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MedRxiv : the Preprint Server For... Jun 2024Cerebrovascular reactivity (CVR) reflects the ability of blood vessels to dilate or constrict in response to a vasoactive stimulus, and allows researchers to assess the...
Cerebrovascular reactivity (CVR) reflects the ability of blood vessels to dilate or constrict in response to a vasoactive stimulus, and allows researchers to assess the brain's vascular health. Individuals with spinal cord injury (SCI) are at an increased risk for autonomic dysfunction in addition to cognitive impairments, which have been linked to a decline in CVR; however, there is currently a lack of brain-imaging studies that investigate how CVR is altered after SCI. In this study, we used a breath-holding hypercapnic stimulus and functional near-infrared spectroscopy (fNIRS) to investigate CVR alterations in individuals with SCI (n = 20, 14M, 6F, mean age = 46.3 ± 10.2 years) as compared to age- and sex-matched able-bodied (AB) controls (n = 25, 19M, 6F, mean age = 43.2 ± 12.28 years). CVR was evaluated by its amplitude and delay components separately by using principal component analysis and cross-correlation analysis, respectively. We observed significantly delayed CVR in the right inferior parietal lobe in individuals with SCI compared to AB controls (linear mixed-effects model, fixed-effects estimate = 6.565, Satterthwaite's t-test, t = 2.663, p = 0.008), while the amplitude of CVR was not significantly different. The average CVR delay in the SCI group in the right inferior parietal lobe was 14.21 s (sd: 6.60 s), and for the AB group, the average delay in the right inferior parietal lobe was 7.08 s (sd: 7.39 s). CVR delays were also associated with the duration since injury in individuals with SCI, in which a longer duration since injury was associated with a shortened delay in CVR in the right inferior parietal region (Pearson's r-correlation, r = -0.59, p = 0.04). This study shows that fNIRS can be used to quantify changes in CVR in individuals with SCI, and may be further used in rehabilitative settings to monitor the cerebrovascular health of individuals with SCI.
PubMed: 38883754
DOI: 10.1101/2024.06.03.24307819 -
MedComm Jul 2024Neuropeptide Y (NPY), a 36-amino-acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor...
Neuropeptide Y (NPY), a 36-amino-acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor subfamily. Notably, NPY analogs display varying selectivity and exert diverse physiological effects through their interactions with this receptor family. [Pro]-NPY and [Leu, Pro]-NPY, mainly acting on YR, reportedly increases blood pressure and postsynaptically potentiates the effect of other vasoactive substances above all, while N-terminal cleaved NPY variants in human body primary mediates angiogenesis and neurotransmitter release inhibition through YR. However, the recognition mechanisms of YR and YR with specific agonists remain elusive, thereby hindering subtype receptor-selective drug development. In this study, we report three cryo-electron microscopy (cryo-EM) structures of Gi2-coupled YR and YR in complexes with NPY, as well as YR bound to a selective agonist [Leu, Pro]-NPY. Combined with cell-based assays, our study not only reveals the conserved peptide-binding mode of NPY receptors but also identifies an additional sub-pocket that confers ligand selectivity. Moreover, our analysis of YR evolutionary dynamics suggests that this sub-pocket has undergone functional adaptive evolution across different species. Collectively, our findings shed light on the molecular underpinnings of neuropeptide recognition and receptor activation, and they present a promising avenue for the design of selective drugs targeting the NPY receptor family.
PubMed: 38882210
DOI: 10.1002/mco2.565 -
Journal of Nanobiotechnology Jun 2024Oxygen is necessary for life and plays a key pivotal in maintaining normal physiological functions and treat of diseases. Hemoglobin-based oxygen carriers (HBOCs) have... (Review)
Review
Oxygen is necessary for life and plays a key pivotal in maintaining normal physiological functions and treat of diseases. Hemoglobin-based oxygen carriers (HBOCs) have been studied and developed as a replacement for red blood cells (RBCs) in oxygen transport due to their similar oxygen-carrying capacities. However, applications of HBOCs are hindered by vasoactivity, oxidative toxicity, and a relatively short circulatory half-life. With advancements in nanotechnology, Hb encapsulation, absorption, bioconjugation, entrapment, and attachment to nanomaterials have been used to prepare nanomaterial-related HBOCs to address these challenges and pend their application in several biomedical and therapeutic contexts. This review focuses on the progress of this class of nanomaterial-related HBOCs in the fields of hemorrhagic shock, ischemic stroke, cancer, and wound healing, and speculates on future research directions. The advancements in nanomaterial-related HBOCs are expected to lead significant breakthroughs in blood substitutes, enabling their widespread use in the treatment of clinical diseases.
Topics: Humans; Hemoglobins; Blood Substitutes; Oxygen; Animals; Nanostructures; Liposomes; Nanocapsules; Wound Healing; Neoplasms; Shock, Hemorrhagic
PubMed: 38880905
DOI: 10.1186/s12951-024-02606-1 -
The Journal of Rheumatology Jul 2024Raynaud phenomenon (RP) and digital ulcers (DUs) are the main signs of digital vasculopathy in systemic sclerosis (SSc). Selexipag is an oral prostacyclin agonist...
OBJECTIVE
Raynaud phenomenon (RP) and digital ulcers (DUs) are the main signs of digital vasculopathy in systemic sclerosis (SSc). Selexipag is an oral prostacyclin agonist approved for SSc-related pulmonary arterial hypertension. Following our previous preliminary short-course report, we herein present long-term data on selexipag safety and efficacy in the treatment of SSc digital vasculopathy.
METHODS
Selexipag was administered to patients with SSc with severe digital vasculopathy refractory or with contraindication to all other vasoactive therapies. Each subject was assessed at baseline and after 3, 6, and 12 months. Clinical outcomes related to RP and DUs were evaluated along with modified Rodnan skin score of the fingers. Digital perfusion was assessed by laser speckle contrast analysis (LASCA). Nailfold videocapillaroscopy (NVC) was also performed.
RESULTS
Eight patients with SSc (63% female, mean age 50.1 years) received selexipag. After 12 months of treatment, RP was reported to significantly decrease in the number of daily episodes and mean duration ( < 0.001 and = 0.01, respectively). All patients achieved a complete healing of their DUs ( = 0.03) within 6 months. A progressive reduction of fingers skin score was observed ( = 0.03). No structural changes of capillaries were noted on NVC. Conversely, LASCA revealed an important increase in total digital perfusion ( = 0.004) despite seasonal variability. The safety profile was consistent with that reported in the literature.
CONCLUSION
We observed a sustained efficacy of selexipag on SSc digital vasculopathy during 1 year of administration. Our promising results encourage the design of a new randomized controlled trial to evaluate the effect of selexipag on SSc digital vasculopathy.
PubMed: 38879188
DOI: 10.3899/jrheum.2024-0103 -
ASAIO Journal (American Society For... Jun 2024The presence of adhesions and patent bypass grafts may create challenges for standard 14 mm outflow graft placement during left ventricular assist device implantation....
The presence of adhesions and patent bypass grafts may create challenges for standard 14 mm outflow graft placement during left ventricular assist device implantation. We retrospectively describe our experience using a 10 mm Bioline Fusion graft (Getinge, Goteborg, Sweden) as the outflow graft in patients undergoing primary Heartmate 3 (Abbott, Abbott Park, IL) implantation. One hundred one patients underwent Heartmate 3 left ventricular assist device implantation, 80% via a thoracotomy approach, with the standard 14 mm outflow graft (78) or a 10 mm Bioline Fusion outflow graft (23). Initial postoperative rotor speed-to-flow ratio (the revolutions per minutes (RPMs) required to achieve a given flow) was significantly higher in 10 mm graft patients (1,472 vs. 1,283 RPM/L/min; p = 0.03), suggesting elevated resistance in the smaller graft. Furthermore, the initial postoperative vasoactive-inotrope score was higher in the 10 mm graft patients (24.1 vs. 17.6; p = 0.022). Postoperative outcomes were similar between groups. In conclusion, the use of a 10 mm graft was associated with higher RPMs needed to generate a given flow and a higher vasoactive-inotrope score, but these differences were not associated with increased right ventricular failure or mortality.
PubMed: 38875452
DOI: 10.1097/MAT.0000000000002249 -
Frontiers in Pediatrics 2024To evaluate the incidence, outcome, and prognostic factors of prolonged mechanical ventilation (PMV) in children in Mainland China.
OBJECTIVE
To evaluate the incidence, outcome, and prognostic factors of prolonged mechanical ventilation (PMV) in children in Mainland China.
METHODS
A prospective study was conducted in 11 pediatric intensive care units (PICUs) from May 1, 2021, to April 30, 2022. All pediatric patients on mechanical ventilation meeting the criteria for PMV were included in the study.
RESULTS
Out of 5,292 patients receiving mechanical ventilation, 278 children met the criteria for PMV (5.3%). After excluding case with incomplete data or lost to follow-up, the study included 250 patients. Among them, 115 were successfully weaned from mechanical ventilation, 90 died, and 45 were still on mechanical ventilation. The 6-month survival rate was 64%. The primary associated conditions of PMV were lower airway diseases (36%), central nervous system diseases (32%), and neuromuscular diseases (14%). The stepwise multiple logistic regression analysis indicated that the utilization of vasoactive agents and an elevated pediatric logistic organ dysfunction-2 (PELOD-2) score on the day of PMV diagnosis were significantly associated with an increased of PMV death. Specifically, the odds ratio (OR) for vasoactive agent use was 2.86; (95% CI: 0.15-0.84; = 0.018), and for the PELOD-2 score, it was 1.37; 95% CI: 1.17-1.61; < .001). Conversely, early rehabilitation intervention was negatively associated with the risk of PMV death (OR = 0.45; 95% CI: 0.22-0.93; = .032). Furthermore, the tracheotomy timing emerged as an independent predictor of failure to wean from PMV, with an OR of 1.08, (95% CI: 1.01-1.16; .030).
CONCLUSIONS
The study revealed a 5.3% incidence of PMV in children requiring mechanical ventilation in China. The use of vasoactive agents and a higher PELOD-2 score at PMV diagnosis were significantly associated with an increased risk of PMV death, whereas early rehabilitation intervention was identified as crucial for improving patient outcomes. The timing of tracheostomy was identified as a high-risk factor for failure to wean from mechanical ventilation.
PubMed: 38873585
DOI: 10.3389/fped.2024.1413094 -
Frontiers in Neurology 2024Severe acute respiratory syndrome corona virus 2 (SARS CoV-2) is the cause of Corona virus disease 2019 (COVID-19), which turned into a pandemic in late 2019 and early...
Severe acute respiratory syndrome corona virus 2 (SARS CoV-2) is the cause of Corona virus disease 2019 (COVID-19), which turned into a pandemic in late 2019 and early 2020. SARS CoV-2 causes endothelial cell destruction and swelling, microthrombosis, constriction of capillaries, and malfunction of pericytes, all of which are detrimental to capillary integrity, angiogenesis, and healing processes. Cytokine storming has been connected to COVID-19 disease. Hypoxemia and tissue hypoxia may arise from impaired oxygen diffusion exchange in the lungs due to capillary damage and congestion. This personal view will look at how inflammation and capillary damage affect blood and tissue oxygenation, cognitive function, and the duration and intensity of COVID-19 disease. The general effects of microvascular injury, hypoxia, and capillary damage caused by COVID-19 in key organs are also covered in this point of view. Once initiated, this vicious cycle leads to diminished capillary function, which exacerbates inflammation and tissue damage, and increased inflammation due to hypoxia. Brain damage may result from low oxygen levels and high cytokines in brain tissue. In this paper we give a summary in this direction with focus on the role of the neuropeptide Substance P. On the basis of this, we discuss selected approaches to the question: "How Substance P is involved in the etiology of the COVID-19 and how results of our research could improve the prevention or therapy of corona? Thereby pointing out the role of Substance P in the post-corona syndrome and providing novel concepts for therapy and prevention.
PubMed: 38872816
DOI: 10.3389/fneur.2024.1370454 -
Current Opinion in Critical Care Jun 2024Treatment of cardiogenic shock remains largely driven by expert consensus due to limited evidence from randomized controlled trials. In this review, we aim to summarize...
PURPOSE OF REVIEW
Treatment of cardiogenic shock remains largely driven by expert consensus due to limited evidence from randomized controlled trials. In this review, we aim to summarize the approach to the management of patients with cardiogenic shock in the ICU prior to mechanical circulatory support (MCS).
RECENT FINDINGS
Main topics covered in this article include diagnosis, monitoring, initial management and key aspects of pharmacological therapy in the ICU for patients with cardiogenic shock.
SUMMARY
Despite efforts to improve therapy, short-term mortality in patients with cardiogenic shock is still reaching 40-50%. Early recognition and treatment of cardiogenic shock are crucial, including early revascularization of the culprit lesion with possible staged revascularization in acute myocardial infarction (AMI)-CS. Optimal volume management and vasoactive drugs titrated to restore arterial pressure and perfusion are the cornerstone of cardiogenic shock therapy. The choice of vasoactive drugs depends on the underlying cause and phenotype of cardiogenic shock. Their use should be limited to the shortest duration and lowest possible dose. According to recent observational evidence, assessment of the complete hemodynamic profile with a pulmonary artery catheter (PAC) was associated with improved outcomes and should be considered early in patients not responding to initial therapy or with unclear shock. A multidisciplinary shock team should be involved early in order to identify potential candidates for temporary and/or durable MCS.
PubMed: 38872375
DOI: 10.1097/MCC.0000000000001182 -
Zhongguo Zhen Jiu = Chinese Acupuncture... Jun 2024To observe the effect of acupuncture on gastroesophageal reflux disease (GERD) based on the "heart-stomach connection" theory, and to explore its possible mechanisms. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To observe the effect of acupuncture on gastroesophageal reflux disease (GERD) based on the "heart-stomach connection" theory, and to explore its possible mechanisms.
METHODS
Seventy patients with GERD were randomly divided into an acupuncture group (35 cases, 2 cases dropped out) and a medication group (35 cases, 1 case dropped out). The patients in the acupuncture group received acupuncture at bilateral Shenmen (HT 7), Neiguan (PC 6), Burong (ST 19), Tianshu (ST 25), Zusanli (ST 36), Gongsun (SP 4), and Zhongwan (CV 12), with needles retained for 30 min, every other day, three times a week. The patients in the medication group were treated with oral omeprazole capsules, once daily, 20 mg each time. Both groups were treated for 8 weeks. Before and after treatment, the GERD questionnaire (GERDQ), GERD-quality of life scale (GERD-QOL), Hamilton depression scale-24 (HAMD-24), Zung self-rating depression scale (SDS), and Zung self-rating anxiety scale (SAS) scores were observed. Serum levels of gastrointestinal hormones (gastrin [GAS], motilin [MTL], and vasoactive intestinal peptide [VIP]) were measured, and the clinical efficacy of both groups was evaluated. Correlation between pre-treatment GERDQ score and GERD-QOL score, HAMD-24 score, SDS score, and SAS score was analyzed.
RESULTS
After treatment, the scores of GERDQ, HAMD-24, SDS, and SAS were decreased (<0.001) and the scores of GERD-QOL were increased (<0.001), serum levels of GAS and MTL were increased (<0.001) in both groups, while the serum level of VIP in the acupuncture group was decreased (<0.001) compared with those before treatment. The acupuncture group had higher GERD-QOL score and lower SAS score than the medication group (<0.05), with lower serum VIP level (<0.05). The total effective rate was 75.8% (25/33) in the acupuncture group, and 76.5% (26/34) in the medication group, with no significant difference between the two groups (>0.05). GERDQ score was negatively correlated with GERD-QOL scores ( =-0.762, <0.01) and positively correlated with HAMD-24 score, SDS score, and SAS score ( =0.709, 0.649, 0.689, <0.01) before treatment.
CONCLUSION
Based on the "heart-stomach connection" theory, acupuncture could effectively improve clinical symptoms, quality of life, and negative emotions in patients with GERD. Its mechanism may be related to the regulation of gastrointestinal hormone levels, thereby promoting the contraction of the lower esophageal sphincter.
Topics: Humans; Gastroesophageal Reflux; Acupuncture Therapy; Male; Female; Middle Aged; Adult; Aged; Gastrointestinal Hormones; Acupuncture Points; Young Adult; Stomach; Heart; Motilin
PubMed: 38867622
DOI: 10.13703/j.0255-2930.20230818-0004 -
Critical Care Nursing QuarterlyCardiogenic shock (CS) is a complex and dreadful condition for which effective treatments remain unclear. The concerningly high mortality rate of CS emphasizes a need... (Review)
Review
Cardiogenic shock (CS) is a complex and dreadful condition for which effective treatments remain unclear. The concerningly high mortality rate of CS emphasizes a need for developing effective therapies to reduce its mortality and reverse its detrimental course. This article aims to provide an updated and evidence-based review of the pathophysiology of CS and the related pharmacotherapeutics with a special focus on vasoactive and inotropic agents.
Topics: Humans; Shock, Cardiogenic; Cardiotonic Agents; Vasoconstrictor Agents
PubMed: 38860953
DOI: 10.1097/CNQ.0000000000000513