Guillain-Barré syndrome in a patient previously diagnosed with COVID-19.

As the COVID-19 pandemic continues to progress, the medical community is rapidly trying to identify complications and patterns of disease to improve patient outcomes. In a recent systematic review, it has been reported that isolated cases of Guillain-Barre Syndrome (GBS) have occurred secondary to COVID-19 infection. GBS is defined as a rare, but potentially fatal, immune mediated disease of peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and 2015 in Latin America. While several cases of GBS secondary to COVID-19 infection have been reported in Italy, only one case has been reported in the United States (US). The reported case in the US was a 54- year old male. We present a case of GBS secondary to a COVID-19 infection and believe this to be the first documented female case in the US and the second documented case in the US overall. The presented case aims to supplement the existing body of knowledge and to assist clinicians in managing complications of COVID-19.

Bacterial and Viral Products Affect Differential Pattern Recognition Receptor Activation of Chicken Thrombocytes Evidenced through RNA Sequencing.

It is now well understood that thrombocytes (nucleated platelets) express TLRs and respond to both bacterial and viral products. Release of proinflammatory molecules can be expected following relatively short exposure times to LPS, lipoteichoic acid (LTA), thymidine homopolymer phosphorothioate oligonucleotide [Poly(dT)], and polyinosinic-polycytidylic acid [Poly(I:C)]. This study reports the varied expressions of genes encoded for components of the TLR, nucleotide binding oligomerization domain-like receptor, and retinoic acid-inducible gene RIG-like receptor signaling pathways in response to the TLR ligands listed above. Highly sensitive RNA-sequencing technologies were used to analyze the complete transcriptome of thrombocytes treated with all four microbial products for a period of 1 h. A total of 14,326 gene transcripts were found in chicken thrombocytes across all ligand exposures. After 1 h of stimulation with ligands, 87, 138, 1013, and 22 genes were upregulated for LTA, LPS, Poly(dT), and Poly(I:C), and 12, 142, 249, and 16 genes were downregulated for LTA, LPS, Poly(dT), and Poly(I:C), respectively, with at least a 1-fold change relative to unexposed thrombocytes. Summarizations of biological processes, protein classes, and biochemical pathways reveal the role of chicken thrombocytes in proinflammatory responses linked to key signaling pathways. TLR, nucleotide binding oligomerization domain-like receptor, and retinoic acid-inducible gene RIG-like receptor pathways were mapped based on the transcriptome results with gene expression for common signal and proinflammatory mediators highlighted. The information reported in this study is useful for defining a limited set of proinflammatory molecules to evaluate in cases of either bacterial or viral disease monitoring.

Neuroscience may supersede ethics and law.

Advances in technology now make it possible to monitor the activity of the human brain in action, however crudely. As this emerging science continues to offer correlations between neural activity and mental functions, mind and brain may eventually prove to be one. If so, such a full comprehension of the electrochemical bases of mind may render current concepts of ethics, law, and even free will irrelevant.

Correction: Transcriptome Profile of the Chicken Thrombocyte: New Implications as an Advanced Immune Effector Cell.

[This corrects the article DOI: 10.1371/journal.pone.0163890.].

Satiety-responsive neurons in the medial orbitofrontal cortex of the macaque.

Feeding-related gustatory, olfactory, and visual activation of the orbitofrontal cortex (OFC) decreases following satiety. Previous neurophysiological studies have concentrated on the caudolateral OFC (clOFC). We describe satiety-induced modulation of 23 gustatory, 5 water, and 15 control neurons in the medial OFC (mOFC), where gustatory neurons represent a much larger percentage of the population. For 15 of the 23 gustatory neurons (65%), every significant taste response evoked during pre-satiety testing decreased following satiety (X=70%). Responses evoked by the ineffective taste stimuli during pre-satiety testing were unchanged following satiety. The graded response decrements of the mOFC gustatory neurons stand in marked contrast to the clOFC responses, which are almost completely suppressed by satiety. Two other novel findings are reported here. First, all significant pre-satiety taste responses of four gustatory neurons increased following satiety (X=51%). Second, post-satiety emergent taste responses were observed in 7 of 15 neurons (47%) classified as non-responsive during pre-satiety testing. The presence of increased responsiveness and emergent gustatory neurons in the mOFC suggests that meal termination may require active processes as well as the passive loss of hedonic value.

Taste in the medial orbitofrontal cortex of the macaque.

Taste activates about 6% of the neurons in the anterior insula (primary taste cortex) of the macaque. The anterior insula has many direct and indirect projections to the orbitofrontal cortex (OFC), including the caudolateral OFC (clOFC), where only 2% of the neurons respond to taste. We have identified a 12-mm(2) region in the medial OFC (mOFC) where taste represents 7-28% of the population. This rich trove of taste cells has functional characteristics typical of both the insular cortex that projects to it and the clOFC to which it projects. Mean spontaneous rate was 3.1 spikes/s, nearly identical to that in the insula, but double that of the clOFC. In the mOFC, 19% of the taste cells also responded to other modalities, most commonly olfaction and touch, slightly less than the 27% in the clOFC. The distribution of best stimulus neurons was almost even across the four prototypical stimuli in the mOFC, as in insula, but discrepant from the clOFC, where sugar responsiveness dominated. The broadly tuned taste neurons in the mOFC were similar to those in the insula and strikingly different from the more specialized cells of the clOFC. Whereas the responsiveness to the taste of a satiating stimulus declines among the narrowly tuned clOFC cells, satiety has much less impact on the responsiveness of mOFC neurons. The mOFC is a robust area worthy of exploration for its involvement in gustatory coding, the amalgamation of sensory inputs to create flavor, and the hedonics that guide feeding.

Gustatory neural responses in the medial orbitofrontal cortex of the old world monkey.

The primary taste cortex has widespread and occasionally dense projections to the orbitofrontal cortex (OFC) in the macaque. Nonetheless, electrophysiological studies have revealed that only 2-8% of the cells in the OFC are activated by taste stimuli on the tongue. We describe an area centered in Brodmann's area 13m of the medial OFC (mOFC) where taste neurons are more concentrated. It consists of a 12 mm2 core, where gustatory neurons constituted 20% of the population, and a 1 mm perimeter in which 8% of the cells responded to taste. Data were collected from three awake cynomolgus monkeys (Macaca fascicularis) prepared for chronic recording. Single neurons were isolated with epoxylite-coated tungsten microelectrodes and tested for responsiveness to 1.0 m glucose, 0.3 m NaCl, 0.03 m HCl, and 0.001 m QHCl. These stimuli elicited responses that were 96% excitatory and ranged from 5.2 to 5.9 spikes/s. Cells were broadly tuned (H = 0.79), similar to those in the anterior insula (H = 0.70), and decidedly unlike the narrowly tuned taste neurons in the caudolateral OFC (clOFC; H = 0.39). Whereas 82% of the taste cells in the clOFC respond to glucose, in the mOFC, HCl-responsive (56%), glucose-responsive (50%), NaCl-responsive (43%), and QHCl-responsive (40%) cells were almost evenly represented. The mOFC taste area appears to comprise a major gustatory relay that lies anatomically and functionally between the anterior insula and the clOFC.

Tumor-Associated Macrophages in Oncolytic Virotherapy: Friend or Foe?

Cancer therapy remains a challenge due to toxicity limitations of chemotherapy and radiation therapy. Oncolytic viruses that selectively replicate and destroy cancer cells are of increasing interest. In addition to direct cell lysis, these vectors stimulate an anti-tumor immune response. A key regulator of tumor immunity is the tumor-associated macrophage population. Macrophages can either support oncolytic virus therapy through pro-inflammatory stimulation of the anti-tumor response at the cost of hindering direct oncolysis or through immunosuppressive protection of virus replication at the cost of hindering the anti-tumor immune response. Despite similarities in macrophage interaction between adult and pediatric tumors and the abundance of research supporting macrophage modulation in adult tumors, there are few studies investigating macrophage modulation in pediatric cancers or modulation of immunotherapy. We review the current state of knowledge regarding macrophages in cancers and their influence on oncolytic virotherapy.

Transcriptome Profile of the Chicken Thrombocyte: New Implications as an Advanced Immune Effector Cell.

Thrombocytes are nucleated platelets involved in immune functions such as pathogen recognition and release of pro-inflammatory bioactive compounds when exposed to bacterial and viral molecules. However, the complete role of these cells in innate and adaptive immune responses is not understood, and little is known about their biology at the molecular-genetic level. Highly sensitive RNA-sequencing technologies were used to analyze the complete transcriptome of thrombocytes for the first time with analytical resolution focused on cell-based components of the immune system/response. Amongst all the genes listed in the current chicken genome assembly, 10,041 gene transcripts were found in the chicken thrombocyte. After 1-hour in vitro stimulation with lipopolysaccharide (LPS, Salmonella minnesota), 490 genes were upregulated and 359 genes were downregulated, respectively, with at least a 1-fold change relative to unexposed thrombocytes. Additionally, by constructing a de novo assembly, we were able to identify a total of 3,030 novel genes in the thrombocyte transcriptome. The information generated here is useful in development of novel solutions to lower the economic burden and zoonotic threat that accompanies infectious diseases for birds and fish. In addition, the resources created here have translational utility as a model system to find orthologous genes and genes related to its enucleated counterpart, the platelet.

Involvement of the supramammillary nucleus in aversive conditioning.

Mechanisms for the retention and retrieval of conditioned taste aversions (CTAs) have yet to be fully defined. The authors explored relevant subcortical forebrain regions by tracking the expression of immediate early genes, c-fos and zif268. The supramammillary nucleus (SuM) was activated following both viscerally based CTA and somatically based inhibitory avoidance (IA). Excitotoxic lesions of the SuM before conditioning caused no disruption of acquisition but accelerated the extinction of both the CTA and IA. In contrast, lesions after CTA conditioning did not impair retention or retrieval. The present study indicates that the SuM is activated by memory-elicited discomfort during retrieval, suggesting that it plays a role in resisting the extinction of a long-term aversive memory.

Artificial neural network analysis of gustatory responses in the thalamic taste relay of the rat.

We used an artificial neural network (ANN) as a model for analyzing single-neuron responses from the thalamic taste relay of rats. The network consisted of: (1) a layer of 44 input units, representing the responses of the 44 thalamic taste cells; (2) a layer of hidden units of varying numbers; and (3) a layer of four output units. We used the back-propagation algorithm to train the output units to discriminate among tastants based on inputs from the thalamic neurons. As the network became fully trained, we found that: (1) only two hidden units were necessary to provide nearly the full discriminative capacity of the network; (2) the loss of even a few of the input units that had the highest impact on hidden units caused a drastic reduction of discriminative power, implying that not all neurons contribute equally to the neural code; and (3) adding a temporal component to the input, by representing each 100-ms time bin as a separate input unit, increased the accuracy with which output units were able to identify tastants. We used data from behavioral discrimination tasks as a measure of the capacity of the network to identify stimuli correctly. A network with two hidden units was about as effective as an across-pattern analysis in accounting for the rat's discriminative ability.

Taste as a basis for body wisdom.

The sense of taste uses a variety of discrete receptor mechanisms to identify nutrients and toxins. Information from receptors is arrayed along a dimension of physiological welfare, which serves as the organizing principle of the taste system. This, in turn, drives central physiological and neurochemical processes that underlie hedonics: nutrients elicit reward; toxins, aversion. The sensitivity of the taste system, and so the placement of chemical stimuli along the welfare dimension, is modifiable based on level of satiety, experience, or physiological need. These modifications may be sufficient to guide the animal's food choices according to those that satisfy its needs at the moment. Thus, judicious changes in taste sensitivity of the rodent may underlie the demonstrated behavior of body wisdom.

Learning through the taste system.

Taste is the final arbiter of which chemicals from the environment will be admitted to the body. The action of swallowing a substance leads to a physiological consequence of which the taste system should be informed. Accordingly, taste neurons in the central nervous system are closely allied with those that receive input from the viscera so as to monitor the impact of a recently ingested substance. There is behavioral, anatomical, electrophysiological, gene expression, and neurochemical evidence that the consequences of ingestion influence subsequent food selection through development of either a conditioned taste aversion (CTA) (if illness ensues) or a conditioned taste preference (CTP) (if nutrition). This ongoing communication between taste and the viscera permits the animal to tailor its taste system to its individual needs over a lifetime.

The role of the parabrachial nucleus in taste processing and feeding.

The parabrachial nucleus (PBN) was identified as a taste relay in rodents in 1971. Early recordings suggested that the PBN transmitted a faithful representation of taste activity from the nucleus of the solitary tract (NTS). However, its role assumed greater significance as its subnuclei were shown to deal with different aspects of taste, visceral sensations, hedonics, and conditioned aversions. The discovery of parallel projections from PBN to the thalamus and to ventral forebrain, and evidence that the former carried sensory information while the latter signaled hedonics, conferred on PBN a central role in guiding feeding. Thus, it was surprising to discover that the PBN is not a taste relay in primates. So arose a distinction between rodents, in which parallel processing of taste and hedonic information is the rule, and primates, where serial processing through the cortex precedes a hedonic assessment. Where does the integration of taste and hedonics occur, and how does this affect feeding? Neurons in both NTS and PBN of rodents are modified by changing physiological conditions. That altered activity parallels and perhaps directs the rodent's feeding behavior. Information from primate NTS implies no such modification. These interactions are reserved for orbitofrontal cortex and ventral forebrain. The implication is that in rodents, hindbrain alterations not only control the reflexes associated with taste, but also direct food selection through the PBN-ventral forebrain projections. In primates, the apparatus is in place for an independent cognitive analysis unaltered by physiological state, upon which a hedonic assessment is subsequently overlaid.

Developmental toxicity in white leghorn chickens following in ovo exposure to perfluorooctane sulfonate (PFOS).

Studies show that perfluorinated compounds cause various toxicological effects; nevertheless, effects on immune function and developmental endpoints have not been addressed at length. This study examined the effects of perfluorooctane sulfonate (PFOS) in white leghorn hatchlings on various developmental, immunological, and clinical health parameters. In addition, serum PFOS concentrations were determined by LC/MS/MS. Embryonic day (ED) 0 eggs were injected with either safflower oil/10% DMSO (control, 0mg/kg egg wt) or PFOS in safflower oil/10% DMSO at 1, 2.5, or 5mg/kg egg wt, and the chicks were grown to post-hatch day (PHD) 14. Treatment with PFOS did not affect hatch rate. Following in ovo exposure chicks exhibited increases in spleen mass at all treatment levels, in liver mass at 2.5 and 5mg/kg egg wt, and in body length (crown-rump length) at the 5mg/kg treatment. Right wings were shorter in all treatments compared to control. Increases in the frequency of brain asymmetry were evident in all treatment groups. SRBC-specific immunoglobulin (IgM and IgY combined) titers were decreased significantly at all treatment levels, while plasma lysozyme activity was increased at all treatment levels. The PHA skin test response decreased in relation to increasing PFOS dose. Serum concentrations where significant immunological, morphological, and neurological effects were observed at the lowest dose (1mg/kg egg wt) averaged 154 ng PFOS/g serum. These concentrations fall within environmental ranges reported in blood samples from wild caught avian species; thereby, verifying that the environmental egg concentrations used for the injections do indeed relate to serum levels in hatchlings that are also environmentally relevant. These data indicate that immune alterations and brain asymmetry can occur in birds following in ovo exposure to environmentally relevant concentrations of PFOS and demonstrates the need for further research on the developmental effects of perfluorinated compounds in various species.

Effect of amiloride on gustatory responses in the ventroposteromedial nucleus of the thalamus in rats.

The existence of gustatory neuron types has been demonstrated in the chorda tympani nerve and the nucleus of the solitary tract (NTS) of rats and hamsters through the oral application of amiloride, a sodium channel blocker. At these lower-order levels, amiloride was shown to reduce the response to sodium and lithium salts in sodium- and sugar-oriented cells, while leaving those of acid- and quinine-oriented neurons unmodified. We extended this investigation to higher-order levels by determining whether amiloride suppressed the responses of cells at the 4th-order gustatory relay in the thalamus, which neurons were affected, the degree of suppression, and whether the subsequent neural code for sodium was altered. We stimulated the whole oral cavity of anesthetized rats with a variety of tastants while recording the responses of 42 single thalamic neurons before and after the application of amiloride. The results revealed a similar pattern to that reported in the NTS. Amiloride inhibited only sodium- and sugar-oriented neurons, and specifically their responses to sodium- or lithium-containing stimuli. Moreover, there was a significant relationship between the degree of sodium specificity of a neuron and its sensitivity to inhibition by amiloride. These results demonstrate a relationship between a cell's response profile and its susceptibility to amiloride, and so offer evidence that gustatory neuron types exist through the level of the thalamus in rats. Thus membership in a neuronal group retains functional significance based on a receptor event 4 synapses away.