Comparison Between Kidney Transplantation After Circulatory Death and After Brain Death: A Monocentric Retrospective Study After 1 Year of Follow-up.

BACKGROUND: Donation after circulatory death (DCD) is a solid resource to widen the kidney donor pool. Italian activity has grown in the last years with encouraging results. Our center has been active in DCD kidney transplantation (KTX) since November 2017, providing 22.5% of Italian DCD donations in 2018. We present a single-center retrospective analysis after a 1-year follow-up comparing DCD and donation after brain death (DBD) KTX outcomes. METHODS: DCD (controlled only) and DBD KTX performed in our center from November 2017 to December 2018 were considered. All DCDs underwent in situ normothermic perfusion with extracorporeal membrane oxygenation, ex situ hypothermic oxygenated perfusion, and renal biopsy prior to allocation. We considered features of donors and recipients, immunosuppressive regimen, delayed graft function (DGF), primary nonfunction (PNF), graft and patient survival (Kaplan-Meier), creatinine, and estimated glomerular filtration rate at 1 year. Mean comparison with a Student t test and with χ2 test for frequencies were elaborated. RESULTS: Twenty-eight DBD, 18 double (64.3%) and 10 single (35.7%), were performed; 7 DCD, 3 double (42.8%) and 4 single (57.2%), were performed. By comparing single and double KTX, no statistically significant difference was found. We recorded 7 DGFs (25%) in DBD and 1 (14.3%) in the DCD group (P > .99) and no PNF. No graft was lost during the first year. One-year estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration) was, respectively, 62.7 ± 25.3 and 54.71 ± 14.66 mL/min (P = .25). DBD patient survival rate was 92.8%, DCD was 100%, and Kaplan-Meier was not statistically significant (P = .72). CONCLUSIONS: Controlled DCD is a valid resource for KTX, with similar outcomes to DBD. A multidisciplinary donor evaluation, combining clinical, perfusion, and histologic data in the allocation process, allows excellent results.

University of Modena Experience With Liver Grafts From Donation After Circulatory Death: What Really Matters in Organ Selection?

INTRODUCTION: The use of grafts from donation after circulatory death (DCD) is an important additional source to implement within the donor pool. We herein report the outcomes of our early experience with DCD grafts for liver transplantation (LT). METHODS: Ten patients successfully underwent LT with grafts from DCD donors between August 2017 and January 2019 at the Hepato-Pancreato-Biliary Surgery and Liver Transplant Unit of University of Modena and Reggio Emilia. All donors underwent normothermic regional perfusion after death declaration and, after the procurement, all the suitable grafts underwent ex situ hypothermic perfusion prior to transplantation. RESULTS: Mean postoperative hospital stay after transplant was 12.7 days (range, 5-26), and in 5 cases we placed a biliary drainage (Kehr tube) during surgery. Primary graft nonfunction did not occur after LT in this cohort, although, we registered one case of biliary anastomosis stricture that was managed endoscopically by endoscopic retrograde cholangiopancreatography. All patients are alive and none required retransplantation. CONCLUSIONS: In our experience with controlled DCD donors, the demonstration of: (1) a negative trend of lactate during normothermic regional perfusion; (2) an aspartate aminotransferase and alanine aminotransferase level lower than 2000 mU/dL; and (3) less than 1 hour of functional warm ischemia time along with no signs of microscopic or macroscopic ischemia of the grafts, are related to positive outcomes in the first year after transplant. A DCD risk score based on Italian population characteristics and regulations on death observation may improve donor-recipient match and avoid futile transplants.

Awake craniotomy anesthetic management using dexmedetomidine, propofol, and remifentanil.

INTRODUCTION: Awake craniotomy allows continuous monitoring of patients' neurological functions during open surgery. Anesthesiologists have to sedate patients in a way so that they are compliant throughout the whole surgical procedure, nevertheless maintaining adequate analgesia and anxiolysis. Currently, the use of α2-receptor agonist dexmedetomidine as the primary hypnotic-sedative medication is increasing. METHODS: Nine patients undergoing awake craniotomy were treated with refined monitored anesthesia care (MAC) protocol consisting of a combination of local anesthesia without scalp block, low-dose infusion of dexmedetomidine, propofol, and remifentanil, without the need of airways management. RESULTS: The anesthetic protocol applied in our study has the advantage of decreasing the dose of each drug and thus reducing the occurrence of side effects. All patients had smooth and rapid awakenings. The brain remained relaxed during the entire procedure. CONCLUSION: In our experience, this protocol is safe and effective during awake brain surgery. Nevertheless, prospective randomized trials are necessary to confirm the optimal anesthetic technique to be used.

Neuropsychological Testing in Interventional Cardiology Staff after Long-Term Exposure to Ionizing Radiation.

This study aimed at comparing neuropsychological test scores in 83 cardiologists and nurses (exposed group, EG) working in the cardiac catheterization laboratory, and 83 control participants (non exposed group, nEG), to explore possible cognitive impairments. The neuropsychological assessment was carried out by means of a battery called "Esame Neuropsicologico Breve." EG participants showed significantly lower scores on the delayed recall, visual short-term memory, and semantic lexical access ability than the nEG ones. No dose response could be detected. EG participants showed lower memory and verbal fluency performances, as compared with nEG. These reduced skills suggest alterations of some left hemisphere structures that are more exposed to IR in interventional cardiology staff. On the basis of these findings, therefore, head protection would be a mandatory good practice to reduce effects of head exposure to ionizing radiation among invasive cardiology personnel (and among other exposed professionals).

Intraoperative Functional and Perfusion Monitoring During Surgery for Giant Serpentine Middle Cerebral Artery Aneurysms.

BACKGROUND: Giant serpentine aneurysms are a rare entity, which can be managed using either endovascular or surgical techniques. Although the perioperative morbidity and mortality have decreased since the development of bypass revascularization procedures, their surgical treatment is still challenging. Intraoperative functional and perfusion monitoring techniques can be precious to make better decisions and improve outcomes. CASE DESCRIPTION: We report on the case of a giant, unruptured, partially thrombosed, serpentine middle cerebral artery aneurysm that was treated with partial endovascular coiling of intra-aneurysmal vascular channels, surgical resection of the aneurysm, and end-to-end M1-temporal M2 anastomosis. CONCLUSIONS: Intraoperative continuous motor evoked potentials monitoring, flowmetry, and indocyanine-green angiography provide precise and reproducible information about cerebral function and perfusion, respectively, allowing for more rational decision making during surgery for these challenging malformations.

The inflammatory hypothesis of mood spectrum broadened to fibromyalgia and chronic fatigue syndrome.

OBJECTIVES: The present paper aimed at reviewing literature data on the inflammatory hypothesis of mood spectrum, as well as the overlapping features with some chronic rheumatologic disorders, in particular fibromyalgia and chronic fatigue syndrome. METHODS: A literature search was carried out for English papers published in the years 2000-2014, while using the following words: mood spectrum, depression, bipolar disorders, fibromyalgia, chronic fatigue syndrome, neurotransmitters, inflammation, neuroinflammation, cytokines. RESULTS: Overlapping features were highlighted between mood spectrum, fibromyalgia and chronic fatigue syndrome suggesting common underlying mechanisms at pathophysiological level involving both central nervous and the immune systems. CONCLUSIONS: Taken together, the literature would suggest that the borders between different medical domains should be reconsidered in the light of common processes linking them.

Food addiction spectrum: a theoretical model from normality to eating and overeating disorders.

The authors comment on the recently proposed food addiction spectrum that represents a theoretical model to understand the continuum between several conditions ranging from normality to pathological states, including eating disorders and obesity, as well as why some individuals show a peculiar attachment to food that can become an addiction. Further, they review the possible neurobiological underpinnings of these conditions that include dopaminergic neurotransmission and circuits that have long been implicated in drug addiction. The aim of this article is also that at stimulating a debate regarding the possible model of a food (or eating) addiction spectrum that may be helpful towards the search of novel therapeutic approaches to different pathological states related to disturbed feeding or overeating.

Clozapine effects on adenylyl cyclase activity and serotonin type 1A receptors in human brain post-mortem.

Although the pharmacological profile of the atypical antipsychotic clozapine has been extensively studied in animal models, little information is available on its effects in the human brain. In particular, much interest is focused on the understanding of clozapine activity on serotonin (5-HT) neurotransmission, particularly on 5-HT receptor of type 1A (5-HT(1A)) that seems to play a pivotal role in the control of the 5-HT system. The present work, therefore, aimed at evaluating the effects of clozapine and its major metabolite, norclozapine, on the modulation of adenylyl cyclase (AC) velocity via 5-HT(1A) receptors in human post-mortem brain regions, in particular the prefrontal cortex, hippocampus and raphe nuclei. Concomitantly, the ability of the two compounds to displace the specific binding of the 5-HT(1A) receptor agonist [³H]-8-hydroxy-(2-di-N-propylamino) tetralin ([³H]-8-OH-DPAT) was evaluated in the same brain areas. The results showed that both clozapine and norclozapine, although with a 20-fold lower affinity, displaced [³H]8-OH-DPAT binding in all of the brain regions analysed, suggesting their interaction with 5-HT(1A) receptors. At the same time, clozapine and, to a lesser extent, norclozapine were found to inhibit the forskolin (FK)-stimulated AC system, while decreasing cyclic adenosine monophosphate (cAMP) concentrations in the hippocampus only. The receptor characterisation of the clozapine effect on AC observed in the hippocampus by the use of antagonists showed a mixed profile, involving not only the 5-HT(1A) receptor but also a muscarinic (M) receptor subtype, most likely the M4 one. These findings, while considering all the limitations due to the use of post-mortem tissues, are strongly suggestive of a region-dependent pharmacological action of clozapine in the human brain that may explain its peculiar clinical effects and open up research towards novel targets for future antipsychotic drugs.

[New developments on the serotonin hypothesis of depression: shunt of tryptophan]. / Nuovi sviluppi dell'ipotesi serotoninergica della depressione: shunt del triptofano.

Since the late 1960s, the serotonin deficiency, as demonstrated in major depression, was related to an increased activity of the liver enzyme tryptophan-pyrrolase stimulated by an excess of circulating corticosteroids, which would shift the metabolism of tryptophan from serotonin to kynurenine production. The finding that the kynurenine causes different effects in central nervous system suggested that an up-regulation of the tryptophan-kynurenine pathway determined not only a deficiency of serotonin, but could also play a role in the development of anxiety, psychotic symptoms and cognitive impairment associated with depression. This review aims to evaluate the different hormonal and genetic factors regulating the metabolism of tryptophan via kynurenine, and to highlight how this metabolic pathway may be involved in depression pathogenesis. Rate-limiting enzymes of kynurenine formation are two: tryptophan 2,3-dioxygenas (TDO) activated by stress hormones, and indoleamine 2,3-dioxygenase (IDO), activated by proinflammatory cytokines. The increased expression of the genes that produce inflammatory cytokines (interferon-gamma and tumor necrosis factor alpha) would determine a genetic predisposition to develop depression by up-regulating the IDO pathway, while environmental stressors would activate TDO via hormonal activation. Therefore, it can be reasonably assumed that the pathway of tryptophan-kynurenine represents one of the main melting points of the interaction between genetic and environmental factors involved in the pathophysiology of depression, as well as new targets for future antidepressant strategies.

Oxygen dissociation by concerted action of di-iron centers in metal-organic coordination networks at surfaces: modeling non-heme iron enzymes.

The high chemical reactivity of unsaturated metal sites is a key factor for the development of novel devices with applications in sensor engineering and catalysis. It is also central in the research for sustainable energy concepts, e.g., the efficient production and conversion of chemical fuels. Here, we study the process of oxygen dissociation by a surface-supported metal-organic network that displays close structural and functional analogies with the cofactors of non-heme enzymes. We synthesize a two-dimensional array of chemically active di-iron sites on a Cu(001) surface where molecular oxygen readily dissociates at room temperature. We provide an atomic-level structural and electronic characterization before and after reaction by combining scanning tunneling microscopy, X-ray absorption spectroscopy, and density functional theory. The latter identifies a novel mechanism for O2 dissociation controlled by the cooperative catalytic action of two Fe2+ ions. The high structural flexibility of the organic ligands, the mobility of the metal centers, and the hydrogen bonding formation are shown to be essential for the functionality of these active centers allowing to mimick biologically relevant reactions in a confined environment.

Presence of D4 dopamine receptors in human prefrontal cortex: a postmortem study

OBJECTIVE: The aim of our study was to explore the presence and the distribution of D4 dopamine receptors in postmortem human prefrontal cortex, by means of the binding of [³H]YM-09151-2, an antagonist that has equal affinity for D2, D3 and D4 receptors. It was therefore necessary to devise a unique assay method in order to distinguish and detect the D4 component. METHOD: Frontal cortex samples were harvested postmortem, during autopsy sessions, from 5 subjects. In the first assay, tissue homogenates were incubated with increasing concentrations of [³H]YM-09151-2, whereas L-745870, which has a high affinity for D4 and a low affinity for D2/D3 receptors, was used as the displacer. In the second assay, raclopride, which has a high affinity for D2/D3 receptors and a low affinity for D4 receptors, was used to block D2/D3. The L-745870 (500 nM) was added to both assays in order to determine the nonspecific binding. RESULTS: Our experiments revealed the presence of specific and saturable binding of [³H]YM-09151-2. The blockade of D2 and D3 receptors with raclopride ensured that the D4 receptors were labeled. The mean maximum binding capacity was 88 ± 25 fmol/mg protein, and the dissociation constant was 0.8 ± 0.4 nM. DISCUSSION AND CONCLUSIONS: Our findings, although not conclusive, suggest that the density of D4 receptors is low in the human prefrontal cortex.

OBJETIVO: O objetivo deste estudo foi quantificar a presença e a distribuição de receptores dopaminérgicos do tipo 4 (D4) no córtex cerebral humano em amostras post-mortem através do bloqueio com ³H-YM-09151-2 - um antagonista com afinidade equivalente pelos receptores D2, D3 e D4 - e do desenvolvimento de um método para a detecção específica do componente D4. MÉTODO: Foram obtidas amostras de córtex cerebral de cinco cadáveres. Em um primeiro ensaio, os homogeneizados de tecido cerebral foram incubados em concentrações crescentes de ³H-YM-09151-2, enquanto que o L-745,870, ligante que apresenta grande afinidade pelo receptor D4 e baixa afinidade por D2 e D3, foi utilizado como controle. Em um segundo ensaio, a racloprida, que apresenta alta afinidade por receptores D2 e D3, mas baixa afinidade por D4, foi usada para bloquear D2 e D3. O L-745,870 foi adicionado em ambos os ensaios para determinar o bloqueio não específico. RESULTADOS: Os resultados do experimento demonstraram a presença de um bloqueio específico e saturável com ³H-YM-09151-2. O bloqueio de receptores D2 e D3 com racloprida confirmou que apenas os receptores D4 livres foram avaliados. A Bmax (média ± DP) foi de 88 ± 25 fmol/mg de proteínas, enquanto que a Kd (média ± DP) foi de 0,8 ± 0,4 nM. DISCUSSÃO E CONCLUSÕES: Tais achados, ainda que não definitivamente conclusivos, sugerem a presença de uma baixa densidade de receptores D4 no córtex pré-frontal humano.

Spin-flop ordering from frustrated ferro- and antiferromagnetic interactions: a combined theoretical and experimental study of a Mn/Fe(100) monolayer.

The occurrence of a noncollinear magnetic structure at a Mn monolayer grown epitaxially on Fe(100) is predicted theoretically, using spinor density-functional theory, and observed experimentally, using x-ray magnetic circular dichroism (XMCD) and linear dichroism (XMLD) spectroscopies. The combined use of XMCD and XMLD at the Mn-absorption edge allows us to assess the existence of ferromagnetic and antiferromagnetic order at the interface, and also to determine the moment orientations with element specificity. The experimental results thus obtained are in excellent agreement with the magnetic structure determined theoretically.

Decreased density of peripheral benzodiazepine receptors in psychiatric patients after a suicide attempt.

To date, two main types of benzodiazepine (BDZ) receptors have been identified: one of these is the so-called central receptor which is found mainly in the cortex, limbic areas and cerebellum, and the other is known as the peripheral receptor, which is found in the kidneys, lungs, ovaries, testes, adrenal glands and blood cells, but is present also in the central nervous system (CNS), in particular in glial cells. Although for some time the peripheral BDZ receptor has been considered an acceptor site with no pharmacological activity, recent data have suggested that it may be involved in a variety of actions, such as the response to stress. The presence of these receptors in blood platelets, which are considered a reliable, peripheral mirror of the same structures located in the SNC, prompted us to evaluate them in a group of psychiatric patients after a suicide attempt, as compared with healthy control subjects, by means of the specific binding of 3H-PK 11195. Suicide, with no doubt, may be considered one of the most stressful situations occurring to humans. The results showed the presence of a significant decrease in the density of 3H-PK 11195 binding sites in the patients, as compared with healthy control subjects. This finding may represent a non-specific indicator of a condition of stress, since peripheral BDZ receptors are modulated by stress and hormones, or it may result more from an abnormal metabolism of steroid substances which could play a pivotal role in the development of vulnerability towards suicide.