【In Press】 Is Marcus Gunn jaw winking a primitive reflex? I. Rat neuroanatomy

AIM: To investigate a possible trigeminal proprioceptive-oculomotor neural pathway and explore possible synaptic connections between neurons in this pathway. Attempt to bring a new insight to mechanism of Marcus Gunn Syndrome (MGS). METHODS: Anterograde and retrograde tract tracing combined with immunofluorescent stain in rats. Intracellular injection of tracer into electrophysiologically identified rat mesencephalic trigeminal nucleus (Vme) neurons and tracing axon trajectory. RESULTS: Following injections of anterograde tracers into the Vme, labeled terminals were observed ipsilateral in oculomotor and trochlear nuclei (III/IV), as well as in their premotor neurons in interstitial nucleus of Cajal and Darkschewitsch nucleus (INC/DN). Combining with Choline Acetyltransferase (ChAT) immunofluorescent stain, it showed that Vme projecting terminals contact upon ChAT positive III/IV motoneurons under confocal microscope. By retrograde labeling premotor neurons of the III, it showed that Vme neuronal terminals contact with retrogradely labeled pre-oculomotor neurons in the INC/DN. Axons of intracellularly labeled Vme neurons that respond to electric stimuli of the masseter nerve traveled into the ipsilateral III. CONCLUSIONS: There may exist a trigeminal proprioceptive-oculomotor system neural circuit in the rat, which is related to vertical-torsional eye movements. Possible association of this pathway with MGS etiology was discussed.     

Corticobulbar projections from distinct motor cortical areas to the reticular formation in macaque monkeys

Corticospinal and corticobulbar descending pathways act in parallel with brainstem systems, such as the reticulospinal tract, to ensure the control of voluntary movements via direct or indirect influences onto spinal motoneurons. The aim of this study was to investigate the corticobulbar projections from distinct motor cortical areas onto different nuclei of the reticular formation. Seven adult macaque monkeys were analysed for the location of corticobulbar axonal boutons, and one monkey for reticulospinal neurons' location. The anterograde tracer BDA was injected in the premotor cortex (PM), in the primary motor cortex (M1) or in the supplementary motor area (SMA), in 3, 3 and 1 monkeys respectively. BDA anterograde labelling of corticobulbar axons were analysed on brainstem histological sections and overlapped with adjacent Nissl‐stained sections for cytoarchitecture. One adult monkey was analysed for retrograde CB tracer injected in C5‐C8 hemispinal cord to visualise reticulospinal neurons. The corticobulbar axons formed bilateral terminal fields with boutons terminaux and en passant, which were quantified in various nuclei belonging to the Ponto‐Medullary Reticular Formation (PMRF). The corticobulbar projections from both PM and SMA tended to end mainly ipsilaterally in PMRF, but contralaterally when originating from M1. Furthermore, the corticobulbar projection was less dense when originating from M1 than from non‐primary motor areas (PM, SMA). The main nuclei of bouton terminals corresponded to the regions where reticulospinal neurons were located with CB retrograde tracing. In conclusion, the corticobulbar projection differs according to the motor cortical area of origin in density and laterality.     

Architecture and organization of mouse posterior parietal cortex relative to extrastriate areas

The posterior parietal cortex (PPC) is a multifaceted region of cortex, contributing to several cognitive processes, including sensorimotor integration and spatial navigation. Although recent years have seen a considerable rise in the use of rodents, particularly mice, to investigate PPC and related networks, a coherent anatomical definition of PPC in the mouse is still lacking. To address this, we delineated the mouse PPC, using cyto‐ and chemoarchitectural markers from Nissl‐, parvalbumin‐and muscarinic acetylcholine receptor M2‐staining. Additionally, we performed bilateral triple anterograde tracer injections in primary visual cortex (V1) and prepared flattened tangential sections from one hemisphere and coronal sections from the other, allowing us to co‐register the cytoarchitectural features of PPC with V1 projections. This revealed that extrastriate area A was largely contained within lateral PPC, that medial PPC overlapped with the anterior portion of area AM, and that anterior RL overlapped partially with area PtP. Furthermore, triple anterograde tracer injections in PPC showed strong projections to associative thalamic nuclei as well as higher visual areas, orbitofrontal, cingulate and secondary motor cortices. Retrograde circuit mapping with rabies virus further showed that all cortical connections were reciprocal. These combined approaches provide a coherent definition of mouse PPC that incorporates laminar architecture, extrastriate projections, thalamic, and cortico–cortical connections.     

Automatic contour segmentation of cervical cancer using artificial intelligence

In cervical cancer treatment, radiation therapy is selected based on the degree of tumor progression, and radiation oncologists are required to delineate tumor contours. To reduce the burden on radiation oncologists, an automatic segmentation of the tumor contours would prove useful. To the best of our knowledge, automatic tumor contour segmentation has rarely been applied to cervical cancer treatment. In this study, diffusion-weighted images (DWI) of 98 patients with cervical cancer were acquired. We trained an automatic tumor contour segmentation model using 2D U-Net and 3D U-Net to investigate the possibility of applying such a model to clinical practice. A total of 98 cases were employed for the training, and they were then predicted by swapping the training and test images. To predict tumor contours, six prediction images were obtained after six training sessions for one case. The six images were then summed and binarized to output a final image through automatic contour segmentation. For the evaluation, the Dice similarity coefficient (DSC) and Hausdorff distance (HD) was applied to analyze the difference between tumor contour delineation by radiation oncologists and the output image. The DSC ranged from 0.13 to 0.93 (median 0.83, mean 0.77). The cases with DSC <0.65 included tumors with a maximum diameter < 40 mm and heterogeneous intracavitary concentration due to necrosis. The HD ranged from 2.7 to 9.6 mm (median 4.7 mm). Thus, the study confirmed that the tumor contours of cervical cancer can be automatically segmented with high accuracy.     

Consequences of an unrecognized measles exposure in an emergency department

A recent measles case in a paediatric hospital ED resulted in 111 individuals (patients, family members and health‐care workers) potentially being exposed to measles. This report documents the efforts taken to contact trace and provide best practice care for all those exposed to the index case. It also provides a snapshot of community prevalence information on immunity to measles. One hundred per cent of contacted children (n= 24) eligible for vaccination were immunized, whereas 96% of adults surveyed or tested (n= 44) had assumed or proven immunity. However, six infants aged between 6 and 9 months were exposed and might have been a sufficiently large reservoir to facilitate the ongoing spread of measles in the community, if contact tracing and preventative measures had not occurred. This scenario also highlights the need to consider measles in the ED, particularly among travellers, with urgent isolation of suspected cases in the ED according to guidelines discussed.     

Functional organization of mustached bat inferior colliculus: II. Connections of the FM2 region

Echolocating bats estimate target distance by analyzing the time delay between frequency-modulated portions of their emitted ultrasonic vocalizations and the resultant echoes. In the companion paper we investigated, in the central nucleus of the inferior colliculus, the representation of the predominant second-harmonic frequency-modulated component (FM2) of the mustached bat biosonar signal (O'Neill et al.: J. Comp. Neurol. 283:000-000,'89). In the present paper we report the connections of this part of the colliculus, as determined by focal, iontophoretic injections of HRP following single-unit mapping of the FM2 representation. It was found that the major inputs to the FM2 region of the inferior colliculus come from the contralateral cochlear nucleus; ipsilaterally from the medial superior olive, periolivary nuclei, and ventral and intermediate nuclei of the lateral lemniscus; and bilaterally from the lateral superior olive and dorsal nucleus of the lateral lemniscus. This study identifies for the first time those specific regions of brainstem nuclei providing input to the central nucleus of the inferior colliculus that process FM2 information in the mustached bat. The primary outputs of the FM2 region project to the medial and dorsal divisions of the medial geniculate body. In sharp contrast to other mammals, we found little evidence of connections to the ventral division of the medial geniculate. Other regions receiving significant inputs from the FM2 area include the deep superior colliculus ipsilaterally and the ipsilateral lateral pontine nuclei. Some fibers also terminated near the midline in the dorsal midbrain periaqueductal gray. Sparse intrinsic connections were also seen to the ipsilateral dorsoposterior division of the central nucleus and to the contralateral inferior colliculus at a location homologous to the injection site in the anterolateral division. The finding that FM2 projections to the medial geniculate heavily favor the medial and dorsal divisions is consistent with the location of "FM-FM" delay-dependent facilitation neurons found by Olsen (Processing of Biosonar Information by the Medical Geniculate Body of the Mustached Bat, Pteronotus parnellii. Dissertation, Washington Univ., St. Louis, '86) in these divisions, and with thalamocortical projection patterns in this species. These findings demonstrate that for the FM portions of the biosonar signal, a transformation from a tonotopic form of processing to a more specialized, convergent pattern of organization occurs at the level of the inferior colliculus outputs.     

Projections to the rostral reticular thalamic nucleus in the rat

Summary Afferent pathways to the rostral reticular thalamic nucleus (Rt) in the rat were studied using anterograde and retrograde lectin tracing techniques, with sensitive immunocytochemical methods. The analysis was carried out to further investigate previously described subregions of the reticular thalamic nucleus, which are related to subdivisions of the dorsal thalamus, in the paraventricular and midline nuclei and three segments of the mediodorsal thalamic nucleus. Cortical inputs to the rostral reticular nucleus were found from lamina VI of cingulate, orbital and infralimbic cortex. These projected with a clear topography to lateral, intermediate and medial reticular nucleus respectively. Thalamic inputs were found from lateral and central segments of the mediodorsal nucleus to the lateral and intermediate rostral reticular nucleus respectively and heavy paraventricular thalamic inputs were found to the medial reticular nucleus. In the basal forebrain, afferents were found from the vertical and horizontal limbs of the diagonal band, substantia innominata, ventral pallidum and medial globus pallidus. Brainstem projections were identified from ventrolateral periaqueductal grey and adjacent sites in the mesencephalic reticular formation, laterodorsal tegmental nucleus, pedunculopontine nucleus, medial pretectum and ventral tegmental area. The results suggest a general similarity in the organisation of some brainstem Rt afferents in rat and cat, but also show previously unsuspected inputs. Furthermore, there appear to be at least two functional subdivisions of rostral Rt which is reflected by their connections with cortex and thalamus. The studies also extend recent findings that the ventral striatum, via inputs from the paraventricular thalamic nucleus, is included in the circuitry of the rostral Rt, providing further evidence that basal ganglia may function in concert with Rt. Evidence is also outlined with regard to the possibility that rostral Rt plays a significant role in visuomotor functions.Abbreviations ac anterior commissure - aca anterior commissure, anterior - Acb accumbens nucleus - AI agranular insular cortex - AM anteromedial thalamic nucleus - AV anteroventral thalamic nucleus - BST bed nucleus of stria terminalis - Cg cingulate cortex - CG central gray - CL centrolateral thalamic nucleus - CM central medial thalamic nucleus - CPu caudate putamen - DR dorsal raphe nucleus - DTg dorsal tegmental nucleus - EP entopeduncular nucleus - f fornix - Fr2 Frontal cortex, area 2 - G gelatinosus thalamic nucleus - GP globus pallidus - Hb habenula - HDB horizontal limb of diagonal band - IAM interanterodorsal thalamic nucleus - ic internal capsule - INC interstitial nucleus of Cajal - IF interfascicular nucleus - IL infralimbic cortex - IP interpeduncular nucleus - LC locus coeruleus - LDTg laterodorsal tegmental nucleus - LH lateral hypothalamus - LHb lateral habenular nucleus - ll lateral lemniscus - LO lateral orbital cortex - LPB lateral parabrachial nucleus - MD mediodorsal thalamic nucleus - MDL mediodorsal thalamic nucleus, lateral segment - Me5 mesencephalic trigeminal nucleus - MHb medial habenular nucleus - mlf medial longitudinal fasciculus - MnR median raphe nucleus - MO medial orbital cortex - mt mammillothalamic tract - OPT olivary pretectal nucleus - pc posterior commissure - PC paracentral thalamic nucleus - PF parafascicular thalamic nucleus - PPTg pedunculopontine tegmental nucleus - PrC precommissural nucleus - PT paratenial thalamic nucleus - PV paraventricular thalamic nucleus - PVA paraventricular thalamic nucleus, anterior - R red nucleus - Re reuniens thalamic nucleus - RRF retrorubral field - Rt reticular thalamic nucleus - Scp superior cerebellar peduncle - SI substantia innominata - sm stria medullaris - SNR substantia nigra, reticular - st stria terminalis - TT tenia tecta - VL ventrolateral thalamic nucleus - VO ventral orbital cortex - VP ventral pallidum - VPL ventral posterolateral thalamic nucleus - VTA ventral tegmental area - 3 oculomotor nucleus - 3V 3rd ventricle - 4 trochlear nucleus     

Identifying Contact Risks for SARS-CoV-2 Transmission to Healthcare Workers during Outbreak on COVID-19 Ward

We assessed the risk for different exposures to SARS-CoV-2 during a COVID-19 outbreak among healthcare workers on a hospital ward in late 2020. We found working with isolated COVID-19 patients did not increase the risk of COVID-19 among workers, but working shifts with presymptomatic healthcare coworkers did.