System dynamics of diabetes in the presence of social determinants

Diabetes is a chronic and persistent disease that is on the rise in the U.S. in spite of medical advances and current public health efforts to address it. There is a relationship between socioeconomic factors such as poverty and education and the risk of developing diabetes and the progression of the disease. A systems approach is employed to develop a dynamic hypothesis with a stock and flow model will uncover and analyze these relationships to gain a better understanding of the socioeconomic dynamics of diabetes. Social factors have a significant impact on health outcomes and their consideration is essential to developing policies that will help to reduce diabetes incidence

Neuroanatomical and Morphological Properties of Neurons that Generate Inspiratory Related Breathing Rhythm and Influence Respiratory Motor Pattern in Mice

The relationship between neuron morphology and function is a perennial issue in neuroscience. Information about synaptic integration, network connectivity, and the specific roles of neuronal subpopulations can be obtained through morphological analysis of key neurons within any given microcircuit. Breathing is essential behavior for humans and all mammals, yet the neural microcircuit that governs respiration is not completely understood. The respiratory neural microcircuit resides within the ventral respiratory column located in the medulla. Within the respiratory column, the site of respiratory rhythm generation is the bilaterally distributed preBötzinger complex (preBötC). Rhythm-generating neurons in the preBötC are derived from a single genetic line, i.e., precursor cells expressing the transcription factor Developing brain homeobox-1 (Dbx1). An analysis of over 40 dendritic morphological features of rhythmogenic Dbx1 preBötC neurons and putatively premotor Dbx1 neurons in the intermediate reticular formation, revealed these two populations are similar except reticular neurons have a larger dendritic diameter, which may contribute to a greater passive transmembrane conductance. Both populations showed commissural axon projections and reticular formation neurons show premotor-like projections to the XII motor nucleus. These morphological data provide additional evidence supporting bilateral synchronization the preBötC through Dbx1 neurons, and demonstrate that Dbx1 preBötC neuron connectivity includes recurrent interconnections. On the molecular level, the ion channels that mediate rhythm-generating whole-cell ion currents have not been not identified, and were investigated using principally an anatomical approach. The nonspecific cation current, ICAN, underlies robust inspiratory drive potentials in the preBötC and the persistent sodium current, INaP may play a role in the production of robust bursts when respiration is challenged in such cases as anoxia or hypoxia. The leading candidate for ion channels that contribute to ICAN belong to the transient membrane receptor (Trp) ion channel superfamily and the leading ion channel candidate for INaP is Nav1.6. I determined the presence of Trpc3 ion channels and Nav1.6 ion channels on Dbx1 preBötC neurons (as well as their expression in neighboring non-Dbx1 preBötC neurons). Finally, breathing behavior involves periodic sighs, which are slower than normal eupneic breathing but critical for lung function. I examined receptor expression for bomebsin-like peptides neuromedin B (NMB) and gastrin releasing peptide (GRP), which are important for sigh behavior. I show that NMB and GRP receptors are expressed in Dbx1 preBötC neurons and are not expressed by glia in the preBötC, as posited by some because of the low frequency of sigh breaths. These advances in morphological and anatomical knowledge can be used to design targeted in vitro and in vivo experiments to further explore their role in respiratory rhythm and pattern generation

System dynamics of diabetes in the presence of social determinants

Diabetes is a chronic and persistent disease that is on the rise in the U.S. in spite of medical advances and current public health efforts to address it. There is a relationship between socioeconomic factors such as poverty and education and the risk of developing diabetes and the progression of the disease. A systems approach is employed to develop a dynamic hypothesis with a stock and flow model will uncover and analyze these relationships to gain a better understanding of the socioeconomic dynamics of diabetes. Social factors have a significant impact on health outcomes and their consideration is essential to developing policies that will help to reduce diabetes incidence

Physiological and morphological properties of Dbx1-derived respiratory neurons in the pre-Botzinger complex of neonatal mice

Key points center dot The transcription factor Dbx1 gives rise to putatively respiratory rhythm-generating neurons in the pre-Botzinger complex. Comparative analysis of Dbx1-derived (Dbx1+) and non-Dbx1- derived (Dbx1) neurons can help elucidate the cellular bases of respiratory rhythm generation. center dot In vitro, Dbx1+ neurons activate earlier in the respiratory cycle, discharge larger magnitude inspiratory bursts and exhibit a lower rheobase compared with Dbx1 neurons. center dot The Dbx1+ neurons tend to express the intrinsic currents IA (transient outward A-current) and Ih (hyperpolarization-activated current) in diametric opposition, which may facilitate temporal summation of excitatory synaptic inputs, whereas the Dbx1 neurons show no significant pattern of expression regarding IA and Ih. center dot The Dbx1+ neurons exhibit smooth, spineless dendrites that project in the transverse plane, whereas the Dbx1 neurons are confined to the transverse plane to a lesser extent and sometimes exhibit spines. center dot The properties of Dbx1+ neurons that may contribute to respiratory rhythmogenesis include a high level of excitability linked to ongoing network activity and dendritic properties that may facilitate synaptic integration. Abstract Breathing in mammals depends on an inspiratory-related rhythm that is generated by glutamatergic neurons in the pre-Botzinger complex (preBotC) of the lower brainstem. A substantial subset of putative rhythm-generating preBotC neurons derive from a single genetic line that expresses the transcription factor Dbx1, but the cellular mechanisms of rhythmogenesis remain incompletely understood. To elucidate these mechanisms, we carried out a comparative analysis of Dbx1-expressing neurons (Dbx1+) and non-Dbx1-derived (Dbx1) neurons in the preBotC. Whole-cell recordings in rhythmically active newborn mouse slice preparations showed that Dbx1+ neurons activate earlier in the respiratory cycle and discharge greater magnitude inspiratory bursts compared with Dbx1 neurons. Furthermore, Dbx1+ neurons required less input current to discharge spikes (rheobase) in the context of network activity. The expression of intrinsic membrane properties indicative of A-current (IA) and hyperpolarization-activated current (Ih) tended to be mutually exclusive in Dbx1+ neurons. In contrast, there was no such relationship in the expression of currents IA and Ih in Dbx1 neurons. Confocal imaging and digital morphological reconstruction of recorded neurons revealed dendritic spines on Dbx1 neurons, but Dbx1+ neurons were spineless. The morphology of Dbx1+ neurons was largely confined to the transverse plane, whereas Dbx1 neurons projected dendrites to a greater extent in the parasagittal plane. The putative rhythmogenic nature of Dbx1+ neurons may be attributable, in part, to a higher level of intrinsic excitability in the context of network synaptic activity. Furthermore, Dbx1+ neuronal morphology may facilitate temporal summation and integration of local synaptic inputs from other Dbx1+ neurons, taking place largely in the dendrites, which could be important for initiating and maintaining bursts and synchronizing activity during the inspiratory phase

Morphology of Dbx1 respiratory neurons in the preBotzinger complex and reticular formation of neonatal mice

The relationship between neuron morphology and function is a perennial issue in neuroscience. Information about synaptic integration, network connectivity, and the specific roles of neuronal subpopulations can be obtained through morphological analysis of key neurons within a microcircuit. Here we present morphologies of two classes of brainstem respiratory neurons. First, interneurons derived from Dbx1-expressing precursors (Dbx1 neurons) in the preBotzinger complex (preBotC) of the ventral medulla that generate the rhythm for inspiratory breathing movements. Second, Dbx1 neurons of the intermediate reticular formation that influence the motor pattern of pharyngeal and lingual movements during the inspiratory phase of the breathing cycle. We describe the image acquisition and subsequent digitization of morphologies of respiratory Dbx1 neurons from the preBotC and the intermediate reticular formation that were first recorded in vitro. These data can be analyzed comparatively to examine how morphology influences the roles of Dbx1 preBotC and Dbx1 reticular interneurons in respiration and can also be utilized to create morphologically accurate compartmental models for simulation and modeling of respiratory circuits

Miscellany

Art Writinghttps://digitalcommons.georgiasouthern.edu/miscell/1000/thumbnail.jp

Nurses’ Attitudes Toward Caring for Adults with Intellectual and Developmental Disabilities Hospitalized to Inpatient Medical Settings: A Systematic Review

Objective. The purpose of this systematic review was to elucidate current evidence regarding nurses’ attitudes about providing care to adults with intellectual and developmental disability (IDD) who are hospitalized in medical settings. Background. Individuals who have an Autism Spectrum Disorder (ASD) or IDD are hospitalized 6 times more often than the general population, 1.44 times more likely to die in the hospital than are those in the general population and face higher hospital costs. Furthermore, the number of individuals having IDD is increasing in the United States. Studies revealed that nurses report more negative emotions about providing care to individuals with IDD. Methods. A seven-person team consisting of faculty and doctoral students conducted extensive literature search strategies to locate and appraise relevant literature reporting original data studies. The data were appraised using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results. Eight articles published up to November 2019 were included. Improved training, consistent patient information, and improved communication is needed. Conclusion. This systematic review illuminates the critical gaps in the scientific body of knowledge regarding effective interventions to address the persistent disparity in attitudes of registered nurses regarding caring for patients with IDD. Research data to inform the implementation of interventions to improve the attitude and emotions toward adults with IDD among nurses employed in acute care facilities is lacking. This dearth hinders the delivery of effective healthcare which results in an impaired nurse-patient relationship and increased costs. Grants. This study was not grant funded

Claimed Detection of PH3 in the Clouds of Venus Is Consistent with Mesospheric SO2

Abstract The observation of a 266.94 GHz feature in the Venus spectrum has been attributed to phosphine (PH3) in the Venus clouds, suggesting unexpected geological, chemical, or even biological processes. Since both PH3 and sulfur dioxide (SO2) are spectrally active near 266.94 GHz, the contribution to this line from SO2 must be determined before it can be attributed, in whole or part, to PH3. An undetected SO2 reference line, interpreted as an unexpectedly low SO2 abundance, suggested that the 266.94 GHz feature could be attributed primarily to PH3. However, the low SO2 and the inference that PH3 was in the cloud deck posed an apparent contradiction. Here we use a radiative transfer model to analyze the PH3 discovery, and explore the detectability of different vertical distributions of PH3 and SO2. We find that the 266.94 GHz line does not originate in the clouds, but above 80 km in the Venus mesosphere. This level of line formation is inconsistent with chemical modeling that assumes generation of PH3 in the Venus clouds. Given the extremely short chemical lifetime of PH3 in the Venus mesosphere, an implausibly high source flux would be needed to maintain the observed value of 20 ± 10 ppb. We find that typical Venus SO2 vertical distributions and abundances fit the JCMT 266.94 GHz feature, and the resulting SO2 reference line at 267.54 GHz would have remained undetectable in the ALMA data due to line dilution. We conclude that nominal mesospheric SO2 is a more plausible explanation for the JCMT and ALMA data than PH3

Trpm4 Ion Channels in pre-Bo¨tzinger Complex Interneurons Are Essential for Breathing Motor Pattern But Not Rhythm

Inspiratory breathing movements depend on pre-Bötzinger complex (preBötC) interneurons that express calcium (Ca2+)-activated nonselective cationic current (ICAN) to generate robust neural bursts. Hypothesized to be rhythmogenic, reducing ICAN is predicted to slow down or stop breathing; its contributions to motor pattern would be reflected in the magnitude of movements (output). We tested the role(s) of ICAN using reverse genetic techniques to diminish its putative ion channels Trpm4 or Trpc3 in preBötC neurons in vivo. Adult mice transduced with Trpm4-targeted short hairpin RNA (shRNA) progressively decreased the tidal volume of breaths yet surprisingly increased breathing frequency, often followed by gasping and fatal respiratory failure. Mice transduced with Trpc3-targeted shRNA survived with no changes in breathing. Patch-clamp and field recordings from the preBötC in mouse slices also showed an increase in the frequency and a decrease in the magnitude of preBötC neural bursts in the presence of Trpm4 antagonist 9-phenanthrol, whereas the Trpc3 antagonist pyrazole-3 (pyr-3) showed inconsistent effects on magnitude and no effect on frequency. These data suggest that Trpm4 mediates ICAN, whose influence on frequency contradicts a direct role in rhythm generation. We conclude that Trpm4-mediated ICAN is indispensable for motor output but not the rhythmogenic core mechanism of the breathing central pattern generator

Trpm4 ion channels in pre-Bötzinger complex interneurons are essential for breathing motor pattern but not rhythm.

Inspiratory breathing movements depend on pre-Bötzinger complex (preBötC) interneurons that express calcium (Ca2+)-activated nonselective cationic current (ICAN) to generate robust neural bursts. Hypothesized to be rhythmogenic, reducing ICAN is predicted to slow down or stop breathing; its contributions to motor pattern would be reflected in the magnitude of movements (output). We tested the role(s) of ICAN using reverse genetic techniques to diminish its putative ion channels Trpm4 or Trpc3 in preBötC neurons in vivo. Adult mice transduced with Trpm4-targeted short hairpin RNA (shRNA) progressively decreased the tidal volume of breaths yet surprisingly increased breathing frequency, often followed by gasping and fatal respiratory failure. Mice transduced with Trpc3-targeted shRNA survived with no changes in breathing. Patch-clamp and field recordings from the preBötC in mouse slices also showed an increase in the frequency and a decrease in the magnitude of preBötC neural bursts in the presence of Trpm4 antagonist 9-phenanthrol, whereas the Trpc3 antagonist pyrazole-3 (pyr-3) showed inconsistent effects on magnitude and no effect on frequency. These data suggest that Trpm4 mediates ICAN, whose influence on frequency contradicts a direct role in rhythm generation. We conclude that Trpm4-mediated ICAN is indispensable for motor output but not the rhythmogenic core mechanism of the breathing central pattern generator