Sentinels at the wall: epithelial‐derived cytokines serve as triggers of upper airway type 2 inflammation

Recent evidence has demonstrated an expanding role of respiratory epithelial cells in immune surveillance and modulation. Studies have been focusing on the earliest events that link epithelial injury to downstream inflammatory responses. Cytokines produced by and released from respiratory epithelial cells are among these early trigger signals. Epithelial‐derived cytokines, namely thymic stromal lymphopoietin (TSLP), interleukin (IL)‐25, and IL‐33, have come to the forefront of recent investigations. Each of these 3 cytokines has been implicated in chronic rhinosinusitis (CRS), asthma, and atopy. Herein we review studies elucidating the roles of epithelial‐derived cytokines in the pathobiology of upper airway disease, with particular emphasis on type 2 inflammatory conditions.     

Deep‐learning based fully automatic segmentation of the globus pallidus interna and externa using ultra‐high 7 Tesla MRI

Deep brain stimulation (DBS) surgery has been shown to dramatically improve the quality of life for patients with various motor dysfunctions, such as those afflicted with Parkinson''s disease (PD), dystonia, and essential tremor (ET), by relieving motor symptoms associated with such pathologies. The success of DBS procedures is directly related to the proper placement of the electrodes, which requires the ability to accurately detect and identify relevant target structures within the subcortical basal ganglia region. In particular, accurate and reliable segmentation of the globus pallidus (GP) interna is of great interest for DBS surgery for PD and dystonia. In this study, we present a deep‐learning based neural network, which we term GP‐net, for the automatic segmentation of both the external and internal segments of the globus pallidus. High resolution 7 Tesla images from 101 subjects were used in this study; GP‐net is trained on a cohort of 58 subjects, containing patients with movement disorders as well as healthy control subjects. GP‐net performs 3D inference in a patient‐specific manner, alleviating the need for atlas‐based segmentation. GP‐net was extensively validated, both quantitatively and qualitatively over 43 test subjects including patients with movement disorders and healthy control and is shown to consistently produce improved segmentation results compared with state‐of‐the‐art atlas‐based segmentations. We also demonstrate a postoperative lead location assessment with respect to a segmented globus pallidus obtained by GP‐net.     

Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection

SARS-CoV-2, a member of the coronavirus family, is the causative agent of the COVID-19 pandemic. Currently, there is still an urgent need in developing an efficient therapeutic intervention. In this study, we aimed at evaluating the therapeutic effect of a single intranasal treatment of the TLR3/MDA5 synthetic agonist Poly(I:C) against a lethal dose of SARS-CoV-2 in K18-hACE2 transgenic mice. We demonstrate here that early Poly(I:C) treatment acts synergistically with SARS-CoV-2 to induce an intense, immediate and transient upregulation of innate immunity-related genes in lungs. This effect is accompanied by viral load reduction, lung and brain cytokine storms prevention and increased levels of macrophages and NK cells, resulting in 83% mice survival, concomitantly with long-term immunization. Thus, priming the lung innate immunity by Poly(I:C) or alike may provide an immediate, efficient and safe protective measure against SARS-CoV-2 infection.     

Hyperdense middle cerebral artery sign: can it be used to select intra-arterial versus intravenous thrombolysis in acute ischemic stroke?

BACKGROUND: Stroke patients with a hyperdense middle cerebral artery sign (HMCAS) may respond less favorably to intravenous (IV) thrombolysis. OBJECTIVE: To compare outcomes of patients with and without early CT findings treated with IV versus intra-arterial (IA) recombinant tissue plasminogen activator (rtPA). METHODS: Initial and 24-hour CT scans of the head were evaluated in 83 consecutive stroke patients (66 on IV rtPA, 17 on IA rtPA). Time permitting, a CT angiogram was performed immediately after the initial CT scan to ascertain major cerebral artery occlusion. Demographics and etiological stroke subtype, times to thrombolysis and CT scan, baseline (prethrombolysis) and 24-hour National Institutes of Health stroke scale (NIHSS) score, discharge NIHSS score and 90-day modified Rankin scale (mRS) were recorded. The initial CT of these patients was examined for early signs of stroke. The 24-hour scan was reviewed for the presence of infarct, hemorrhage and persistence of HCMAS. RESULTS: A favorable outcome, indicated by a significant improvement in the discharge NIHSS score, was noted with IA rtPA, irrespective of the presence (p = 0.001) or absence (p = 0.01) of HCMAS. A less favorable outcome in discharge NIHSS score was noted with IV rtPA in patients with HCMAS (p = not significant) than those without the sign (p < 0.001). A similar proportion of patients with HCMAS exhibited a neurological improvement at 24 h as those without the sign in the IA rtPA group (p = 0.9). However, a smaller proportion of patients with HCMAS exhibited a neurological improvement at 24 h than those without the sign in the IV rtPA group (p = 0.005). The results were similar using 90-day mRS 相似文献   

Multiple de novo MPZ (P0) point mutations in a sporadic Dejerine-Sottas case

Dejerine-Sottas syndrome (DSS), a severe demyelinating peripheral neuropathy with onset in infancy, has been associated with mutations in either PMP22 or MPZ. Most cases of DSS are caused by a single heterozygous dominant point mutation. We identified three de novo point mutations in MPZ exon 3 in a sporadic DSS patient. These three point mutations occur on the same allele and result in three novel amino acid substitutions: Ile(85)Thr, Asn(87)His, and Asp(99)Asn. Our data raise the question as to the potential mechanism(s) involved in the formation of multiple point mutations at a given locus. Hum Mutat 10:21–24, 1997. © 1997 Wiley-Liss, Inc.     

Cognitive impairment in geriatric chronic schizophrenic patients: a cross-national study in New York and London

Severe cognitive impairment has been reported in large numbers of geriatric chronic schizophrenic patients in the US, with this impairment also being related to severe negative symptoms and adaptive deficits. It is not clear if this impairment is related to the particular environment of the American state hospitals and would not generalize to other countries. In this study, a sample composed of geriatric (age > 70) chronic schizophrenic patients in London, who were assessed by the Team for Assessment of Psychiatric Services (TAPS) (N = 137), and a group of geriatric chronic schizophrenic patients in a New York psychiatric center (N = 86) were compared for the severity of cognitive impairment and on measures of adaptive functioning. Patients received essentially identical Mini-Mental State Examination (MMSE) scores, but differed on 3/4 measures of adaptive functioning. The correlations among all four aspects of adaptive deficit and MMSE scores were very similar in the two samples, suggesting that cognitive deficits and their relationship with adaptive impairments are relatively invariant across different psychiatric systems of care, while adaptive functioning deficits are more variable and possibly more influenced by environmental factors. These data add to previous results suggesting that cognitive impairment is a common feature in poor outcome geriatric patients with schizophrenia. © 1997 John Wiley & Sons, Ltd.