VP1 is the primary determinant of neuropathogenesis in a mouse model of enterovirus D68 acute flaccid myelitis.

Enterovirus D68 (EV-D68) is an emerging pathogen that can cause severe respiratory and neurologic disease [acute flaccid myelitis (AFM)]. Intramuscular (IM) injection of neonatal Swiss Webster (SW) mice with US/IL/14-18952 (IL52), a clinical isolate from the 2014 EV-D68 epidemic, results in many of the pathogenic features of human AFM, including viral infection of the spinal cord, death of motor neurons, and resultant progressive paralysis. In distinction, CA/14-4231 (CA4231), another clinical isolate from the 2014 EV-D68 outbreak, does not cause paralysis in mice, does not grow in the spinal cord, and does not cause motor neuron loss following IM injection. A panel of chimeric viruses containing sequences from IL52 and CA4231 was used to demonstrate that VP1 is the main determinant of EV-D68 neurovirulence following IM injection of neonatal SW mice. VP1 contains four amino acid differences between IL52 and CA4231. Mutations resulting in substituting these four amino acids (CA4231 residues into the IL52 polyprotein) completely abolished neurovirulence. Conversely, mutations resulting in substituting VP1 IL52 amino acid residues into the CA4231 polyprotein created a virus that induced paralysis to the same degree as IL52. Neurovirulence following infection of neonatal SW mice with parental and chimeric viruses was associated with viral growth in the spinal cord. IMPORTANCE: Emerging viruses allow us to investigate mutations leading to increased disease severity. Enterovirus D68 (EV-D68), once the cause of rare cases of respiratory illness, recently acquired the ability to cause severe respiratory and neurologic disease. Chimeric viruses were used to demonstrate that viral structural protein VP1 determines growth in the spinal cord, motor neuron loss, and paralysis following intramuscular (IM) injection of neonatal Swiss Webster (SW) mice with EV-D68. These results have relevance for predicting the clinical outcome of future EV-D68 epidemics as well as targeting retrograde transport as a potential strategy for treating virus-induced neurologic disease.

The proton channel OTOP1 is a sensor for the taste of ammonium chloride.

Ammonium (NH4+), a breakdown product of amino acids that can be toxic at high levels, is detected by taste systems of organisms ranging from C. elegans to humans and has been used for decades in vertebrate taste research. Here we report that OTOP1, a proton-selective ion channel expressed in sour (Type III) taste receptor cells (TRCs), functions as sensor for ammonium chloride (NH4Cl). Extracellular NH4Cl evoked large dose-dependent inward currents in HEK-293 cells expressing murine OTOP1 (mOTOP1), human OTOP1 and other species variants of OTOP1, that correlated with its ability to alkalinize the cell cytosol. Mutation of a conserved intracellular arginine residue (R292) in the mOTOP1 tm 6-tm 7 linker specifically decreased responses to NH4Cl relative to acid stimuli. Taste responses to NH4Cl measured from isolated Type III TRCs, or gustatory nerves were strongly attenuated or eliminated in an Otop1-/- mouse strain. Behavioral aversion of mice to NH4Cl, reduced in Skn-1a-/- mice lacking Type II TRCs, was entirely abolished in a double knockout with Otop1. These data together reveal an unexpected role for the proton channel OTOP1 in mediating a major component of the taste of NH4Cl and a previously undescribed channel activation mechanism.

Exposure to Campus Messages about Dating and Sexual Violence: A Latent Class Analysis.

This study investigates college students' exposure to messages about campus dating and sexual violence (DSV) to discover classes of students based on the message source. Latent class analysis was performed with data assessing 5,284 students' exposure to 16 different sources of information regarding DSV, from having a professor discuss these topics to participating in related campus events. Several variables were included in the analysis to understand students' class membership in relation to pertinent student demographic factors. The best model indicated that there are five classes of students based on their exposure to messages, with some subgroups of students having high exposure to various sources of messages about DSV while others have low exposure. Still other subgroups are primarily exposed to messages through nonactive or noninstitutional sources of information. Subgroups of students, based on their exposure to DSV messaging, also differ regarding demographic makeup. The implications from these results include the need to tailor DSV programming on campus to subgroups of students based on their varying baseline levels of message exposure. As students are exposed to messaging through differing sources, including passive and noninstitutional, institutions can use this information when designing outreach efforts to better fit with the needs of various subgroups of students.

The Relationship Between Brain Fog and Medication Adherence for Individuals With Hypothyroidism.

Individuals with hypothyroidism suffer from symptoms including impairments to cognition (i.e., "brain fog"). Medication can help reduce symptoms of hypothyroidism; however, brain fog may hinder adherence. The aim of this study was to determine if memory impairment and cognitive failures are related to treatment nonadherence in 441 individuals with hypothyroidism. Participants with a diagnosis of hypothyroidism and currently prescribed a thyroid hormone replacement medication were placed in two groups according to adherence level and compared on validated scales assessing impairments to memory and cognition. Results indicated a significant association between treatment nonadherence and self-reported brain fog, represented by greater cognitive and memory impairments. Nonadherent individuals indicated impairments with prospective, retrospective, and short- and long-term memory; and more cognitive failures, compared to adherent individuals. Findings suggest the importance of interventions to enhance adherence for individuals with brain fog, such as encouraging the use of reminders.

Taste Bud Connectome: Implications for Taste Information Processing.

Taste buds contain multiple cell types, two of which mediate transduction of specific taste qualities: Type III cells transduce sour while Type II cells transduce either sweet, or bitter or umami. In order to discern the degree of interaction between different cell types and specificity of connectivity with the afferent nerve fibers (NFs), we employed serial blockface scanning electron microscopy (sbfSEM) through five circumvallate mouse taste buds. Points of contact between Type II and Type III cells are rare and lack morphologically identifiable synapses, suggesting that interaction between these cell types does not occur via synapses. Of the 127 NFs that make synaptic contacts with taste cells in the sampling volume, ∼70% (n = 91) synapse with only one taste cell while 32 fibers synapse exclusively with multiple Type II cells or multiple Type III cells. Our data do not rule out multimodal fibers innervating Type II cells of separate taste qualities. Notably, four fibers (∼3%) synapse with both Type II and Type III cells, forming both mitochondrial and vesicular synapses on the different cell types. Since Type II and Type III cells transduce different taste qualities, these dual connected fibers are not consistent with a absolute labeled-line encoding system. Further, our data reveal considerable variation in both the number of synapses per cell/nerve pair and the number of innervating NFs per taste cell, both of which likely have consequences for encoding taste quality and concentration. Finally, we identify a subset of Type II cells which may represent an immature stage.SIGNIFICANCE STATEMENT Taste buds, the sensory end organs for the sense of taste, contain multiple types of sensory cells, with each responding to one of the primary tastes: salt, sweet, sour, bitter, and umami. In order to determine the degree of interaction between cell types and specificity of connectivity to afferent nerves, we employed serial blockface electron microscopy (EM) of mouse circumvallate taste buds. We find no synapses between cell types within the taste bud suggesting that any interactions are indirect. While the majority of nerve fibers (NFs) connect to a single type of taste cell, 3.1% of the fibers branch to receive input from taste cells of different specificities. Thus, taste cannot entirely be carried along NFs dedicated to single taste qualities.

Role of Nursing Home Quality on COVID-19 Cases and Deaths: Evidence from Florida Nursing Homes.

The Coronavirus disease 2019 (COVID-19) disproportionately affects nursing home residents, resulting in an elevated risk for COVID-19 morbidity and mortality for this frail population. It is critical to understand whether nursing home quality is related to COVID-19 cases and deaths. Using publicly available data obtained from Centers for Medicare & Medicaid Services COVID-19 Nursing Home Dataset, Nursing Home Compare and Long-Term Care Focus, this study compares key nursing home characteristics, infection prevention and control deficiencies, and five-star ratings among Florida nursing homes with and without resident COVID-19 cases and deaths. The study further examines the association between facility and resident characteristics, quality indicators, and COVID-19 cases and deaths. Findings from our study indicate that through late October 2020, over 90% of Florida nursing homes have at least one resident case and 65% have at least one resident death. The likelihood of having COVID-19 cases is more related to ownership status, facility size and average occupancy rate, rather than quality indicators. Associations between infection prevention and control deficiencies, overall quality ratings, and presence of COVID-19 resident deaths varied across different phases of the pandemic (e.g., overall five-star rating was found related to the odds of having resident deaths after, but not during, the surging stage). Training, uptake, and adherence to infection control procedures are needed to better protect the vulnerable nursing home resident population.

Genetic Deletion of TrpV1 and TrpA1 Does Not Alter Avoidance of or Patterns of Brainstem Activation to Citric Acid in Mice.

Exposure of the oral cavity to acidic solutions evokes not only a sensation of sour, but also of sharp or tangy. Acidic substances potentially stimulate both taste buds and acid-sensitive mucosal free nerve endings. Mice lacking taste function (P2X2/P2X3 double-KO mice) refuse acidic solutions similar to wildtype (WT) mice and intraoral infusion of acidic solutions in these KO animals evokes substantial c-Fos activity within orosensory trigeminal nuclei as well as of the nucleus of the solitary tract (nTS) (Stratford, Thompson, et al. 2017). This residual acid-evoked, non-taste activity includes areas that receive inputs from trigeminal and glossopharyngeal peptidergic (CGRP-containing) nerve fibers that express TrpA1 and TrpV1 both of which are activated by low pH. We compared avoidance responses in WT and TrpA1/V1 double-KO (TRPA1/V1Dbl-/-) mice in brief-access behavioral assay (lickometer) to 1, 3, 10, and 30 mM citric acid, along with 100 µM SC45647 and H2O. Both WT and TRPA1/V1Dbl-/- show similar avoidance, including to higher concentrations of citric acid (10 and 30 mM; pH 2.62 and pH 2.36, respectively), indicating that neither TrpA1 nor TrpV1 is necessary for the acid-avoidance behavior in animals with an intact taste system. Similarly, induction of c-Fos in the nTS and dorsomedial spinal trigeminal nucleus was similar in the WT and TRPA1/V1Dbl-/- animals. Taken together these results suggest non-TrpV1 and non-TrpA1 receptors underlie the residual responses to acids in mice lacking taste function.

Optogenetic Activation of Type III Taste Cells Modulates Taste Responses.

Studies have suggested that communication between taste cells shapes the gustatory signal before transmission to the brain. To further explore the possibility of intragemmal signal modulation, we adopted an optogenetic approach to stimulate sour-sensitive (Type III) taste cells using mice expressing Cre recombinase under a specific Type III cell promoter, Pkd2l1 (polycystic kidney disease-2-like 1), crossed with mice expressing Cre-dependent channelrhodopsin (ChR2). The application of blue light onto the tongue allowed for the specific stimulation of Type III cells and circumvented the nonspecific effects of chemical stimulation. To understand whether taste modality information is preprocessed in the taste bud before transmission to the sensory nerves, we recorded chorda tympani nerve activity during light and/or chemical tastant application to the tongue. To assess intragemmal modulation, we compared nerve responses to various tastants with or without concurrent light-induced activation of the Type III cells. Our results show that light significantly decreased taste responses to sweet, bitter, salty, and acidic stimuli. On the contrary, the light response was not consistently affected by sweet or bitter stimuli, suggesting that activation of Type II cells does not affect nerve responses to stimuli that activate Type III cells.

Physiological and molecular analysis of glyphosate resistance in non-rapid response Ambrosia trifida from Wisconsin.

BACKGROUND: We previously identified a glyphosate-resistant A. trifida phenotype from Wisconsin USA that showed a non-rapid response to glyphosate. The mechanism of glyphosate resistance in this phenotype has yet to be elucidated. We conducted experiments to investigate non-target-site resistance and target-site resistance mechanisms. The roles of glyphosate absorption, translocation, and metabolism in resistance of this phenotype have not been reported previously, nor have EPSPS protein abundance or mutations to the full-length sequence of EPSPS. RESULTS: Whole-plant dose-response results confirmed a 6.5-level of glyphosate resistance for the resistant (R) phenotype compared to a susceptible (S) phenotype. Absorption and translocation of 14 C-glyphosate were similar between R and S phenotypes over 72 h. Glyphosate and AMPA concentrations in leaf tissue did not differ between R and S phenotypes over 96 h. In vivo shikimate leaf disc assays confirmed that glyphosate EC50 values were 4.6- to 5.4-fold greater for the R than S phenotype. Shikimate accumulation was similar between phenotypes at high glyphosate concentrations (>1000 µM), suggesting that glyphosate entered chloroplasts and inhibited EPSPS. This finding was supported by results showing that EPSPS copy number and EPSPS protein abundance did not differ between R and S phenotypes, nor did EPSPS sequence at Gly101, Thr102, and Pro106 positions. Comparison of full-length EPSPS sequences found five nonsynonymous polymorphisms that differed between R and S phenotypes. However, their locations were distant from the glyphosate target site and, therefore, not likely to affect enzyme-glyphosate interaction. CONCLUSION: The results suggest that a novel mechanism confers glyphosate resistance in this A. trifida phenotype. © 2019 Society of Chemical Industry.

Three-dimensional reconstructions of mouse circumvallate taste buds using serial blockface scanning electron microscopy: I. Cell types and the apical region of the taste bud.

Taste buds comprise four types of taste cells: three mature, elongate types, Types I-III; and basally situated, immature postmitotic type, Type IV cells. We employed serial blockface scanning electron microscopy to delineate the characteristics and interrelationships of the taste cells in the circumvallate papillae of adult mice. Type I cells have an indented, elongate nucleus with invaginations, folded plasma membrane, and multiple apical microvilli in the taste pore. Type I microvilli may be either restricted to the bottom of the pore or extend outward reaching midway up into the taste pore. Type II cells (aka receptor cells) possess a large round or oval nucleus, a single apical microvillus extending through the taste pore, and specialized "atypical" mitochondria at functional points of contact with nerve fibers. Type III cells (aka "synaptic cells") are elongate with an indented nucleus, possess a single, apical microvillus extending through the taste pore, and are characterized by a small accumulation of synaptic vesicles at points of contact with nerve fibers. About one-quarter of Type III cells also exhibit an atypical mitochondrion near the presynaptic vesicle clusters at the synapse. Type IV cells (nonproliferative "basal cells") have a nucleus in the lower quarter of the taste bud and a foot process extending to the basement membrane often contacting nerve processes along the way. In murine circumvallate taste buds, Type I cells represent just over 50% of the population, whereas Types II, III, and IV (basal cells) represent 19, 15, and 14%, respectively.

Exploring the relationship between resilience and grit among nursing students: A correlational research study.

BACKGROUND: Nurse turnover is a critical issue around the world. Finding factors that can increase job persistence in nursing can have a positive impact on both the quality and cost of health care. Resilience and grit have been studied as factors that help an individual persist in the pursuit of their goals. Resilience and grit are related terms that have frequently been used interchangeably, although some studies suggest that they are different constructs. Determining if they are different constructs is important as we seek to develop qualities in new nurses that increase their job persistence and satisfaction. OBJECTIVES: The purpose of this study was to explore the relationship between resilience and grit in pre-licensure nursing students. DESIGN/SETTING: This descriptive correlational study was conducted at a midsize private University in the United States. PARTICIPANTS: The convenience sample consisted of students from 3 pre-licensure programs: Traditional Bachelor of Science in Nursing (TBSN), Accelerated Bachelor of Science in Nursing (ABSN) and Direct Entry Masters of Science in Nursing (DEMSN). The final sample was 348 students: 79% TBSN, 7% ABSN and 14% DEMSN. METHODS: Resilience was measured with the Conner-Davidson Resilience 10 item scale. Grit was measured utilizing the Short Grit Scale. RESULTS: Inspection of the interfactor correlations suggest that resilience and grit scales are distinct, though tend to correlate well. Notably, the relationship between resilience and the persistent effort component of grit was moderate. That correlation was higher than the relationship between the consistent interest component of grit and resilience. CONCLUSION: This study concludes that grit and resilience are related concepts but are not synonymous. Being mindful of the difference in these two attributes may be important in the development of educational offerings in both Schools of Nursing and in new nurse residency programs to increase retention in nursing.

Cellular and Neural Responses to Sour Stimuli Require the Proton Channel Otop1.

The sense of taste allows animals to sample chemicals in the environment prior to ingestion. Of the five basic tastes, sour, the taste of acids, had remained among the most mysterious. Acids are detected by type III taste receptor cells (TRCs), located in taste buds across the tongue and palate epithelium. The first step in sour taste transduction is believed to be entry of protons into the cell cytosol, which leads to cytosolic acidification and the generation of action potentials. The proton-selective ion channel Otop1 is expressed in type III TRCs and is a candidate sour receptor. Here, we tested the contribution of Otop1 to taste cell and gustatory nerve responses to acids in mice in which Otop1 was genetically inactivated (Otop1-KO mice). We first show that Otop1 is required for the inward proton current in type III TRCs from different parts of the tongue that are otherwise molecularly heterogeneous. We next show that in type III TRCs from Otop1-KO mice, intracellular pH does not track with extracellular pH and that moderately acidic stimuli do not elicit trains of action potentials, as they do in type III TRCs from wild-type mice. Moreover, gustatory nerve responses in Otop1-KO mice were severely and selectively attenuated for acidic stimuli, including citric acid and HCl. These results establish that the Otop1 proton channel plays a critical role in acid detection in the mouse gustatory system, evidence that it is a bona fide sour taste receptor.

Physiological and Behavioral Responses to Optogenetic Stimulation of PKD2L1+ Type III Taste Cells.

Type III taste cells in mammalian taste buds are implicated in the detection and communication of sour and some salty stimuli, as well as carbonation and water. With this variety of proposed roles, it is unclear what information activated type III cells are communicating to the CNS. To better elucidate the role of type III cells in the taste bud, we use a type III cell-specific protein (polycystic kidney disease 2-like 1) to drive Cre-dependent expression of light-sensitive channelrhodopsin (Ai32) in mouse type III taste cells. Activation of these cells with light produces a taste nerve response in both the chorda tympani and glossopharyngeal nerves, and elicits a slight but significant aversion in two-bottle preference tests in both male and female mice. Unlike previous reports (Zocchi et al., 2017), our mice did not react to blue light stimulation with sustained drinking responses. These data suggest that type III cells are capable of communicating the presence of aversive stimuli in the oral cavity, which is in line with their responsiveness to sour and high concentrations of salt stimuli.

Type III Cells in Anterior Taste Fields Are More Immunohistochemically Diverse Than Those of Posterior Taste Fields in Mice.

Activation of Type III cells in mammalian taste buds is implicated in the transduction of acids (sour) and salty stimuli. Several lines of evidence suggest that function of Type III cells in the anterior taste fields may differ from that of Type III cells in posterior taste fields. Underlying anatomy to support this observation is, however, scant. Most existing immunohistochemical data characterizing this cell type focus on circumvallate taste buds in the posterior tongue. Equivalent data from anterior taste fields-fungiform papillae and soft palate-are lacking. Here, we compare Type III cells in four taste fields: fungiform, soft palate, circumvallate, and foliate in terms of reactivity to four canonical markers of Type III cells: polycystic kidney disease 2-like 1 (PKD2L1), synaptosomal associated protein 25 (SNAP25), serotonin (5-HT), and glutamate decarboxylase 67 (GAD67). Our findings indicate that while PKD2L1, 5-HT, and SNAP25 are highly coincident in posterior taste fields, they diverge in anterior taste fields. In particular, a subset of taste cells expresses PKD2L1 without the synaptic markers, and a subset of SNAP25 cells lacks expression of PKD2L1. In posterior taste fields, GAD67-positive cells are a subset of PKD2L1 expressing taste cells, but anterior taste fields also contain a significant population of GAD67-only expressing cells. These differences in expression patterns may underlie the observed functional differences between anterior and posterior taste fields.

Self-reported food skills of university students.

University students experience a life transition that often results in poor dietary behaviors and weight gain. Adequate food skills may improve diet quality and prevent chronic disease. Research is limited, however, on students' food skills and food-related behaviors. The objective of this study was to assess whether self-perceived food skills and related behaviors of students at a large, Canadian university differed based on sex, having taken a Food and Nutrition (FN) course, and living conditions, using a cross-sectional online survey. The response rate was 21.9% (n = 6638). Students (age, M ± SD 19.9 ± 2.1 years) self-reported their abilities for seven distinct food skills. Students rated (out of 100) their ability for some skills significantly higher than others (79.7 ± 20.9 for peeling, chopping, and slicing vs. 56.1 ± 29.1 for weekly meal planning; p < 0.001). Females reported higher total food skill scores than males (487.0 ± 141.1 out of a possible 700 vs. 441.9 ± 151.8, respectively; p < 0.001). Respondents who had taken a FN course reported higher total food skill scores than those who had not (494.9 ± 137.0 vs. 461.9 ± 149.2; p < 0.001). Students who resided away from their parental home for longer than one year reported significantly higher total food skill scores than those living away for one year or less (488.9 ± 134.6 vs. 443.3 ± 153.0, respectively; p < 0.001). Results indicate that students' self-perceived food skills vary by sex, FN education, and living condition. Higher abilities were reported for mechanical food skills; conceptual skills were significantly lower. These results may assist in effectively targeting this population with nutrition education interventions.

Endogenous Neoantigen-Specific CD8 T Cells Identified in Two Glioblastoma Models Using a Cancer Immunogenomics Approach.

The "cancer immunogenomics" paradigm has facilitated the search for tumor-specific antigens over the last 4 years by applying comprehensive cancer genomics to tumor antigen discovery. We applied this methodology to identify tumor-specific "neoantigens" in the C57BL/6-derived GL261 and VM/Dk-derived SMA-560 tumor models. Following DNA whole-exome and RNA sequencing, high-affinity candidate neoepitopes were predicted and screened for immunogenicity by ELISPOT and tetramer analyses. GL261 and SMA-560 harbored 4,932 and 2,171 nonsynonymous exome mutations, respectively, of which less than half were expressed. To establish the immunogenicities of H-2Kb and H-2Db candidate neoantigens, we assessed the ability of the epitopes predicted in silico to be the highest affinity binders to activate tumor-infiltrating T cells harvested from GL261 and SMA-560 tumors. Using IFNγ ELISPOT, we confirmed H-2Db-restricted Imp3D81N (GL261) and Odc1Q129L (SMA-560) along with H-2Kb-restricted E2f8K272R (SMA-560) as endogenous tumor-specific neoantigens that are functionally immunogenic. Furthermore, neoantigen-specific T cells to Imp3D81N and Odc1Q129L were detected within intracranial tumors as well as cervical draining lymph nodes by tetramer analysis. By establishing the immunogenicities of predicted high-affinity neoepitopes in these models, we extend the immunogenomics-based neoantigen discovery pipeline to glioblastoma models and provide a tractable system to further study the mechanism of action of T cell-activating immunotherapeutic approaches in preclinical models of glioblastoma. Cancer Immunol Res; 4(12); 1007-15. ©2016 AACR.

A systematic review of preoperative predictors for postoperative clinical outcomes following lumbar discectomy.

BACKGROUND CONTEXT: Sciatica is often caused by a herniated lumbar intervertebral disc. When conservative treatment fails, a lumbar discectomy can be performed. Surgical treatment via lumbar discectomy is not always successful and may depend on a variety of preoperative factors. It remains unclear which, if any, preoperative factors can predict postsurgical clinical outcomes. PURPOSE: This review aimed to determine preoperative predictors that are associated with postsurgical clinical outcomes in patients undergoing lumbar discectomy. STUDY DESIGN: This is a systematic review. METHODS: This systematic review of the scientific literature followed the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. MEDLINE and PubMed were systematically searched through June 2014. Results were screened for relevance independently, and full-text studies were assessed for eligibility. Reporting quality was assessed using a modified Newcastle-Ottawa Scale. Quality of evidence was assessed using a modified version of Sackett's Criteria of Evidence Support. No financial support was provided for this study. No potential conflict of interest-associated biases were present from any of the authors. RESULTS: The search strategy yielded 1,147 studies, of which a total of 40 high-quality studies were included. There were 17 positive predictors, 20 negative predictors, 43 non-significant predictors, and 15 conflicting predictors determined. Preoperative predictors associated with positive postoperative outcomes included more severe leg pain, better mental health status, shorter duration of symptoms, and younger age. Preoperative predictors associated with negative postoperative outcomes included intact annulus fibrosus, longer duration of sick leave, worker's compensation, and greater severity of baseline symptoms. Several preoperative factors including motor deficit, side and level of herniation, presence of type 1 Modic changes and degeneration, age, and gender had non-significant associations with postoperative clinical outcomes. CONCLUSIONS: It may be possible for certain preoperative factors to be targeted for clinical evaluation by spine surgeons to assess the suitability of patients for lumbar discectomy surgery, the hope being to thereby improve postoperative clinical outcomes. Prospective cohort studies are required to increase the level of evidence with regard to significant predictive factors.

The K+ channel KIR2.1 functions in tandem with proton influx to mediate sour taste transduction.

Sour taste is detected by a subset of taste cells on the tongue and palate epithelium that respond to acids with trains of action potentials. Entry of protons through a Zn(2+)-sensitive proton conductance that is specific to sour taste cells has been shown to be the initial event in sour taste transduction. Whether this conductance acts in concert with other channels sensitive to changes in intracellular pH, however, is not known. Here, we show that intracellular acidification generates excitatory responses in sour taste cells, which can be attributed to block of a resting K(+) current. We identify KIR2.1 as the acid-sensitive K(+) channel in sour taste cells using pharmacological and RNA expression profiling and confirm its contribution to sour taste with tissue-specific knockout of the Kcnj2 gene. Surprisingly, acid sensitivity is not conferred on sour taste cells by the specific expression of Kir2.1, but by the relatively small magnitude of the current, which makes the cells exquisitely sensitive to changes in intracellular pH. Consistent with a role of the K(+) current in amplifying the sensory response, entry of protons through the Zn(2+)-sensitive conductance produces a transient block of the KIR2.1 current. The identification in sour taste cells of an acid-sensitive K(+) channel suggests a mechanism for amplification of sour taste and may explain why weak acids that produce intracellular acidification, such as acetic acid, taste more sour than strong acids.

Effect of head and face insulation on cooling rate during snow burial.

OBJECTIVES: Avalanche victims are subjected to a number of physiological stressors during burial. We simulated avalanche burial to monitor physiological data and determine whether wearing head and face insulation slows cooling rate during snow burial. In addition, we sought to compare 3 different types of temperature measurement methods. METHODS: Nine subjects underwent 2 burials each, 1 with head and face insulation and 1 without. Burials consisted of a 60-minute burial phase followed by a 60-minute rewarming phase. Temperature was measured via 3 methods: esophageal probe, ingestible capsule, and rectal probe. RESULTS: Cooling and rewarming rates were not statistically different between the 2 testing conditions when measured by the 3 measurement methods. All temperature measurement methods correlated significantly. CONCLUSIONS: Head and face insulation did not protect the simulated avalanche victim from faster cooling or rewarming. Because the 3 temperature measurement methods correlated, the ingestible capsule may provide an advantageous noninvasive method for snow burial and future hypothermia studies if interruptions in data transmission can be minimized.

Feline gangrenous mastitis.

A 3.7-kg, 3-year-old intact female domestic shorthaired cat was presented with the chief complaint of anorexia and lethargy of 3 days duration with a noticeable decrease in body condition and a large open wound on her ventral caudal abdomen. A diagnosis of acute mastitis with gland abscessation was made. The patient was successfully treated with oral antibiotics and open wound management using surgical debridement and lavage followed by wound dressings using honey.

Mammite nécrotique féline. Une chatte domestique intacte pesant 3,7 kg et âgée de 3 ans a été présentée pour des plaintes portant principalement sur l'anorexie et l'abattement depuis 3 jours avec une dégradation marquée de la condition physique et une grande plaie ouverte sur l'abdomen caudal ventral. Un diagnostic de mammite aiguë avec un abcès glandulaire a été posé. La patiente a été traitée avec succès à l'aide d'antibiotiques oraux et la plaie ouverte a été gérée à l'aide d'un parage chirurgical et d'un lavage suivis d'un pansement de la plaie avec du miel.(Traduit par Isabelle Vallières).