Trust with increasing and decreasing reliability.

OBJECTIVE: The primary purpose was to determine how trust changes over time when automation reliability increases or decreases. A secondary purpose was to determine how task-specific self-confidence is associated with trust and reliability level. BACKGROUND: Both overtrust and undertrust can be detrimental to system performance; therefore, the temporal dynamics of trust with changing reliability level need to be explored. METHOD: Two experiments used a dominant-color identification task, where automation provided a recommendation to users, with the reliability of the recommendation changing over 300 trials. In Experiment 1, two groups of participants interacted with the system: one group started with a 50% reliable system which increased to 100%, while the other used a system that decreased from 100% to 50%. Experiment 2 included a group where automation reliability increased from 70% to 100%. RESULTS: Trust was initially high in the decreasing group and then declined as reliability level decreased; however, trust also declined in the 50% increasing reliability group. Furthermore, when user self-confidence increased, automation reliability had a greater influence on trust. In Experiment 2, the 70% increasing reliability group showed increased trust in the system. CONCLUSION: Trust does not always track the reliability of automated systems; in particular, it is difficult for trust to recover once the user has interacted with a low reliability system. APPLICATIONS: This study provides initial evidence into the dynamics of trust for automation that gets better over time suggesting that users should only start interacting with automation when it is sufficiently reliable.

Activation and modulation of recombinantly expressed serotonin receptor type 3A by terpenes and pungent substances.

Serotonin receptor type 3 (5-HT3 receptor) is a ligand-gated ion channel that is expressed in the central nervous system (CNS) as well as in the peripheral nervous system (PNS). The receptor plays an important role in regulating peristalsis of the gastrointestinal tract and in functions such as emesis, cognition and anxiety. Therefore, a variety of pharmacologically active substances target the 5-HT3 receptor to treat chemotherapy-induced nausea and vomiting. The 5-HT3 receptors are activated, antagonized, or modulated by a wide range of chemically different substances, such as 2-methyl-serotonin, phenylbiguanide, setrones, or cannabinoids. Whereas the action of all of these substances is well described, less is known about the effect of terpenoids or fragrances on 5-HT3A receptors. In this study, we screened a large number of natural odorous and pungent substances for their pharmacological action on recombinantly expressed human 5-HT3A receptors. The receptors were functionally expressed in Xenopus oocytes and characterized by electrophysiological recordings using the two-electrode voltage-clamp technique. A screening of two odorous mixes containing a total of 200 substances revealed that the monoterpenes, thymol and carvacrol, act as both weak partial agonists and positive modulators on the 5-HT3A receptor. In contrast, the most effective blockers were the terpenes, citronellol and geraniol, as well as the pungent substances gingerol, capsaicin and polygodial. In our study, we identified new modulators of 5-HT3A receptors out of the classes of monoterpenes and vanilloid substances that frequently occur in various plants.

Deep sequencing of the murine olfactory receptor neuron transcriptome.

The ability of animals to sense and differentiate among thousands of odorants relies on a large set of olfactory receptors (OR) and a multitude of accessory proteins within the olfactory epithelium (OE). ORs and related signaling mechanisms have been the subject of intensive studies over the past years, but our knowledge regarding olfactory processing remains limited. The recent development of next generation sequencing (NGS) techniques encouraged us to assess the transcriptome of the murine OE. We analyzed RNA from OEs of female and male adult mice and from fluorescence-activated cell sorting (FACS)-sorted olfactory receptor neurons (ORNs) obtained from transgenic OMP-GFP mice. The Illumina RNA-Seq protocol was utilized to generate up to 86 million reads per transcriptome. In OE samples, nearly all OR and trace amine-associated receptor (TAAR) genes involved in the perception of volatile amines were detectably expressed. Other genes known to participate in olfactory signaling pathways were among the 200 genes with the highest expression levels in the OE. To identify OE-specific genes, we compared olfactory neuron expression profiles with RNA-Seq transcriptome data from different murine tissues. By analyzing different transcript classes, we detected the expression of non-olfactory GPCRs in ORNs and established an expression ranking for GPCRs detected in the OE. We also identified other previously undescribed membrane proteins as potential new players in olfaction. The quantitative and comprehensive transcriptome data provide a virtually complete catalogue of genes expressed in the OE and present a useful tool to uncover candidate genes involved in, for example, olfactory signaling, OR trafficking and recycling, and proliferation.

Characterization of the Olfactory Receptors Expressed in Human Spermatozoa.

The detection of external cues is fundamental for human spermatozoa to locate the oocyte in the female reproductive tract. This task requires a specific chemoreceptor repertoire that is expressed on the surface of human spermatozoa, which is not fully identified to date. Olfactory receptors (ORs) are candidate molecules and have been attributed to be involved in sperm chemotaxis and chemokinesis, indicating an important role in mammalian spermatozoa. An increasing importance has been suggested for spermatozoal RNA, which led us to investigate the expression of all 387 OR genes. This study provides the first comprehensive analysis of OR transcripts in human spermatozoa of several individuals by RNA-Seq. We detected 91 different transcripts in the spermatozoa samples that could be aligned to annotated OR genes. Using stranded mRNA-Seq, we detected a class of these putative OR transcripts in an antisense orientation, indicating a different function, rather than coding for a functional OR protein. Nevertheless, we were able to detect OR proteins in various compartments of human spermatozoa, indicating distinct functions in human sperm. A panel of various OR ligands induced Ca(2+) signals in human spermatozoa, which could be inhibited by mibefradil. This study indicates that a variety of ORs are expressed at the mRNA and protein level in human spermatozoa.

Direct action and modulating effect of (+)- and (-)-nicotine on ion channels expressed in trigeminal sensory neurons.

Nicotine sensory perception is generally thought to be mediated by nicotinic acetylcholine (nACh) receptors. However, recent data strongly support the idea that other receptors (e.g., transient receptor potential A1 channel, TRPA1) and other pathways contribute to the detection mechanisms underlying the olfactory and trigeminal cell response to nicotine flavor. This is in accordance with the reported ability of humans to discriminate between (+)- and (-)- nicotine enantiomers. To get a more detailed understanding of the molecular and cellular basis underlying the sensory perception of nicotine, we studied the activity of (+)- and (-)-nicotine on cultured murine trigeminal sensory neurons and on a range of heterologously expressed receptors. The human TRPA1 channel is activated by (-)-nicotine. In this work, we show that (+)-nicotine is also an activator of this channel. Pharmacological experiments using nicotinic acetylcholine receptors and transient receptor potential blockers revealed that trigeminal neurons express one or more unidentified receptors that are sensitive to (+)- and/or (-)-nicotine. Results also indicate that the presence of extracellular calcium ions is required to elicit trigeminal neuron responses to (+)- and (-)-nicotine. Results also show that both (+)-nicotine and (-)-nicotine can block 5-hydroxytryptamine type 3 (5-HT3) receptor-mediated responses in recombinant expression systems and in cultured trigeminal neurons expressing 5-HT3 receptors. Our investigations broaden the spectra of receptors that are targets for nicotine enantiomers and give new insights into the physiological role of nicotine.

Comprehensive RNA-Seq expression analysis of sensory ganglia with a focus on ion channels and GPCRs in Trigeminal ganglia.

The specific functions of sensory systems depend on the tissue-specific expression of genes that code for molecular sensor proteins that are necessary for stimulus detection and membrane signaling. Using the Next Generation Sequencing technique (RNA-Seq), we analyzed the complete transcriptome of the trigeminal ganglia (TG) and dorsal root ganglia (DRG) of adult mice. Focusing on genes with an expression level higher than 1 FPKM (fragments per kilobase of transcript per million mapped reads), we detected the expression of 12984 genes in the TG and 13195 in the DRG. To analyze the specific gene expression patterns of the peripheral neuronal tissues, we compared their gene expression profiles with that of the liver, brain, olfactory epithelium, and skeletal muscle. The transcriptome data of the TG and DRG were scanned for virtually all known G-protein-coupled receptors (GPCRs) as well as for ion channels. The expression profile was ranked with regard to the level and specificity for the TG. In total, we detected 106 non-olfactory GPCRs and 33 ion channels that had not been previously described as expressed in the TG. To validate the RNA-Seq data, in situ hybridization experiments were performed for several of the newly detected transcripts. To identify differences in expression profiles between the sensory ganglia, the RNA-Seq data of the TG and DRG were compared. Among the differentially expressed genes (> 1 FPKM), 65 and 117 were expressed at least 10-fold higher in the TG and DRG, respectively. Our transcriptome analysis allows a comprehensive overview of all ion channels and G protein-coupled receptors that are expressed in trigeminal ganglia and provides additional approaches for the investigation of trigeminal sensing as well as for the physiological and pathophysiological mechanisms of pain.

Trigeminal ganglion neurons of mice show intracellular chloride accumulation and chloride-dependent amplification of capsaicin-induced responses.

Intracellular Cl(-) concentrations ([Cl(-)](i)) of sensory neurons regulate signal transmission and signal amplification. In dorsal root ganglion (DRG) and olfactory sensory neurons (OSNs), Cl(-) is accumulated by the Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1), resulting in a [Cl(-)](i) above electrochemical equilibrium and a depolarizing Cl(-) efflux upon Cl(-) channel opening. Here, we investigate the [Cl(-)](i) and function of Cl(-) in primary sensory neurons of trigeminal ganglia (TG) of wild type (WT) and NKCC1(-/-) mice using pharmacological and imaging approaches, patch-clamping, as well as behavioral testing. The [Cl(-)](i) of WT TG neurons indicated active NKCC1-dependent Cl(-) accumulation. Gamma-aminobutyric acid (GABA)(A) receptor activation induced a reduction of [Cl(-)](i) as well as Ca(2+) transients in a corresponding fraction of TG neurons. Ca(2+) transients were sensitive to inhibition of NKCC1 and voltage-gated Ca(2+) channels (VGCCs). Ca(2+) responses induced by capsaicin, a prototypical stimulus of transient receptor potential vanilloid subfamily member-1 (TRPV1) were diminished in NKCC1(-/-) TG neurons, but elevated under conditions of a lowered [Cl(-)](o) suggesting a Cl(-)-dependent amplification of capsaicin-induced responses. Using next generation sequencing (NGS), we found expression of different Ca(2+)-activated Cl(-) channels (CaCCs) in TGs of mice. Pharmacological inhibition of CaCCs reduced the amplitude of capsaicin-induced responses of TG neurons in Ca(2+) imaging and electrophysiological recordings. In a behavioral paradigm, NKCC1(-/-) mice showed less avoidance of the aversive stimulus capsaicin. In summary, our results strongly argue for a Ca(2+)-activated Cl(-)-dependent signal amplification mechanism in TG neurons that requires intracellular Cl(-) accumulation by NKCC1 and the activation of CaCCs.

Cleistanthus collinus poisoning.

Cleistanthus collinus is an extremely toxic plant poison. Cleistanthin A and B, the toxins of Cleistanthus collinus, are diphyllin glycosides which produce cardiac arrhythmias, urinary potassium wasting, hypoxia, metabolic acidosis and hypotension. We report ARDS, distal renal tubular acidosis and distributive shock secondary to inappropriate vasodilatation in a case following ingestion of its leaves.

Homology, behaviour and spider webs: web construction behaviour of Linyphia hortensis and L. triangularis (Araneae: Linyphiidae) and its evolutionary significance.

Linyphiidae is the second largest family of spiders. Using Linyphia hortensis and L. triangularis, we describe linyphiid sheet-web construction behaviour. Orb-web construction behaviour is reviewed and compared with that of nonorb-weaving orbicularians. Phylogenetic comparisons and the biogenetic law are applied to deduce behavioural homology. Linyphia webs were constructed gradually and in segments over a period of many days and had a long lifespan. Two construction behaviours, supporting structure and sticky thread (ST) (within the sheet) were observed. ST construction behaviour in linyphiids is considered homologous to sticky spiral construction in orb-weavers. Overall web construction conformed to the pattern of alternate construction of sticky and nonsticky parts as observed in theridiids. Linyphiids had no problem in switching between structure construction and ST construction even during a single behavioural bout. Both web construction behaviours in linyphiids were nonstereotypic, which is unusual in orbicularians. This might be due to the loss of control mechanisms at genetic level, probably by macro mutation. Lack of stereotypic behaviour might have played a substantial role in the origin of the diverse web forms seen in nonorb-weaving orbicularians. This hypothesis is consistent with patterns observed in the orbicularian phylogeny.

Malignant melanoma primary in lymph node. The case of the missing link.

When malignant melanoma occurs in a lymph node, it is presumed to be metastatic, and the primary cutaneous/mucosal process is discovered to be either active, spontaneously regressed, previously excised, or occult. Nevus cell aggregates and nodal blue nevi are well-documented morphologic curiosities occurring in lymph nodes. It has been hypothesized that these nevus cell aggregates and blue nevi could be progenitors of lymph nodal malignant melanoma in patients without an obvious extranodal site of origin. We document a prototypical case of primary malignant melanoma evolving from precursor nevus cell aggregates associated with blue nevi in an axillary lymph node. The coexistence of nodal blue nevi and nevus cell aggregates implies a common origin from migratory neural crest cells arrested within mesenchyme.

Expression of monocytic--histiocytic cytochemical markers in epithelial neoplasia.

The diagnosis of malignant histiocytosis is usually based upon typical light microscopic features of the neoplasm. Supplementary cytochemical and immunologic features have been suggested as typical of malignant histiocytosis. The present study was prompted by an unusual erythropagocytic hepatocellular carcinoma having immunologic and cytochemical markers suggesting mononuclear phagocytic origin. Twenty-four neoplasms of unquestionable epithelial origin were prospectively evaluated for activity of alpha-naphthyl acetate esterase, a cytochemical marker useful in distinguishing between the non-Hodgkin's lymphomas and malignant histiocytosis. The epithelial tumors represented a broad spectrum of tissue origins and consistently demonstrated alpha-naphthyl acetate esterase activity. Thus, erythrophagocytosis and alpha-naphthyl acetate esterase positivity may be misleading in the unusual instance in which the histopathologic differential diagnosis includes malignant histiocytosis and epithelial neoplasia. Ultrastructural assessment is useful in the exclusion of poorly differentiated carcinoma.

Immunocytochemical identification of human chorionic gonadotropin. Comparative study of diaminobenzidine and 3-amino, 9-ethylcarbazole, a nonhazardous chromogen.

An immunomicroscopic study evaluated 55 fixed, paraffin-embedded tissues from surgical and necropsy-accessioned material reflecting a variety of physiologic and pathologic disorders. The sensitive unlabeled (peroxidase-antiperoxidase) immunoperoxidase technique was used. Cytoplasmic human chorionic gonadotropin (CHCG) was readily identified in syncytial trophoblastic cells. The only tissue sections that did not demonstrate CHCG activity were primary and secondary testicular teratocarcinomas without choriocarcinoma components. When the technique was reevaluated for the non-hazardous chromogen 3-amino, 9-ethylcarbazole, excellent results were achieved with equivalent staining distribution and intensity. The unlabeled immunoperoxidase method for the identification of CHCG is a sensitive, reliable, confirmatory immunohistochemical stain. A relatively safe chromogen can be substituted for the benzidine derivatives in the procedure with equivalent results.

Recurrent stenosis after carotid endarterectomy.

Thirteen of 1,250 patients required a second operation for recurrent stenosis following carotid endarterectomy performed at the Cleveland Clinic between 1958 and 1978. Two other patients underwent reoperation because of recurrent stenosis following primary operations at other institutions. Thirteen of the 15 patients experienced neurologic symptoms caused by recurent stenosis, while two patients remained asymptomatic. Atherosclerosis was responsible for recurrent stenosis in 12 patients and appeared to be related to hypercholesterolemia. Three of the patients had myointimal fibroplasia. Eleven of the 16 reoperations for recurrent stenosis of the carotid artery consisted of carotid endarterectomy with vein patch angioplasty. Three patients had carotid endarterectomy with closure of the primary arteriotomy. One patient with occlusion of the internal carotid artery underwent endarterectomy of the external carotid artery because of amaurosis fugax, and a saphenous vein interposition graft was used to replace a previous Dacron graft in one patient with anastomotic stenosis. One patient had a stroke during reoperation manifest as multiple retinal emboli. Fourteen patients have remained asymptomatic from one to 70 months following reoperation. One patient with occlusion of the contralateral internal carotid artery has experienced persistent vertebrobasilar symptoms.

Recurrent subarachnoid hemorrhage associated with aminocaproic acid therapy and acute renal artery thrombosis. Case report.

Epsilon aminocaproic acid (EACA) has been used to prevent rebleeding in patients with subarachnoid hemorrhage (SAH). Although this agent does decrease the frequency of rebleeding, several reports have described thrombotic complications of EACA therapy. These complications have included clinical deterioration and intracranial vascular thrombosis in patients with SAH, arteriolar and capillary fibrin thrombi in patients with fibrinolytic syndromes treated with EACA, or other thromboembolic phenomena. Since intravascular fibrin thrombi are often observed in patients with fibrinolytic disorders, EACA should not be implicated in the pathogenesis of fibrin thrombi in patients with disseminated intravascular coagulation or other "consumption coagulopathies." This report describes subtotal infarction of the kidney due to thrombosis of a normal renal artery. This occlusion occurred after EACA therapy in a patient with SAH and histopathological documentation of recurrent SAH. The corresponding clinical event was characterized by marked hypertension and abrupt neurological deterioration.

Pseudomembranous enterocolitis in adults.

Twenty-one patients with pseudomembranous enterocolitis were seen over a 17 year period. Major inciting factors appeared to be an antecedent operation or a serious medical illness. The most common symptoms were fever, diarrhea and abdominal pain. The most commonly involved organ was the colon. The diagnosis was missed in the majority of patients. Neither conservative treatment or surgical treatment were successful. Awareness of the disease and its course will lead to earlier diagnosis and hopefully to a higher cure rate.

Colonoscopy and the management of polyps containing invasive carcinoma.

Experiences with 565 colonoscopic polypectomies and 91 colonic and rectal resections containing infiltrating carcinoma in polyps are reviewed. A plan of management based on pathologic study of resected polyps is formulated to avoid further unnecessary surgery. It was concluded that: (1) Tubular adenomas containing invasive carcinomas have a low incidence of metastatic node involvement. This incidence is related to the depth of carcinomatous involvement. Resection of these polyps with a margin free of carcinoma constitutes definitive and adequate treatment and that (2) Villous adenomas containing invasive carcinoma have a high incidence of metastatic nodal involvement, and operative resection of the involved area of the colon is recommended, and that (3) Pedunculated tubulovillous adenomas containing invasive carcinoma behave like tubular adenomas, and the recommendations for further surgery in the patient with tubular adenomas with carcinoma apply equally well for these lesions. Sessile tubulovillous polyps tend to behave like villous adenomas, and if invasive carcinoma is demonstrated, further operation is recommended.

Surface and transmission ultrastructural characteristics of desquamative interstitial pneumonitis.

A prospective study of eight patients with desquamative interstitial pneumonitis was performed, correlating surface ultrastructure as elucidated by scanning electron microscopy, transmission electron microscopy, viral cultures of fresh sterile lung tissue obtained at thoracotomy, and immunomicroscopy. The hypothesis that environmental pollutants may act as sensitizing agents to induce macrophage migration was pursued using high resolution elemental analysis to obtain a profile of the inorganic content of phagolysosomes in the free alveolar cell population. Four surface ultrastructural changes were observed: mild alveolar septal thickening, an apparent decrease in the number of pores of Kohn, alteration of the predominant alveolar lining population from membranous to granular pneumonocytes, and prominent intra-alveolar collections of cells with broad based ruffled projections and pseudopodia representing a macrophage population. Transmission electron microscopy corroborated these observations. Individual pneumonocyte degeneration manifested as cytoplasmic dissolution, mitochondrial swelling, chromatin disruption, and loss of lamellar bodies and endoplasmic reticulum was identified; occasionally degenerating granular pneumonocytes were displaced into the alveolar space by a supraseptal bulla containing fibrin and extracellular fluid. Viruses were not identified by ultrastructural or tissue culture techniques. High resolution elemental analysis of individual phagolysosome contents failed to reveal the presence of heavy metals or other inorganic compounds. Immune complexes were not identified by immunofluorescence microscopy. However, alveolar transeptal macrophage migration was observed by transmission electron microscopy. These observations suggest that desquamative interstitial pneumonitis represents a disease in which cellular, rather than humoral, immune processes predominate. Other nonspecific cellular immune responses under the influence of various lymphokines may be responsible for the observed morphologic alterations.