The introduction and current status of the multidimensional model of pain neurobiology.

Conceptual models are useful because they guide our practical actions related to whatever is represented by the model; this includes research that reveals the limitations of these actions and the potential for their improvement. These statements apply to many aspects of daily life and especially to pain as a challenge for both clinical practice specifically and neurobiology generally. In the first half of the 20th century, our conceptual model of pain, to the extent that it existed at all, was based on evidence supporting the proposition that pain emerged from activity within a very spatially limited set of central nervous system (CNS) structures located within the cerebral cortex and it's oligosynaptic connections with the thalamus. This CNS activity was strongly associated with the activation of physiologically distinct and specialized somatovisceral afferent fibers. All, or nearly all, aspects of the pain experience were thought to arise from, and be modified by, changes in that localized CNS activity. There was no compelling and widely accepted reason to consider an alternative model. However, neurophysiological, neuroanatomical, behavioral, and clinical evidence emerging in the late mid-20th century prompted a reconsideration of the prevailing model of pain neurobiology. Based on this new evidence and the perceived limitations of the prevailing model, pain could then be reasonably conceived as a multidimensional experience arising from the conjoint activation of physiologically and anatomically distinct but interacting CNS structures each separately mediating sensory discriminative, affective, and cognitive aspects of pain. This brief historical review describes the intellectual climate at the time this multidimensional model was proposed, the dispositions for resisting or accepting it, and concludes with a comment on the current status of the model as a fusion of distributed activations that create a unified perception of pain.

Respiratory Management of Patients With Neuromuscular Weakness: An American College of Chest Physicians Clinical Practice Guideline and Expert Panel Report.

BACKGROUND: Respiratory failure is a significant concern in neuromuscular diseases (NMDs). This CHEST guideline examines the literature on the respiratory management of patients with NMD to provide evidence-based recommendations. STUDY DESIGN AND METHODS: An expert panel conducted a systematic review addressing the respiratory management of NMD and applied the Grading of Recommendations, Assessment, Development, and Evaluations approach for assessing the certainty of the evidence and formulating and grading recommendations. A modified Delphi technique was used to reach a consensus on the recommendations. RESULTS: Based on 128 studies, the panel generated 15 graded recommendations, one good practice statement, and one consensus-based statement. INTERPRETATION: Evidence of best practices for respiratory management in NMD is limited and is based primarily on observational data in amyotrophic lateral sclerosis. The panel found that pulmonary function testing every 6 months may be beneficial and may be used to initiate noninvasive ventilation (NIV) when clinically indicated. An individualized approach to NIV settings may benefit patients with chronic respiratory failure and sleep-disordered breathing related to NMD. When resources allow, polysomnography or overnight oximetry can help to guide the initiation of NIV. The panel provided guidelines for mouthpiece ventilation, transition to home mechanical ventilation, salivary secretion management, and airway clearance therapies. The guideline panel emphasizes that NMD pathologic characteristics represent a diverse group of disorders with differing rates of decline in lung function. The clinician's role is to add evaluation at the bedside to shared decision-making with patients and families, including respect for patient preferences and treatment goals, considerations of quality of life, and appropriate use of available resources in decision-making.

Condensed and Hydrolyzable Tannins for Reducing Methane and Nitrous Oxide Emissions in Dairy Manure-A Laboratory Incubation Study.

The objectives of this study were to (1) examine the effects of plant condensed (CT) and hydrolyzable tannin (HT) extracts on CH4 and N2O emissions; (2) identify the reactions responsible for manure-derived GHG emissions, and (3) examine accompanying microbial community changes in fresh dairy manure. Five treatments were applied in triplicate to the freshly collected dairy manure, including 4% CT, 8% CT, 4% HT, 8% HT (V/V), and control (no tannin addition). Fresh dairy manure was placed into 710 mL glass incubation chambers. In vitro composted dairy manure samples were collected at 0, 24, 48, and 336 h after the start of incubation. Fluxes of N2O and CH4 were measured for 5-min/h for 14 d at a constant ambient incubation temperature of 39 °C. The addition of quebracho CT significantly decreased the CH4 flux rates compared to the tannin-free controls (215.9 mg/m2/h), with peaks of 75.6 and 89.6 mg/m2/h for 4 and 8% CT inclusion rates, respectively. Furthermore, CT significantly reduced cumulative CH4 emission by 68.2 and 57.3% at 4 and 8% CT addition, respectively. The HT treatments failed to affect CH4 reduction. However, both CT and HT reduced (p < 0.001) cumulative and flux rates of N2O emissions. The decrease in CH4 flux with CT was associated with a reduction in the abundance of Bacteroidetes and Proteobacteria.

Comparison of monensin sodium sources for finishing beef cattle.

The objective of this study was to evaluate the ruminal fermentation characteristics of ruminally fistulated beef steers consuming a steam-flaked corn (SFC) or dry-rolled corn (DRC) based diet containing either Rumensin 90 (RUM; Elanco, Greenfield, IN), or Monovet 90 (MV; Huvepharma, Peachtree City, GA). Six ruminally fistulated steers (657.7 kg ± 72.6) housed individually were used in a 6 × 6 Latin square design with 2 × 3 factorial treatment arrangement. Each of the 6 periods were 15 d with 14 d for diet adaptation and 1 d of rumen fluid collections. Dietary treatments were DRC without monensin sodium (DRC-C), SFC without monensin sodium (SFC-C), DRC with Rumensin 90 (DRC-R), DRC with Monovet 90 (DRC-MV), SFC with Rumensin 90 (SFC-R), and SFC with Monovet 90 (SFC-MV). Rumen contents and fluid were collected through the fistula of each animal at 0, 3, 6, 12, and 24 h on d 15 of each period. Rumen fluid collected at 6 h post-feeding each period was used for in vitro analyses. Steer was the experimental unit and the model included fixed effects of grain processing, additive, and grain processing × additive. Total gas produced was composited from each in vitro bottle into a gas collection bag for the 48-h determination of methane concentration. No differences were detected for DMI (P = 0.81). Ruminal pH did not differ for the control or additive treatments (P = 0.33). However, ruminal pH was lower (P < 0.01) with SFC compared to DRC. There was a significant difference in acetate to propionate ratio for grain type (P = 0.01) and a tendency for additive inclusion (P = 0.06). Additive inclusion reduced methane proportion of total gas compared to control treatments (P ≤ 0.01). Overall, monensin sodium reduced methane concentration though source had no effect on DMI or ruminal pH.

Long-term tillage effect on with-in season variations in soil conditions and respiration from dryland winter wheat and soybean cropping systems.

Soil respiration from agricultural soils is a major anthropogenic source of CO2 to the atmosphere. With-in season emission of soil CO2 from croplands are affected by changes in weather, tillage, plant row spacing, and plant growth stage. Tillage involves physical turning of soils which accelerate residue decomposition and CO2 emission. No-tillage lacks soil disturbance and residues undergo slower decomposition at the surface. In this study, we compared with-in season soil conditions (temperature and moisture) and soil respiration from two major crops (soybean and winter wheat) by making high temporal frequency measurements using automated chambers at half-hourly intervals. The experiment lasted for 179 days. Total number of measurements made from conventional and no-tillage soybean and winter wheat plots were 6480 and 4456, respectively. Average flux after the winter-dormancy period of wheat was 37% higher in tilled soil compared to no-till soil. However, average flux during the soybean growing season was 8% lower in conventional till compared to no-till soil. This differential response of soil respiration in wheat and soybean was primarily due to tillage-induced changes in surface characteristics (residue cover) and soil environmental conditions (soil temperature and soil moisture). Results from this study can help elucidate relationships for modeling and assessment of field-scale soil CO2 emissions from dryland wheat and soybean crops grown in sub-tropics.

Impact of chronic migraine attacks and their severity on the endogenous µ-opioid neurotransmission in the limbic system.

OBJECTIVE: To evaluate, in vivo, the impact of ongoing chronic migraine (CM) attacks on the endogenous µ-opioid neurotransmission. BACKGROUND: CM is associated with cognitive-emotional dysfunction. CM is commonly associated with frequent acute medication use, including opioids. METHODS: We scanned 15 migraine patients during the spontaneous headache attack (ictal phase): 7 individuals with CM and 8 with episodic migraine (EM), as well as 7 healthy controls (HC), using positron emission tomography (PET) with the selective µ-opioid receptor (µOR) radiotracer [11C]carfentanil. Migraineurs were scanned in two paradigms, one with thermal pain threshold challenge applied to the site of the headache, and one without thermal challenge. Multivariable analysis was performed between the µ-opioid receptor availability and the clinical data. RESULTS: µOR availability, measured with [11C]carfentanil nondisplaceable binding potential (BPND), in the left thalamus (P-value = 0.005) and left caudate (P-value = 0.003) were decreased in CM patients with thermal pain threshold during the ictal phase relative to HC. Lower µOR BPND in the right parahippocampal region (P-value = 0.001) and right amygdala (P-value = 0.002) were seen in CM relative to EM patients. Lower µOR BPND values indicate either a decrease in µOR concentration or an increase in endogenous µ-opioid release in CM patients. In the right amygdala, 71% of the overall variance in µOR BPND levels was explained by the type of migraine (CM vs. EM: partial-R2 = 0.47, P-value<0.001, Cohen's effect size d = 2.6SD), the severity of the attack (pain area and intensity number summation [P.A.I.N.S.]: partial-R2 = 0.16, P-value = 0.031), and the thermal pain threshold (allodynia: partial-R2 = 0.08). CONCLUSIONS: Increased endogenous µ-opioid receptor-mediated neurotransmission is seen in the limbic system of CM patients, especially in right amygdala, which is highly modulated by the attack frequency, pain severity, and sensitivity. This study demonstrates for the first time the negative impact of chronification and exacerbation of headache attacks on the endogenous µ-opioid mechanisms of migraine patients. ClinicalTrials.gov identifier: NCT03004313.

A Sleep Medicine Curriculum for Pulmonary and Pulmonary/Critical Care Fellowship Programs: A Multisociety Expert Panel Report.

BACKGROUND: Pulmonary medicine specialists find themselves responsible for the diagnosis and management of patients with sleep disorders. Despite the increasing prevalence of many of these conditions, many sleep medicine fellowship training slots go unfilled, leading to a growing gap between the volume of patients seeking care for sleep abnormalities and the number of physicians formally trained to manage them. To address this need, we convened a multisociety panel to develop a list of curricular recommendations related to sleep medicine for pulmonary fellowship training programs. METHODS: Surveys of pulmonary and pulmonary/critical care fellowship program directors and recent graduates of these programs were performed to assess the current state of sleep medicine education in pulmonary training, as well as the current scope of practice of pulmonary specialists. These data were used to inform a modified Delphi process focused on developing curricular recommendations relevant to sleep medicine. RESULTS: Surveys confirmed that pulmonary medicine specialists are often responsible for the diagnosis and treatment of a number of sleep conditions, including several that are not traditionally considered related to respiratory medicine. Through five rounds of voting, the panel crafted a list of 52 curricular competencies relevant to sleep medicine for recommended inclusion in pulmonary training programs. CONCLUSIONS: Practicing pulmonary specialists require a broad knowledge of sleep medicine to provide appropriate care to patients they will be expected to manage. Training program directors may use the list of competencies as a framework to ensure adequate mastery of important content by graduating fellows.

Sleep disorders: Serious threats among kidney transplant recipients.

In patients with chronic kidney disease (CKD) and kidney transplant recipients who continue to have some degree of CKD, the prevalence of sleep-related disorders is very high. Common sleep disorders in both groups include insomnia, sleep-disordered breathing (SDB), restless legs syndrome (RLS), excessive daytime sleepiness (EDS), and others. Depending on the kidney graft function, some patients see sleep disorders resolve after kidney transplantation, while others continue to have persistent sleep disorders or develop new ones. Kidney transplant recipients (KTRs) are unique patients due to the presence of a single kidney, the use of immunosuppressive medications, and other comorbidities including obesity, a high risk of cardiovascular disease, malignancy, and the anxiety of losing their allograft. All of these factors contribute to the risk for sleep disorders. CKD and sleep disorders have a bidirectional relationship; that is, CKD may increase the risk of sleep disorders and sleep disorders may increase the risk of CKD. Obstructive sleep apnea (OSA) is the most common form of SDB and is known to alter renal hemodynamics. OSA leads to hypoxemia and sleeps fragmentation, which activates the sympathetic nervous system. This activates the renin-angiotensin-aldosterone system and ultimately alters cardiovascular hemodynamics. Sleep disorders may have deleterious effects on the kidney allograft and proper screening and management are important for both graft and patient survival.

Position Paper for the Treatment of Nightmare Disorder in Adults: An American Academy of Sleep Medicine Position Paper.

INTRODUCTION: Nightmare disorder affects approximately 4% of adults, occurring in isolation or as part of other disorders such as posttraumatic stress disorder (PTSD), and can significantly impair quality of life. This paper provides the American Academy of Sleep Medicine (AASM) position regarding various treatments of nightmare disorder in adults. METHODS: A literature search was performed based upon the keywords and MeSH terms from the Best Practice Guide for the Treatment of Nightmare Disorder in Adults that was published in 2010 by the AASM. The search used the date range March 2009 to August of 2017, and sought to find available evidence pertaining to the use of behavioral, psychological, and pharmacologic therapies for the treatment of nightmares. A task force developed position statements based on a thorough review of these studies and their clinical expertise. The AASM Board of Directors approved the final position statements. DETERMINATION OF POSITION: Positions of "recommended" and "not recommended" indicate that a treatment option is determined to be clearly useful or ineffective/harmful for most patients, respectively, based on a qualitative assessment of the available evidence and clinical judgement of the task force. Positions of "may be used" indicate that the evidence or expert consensus is less clear, either in favor or against the use of a treatment option. The interventions listed below are in alphabetical order within the position statements rather than clinical preference: this is not meant to be instructive of the order in which interventions should be used. POSITION STATEMENTS: The following therapy is recommended for the treatment of PTSD-associated nightmares and nightmare disorder: image rehearsal therapy. The following therapies may be used for the treatment of PTSD-associated nightmares: cognitive behavioral therapy; cognitive behavioral therapy for insomnia; eye movement desensitization and reprocessing; exposure, relaxation, and rescripting therapy; the atypical antipsychotics olanzapine, risperidone and aripiprazole; clonidine; cyproheptadine; fluvoxamine; gabapentin; nabilone; phenelzine; prazosin; topiramate; trazodone; and tricyclic antidepressants. The following therapies may be used for the treatment of nightmare disorder: cognitive behavioral therapy; exposure, relaxation, and rescripting therapy; hypnosis; lucid dreaming therapy; progressive deep muscle relaxation; sleep dynamic therapy; self-exposure therapy; systematic desensitization; testimony method; nitrazepam; prazosin; and triazolam. The following are not recommended for the treatment of nightmare disorder: clonazepam and venlafaxine. The ultimate judgment regarding propriety of any specific care must be made by the clinician, in light of the individual circumstances presented by the patient, accessible treatment options, and resources.

Making the GRADE: CHEST Updates Its Methodology.

The American College of Chest Physicians (CHEST) has been at the forefront of evidence-based clinical practice guideline development for more than 2 decades. In 2006, CHEST adopted a modified system of Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to support their rigorous guideline development methodology. The evolution of CHEST's Living Guidelines Model, as well as their collaborative efforts with other organizations, has necessitated improvements in their guideline development methodology. CHEST has made the decision to transition to the standard GRADE method for rating the certainty of evidence and grading recommendations in their evidence-based clinical practice guidelines, a deviation from the modified approach that was adopted in 2006. The standard GRADE approach will be used to grade recommendations in all CHEST guidelines, including updates to previously published guidelines. CHEST's adoption of a standard GRADE approach will ensure that its guideline development methodology is more consistent with that used by other organizations, will better align evidence synthesis methods, and will result in more explicit and easy to understand recommendations.

Temporal Nitrous Oxide Emissions from Beef Cattle Feedlot Manure after a Simulated Rainfall Event.

Nitrous oxide (NO) is a greenhouse gas (GHG) emitted from agricultural operations. The objective of this research was to quantify NO-N emissions from simulated open-lot beef cattle feedlot pens after rainfall. A recirculating-flow-through, non-steady state chamber system consisting of five 1-m steel pans was designed for quantifying emissions. A lid was placed sequentially on each pan, and headspace air was recirculated between the pan and a real-time NO analyzer, measuring concentrations every 1 s. Air-dried manure (89.2% dry matter) from a commercial feedlot in the Texas Panhandle was placed in the pans and then 0, 6.3, 12.7, 25.4, or 50.8 mm of water was applied to simulate a one-time rainfall event. Emissions of NO-N were monitored for 45 d, where two distinct episodes of NO-N production were observed over time. The first NO-N episode had a duration of 10 h and peaked 2 h after rainfall at a flux of 1.0 to 200 mg m h. The second episode had a duration of 40 d and peaked 15 d after rainfall at a flux of 0.06 to 35 mg m h. The second episode accounted for 69 to 91% of the cumulative NO-N emitted over the 45-d period. Each millimeter of rainfall increased cumulative NO-N emitted by 167.9 mg m ( = 0.99, < 0.001). This rainfall vs. cumulative emissions relationship will be useful for modeling annual NO-N emissions from open-lot beef cattle feedlots, and for assessing the effectiveness of best management practices for reducing feedlot GHG emissions.

Dopamine D2/D3 imbalance during migraine attack and allodynia in vivo.

OBJECTIVE: To evaluate in vivo the dynamics of endogenous dopamine (DA) neurotransmission during migraine ictus with allodynia. METHODS: We examined 8 episodic migraineurs and 8 healthy controls (HC) using PET with [11C]raclopride. The uptake measure of [11C]raclopride, nondisplaceable binding potential (BPND), would increase when there was a reduction in endogenous DA release. The opposite is true for a decrease in [11C]raclopride BPND. Patients were scanned twice: one PET session was during a spontaneous migraine ictus at rest, followed by a sustained thermal pain threshold (STPT) challenge on the trigeminal region, eliciting an allodynia experience; another was during interictal phase. RESULTS: Striatal BPND of [11C]raclopride in migraineurs did not differ from HC. We found a significant increase in [11C]raclopride BPND in the striatum region of migraineurs during both headache attack and allodynia relative to interictal phase. However, when compared to the migraine attack at rest, migraineurs during the STPT challenge had a significant sudden reduction in [11C]raclopride BPND in the insula. Such directional change was also observed in the caudate of HC relative to the interictal phase during challenge. Furthermore, ictal changes in [11C]raclopride BPND in migraineurs at rest were positively correlated with the chronicity of migraine attacks, and negatively correlated with the frequency during challenge. CONCLUSIONS: Our findings demonstrate that there is an imbalanced uptake of [11C]raclopride during the headache attack and ictal allodynia, which indicates reduction and fluctuation in ictal endogenous DA release in migraineurs. Moreover, the longer the history and recurrence of migraine attacks, the lower the ictal endogenous DA release.

Nitrous Oxide Emissions from Open-Lot Cattle Feedyards: A Review.

Nitrous oxide (NO) emissions from concentrated animal feeding operations, including cattle feedyards, have become an important research topic. However, there are limitations to current measurement techniques, uncertainty in the magnitude of feedyard NO fluxes, and a lack of effective mitigation methods. The objective of this review was to assess NO emission from cattle feedyards, including comparison of measured and modeled emission rates, discussion of measurement methods, and evaluation of mitigation options. Published annual per capita flux rates for beef cattle feedyards and open-lot dairies were highly variable and ranged from 0.002 to 4.3 kg NO animal yr. On an area basis, published emission rates ranged from 0 to 41 mg NO m h. From these studies and Intergovernmental Panel on Climate Change emission factors, calculated daily per capita NO fluxes averaged 18 ± 10 g NO animal d (range, 0.04-67 g NO animal d). This variation was due to inconsistency in measurement techniques as well as irregularity in NO production and emission attributable to management, animal diet, and environmental conditions. Based on this review, it is clear that the magnitude and dynamics of NO emissions from open-lot cattle systems are not well understood. Further research is required to quantify feedyard NO fluxes and develop cost-effective mitigation methods.

Updated Adaptive Servo-Ventilation Recommendations for the 2012 AASM Guideline: "The Treatment of Central Sleep Apnea Syndromes in Adults: Practice Parameters with an Evidence-Based Literature Review and Meta-Analyses".

ABSTRACT: An update of the 2012 systematic review and meta-analyses were performed and a modified-GRADE approach was used to update the recommendation for the use of adaptive servo-ventilation (ASV) for the treatment of central sleep apnea syndrome (CSAS) related to congestive heart failure (CHF). Meta-analyses demonstrated an improvement in LVEF and a normalization of AHI in all patients. Analyses also demonstrated an increased risk of cardiac mortality in patients with an LVEF of ≤ 45% and moderate or severe CSA predominant sleep-disordered breathing. These data support a Standard level recommendation against the use of ASV to treat CHF-associated CSAS in patients with an LVEF of ≤ 45% and moderate or severe CSAS, and an Option level recommendation for the use of ASV in the treatment CHF-associated CSAS in patients with an LVEF > 45% or mild CHF-related CSAS. The application of these recommendations is limited to the target patient populations; the ultimate judgment regarding propriety of any specific care must be made by the clinician.

Technical Aspects of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: CHEST Guideline and Expert Panel Report.

BACKGROUND: Endobronchial ultrasound (EBUS) was introduced in the last decade, enabling real-time guidance of transbronchial needle aspiration (TBNA) of mediastinal and hilar structures and parabronchial lung masses. The many publications produced about EBUS-TBNA have led to a better understanding of the performance characteristics of this procedure. The goal of this document was to examine the current literature on the technical aspects of EBUS-TBNA as they relate to patient, technology, and proceduralist factors to provide evidence-based and expert guidance to clinicians. METHODS: Rigorous methodology has been applied to provide a trustworthy evidence-based guideline and expert panel report. A group of approved panelists developed key clinical questions by using the PICO (population, intervention, comparator, and outcome) format that addressed specific topics on the technical aspects of EBUS-TBNA. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion, and well-recognized document evaluation tools were used to assess the quality of included studies, to extract meaningful data, and to grade the level of evidence to support each recommendation or suggestion. RESULTS: Our systematic review and critical analysis of the literature on 15 PICO questions related to the technical aspects of EBUS-TBNA resulted in 12 statements: 7 evidence-based graded recommendations and 5 ungraded consensus-based statements. Three questions did not have sufficient evidence to generate a statement. CONCLUSIONS: Evidence on the technical aspects of EBUS-TBNA varies in strength but is satisfactory in certain areas to guide clinicians on the best conditions to perform EBUS-guided tissue sampling. Additional research is needed to enhance our knowledge regarding the optimal performance of this effective procedure.

Spatial and temporal changes in cumulative human impacts on the world's ocean.

Human pressures on the ocean are thought to be increasing globally, yet we know little about their patterns of cumulative change, which pressures are most responsible for change, and which places are experiencing the greatest increases. Managers and policymakers require such information to make strategic decisions and monitor progress towards management objectives. Here we calculate and map recent change over 5 years in cumulative impacts to marine ecosystems globally from fishing, climate change, and ocean- and land-based stressors. Nearly 66% of the ocean and 77% of national jurisdictions show increased human impact, driven mostly by climate change pressures. Five percent of the ocean is heavily impacted with increasing pressures, requiring management attention. Ten percent has very low impact with decreasing pressures. Our results provide large-scale guidance about where to prioritize management efforts and affirm the importance of addressing climate change to maintain and improve the condition of marine ecosystems.