Background: Extracorporeal membrane oxygenation (ECMO) is frequently used during lung transplantation. Unfractionated heparin (UFH) is mainly used as part of ECMO support for anticoagulation. One of the most common perioperative complications is bleeding, which high-dose UFH can aggravate. Methods: We retrospectively analyzed (n = 141) patients who underwent lung transplantation between 2020 and 2022. All subjects (n = 109) underwent central cannulated VA ECMO with successful intraoperative ECMO weaning. Patients on ECMO bridge, postoperative ECMO, heart-lung transplants and transplants without ECMO were excluded. The dose of UFH for the entire surgical procedure, blood loss and consumption of blood derivatives intraoperatively and 48 h after ICU admission were recorded. Surgical revision for postoperative bleeding were analyzed. Thrombotic complications, mortality and long-term survival were evaluated. Results: Lower doses of UFH administered for intraoperative ECMO anticoagulation contribute to a reduction in intraoperative blood derivates consumption and blood loss with no thrombotic complications related to the patient or the ECMO circuit. Lower doses of UFH may lead to a decreased incidence of surgical revision for hemothorax. Conclusion: Lower doses of UFH as part of intraoperative ECMO anticoagulation might reduce the incidence of complications and lead to better postoperative outcomes.

• MeSH
• Anticoagulants therapeutic use   MeSH
• Heparin therapeutic use   MeSH
• Humans MeSH
• Extracorporeal Membrane Oxygenation * adverse effects   MeSH
• Postoperative Hemorrhage MeSH
• Retrospective Studies MeSH
• Lung Transplantation * methods   MeSH
• Thrombosis * etiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH

The blink reflex (BR) is integrated at the brainstem; however, it is modulated by inputs from various structures such as the striatum, globus pallidus, substantia nigra, and nucleus raphe magnus but also from afferent input from the peripheral nervous system. Therefore, it provides information about the pathophysiology of numerous peripheral and central nervous system disorders. The BR is a valuable tool for studying the integrity of the trigemino-facial system, the relevant brainstem nuclei, and circuits. At the same time, some neurophysiological techniques applying the BR may indicate abnormalities involving structures rostral to the brainstem that modulate or control the BR circuits. This is a state-of-the-art review of the clinical application of BR modulation; physiology is reviewed in part 1. In this review, we aim to present the role of the BR and techniques related to its modulation in understanding pathophysiological mechanisms of motor control and pain disorders, in which these techniques are diagnostically helpful. Furthermore, some BR techniques may have a predictive value or serve as a basis for follow-up evaluation. BR testing may benefit in the diagnosis of hemifacial spasm, dystonia, functional movement disorders, migraine, orofacial pain, and psychiatric disorders. Although the abnormalities in the integrity of the BR pathway itself may provide information about trigeminal or facial nerve disorders, alterations in BR excitability are found in several disease conditions. BR excitability studies are suitable for understanding the common pathophysiological mechanisms behind various clinical entities, elucidating alterations in top-down inhibitory systems, and allowing for follow-up and quantitation of many neurological syndromes.

• MeSH
• Dystonic Disorders * MeSH
• Hemifacial Spasm * MeSH
• Humans MeSH
• Blinking MeSH
• Facial Pain MeSH
• Peripheral Nervous System MeSH
• Reflex physiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Extracorporeal membrane oxygenation (ECMO) has been established as a life-saving technique for patients with the most severe forms of respiratory or cardiac failure. It can, however, be associated with severe complications. Anticoagulation therapy is required to prevent ECMO circuit thrombosis. It is, however, associated with an increased risk of hemocoagulation disorders. Thus, safe anticoagulation is a cornerstone of ECMO therapy. The most frequently used anticoagulant is unfractionated heparin, which can, however, cause significant adverse effects. Novel drugs (e.g., argatroban and bivalirudin) may be superior to heparin in the better predictability of their effects, functioning independently of antithrombin, inhibiting thrombin bound to fibrin, and eliminating heparin-induced thrombocytopenia. It is also necessary to keep in mind that hemocoagulation tests are not specific, and their results, used for setting up the dosage, can be biased by many factors. The knowledge of the advantages and disadvantages of particular drugs, limitations of particular tests, and individualization are cornerstones of prevention against critical events, such as life-threatening bleeding or acute oxygenator failure followed by life-threatening hypoxemia and hemodynamic deterioration. This paper describes the effects of anticoagulant drugs used in ECMO and their monitoring, highlighting specific conditions and factors that might influence coagulation and anticoagulation measurements.

• MeSH
• Anticoagulants adverse effects   MeSH
• Antithrombins therapeutic use   MeSH
• Blood Coagulation MeSH
• Heparin * adverse effects   MeSH
• Humans MeSH
• Extracorporeal Membrane Oxygenation * adverse effects   methods   MeSH
• Retrospective Studies MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

We present a comparison of the intrinsic saturation of firing frequency in four simple neural models: leaky integrate-and-fire model, leaky integrate-and-fire model with reversal potentials, two-point leaky integrate-and-fire model, and a two-point leaky integrate-and-fire model with reversal potentials. "Two-point" means that the equivalent circuit has two nodes (dendritic and somatic) instead of one (somatic only). The results suggest that the reversal potential increases the slope of the "firing rate vs input" curve due to a smaller effective membrane time constant, but does not necessarily induce saturation of the firing rate. The two-point model without the reversal potential does not limit the voltage or the firing rate. In contrast to the previous models, the two-point model with the reversal potential limits the asymptotic voltage and the firing rate, which is the main result of this paper. The case of excitatory inputs is considered first and followed by the case of both excitatory and inhibitory inputs.

• MeSH
• Action Potentials physiology   MeSH
• Physical Phenomena MeSH
• Membrane Potentials physiology   MeSH
• Models, Neurological * MeSH
• Neurons * physiology   MeSH
• Publication type
• Journal Article MeSH

Background: The pathogenesis of adolescent idiopathic scoliosis (AIS), including the role of brain and spinal inhibitory circuits, is still poorly elucidated. The aim of this study was to identify which central inhibitory mechanisms are involved in the pathogenesis of AIS.Design: A prospective neurophysiological study, using a battery of neurophysiological tests, such as cutaneous (CuSP) and cortical (CoSP) silent periods, motor evoked potentials (MEP) and paired-pulse transcranial magnetic stimulation (ppTMS).Settings: Neurophysiological laboratory.Participants: Sixteen patients with AIS (14 females, median age 14.4) and healthy controls.Outcome measures: MEPs were obtained after transcranial magnetic stimulation (TMS) and recorded from the abductor pollicis muscle (APB). ppTMS was obtained at interval ratios (ISI) of 1, 2, 3, 6, 10, 15 and 20 ms. The cortical silent period (CoSP) was recorded from the APB. The cutaneous silent period (CuSP) was measured after painful stimuli delivered to the thumb while the subjects maintained voluntary contraction of the intrinsic hand muscles. The data were analyzed and compared with those from healthy subjects.Results: The CoSP duration was significantly prolonged in AIS patients. A significantly higher amplitude of ppTMS for ISI was found in all AIS patients, without remarkable left-right side differences. No significant difference in MEP latency or amplitude nor in the CuSP duration was obtained.Conclusion: Our observation demonstrates evidence of central nervous system involvement in adolescent idiopathic scoliosis (AIS). Lower intracortical inhibition, higher motor cortex excitability, and preserved spinal inhibitory circuits are the main findings of this study. A possible explanation of these changes could be attributed to impaired sensorimotor integration predominantly at the cortical level.

• MeSH
• Electric Stimulation MeSH
• Electromyography MeSH
• Muscle, Skeletal physiology   MeSH
• Humans MeSH
• Adolescent MeSH
• Evoked Potentials, Motor physiology   MeSH
• Motor Cortex * physiology   MeSH
• Spinal Cord Injuries * MeSH
• Prospective Studies MeSH
• Scoliosis * MeSH
• Transcranial Magnetic Stimulation MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

A 6-year-old boy, born with hypoplastic left heart syndrome, underwent total cavopulmonary connection and later presented in a significantly deteriorated condition. A CT scan revealed multiple thrombi in the extracardiac conduit, although the patient was maintained on an effective anticoagulant therapy. Further examination revealed anamnestic antibodies suggesting that the patient had gone through a clinically inapparent COVID-19 infection, which we conclude most likely contributed to his hypercoagulable state and led to the formation of significant thrombi impairing the patient's haemodynamics. The patient underwent a surgical thrombectomy; there were no post-operative thrombotic complications.

• MeSH
• Anticoagulants therapeutic use   MeSH
• COVID-19 * MeSH
• Child MeSH
• Fontan Procedure * adverse effects   MeSH
• Humans MeSH
• Postoperative Complications MeSH
• Hypoplastic Left Heart Syndrome * surgery   MeSH
• Thrombosis * etiology   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

CONTEXT: Adipose tissue (AT) transcriptome studies provide holistic pictures of adaptation to weight and related bioclinical settings changes. OBJECTIVE: To implement AT gene expression profiling and investigate the link between changes in bioclinical parameters and AT gene expression during 3 steps of a 2-phase dietary intervention (DI). METHODS: AT transcriptome profiling was obtained from sequencing 1051 samples, corresponding to 556 distinct individuals enrolled in a weight loss intervention (8-week low-calorie diet (LCD) at 800 kcal/day) followed with a 6-month ad libitum randomized DI. Transcriptome profiles obtained with QuantSeq sequencing were benchmarked against Illumina RNAseq. Reverse transcription quantitative polymerase chain reaction was used to further confirm associations. Cell specificity was assessed using freshly isolated cells and THP-1 cell line. RESULTS: During LCD, 5 modules were found, of which 3 included at least 1 bioclinical variable. Change in body mass index (BMI) connected with changes in mRNA level of genes with inflammatory response signature. In this module, change in BMI was negatively associated with changes in expression of genes encoding secreted protein (GDF15, CCL3, and SPP1). Through all phases of the DI, change in GDF15 was connected to changes in SPP1, CCL3, LIPA and CD68. Further characterization showed that these genes were specific to macrophages (with LIPA, CD68 and GDF15 expressed in anti-inflammatory macrophages) and GDF15 also expressed in preadipocytes. CONCLUSION: Network analyses identified a novel AT feature with GDF15 upregulated with calorie restriction induced weight loss, concomitantly to macrophage markers. In AT, GDF15 was expressed in preadipocytes and macrophages where it was a hallmark of anti-inflammatory cells.

• MeSH
• Biomarkers metabolism   MeSH
• Adult MeSH
• Gene Regulatory Networks * MeSH
• Weight Loss * MeSH
• Body Mass Index MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Obesity metabolism   pathology   MeSH
• Prognosis MeSH
• Diet, Reducing * MeSH
• Growth Differentiation Factor 15 genetics   metabolism   MeSH
• Transcriptome * MeSH
• Adipose Tissue metabolism   pathology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH

Embólia koronárnych artérií je menej častou príčinou akútneho infarktu myokardu. Predstavujeme kazuistiku 22-ročnej pacientky s dvojvtokovou ľavou komorou, defektom komorového septa a pulmonálnou stenózou po Fontanovej operácii s akútnym spodným STEMI na embolickom podklade. Okrem známych rizík vedúcich k trombotickým komplikáciám spojeným s Fontanovskou cirkuláciou, medzi potenciálne predisponujúce faktory trombembolizmu u tejto pacientky patrili vytvorenie trombu v dolnej dutej žile a nedostatočná antikoagulačná liečba. Táto kazuistika predstavuje jednu z prvých dokumentovaných embolických príčin STEMI u pacienta s Fontanovskou cirkuláciou. Doteraz nie je vytvorený konsenzus, že antikoagulačná terapia warfarínom je u pacientov s Fontanovskou cirkuláciou superiórna voči aspirínu v primárnej prevencii trombembolických príhod.

Coronary artery embolism is an uncommon cause of acute myocardial infarction. We present a case of a 22-year-old patient with double inlet left ventricle (DILV), ventricular septal defect and pulmonary stenosis after Fontan repair with an acute embolic inferior ST-segment elevation myocardial infarction (STEMI). Apart from already known risk factors of thrombotic complications associated with Fontan circulation, additional predispositions in this patient included thrombus formation located in the inferior vena cava and the lack of anticoagulation therapy. This is one of the first reported embolic causes of STEMI in a patient with a Fontan circulation. Up to date, there is no consensus that anticoagulation therapy with warfarin is superior to aspirin in primary prevention of thromboembolism in patients with Fontan circulation.

• MeSH
• Anticoagulants therapeutic use   MeSH
• Fontan Procedure MeSH
• Myocardial Infarction * diagnosis   etiology   therapy   MeSH
• Humans MeSH
• Young Adult MeSH
• Postoperative Complications MeSH
• Thromboembolism MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Young Adult MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

BACKGROUND: Slow neurotransmission including DARPP-32 signalling is implicated in substance use disorders (SUDs) by experimental systems but not yet in the human aetiology. PPP1R12B, encoding another protein in the DARPP-32 family, hasn't been studied in the brain. METHODS: Brain-regional gene activity was assessed in three different animal models of SUDs for mRNA level alterations. Genetic associations were assessed by meta-analysis of pre-existing dbGaP GWAS datasets for main effects and epistasis with known genetic risks, followed by cell type-specific pathway delineation. Parkinson's disease (PD) was included as a dopamine-related disease control for SUDs. FINDINGS: In animal models of SUDs, environmentally-altered PPP1R12B expression sex-dependently involves motivation-related brain regions. In humans with polysubstance abuse, meta-analysis of pre-existing datasets revealed that PPP1R12B and PPP1R1B, although expressed in dopamine vs. dopamine-recipient neurons, exerted similar interactions with known genetic risks such as ACTR1B and DRD2 in men but with ADH1B, HGFAC and DRD3 in women. These interactions reached genome-wide significances (Pmeta<10-20) for SUDs but not for PD (disease selectivity: P = 4.8 × 10-142, OR = 6.7 for PPP1R12B; P = 8.0 × 10-8, OR = 2.1 for PPP1R1B). CADM2 was the common risk in the molecular signalling regardless of gender and cell type. INTERPRETATION: Gender-dependant slow neurotransmission may convey both genetic and environmental vulnerabilities selectively to SUDs. FUNDING: Grants from National Institute on Drug Abuse (NIDA) and National Institute on Alcohol Abuse and Alcoholism (NIAAA) of U.S.A. and National Natural Science Foundation of China (NSFC).

• MeSH
• Genome-Wide Association Study MeSH
• Dopamine and cAMP-Regulated Phosphoprotein 32 genetics   metabolism   MeSH
• Epistasis, Genetic * MeSH
• Genetic Heterogeneity MeSH
• Genetic Predisposition to Disease MeSH
• Gene Regulatory Networks MeSH
• Rats MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Brain metabolism   pathology   MeSH
• Mice MeSH
• Disease Susceptibility MeSH
• Synaptic Transmission genetics   MeSH
• Organ Specificity genetics   MeSH
• Substance-Related Disorders diagnosis   etiology   metabolism   MeSH
• Protein Phosphatase 1 genetics   metabolism   MeSH
• Gene Expression Regulation MeSH
• Sex Factors MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Introduction: Deficits in neurocognitive mechanisms such as inhibition control and cognitive flexibility have been suggested to mediate the symptoms in obsessive-compulsive disorder (OCD). These mechanisms are proposedly controlled by the "affective" and "executive" orbitofronto-striato-thalamo-cortical (CSTC) circuits with well-documented morphological and functional alterations in OCD that are associated with OCD symptoms. The precuneus region has been suggested in OCD as another key structure associated with the mechanism of "thought-action fusion." Our study aimed to elucidate the association of the altered functional coupling of the CSTC nodes (and precuneus), the OCD symptoms, and interference control/cognitive flexibility. Methods: In a group of 36 (17 medicated and 19 drug-free) OCD patients and matched healthy volunteers, we tested functional connectivity (FC) within the constituents of the dorsolateral prefrontal cortex "executive" CSTC, the orbitofrontal cortex/anterior cingulate "affective" CSTC, and precuneus. The functional connections showing the strongest effects were subsequently entered as explanatory variables to multiple regression analyses to identify possible associations between observed alterations of functional coupling and cognitive (Stroop test) and clinical measures (obsessions, compulsions, and anxiety level). Results: We observed increased FC (FWE p < 0.05 corr.) between CSTC seeds and regions of the parieto-occipital cortex, and between the precuneus and the angular gyrus and dorsolateral prefrontal cortex. Decreased FC was observed within the CSTC loop (caudate nucleus and thalamus) and between the anterior cingulate cortex and the limbic lobe. Linear regression identified a relationship between the altered functional coupling of thalamus with the right somatomotor parietal cortex and the Stroop color-word score. Similar association of thalamus FC has been identified also for obsessions severity. No association was observed for compulsions and anxiety. Conclusions: Our findings demonstrate altered FC in OCD patients with a prevailing increase in FC originating in CSTC regions toward other cortical areas, and a decrease in FC within the constituents of CSTC loops. Moreover, our results support the role of precuneus in OCD. The association of the cognitive and clinical symptoms with the FC between the thalamus and somatomotor cortex indicates that cognitive flexibility and inhibitory control are strongly linked and both mechanisms might contribute to the symptomatology of OCD.

• Publication type
• Journal Article MeSH