scholarly journals The pontine respiratory group, particularly the Kölliker-Fuse nucleus, mediates phases of the hypoxic ventilatory response in unanesthetized goats

2010 ◽  
Vol 108 (5) ◽  
pp. 1321-1335 ◽  
Author(s):  
J. M. Bonis ◽  
S. E. Neumueller ◽  
K. L. Krause ◽  
T. Kiner ◽  
A. Smith ◽  
...  

The objective of the present study was to test the hypothesis that, in the in vivo awake goat model, perturbation/lesion in the pontine respiratory group (PRG) would decrease the sensitivity to hypercapnia and hypoxia. The study reported herein was part of two larger studies in which cholinergic modulation in the PRG was attenuated by microdialysis of atropine and subsequently ibotenic acid injections neurotoxically lesioned the PRG. In 14 goats, cannula were bilaterally implanted into either the lateral ( n = 4) or medial ( n = 4) parabrachial nuclei or the Kölliker-Fuse nucleus (KFN, n = 6). Before and after cannula implantation, microdialysis of atropine, and injection of ibotenic acid, hypercapnic and hypoxic ventilatory sensitivities were assessed. Hypercapnic sensitivity was assessed by three 5-min periods at 3, 5, and 7% inspired CO2. In all groups of goats, CO2 sensitivity was unaffected ( P > 0.05) by any PRG perturbations/lesions. Hypoxic sensitivity was assessed with a 30-min period at 10.8% inspired O2. The response to hypoxia was typically triphasic, with a phase 1 increase in pulmonary ventilation, a phase 2 roll-off, and a phase 3 prolonged increase associated with shivering and increased metabolic rate and body temperature. In all groups of goats, the phase 1 of the hypoxic ventilatory responses was unaffected by any PRG perturbations/lesions, and there were no consistent effects on the phase 2 responses. However, in the KFN group of goats, the phase 3 ventilatory, shivering, metabolic rate, and temperature responses were markedly attenuated after the atropine dialysis studies, and the attenuation persisted after the ibotenic acid studies. These findings support an integrative or modulatory role for the KFN in the phase 3 responses to hypoxia.

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241804
Author(s):  
Dong Eun Lee ◽  
Hyun Wook Ryoo ◽  
Sungbae Moon ◽  
Jeong Ho Park ◽  
Sang Do Shin

Improving outcomes after out-of-hospital cardiac arrests (OHCAs) requires an integrated approach by strengthening the chain of survival and emergency care systems. This study aimed to identify the change in outcomes over a decade and effect of citywide intervention on good neurologic outcomes after OHCAs in Daegu. This is a before- and after-intervention study to examine the association between the citywide intervention to improve the chain of survival and outcomes after OHCA. The primary outcome was a good neurologic outcome, defined as a cerebral performance category score of 1 or 2. After dividing into 3 phases according to the citywide intervention, the trends in outcomes after OHCA by primary electrocardiogram rhythm were assessed. Logistic regression analysis was used to analyze the association between the phases and outcomes. Overall, 6203 patients with OHCA were eligible. For 10 years (2008–2017), the rate of survival to discharge and the good neurologic outcomes increased from 2.6% to 8.7% and from 1.5% to 6.6%, respectively. Especially for patients with an initial shockable rhythm, these changes in outcomes were more pronounced (survival to discharge: 23.3% in 2008 to 55.0% in 2017, good neurologic outcomes: 13.3% to 46.0%). Compared with phase 1, the adjusted odds ratio (AOR) and 95% confidence intervals (CI) for good neurologic outcomes was 1.20 (95% CI: 0.78–1.85) for phase 2 and 1.64 (1.09–2.46) for phase 3. For patients with an initial shockable rhythm, the AOR for good neurologic outcomes was 3.76 (1.88–7.52) for phase 2 and 5.51 (2.77–10.98) for phase 3. Citywide improvement was observed in the good neurologic outcomes after OHCAs of medical origin, and the citywide intervention was significantly associated with better outcomes, particularly in those with initial shockable rhythm.


2020 ◽  
Author(s):  
Changju Liao ◽  
Linghong Guo ◽  
Han Wang ◽  
Tengyong Wang ◽  
Yuyang Zhang ◽  
...  

Abstract Background: Falls are serious public health problems associated with irreversible health consequences and substantial economic burden. To effectively reduce the incidence of falls and mitigate fall-related injuries, we designed and verified a multifactorial fall intervention model.Methods: The current study was a longitudinal before-and-after controlled investigation including 3 phases with clinical characteristics of fall patients retrospectively identified in phase 1, a multifactorial fall intervention model designed in phase 2 and prospectively evaluated in phase 3. Phase 1 and 2 were conducted based on 153,601 hospitalized patients between January 2015 and December 2016. Phase 3 was carried out based on 171,776 hospitalized patients between January 2017 and December 2018. The Pearson Chi-squared test was used to compare categorical variables and the Mann-Whitney non-parametric test was utilized for one-way ordered data.Results: In phase 1, baseline characteristics of 491 fall patients revealed that inpatients falls were highly associated with the age, medication and disease. In phase 2, a new multifactorial fall intervention model covering measures for fall prevention, fall-onset management and continuous improvement was developed. Phase 3 recorded a total of 396 falls and demonstrated a remarkably declined fall rate (Reduction in falls by 0.09%, p<0.001) and fall rate per 1000 patient-days (Reduction in falls/1000 patient-days by 0.07‰, p<0.001) as compared with phase 1. The adjusted incident rate ratio of fall was 1.443 (95%CI: 1.263-1.647) (Phase 1 vs. Phase 3). Furthermore, the occurrence and the severity of fall injuries in phase 3 were significantly lower than that in phase 1 (Z=-4.426, p<0.001). More specifically, the number of uninjured falls accounted for 42.42% in phase 3 in comparison of 32.99% in phase 1.Conclusions: This multifactorial fall intervention model exhibited favorable effect on reducing the occurrence of fall and fall injuries.


2013 ◽  
Vol 5 (1) ◽  
Author(s):  
Abdul Hasan Saragih

This classroom research was conducted on the autocad instructions to the first grade of mechinary class of SMK Negeri 1 Stabat aiming at : (1) improving the student’ archievementon autocad instructional to the student of mechinary architecture class of SMK Negeri 1 Stabat, (2) applying Quantum Learning Model to the students of mechinary class of SMK Negeri 1 Stabat, arising the positive response to autocad subject by applying Quantum Learning Model of the students of mechinary class of SMK Negeri 1 Stabat. The result shows that (1) by applying quantum learning model, the students’ achievement improves significantly. The improvement ofthe achievement of the 34 students is very satisfactory; on the first phase, 27 students passed (70.59%), 10 students failed (29.41%). On the second phase 27 students (79.41%) passed and 7 students (20.59%) failed. On the third phase 30 students (88.24%) passed and 4 students (11.76%) failed. The application of quantum learning model in SMK Negeri 1 Stabat proved satisfying. This was visible from the activeness of the students from phase 1 to 3. The activeness average of the students was 74.31% on phase 1,81.35% on phase 2, and 83.63% on phase 3. (3) The application of the quantum learning model on teaching autocad was very positively welcome by the students of mechinary class of SMK Negeri 1 Stabat. On phase 1 the improvement was 81.53% . It improved to 86.15% on phase 3. Therefore, The improvement ofstudent’ response can be categorized good.


2010 ◽  
Vol 9 (4) ◽  
pp. 214-219
Author(s):  
Robyn J. Barst

Drug development is the entire process of introducing a new drug to the market. It involves drug discovery, screening, preclinical testing, an Investigational New Drug (IND) application in the US or a Clinical Trial Application (CTA) in the EU, phase 1–3 clinical trials, a New Drug Application (NDA), Food and Drug Administration (FDA) review and approval, and postapproval studies required for continuing safety evaluation. Preclinical testing assesses safety and biologic activity, phase 1 determines safety and dosage, phase 2 evaluates efficacy and side effects, and phase 3 confirms efficacy and monitors adverse effects in a larger number of patients. Postapproval studies provide additional postmarketing data. On average, it takes 15 years from preclinical studies to regulatory approval by the FDA: about 3.5–6.5 years for preclinical, 1–1.5 years for phase 1, 2 years for phase 2, 3–3.5 years for phase 3, and 1.5–2.5 years for filing the NDA and completing the FDA review process. Of approximately 5000 compounds evaluated in preclinical studies, about 5 compounds enter clinical trials, and 1 compound is approved (Tufts Center for the Study of Drug Development, 2011). Most drug development programs include approximately 35–40 phase 1 studies, 15 phase 2 studies, and 3–5 pivotal trials with more than 5000 patients enrolled. Thus, to produce safe and effective drugs in a regulated environment is a highly complex process. Against this backdrop, what is the best way to develop drugs for pulmonary arterial hypertension (PAH), an orphan disease often rapidly fatal within several years of diagnosis and in which spontaneous regression does not occur?


2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 196-197
Author(s):  
Woo Jung Seok ◽  
Je min Ahn ◽  
Jing Hu ◽  
Dexin Dang ◽  
Yanjiao Li ◽  
...  

Abstract The objective of this study was to evaluate the effects of dietary supplementation of coated omega-3 fatty acid (n-3 CFA) by corn cob power silica on performance of weaning pigs. A total of 200 weaned pigs [(Landrace x Yorkshire) x Duroc, average initial body weight at 6.97 ± 1.22 kg] were randomly assigned to four experimental treatments in a 6-week experiment in 3 phases as follows: CON, basal diet; 2) 0.3CFA, CON + phase 1(0.3% n-3CFA), phase 2(0.2% n-3CFA), phase 3(0.1% n-3CFA); 3) 0.6CFA, CON + phase 1(0.6% n-3CFA), phase 2(0.4% n-3CFA), phase 3(0.2% n-3CFA); 4) 0.9CFA, CON + phase 1(0.9% n-3CFA), phase 2(0.6% n-3CFA), phase 3 (0.3% n-3CFA). Each treatment had 10 replicates with 5 pigs (three gilts and two barrows) per replicate. The data were analyzed using the GLM procedure of SAS as a randomized complete block design. Pen served as the experimental unit. Linear, quadratic and cubic polynomial contrasts were used to examine effect of dietary treatment with coated n-3FA in the basal diet. Variability in the data was expressed as the standard error of means and P&lt; 0.05 was considered to statistically significant. Increasing the level of n-3CFA in the diet linearly increased ADG and G/F of pigs (Table 1). Increasing the level of n-3CFA showed a linear increment in the digestibility of DM (83.59, 84.38, 85.13, 85.89 %) whereas nitrogen digestibility (81.79, 82.38, 82.96, 83.64 %) showed a trend (linear effect, p=0.0594) at the end of experiment. The fecal lactobacillus count was increased (7.22, 7.27, 7.33, 7.35 log10cfu/g) with the increase in the supplemental level of n-3CFA (linear effect; p&lt; 0.05). However, there were no differences in the concentration of serum haptoglobin, or fecal E. coli, Clostridium and Salmonella counts despite the increase in n-3CFA levels in the diet. Supplementation of the diet with coated n-3 fatty acids positively affected growth performance and digestibility of dry matter and nitrogen, and enhanced the count of lactobacillus in weaning pigs.


Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 759
Author(s):  
Vetriselvi Sampath ◽  
Dong Heon Baek ◽  
Sureshkumar Shanmugam ◽  
In Ho Kim

This experiment was performed to examine the hypothesis that blood plasma (BP) with yeast (Saccharomyces cerevisiae) supplement in the diet of weaning pigs could provoke the growth performance, nutrient digestibility, fecal microbial, and reduce harmful gas excretion. A total of one hundred and eighty healthy piglets were taken and assigned (complete random blocks) to three dietary treatments as: Phase 1: Treatment (TRT) 1-6% BP; TRT 2-3% BP + 3% yeast; TRT 3-6% yeast. Phase 2: TRT 1-3%; BP., TRT 2-1.5% BP + 1.5% yeast; TRT 3- 3% yeast. Phase 3: TRT 1- Control (CON) (Basal diet); TRT 2- CON; TRT 3- CON for six- weeks. Each treatment had twelve replicates and five (three gilts and two barrows) pigs per pen. Dietary inclusion of BP with yeast supplementation significantly increased the body weight of piglets during phase 2 (p = 0.003) and phase 3 (p = 0.032). In addition, TRT2 group piglets had a significant improvement in average daily gain at the end of each phase and overall (p = 0.047, 0.025, 0.018 and 0.012, respectively). At phase 3, TRT2 group piglets showed a significant improvement on nutrient digestibility of dry matter (p = 0.012) and nitrogen (p = 0.040). The fecal microbiota of TRT2 group piglets showed a tendency to increase the number of Lactobacillus counts at phase 1 (p = 0.07) and phase 2 (p = 0.06) as well as, a significant improvement at phase 3 (p = 0.021). In addition, TRT2 group piglets had trend to decrease NH3 (p = 0.074) and H2S (p = 0.069) during phase 2, and significantly reduced NH3 (p = 0.038) and H2S (p = 0.046) at phase 3. However, the fecal score of piglets remains unaffected during the entire trial. At the end of phase 1 piglets’ IgG (p = 0.008) was significantly increased with the inclusion of BP with yeast supplementation. Based on the positive effects on body weight, average daily gain, nutrient digestibility, Lactobacillus count, and reduced gas emission, we suggest that dietary supplement with BP and yeast in the diet of weaned piglet could serve as an excellent alternative to antibiotics growth promoters.


Development ◽  
1996 ◽  
Vol 122 (7) ◽  
pp. 1995-2003 ◽  
Author(s):  
G.L. Russo ◽  
K. Kyozuka ◽  
L. Antonazzo ◽  
E. Tosti ◽  
B. Dale

Using the fluorescent dye Calcium Green-dextran, we measured intracellular Ca2+ in oocytes of the ascidian Ciona intestinalis at fertilization and during progression through meiosis. The relative fluorescence intensity increased shortly after insemination in a single transient, the activation peak, and this was followed by several smaller oscillations that lasted for approximately 5 minutes (phase 1). The first polar body was extruded after the completion of the phase 1 transients, about 9 minutes after insemination, and then the intracellular calcium level remained at baseline for a period of 5 minutes (phase 2). At 14 minutes postinsemination a second series of oscillations was initiated that lasted 11 minutes (phase 3) and terminated at the time of second polar body extrusion. Phases 1 and 3 were inhibited by preloading oocytes with 5 mM heparin. Simultaneous measurements of membrane currents, in the whole-cell clamp configuration, showed that the 1–2 nA inward fertilization current correlated temporally with the activation peak, while a series of smaller oscillations of 0.1-0.3 nA amplitude were generated at the time of the phase 3 oscillations. Biochemical characterization of Maturation Promoting Factor (MPF) in ascidian oocytes led to the identification of a Cdc2-like kinase activity. Using p13suc1-sepharose as a reagent to precipitate the MPF complex, a 67 kDa (67 × 10(3) Mr) protein was identified as cyclin B. Histone H1 kinase activity was high at metaphase I and decreased within 5 minutes of insemination reaching a minimum level during phase 2, corresponding to telophase I. During phase 3, H1 kinase activity increased and then decayed again during telophase II. Oocytes preloaded with BAPTA and subsequently inseminated did not generate any calcium transients, nonetheless H1 kinase activity decreased 5 minutes after insemination, as in the controls, and remained low for at least 30 minutes. Injection of BAPTA during phase 2 suppressed the phase 3 calcium transients, and inhibited both the increase in H1 kinase activity normally encountered at metaphase II and second polar body extrusion.


2010 ◽  
Vol 109 (1) ◽  
pp. 171-188 ◽  
Author(s):  
J. M. Bonis ◽  
S. E. Neumueller ◽  
K. L. Krause ◽  
T. Kiner ◽  
A. Smith ◽  
...  

To probe further the contributions of the rostral pons to eupneic respiratory rhythm and pattern, we tested the hypothesis that ibotenic acid (IA) injections in the pontine respiratory group (PRG) would disrupt eupneic respiratory rhythm and pattern in a site- and state-specific manner. In 15 goats, cannulas were bilaterally implanted into the rostral pontine tegmental nuclei (RPTN; n = 3), the lateral (LPBN; n = 4) or medial parabrachial nuclei (MPBN; n = 4), or the Kölliker-Fuse nucleus (KFN; n = 4). After recovery from surgery, 1- and 10-μl injections (1 wk apart) of IA were made bilaterally through the implanted cannulas during the day. Over the first 5 h after the injections, there were site-specific ventilatory effects, with increased ( P < 0.05) breathing frequency in RPTN-injected goats, increased ( P < 0.05) pulmonary ventilation (V̇i) in LPBN-injected goats, no effect ( P < 0.05) in MPBN-injected goats, and a biphasic V̇i response ( P < 0.05) in KFN-injected goats. This biphasic response consisted of a hyperpnea for 30 min, followed by a prolonged hypopnea and hypoventilation with marked apneas, apneusis-like breathing patterns, and/or shifts in the temporal relationships between inspiratory flow and diaphragm activity. In the awake state, 10–15 h after the 1-μl injections, the number of apneas was greater ( P < 0.05) than during other studies at night. However, there were no incidences of terminal apneas. Breathing rhythm and pattern were normal 22 h after the injections. Subsequent histological analysis revealed that for goats with cannulas implanted into the KFN, there were nearly 50% fewer neurons ( P < 0.05) in all three PRG subnuclei than in control goats. We conclude that in awake goats, 1) IA injections into the PRG have site-specific effects on breathing, and 2) the KFN contributes to eupneic respiratory pattern generation.


CJEM ◽  
2017 ◽  
Vol 19 (S1) ◽  
pp. S68 ◽  
Author(s):  
R. Parkash ◽  
K. Magee ◽  
M. McMullen ◽  
M.B. Clory ◽  
M. D’Astous ◽  
...  

Introduction: Atrial fibrillation (AF) is the most common sustained arrhythmia affecting 1-2% of the population. Oral anticoagulation (OAC) reduces stroke risk by 60-80% in AF patients, but only 50% of indicated patients receive OAC. Many patients present to the ED with AF due to arrhythmia symptoms, however; lack of OAC prescription in the ED has been identified as a significant gap in the care of AF patients. Methods: This was a multi-center, pragmatic, three-phase before-after study, in three Canadian sites. Patients who presented to the ED with electrocardiographically (ECG) documented, nonvalvular AF and were discharged home were included. Phase 1 was a retrospective chart review to determine OAC prescription of AF patients in each ED; Phase 2 was a low-intensity knowledge translation intervention where a simple OAC-prescription tool for ED physicians with subsequent short-term OAC prescription was used, as well as an AF patient education package and a letter to family physicians; phase 3 incorporated Phase 2 interventions, but added immediate follow-up in a community AF clinic. The primary outcome of the study was the rate of new OAC prescriptions at ED discharge in AF patients who were OAC eligible and were not on OAC at presentation. Results: A total of 632 patients were included from June, 2015-November, 2016. ED census ranged from 30000-68000 annual visits. Mean age was 71±15, 67±12, 67±13 years, respectively. 47.5% were women, most responsible ED diagnosis was AF in 75.8%. The mean CHA2DS2-VASc score was 2.6±1.8, with no difference amongst groups. There were 266 patients eligible for OAC and were not on this at presentation. In this group, the prescription of new OAC was 15.8% in Phase 1 as compared to 54% and 47%, in Phases 2 and 3, respectively. After adjustment for center, components of the CHA2DS2-VASc score, prior risk of bleeding and most responsible ED diagnosis, the odds ratio for new OAC prescription was 8.0 (95%CI (3.5,18.3) p&lt;0.001) for Phase 3 vs 1, and 10.0 (95%CI (4.4,22.9) p&lt;0.001), for Phase 2 vs 1). No difference in OAC prescription was seen between Phases 2 and 3. Conclusion: Use of a simple OAC-prescription tool was associated with an increase in new OAC prescription in the ED for eligible patients with AF. Further testing in a rigorous study design to assess the effect of this practice on stroke prevention in the AF patients who present to the ED is indicated.


BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e052545
Author(s):  
Michelle Kennedy ◽  
Ratika Kumar ◽  
Nicole M Ryan ◽  
Jessica Bennett ◽  
Gina La Hera Fuentes ◽  
...  

ObjectiveDescribe the development and pretest of a prototype multibehavioural change app MAMA-EMPOWER.DesignMixed-methods study reporting three phases: (1) contextual enquiry included stakeholder engagement and qualitative interviews with Aboriginal women, (2) value specification included user-workshop with an Aboriginal researcher, community members and experts, (3) codesign with Aboriginal researchers and community members, followed by a pretest of the app with Aboriginal women, and feedback from qualitative interviews and the user-Mobile Application Rating Scale (U-MARS) survey tool.SettingsAboriginal women and communities in urban and regional New South Wales, Australia.ParticipantsPhase 1: interviews, 8 Aboriginal women. Phase 2: workshop, 6 Aboriginal women. Phase 3: app trial, 16 Aboriginal women. U-MARS, 5 Aboriginal women.ResultsPhase 1 interviews revealed three themes: current app use, desired app characteristics and implementation. Phase 2 workshop provided guidance for the user experience. Phase 3 app trial assessed all content areas. The highest ratings were for information (mean score of 3.80 out of 5, SD=0.77) and aesthetics (mean score of 3.87 with SD of 0.74), while functionality, engagement and subjective quality had lower scores. Qualitative interviews revealed the acceptability of the app, however, functionality was problematic.ConclusionsDeveloping a mobile phone app, particularly in an Aboriginal community setting, requires extensive consultation, negotiation and design work. Using a strong theoretical foundation of behavioural change technique’s coupled with the consultative approach has added rigour to this process. Using phone apps to implement behavioural interventions in Aboriginal community settings remains a new area for investigation. In the next iteration of the app, we aim to find better ways to personalise the content to women’s needs, then ensure full functionality before conducting a larger trial. We predict the process of development will be of interest to other health researchers and practitioners.


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