-related neuropathy.MethodsWe retrospectively reviewed clinical presentations and electrodiagnostic features of 23 patients studied after receiving immune checkpoint inhibitors (ICIs). The presentations for electrodiagnostic evaluation included an acute neuropathy or neuromuscular junction disorder. We applied established electrodiagnostic criteria for polyneuropathy and acute demyelinating neuropathy.ResultsWe identified acute demyelinating neuropathy (13 cases), axonal sensory motor neuropathy (5), pure sensory neuropathy (4) and mononeuropathy (1). 13 patients had acute demyelinating neuropathy confirmed by demonstrating demyelination in 2 or more nerves; 3 additional patients had demyelination in only one nerve. Analysis of motor nerve conduction parameters revealed demyelination involving median and ulnar nerve distal motor latencies as well as median, ulnar and peroneal nerve conduction velocities. Conduction block was found in median, ulnar and peroneal nerves. The remaining one-third patients without demyelination had acute painful axonal neuropathy. Coexisting myopathic changes (6) and neuromuscular junction dysfunction (4) were also identified.ConclusionsOur findings suggest that, while immune-mediated motor nerve demyelination is the primary underlying mechanism of ICI-related neuropathy, axonal painful neuropathy can also be an important presentation. Early recognition and effective intervention may reduce morbidity and permanent disability.SignificanceElectrophysiological studies might be useful in the evaluation of ICI-related neuropathy.     

Establishment of a convenient system for the long-term culture and study of non-neoplastic human salivary gland epithelial cells

Epithelial cells appear to play an important role in the initiation and maintenance of autoimmune lesions in the salivary glands of patients with Sjögren's syndrome. Therefore, the detailed study of immunological function of salivary gland epithelial cells (SGEC) may provide useful information for the understanding of Sjögren's syndrome pathogenesis. In this report we aimed to formulate a protocol for the establishment of human non‐neoplastic SGEC lines as a tool for the study of the physiology and pathophysiology of these cells. Pointing towards a practical approach, we sought to establish SGEC lines from quite a limited amount of biopsy tissue obtained during the diagnostic evaluation of patients. Herein, the favorable conditions for the long‐term maintenance of human non‐neoplastic SGEC lines are presented and involve the successive application of a serum‐containing and a serum‐free culture medium, supplemented with essential epithelial growth factors. This protocol has been found reliable and convenient, as attested by the reproducible establishment of non‐neoplastic SGEC lines. The analysis of SGEC phenotypic features, as well as a coculture system for the study of interactions between epithelial cells and lymphocytes, are also described. Such techniques may provide valuable means for the functional and molecular investigation of human SGEC and particularly for the study of Sjögren's syndrome and other disorders of glandular epithelia.     

Acute necrotizing encephalopathy associated with parainfluenza virus in a Caucasian child

Acute necrotizing encephalopathy is a severe parainfectious disorder with a clear racial predilection for Oriental children living in the Far East. The prognosis was originally reported as grave; however, a mild form of the disease has recently been described. A case of parainfluenza virus-associated acute necrotizing encephalopathy in a Caucasian child with a mild clinical course and excellent prognosis is presented. In this patient, the initial clinical picture was not very impressive, and the diagnosis was delayed until the third week of the illness, when neuroimaging was performed. Two months later, clinical and neuroimaging findings had almost completely resolved. Suggested criteria for a benign prognosis, such as normal liver function and cerebrospinal fluid protein levels, asymmetric thalamic lesions, and no brainstem involvement, were relevant in the present case. An extended diagnostic work-up for metabolic, vascular, coagulation, and infectious diseases was negative apart from a seroconversion for parainfluenza virus. To our knowledge, this is the first reported case of acute necrotizing encephalopathy associated with parainfluenza virus infection. Acute necrotizing encephalopathy, especially in the mild form, might not be fully recognized and could be underdiagnosed in Europe, where the reported incidence of the syndrome is very low.     

Simultaneous quantification of daptomycin and rifampicin in plasma by ultra performance liquid chromatography: Application to a pharmacokinetic study

A rapid and simple method based on ultra performance liquid chromatography (UPLC) with ultra violet detection has been developed for the determination of daptomycin (DPT) and rifampicin (RFM) in rabbit plasma using 4-nitrophenol as internal standard (IS). Sample preparation involved protein precipitation with an acetonitrile:methanol mixture and centrifugation. Chromatographic separation was achieved on an Acquity BEH C18 column (100 mm × 2.1 mm, 1.7 μm) using gradient elution with methanol and 0.1% aqueous TFA. The total analysis time was 4.5 min with DPT and RFM eluting at 1.9 and 2.1 min, respectively. The method was fully validated with a lower limit of quantitation (LLOQ) of 2 μg mL⁻¹ for both DPT and RFM. The intra- and inter-day precision, measured as % relative standard deviation, were less than 12.1 for DPT and 10.7 for RFM, respectively. This validated method was successfully applied to a pharmacokinetic study involving intravenous administration of 14 mg kg⁻¹ DPT and 30 mg kg⁻¹ RFM to rabbits.     

A role for a novel protein,nucleolin, in Parkinson's disease

Although much has been learned in the last few decades concerning the molecular mechanisms and pathways associated with the development of familial as well as sporadic Parkinson disease (PD), the precise mechanisms and specific proteins responsible for mediating these effects remain to be elucidated. Thus, the identification and biological evaluation of novel proteins involved in these pathways is critical to providing a more comprehensive understanding of PD pathogenesis. Previously, in a cellular model of PD, we identified nucleolin as a protein interacting with α-synuclein and DJ-1, two critical proteins involved in PD pathogenesis. In our current study, we found the expression levels of nucleolin were dramatically reduced in the substantia nigra pars compacta of human PD subjects, compared with controls. Furthermore, manipulation of nucleolin in an in vitro model of PD resulted in significant alterations in the generation of oxidative stress as well as proteasomal inhibition following rotenone exposure. Interestingly, nucleolin expression did not influence mitochondrial complex I activity, suggesting a selective specificity for oxidative stress and proteasomal pathways.