bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single‐unit muscle sympathetic recordings identify in human heart failure unique fibers discharging in response to both unloading and loading of cardiopulmonary receptors (LB735)
Authors: Millar Philip , Murai Hisayoshi , Morris Beverley , Floras John 
Published: June 2021

In healthy men, multi‐unit muscle sympathetic nerve activity (MSNA) has been shown to integrate two populations of single‐units exhibiting directionally opposite discharge to acute selective perturbations in atrial pressure. The behaviour of these single‐units was consistent during application of lower body negative and positive pressure (LBNP and LBPP). The aim of the present study was to compare single‐unit discharge characteristics of patients with and without heart failure (HF). We measured central venous pressure and single‐unit MSNA in 6 HF patients (LVEF: 24±6%; 54±13 years [mean±SD]) and 9 healthy controls (56±8 years) before and during 7 minutes of LBNP and LBPP (±10mmHg). These interventions had no effect on stroke volume, heart rate or systemic blood pressure (All P>0.05). Twelve HF and 22 control single‐units were identified. In controls, single‐unit responses to LBNP and LBPP exhibited either ‘anticipated’ (increased with LBNP and decreased with LBPP) or ‘paradoxical’ (decreased with LBNP and increased with LBPP) firing behavior. In HF, the majority (8/12; 67%) of single‐units exhibited a unique U‐shaped discharge pattern, with ‘anticipated’ responses to LBNP but ‘paradoxical’ responses to LBPP. This novel observation provides evidence for the emergence in HF of a population of cardiopulmonary mechanoreceptors exerting consistently sympathoexcitatory efferent firing characteristics.Grant Funding Source: Supported by the Canadian Institutes of Health Research (PJM) and Canadian Research Chairs program (JSF)
Brilliant Blue G attenuates the effects of intestinal ischemia/reperfusion injury in rats (LB747)
Authors: Palombit Kelly , Mendes Cristina , Castelucci Patricia 
Published: June 2021

During pathological conditions there is an increased release ATP into the extracellular space, activating the P2X7 receptor. Several studies have shown that injury can be attenuated by the antagonist of this receptor, the Brilliant Blue G (BBG). In the present work we analyzed the effects of intestinal ischemia and reperfusion (I/R) and the effects of the BBG on rats ileum. Tissues were obtained from male Wistar rats (n=5). The ileal artery was occluded for 45 minutes with an atraumatic vascular clamp. BBG (50 and 100 mg/kg) or saline (vehicle) was given subcutaneous 1 h after injury (24 h group). The sham group was rats without the arterial occlusion. We analyzed also the I/R 0 h group (not reperfusion). Myenteric neurons were evaluated for immunoreactivity (ir) against the P2X7 receptor, nitric oxide synthase (NOS), neurofilament (NF), choline acetyl transferase (ChAT) and anti‐HuC/D (Hu). Technique histology staining to hematoxylin and eosin (HE) was performed to evaluate the integrity of the intestinal wall and myeloperoxidase technique (MPO) to verify the marking of neutrophils. Our qualitative results showed that I/R caused histological damage to the mucosa and muscle and infiltration of neutrophils into the muscle layers. Our quantitative results showed that there was a decrease in density (neurons/cm2) P2X7‐ir, NOS‐ir, NF‐ir, ChAT‐ir and Hu‐ir neurons in I/R 0 h and 24 h groups. In I/R groups where the antagonist BBG was injected, the neuronal density was less affected. Analysis in the area of the cell body profile different classes showed generally decreases in the profile area in the I/R groups and recovery profile area of the I/R BBG‐50 and BBG‐100 groups. This work indicates that deleterious effects are greater in groups subjected to I/R in rats without application BBG, suggesting that BBG has protective effects on the intestinal wall and in different neuronal classes.Grant Funding Source: FAPESP
Maternal obesity reduces adipogenic progenitor density and DNA methylation of Zpf423 promoter in the visceral fat of offspring mice (LB770)
Authors: Liang Xingwei , Yang Qiyuan , Fu Xing , Rogers Carl , Zhu Meijun , Du Min 
Published: June 2021

Maternal obesity (MO) is a worsening problem. Offspring born to obese mothers have high risks of obesity and type II diabetes, but the underlying mechanisms remain poorly defined. Zfp423 is a key transcription factor committing progenitor cells to preadipocytes, and its transcription is regulated by the DNA methylation. Our hypothesis was that MO reduces Zfp423 DNA methylation in the progenitor cells of offspring adipose tissue, which promotes Zfp423 expression and adipogenic differentiation of progenitors, resulting in a reduction in progenitor density. Diet‐induced obesity model was used. Female mice (4 week old) were subjected to either control (10% energy from fat, CN) or obesogenic (45% energy from fat, OB) diet for two months to induce obesity. Then, mice were mated and maintained in their respective diets during pregnancy and lactation. Visceral adipose tissues were sampled at weaning (21 days). OB weanlings had about 2 folds higher expression of Zfp423 compared to CN. Consistently, the methylation level analyzed by pyrosequencing was 45.1 ± 3.13% lower in OB offspring. We further used CD45‐/Sca1+ as surface markers for sorting adipogenic progenitor cells. OB visceral fat contained 27.9 ± 0.90 % less progenitor cells than CN fat. As in the fat tissue, Zfp423 expression was 35.0 ± 2.38% (p = 0.07) higher in the progenitors of OB than CN weanlings. Consistently, methylation level was 69.2 ± 14.80 % (p < 0.05) lower in OB weanlings. In conclusion, MO reduced the density and Zfp423 DNA methylation of adipogenic progenitor cells in visceral fat. Because progenitor cells are the source of new adipocytes, the reduction in their density and enhancement of adipogenic differentiation will likely impair the renewal and expansion of adipocytes, partially explaining adipose metabolic dysfunction in offspring (The work was funded by NIH R01HD067449).Grant Funding Source: Supported by NIH R01HD067449
Enhanced SpO2 in Response to Intermittent Normobaric Hypoxia in a Patient (Case Study) with COPD (LB787)
Authors: Cardoso S , Samillan V , Werneck M , Pereira P , Quispe M , Romeo L , Horowitz M 
Published: June 2021

Recent studies by Cardoso et al (The FASEB Journal, April 9, 2013; v27, 938.7) using hypoxic pre‐conditioning (HP) add support to its value in the management of T2D, CV and pulmonary disease. We now report enhancement of SpO2 levels (P<0.0001) for a 75 yr old patient with Stage IV COPD when we intermittently employed a set of pre and post conditioning 1 hr interruption (at rest with SpO2 recorded at 1 min intervals) of her 24/7 nasal oxygen flow from Mar 2012 through Dec 2013 (interventions were repeated at 1‐3 month intervals at the patient’s discretion). Normalization of SpO2 was recorded when in late Dec 2013 we added bicycling at 6 mph (off supplemental O2 during exercise) 24 hrs after our 1 hr hypoxic interventions. Mean SpO2 on Dec 30, 2013 = 87.1±3.4 and Jan 6, 9, 14 and 18, 2014 = 91.9±2.3; 95.1± 1.71; 95.7±1.1; 87.9±3.6, respectively (Dec 2013 vs Jan 2014, P<0.0001). All observations were re‐confirmed Feb 14, 2014. The results suggest patients with COPD respond to HP with improved quality of life, and increased tolerance to exercise that may lead, as in our patient, to significantly lower frequency of prescribed medication.Grant Funding Source: San Pedro Univ. Peru; Federal Univ. COPPE, RJ, Brazil, Private donations
Role of endogenous hydrogen sulfide on hypoxia‐induced hypothermia in hypertensive rats (LB792)
Authors: Sabino Joao , Soriano Renato , Traslaviña Guilhermo , Branco Luiz 
Published: June 2021

Role of endogenous hydrogen sulfide on hypoxia‐induced hypothermia in hypertensive rats. Joao Paulo J. Sabino1, Renato N. Soriano1, Guillermo A. Ariza Traslaviña2, Luiz G. S. Branco1. 1Dental School and 2Medical School of Ribeirão Preto, University of São Paulo.Hypoxia causes a regulated drop in body temperature (Tb) but the mechanisms involved are not completely understood. The role of hydrogen sulfide (H2S) a gaseous molecule endogenously produced by cystathionine β‐synthase (CBS) has been recently documented during hypoxia‐induced hypothermia in normotensive rats. However, no information exists regarding the role of H2S during hypoxic hypothermia in spontaneous hypertensive rats (SHR). We then evaluated the effect of the H2S donor (Na2S 4 nmol/1µl) and the CBS inhibitor (AOAA 9 nmol/1µl) microinjections into the central nervous system (fourth ventricle) of rats exposed to 10% hypoxia. The Tb was similar in all groups [Saline Wistar group (37.46±0.18 ºC, n= 10), AOAA Wistar group (37.40±0.33 ºC, n= 5), Na2S Wistar group (37.52±0.13 ºC, n= 7), Saline SHR group (37.43±0.43 ºC, n= 8), AOAA SHR group (37.59±0.16 ºC, n= 10) and Na2S SHR group (37.72±0.15 ºC, n= 6)] during basal normoxic condition. Hypoxia induced a typical decrease in Tb in saline injected rats. The decrease in Tb in the Saline SHR group (Δ= ‐1.16±0.11 ºC) was similar to the Saline Wistar group (Δ= ‐0.81±0.20 ºC). In Wistar rats, Na2S administration prevented hypoxia‐induced hypothermia (Δ= ‐0.58±0.16 ºC), whereas AOAA administration significantly increased hypoxia‐induced hypothermia in Wistar rats (Δ= ‐1.60±0.20 ºC), indicating that H2S plays a key role on hypoxia‐induced changes in Tb. Surprisingly, neither Na2S (Δ= ‐1.33±0.20 ºC) nor AOAA (Δ= ‐1.61±0.21 ºC) caused any change in hypoxia‐induced hypothermia in SHR. In conclusion, the H2S prevents the hypoxia‐induced anapyrexia in normotensive rats, but plays no thermoregulatory role during hypoxia exposition in SHR.Financial support: FAPESP (2011/14779‐4).
Fear conditioning depresses the intrinsic excitability of infralimbic neurons in adult rats (LB82)
Authors: Rivera‐Pérez Luis 
Published: June 2021

Posttraumatic stress disorder (PTSD) is a severe anxiety disorder that may develop after a person experiences a traumatic event. To further increase our understanding of PTSD, we study fear learning in rats, which have brain structures and functions similar to humans. In this animal model, we use Pavlovian fear conditioning to imitate the exposure to a traumatic event in humans. A previous study in our lab found that fear conditioning depresses the intrinsic excitability of neurons in the infralimbic cortex of adolescent rats. Since adolescent are still developing different connections and synapses, the findings in adolescent rats may not apply to adult animals. To test whether fear conditioning also depresses the excitability of IL neurons in adult animals, we used whole‐cell patch‐clamp recordings and behavioral training to compare the intrinsic excitability in infralimbic neurons before and after fear conditioning in adult male Sprague Dawley rats. To acquire cued fear conditioning, rats received 3 tone‐shock pairings (tone: 30 sec; shock: 0.44 mA, 0.5 sec). To test for fear conditioning memory, rats were tested for fear expression to 2 tone alone presentations 2 days later. An untrained control group remained in the home cage until sacrifice. Fear was quantified during the experiment as time freezing during tone presentations. Immediately after the final tone alone presentation, rats were deeply anesthetized, perfused transcardially, and coronal slices of the medial prefrontal cortex were cut with a vibratome. As a measure of intrinsic excitability, we quantified the number of spikes evoked by depolarizing pulses. Infralimbic neurons from the fear conditioning group fired fewer spikes indicating that fear conditioning depressed the intrinsic excitability of infralimbic neurons in adult rats. Currently, we are examining whether fear extinction in adult rats reverses this depression as it does in adolescent rats. These results suggest that depression of prefrontal neuronal excitability could contribute to the development of PTSD in adults.Grant Funding Source: This work is supported by MBRS‐RISE R25 GM096955 to LMR, MBRS‐RISE R25 GM082406 to OS, and by NIMHHD G12MD007579‐27 and R15 MH101700 to JTP.
Visual Cortex Controls the Gain, but Not the Selectivity, of Superior Collicular Responses to Looming Stimuli in Awake Mice (LB827)
Authors: Liu Mingna , Zhao Xinyu , Cang Jianhua 
Published: June 2021

Neural circuits in the brain often receive inputs from multiple sources, such as the bottom‐up input from early processing stages and the top‐down input from higher‐order areas. Here, we study the function of top‐down input in the mouse Superior Colliculus (SC), which receives convergent inputs from the retina and visual cortex. Neurons in the superficial SC display robust speed tuning to looming stimuli that mimic approaching objects. The looming‐evoked responses are reduced by almost half when the visual cortex is optogenetically silenced in awake, but not in anesthetized mice. Silencing the cortex does not change the speed tuning of SC neurons, or the response time course except at the lowest tested speed. Consistent with these findings, we further show that cortical responses to the looming stimuli are speed‐insensitive and slow. The strong gain control we have revealed thus provides a neural substrate for the cortex to modulate SC‐mediated visual behaviors.Grant Funding Source: Supported by US National Institutes of Health (NIH) grant (EY020950) to J.C. and HHMI international student fellowship to X.Z.
TRPM4‐dependent contraction of retinal pericytes (LB846)
Authors: Gonzales Albert , Nelson Mark 
Published: June 2021

Pericytes are an integral part of the neurovascular unit and likely contribute to the neuronal‐dependent regulation of capillary blood flow. Like vascular smooth muscle cells (VSMCs), pericytes are thought to contract through membrane depolarization and activation of voltage‐dependent calcium channels which then causes focal constrictions of capillaries. TRPM4, a melastatin transient receptor potential channel, is essential for VSMC membrane depolarization and contraction. Its role in pericyte contraction is not known. We used immunohistochemistry and confocal microscopy to examine the role of TRPM4 channels in pericyte contraction within the mouse retina. We observed TRPM4‐specific immunolabeling in the smooth muscle cells within precapillary arterioles (<10 µm) and in a sub‐population of pericytes surrounding the capillaries most proximal to the arterioles in the mouse retinal vasculature. In addition, we observed constriction in response to the thromboxane A2 analog, 9,11‐dideoxy‐9α,11α‐methanoepoxy prostaglandin F2α (U46619) in pre‐capillary arterioles and in distal and proximal pericyte‐containing capillaries. This response was blocked by the TRPM4 inhibitor 9‐phenanthrol in pre‐capillary arterioles and proximal pericyte‐containing capillaries, but not in pericyte‐containing capillaries distal to feeding arteriole. These findings suggest that TRPM4 plays a role in pericyte constriction within retinal capillary system.Grant Funding Source: HL044455, R37 DK053832, and 1PO1HL095488
Expression of blood clot‐dissolving proteins in transgenic plant (LB852)
Authors: Wang Kevin , Tull Lauren 
Published: June 2021

Introduction: The formation of a blood clot in the circulatory system can cause heart attack or stroke. Lumbrokinases, found in earthworms, and Nattokinase, found in Bacillus subtilis for soybean fermentation, can dissolve fibrin clots without causing excessive bleeding. Our goal was to clone Lumbrokinase and Nattokinase, to transiently and stably express the proteins in tobacco plants and to prove these recombinant proteins retain anti‐thrombolytic activity.Methods: Codon‐optimized and wild‐type gene fragment of Lumbrokinases (PI293) and Nattokinase (GenBank: AF368283.1) were isolated and inserted into a single‐vector DNA replicon system for transient expression in plant and plant expression vector pCambia2300‐Phas1470‐Nos, for stable plant transformation and expression. We tested gene expression and function of the transient expression vector using fibrin dissolving assay.Results: We optimized Lumbrokinase and Nattokinase gene codon respectively for tobacco codon usage bias. Upon codon optimization, codon adaptation index (CAI) of Lumbrokinase was increased from 0.69 to 0.86 and GC content was changed from 54.02% to 42.65%. CAI of Nattokinase was increased from 0.71 to 0.86 and GC content was changed from 46.78% to 42.61%. Higher CAI value and GC content, closer to that of tobacco plant, provide a good estimation for high expression foreign protein. Total eight vectors for transient expression and stable transformation were developed and confirmed by restriction reactions. The plant transient expression with those vectors tested positive for gene expression and function with the fibrin dissolving assay.Conclusions: Expression Vectors of Lumbrokinase and Nattokinase for both transient and stable plant transformation were developed. The transient expression vectors were successfully expressed in the tobacco plant and tested positive for clot dissolving function.Grant Funding Source: National Institutes of Health through Grant Number 8P20GM103447
Toxicity of Alpha‐Synuclein and Its Impact on Neurotransmitters (LB97)
Authors: Watts Jane , Lee Esther , George Megan , Arpornsuksant Celine , Chareddy Yogitha , Balaji Prerna , Chen Mickey , Link Tina , Sanders Teresa 
Published: June 2021

The loss of the neurotransmitter dopamine (DA) in the substantia nigra, the part of the brain controlling motility, has been associated with Parkinsonʼs Disease (PD) but there has been little evidence to show what causes the loss of DA. New research indicates a relationship between a drop in DA and the presence of Lewy bodies, which include aggregates of a misfolded protein, alpha‐synuclein (α‐syn). Research indicates that α‐syn is a 140 amino acid protein involved in the exocytosis of DA from the synaptic vesicles of neurons. α ‐syn has an identifiable sequence (KTKEGV) that repeats six times at the N‐terminus, which folds a normal protein into amyloid fibers. Mutations, like A53T, A30P, and E46K, or exposure to environmental factors modify the normal quaternary structure of the protein, initiating the aggregation of misfolded α‐syn. The build‐up of abnormal α‐syn highly correlates with the drop in dopamine levels in the brain, which is associated with motor dysfunction in PD patients. The Walton SMART Team (Students Modeling A Research Topic) used 3D printing techniques to see how mutated α‐syn correlates with DA levels.Grant Funding Source: Supported by grants from NIH‐CTSA and NIH‐SEPA.
A Comparison of Drill Guiding and Screw Guiding 3D-Printing Techniques for Intra- and Extrapedicular Screw Insertion
Authors: Pijpker Peter A.J. , Kuijlen Jos M.A. , Kraeima Joep , Groen Rob J.M. , Faber Chris 
Published: June 2021

Study Design.
Screw randomized cadaveric study.

Objective.
To compare the accuracy of three-dimensional (3D)-printed drill guides versus additional screw guiding techniques for challenging intra- and extrapedicular screw trajectories.

Summary of Background Data.
Pedicle screw placement can be technically demanding, especially in syndromic scoliosis with limited bone stock. Recently, 3D-printing and virtual planning technology have become available as new tools to improve pedicle screw insertion. Differences in techniques exist, while some focus on guiding the drill, others also actively guide subsequent screws insertion. The accuracy of various 3D-printing-assisted techniques has been studied; however, direct comparative studies have yet to determine whether there is a benefit of additional screw guidance.

Methods.
Two cadaveric experiments were conducted to compare drill guides with two techniques that introduce additional screw guiding. The screw guiding consisted of either k-wire cannulated screws or modular guides, which were designed to guide the screw in addition to the drill bit. Screws were inserted intra- or extrapedicular using one of each methods according to a randomization scheme. Postoperative computed tomography scanning was performed and fused with the preoperative planning for detailed 3D screw deviation analysis.

Results.
For intrapedicular screw trajectories malpositioning was low (2%) and the modular guides revealed a statistically significant increase of accuracy (P
= 0.05) compared with drill guides. All techniques showed accurate cervical screw insertion without breach. For the extrapedicular screw trajectories both additional screw guiding methods did not significantly (P = 0.09) improve accuracy and malpositioning rates remained high (24%).

Conclusions.
In this cadaveric study it was found that the additional screw-guiding techniques are not superior to the regular 3D-printed drill guides for the technically demanding extrapedicular screw technique. For intrapedicular screw insertion, modular guides can improve insertion; however, at cervical levels regular 3D-printed drill guides already demonstrated very high accuracy and therefore there is no benefit from additional screw guiding techniques.

Level of Evidence.
3
Delivery room resuscitation and short-term outcomes of extremely preterm and extremely low birth weight infants: a multicenter survey in North China
Authors: Li Shuai-Jun , Feng Qi , Tian Xiu-Ying , Zhou Ying , Ji Yong , Li Yue-Mei , Zhai Shu-Fen , Guo Wei , Zhang Fang , Zheng Rong-Xiu , He Hai-Ying , Liu Xia , Wang Jun-Yi , Mei Hua , Wang Hong-Yun , Xie Hua , Zeng Chao-Mei , Ma Li , Zhang Ping-Ping , Li Jin-Yu , Wang Xiao-Ying , Li Li-Hua , Cui Hong , Yang Shu-Lan , Chen Lu , Gu Xiao-Hong , Hu Yan-Ju , Que Sheng-Shun , Sun Li-Xia , Yang Ming , Zhao Wen-Li , Ma Qiu-Yan , Wang Hai-Juan , Guo Jiu-Ye 
Published: June 2021

Abstract

Background:
Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China.

Methods:
The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD.

Results:
A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082–4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606–3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044–1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061–2.424), DRI (OR, 2.094; 95% CI, 1.328–3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679–4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777–6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996–0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379–0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160–0.467) were preventive factors for BPD (all P < 0.05).

Conclusion:
Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.