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Background: Among over-the-counter (OTC) drugs, loperamide has recently emerged for its potential of misuse and cardiotoxicity issues. Hence, we aimed here at assessing the loperamide-related cases being reported to the EMA's EudraVigilance (EV) database., Methods: All spontaneous EV reports relating to loperamide misuse/abuse/dependence/withdrawal and cardiotoxicity issues were here retrieved, performing a descriptive analysis., Findings: During the years 2005-2017, EV collected a number of 1,983 (out of a total of 7,895; 25.11%) loperamide-related misuse/abuse/dependence/withdrawal adverse drug reaction (ADR) reports, with a progressively increasing trend since 2014. Most cases were classified as drug use disorder (37.4%) or intentional overdose (25.4%). Loperamide was used on its own in 41.9% of cases; remaining, polydrug, cases included antidepressants; benzodiazepines; and other OTCs. Some 1,085 (1,085/7,895 = 13.7%) cardiovascular ADRs were reported, being conduction abnormalities and EKG alterations the most frequently identified., Conclusions: EV data may support the levels of concern relating to loperamide potential of abuse and associated cardiotoxicity issues., Competing Interests: The authors have declared that no competing interests exist.

Maintenance of the complex phenotype of primary hepatocytes in vitro represents a limitation for developing liver support systems and reliable tools for biomedical research and drug screening. We herein aimed at developing a biosystem able to preserve human and rodent hepatocytes phenotype in vitro based on the main characteristics of the liver sinusoid: unique cellular architecture, endothelial biodynamic stimulation, and parenchymal zonation. Primary hepatocytes and liver sinusoidal endothelial cells (LSEC) were isolated from control and cirrhotic human or control rat livers and cultured in conventional in vitro platforms or within our liver-resembling device. Hepatocytes phenotype, function, and response to hepatotoxic drugs were analyzed. Results evidenced that mimicking the in vivo sinusoidal environment within our biosystem, primary human and rat hepatocytes cocultured with functional LSEC maintained morphology and showed high albumin and urea production, enhanced cytochrome P450 family 3 subfamily A member 4 (CYP3A4) activity, and maintained expression of hepatocyte nuclear factor 4 alpha (hnf4α) and transporters, showing delayed hepatocyte dedifferentiation. In addition, differentiated hepatocytes cultured within this liver-resembling device responded to acute treatment with known hepatotoxic drugs significantly different from those seen in conventional culture platforms. In conclusion, this study describes a new bioengineered device that mimics the human sinusoid in vitro, representing a novel method to study liver diseases and toxicology., (© 2018 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.)

A recent years' increase in misusing levels of image- and performance- enhancing drugs (IPEDs) has been observed. Out of these drugs, beta-2 agonists have recently emerged for their potential of misuse, especially for slimming and bodybuilding purposes. To this perspective, clenbuterol ('the size zero pill') has been reported as being both popular and widely available from the illegal market. All clenbuterol and salbutamol misuse/abuse/dependence/withdrawal/overdose/off-label spontaneous reports (2006-2016) from the European Medicines Agency (EMA) EudraVigilance (EV) database were collected and analysed by age range, gender, concomitant therapies and source of information. From the EV database, 55 of a total number of 920 'suspect' misuse/abuse/dependence/withdrawal/overdose/off-label ADRs (e.g. 5.97%; corresponding to 25 of 138 individuals) and 1310 of 62,879 ADRs (e.g. 2.08%; corresponding to 474 of 6923 individuals) were, respectively, associated with clenbuterol (typically ingested in combination with a range of anabolic steroids) and salbutamol. Proportional reporting ratio (PRR) value for misuse/abuse ADRs was higher (PRR = 18.38) for clenbuterol in comparison with salbutamol. Clenbuterol misuse/abuse could be a cause for major concern, especially in vulnerable individuals., (© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Transepithelial electrical measurements in the renal tubule have provided a better understanding of how kidney regulates electrolyte and water homeostasis through the reabsorption of molecules and ions (e.g., H 2 O and NaCl). While experiments and measurement techniques using native tissue are difficult to prepare and to reproduce, cell cultures conducted largely with the Ussing chamber lack the effect of fluid shear stress which is a key physiological stimulus in the renal tubule. To overcome these limitations, we present a modular perfusion chamber for long-term culture of renal epithelial cells under flow that allows the continuous and simultaneous monitoring of both transepithelial electrical parameters and transepithelial NaCl transport. The latter is obtained from electrical conductivity measurements since Na + and Cl - are the ions that contribute most to the electrical conductivity of a standard physiological solution. The system was validated with epithelial monolayers of raTAL and NRK-52E cells that were characterized electrophysiologically for 5 days under different flow conditions (i.e., apical perfusion, basal, or both). In addition, apical to basal chemical gradients of NaCl (140/70 and 70/140 mM) were imposed in order to demonstrate the feasibility of this methodology for quantifying and monitoring in real time the transepithelial reabsorption of NaCl, which is a primary function of the renal tubule., (© 2018 Wiley Periodicals, Inc.)

Cell microencapsulation is an attractive strategy for cell-based therapies that allows the implantation of genetically engineered cells and the continuous delivery of de novo produced therapeutic products. However, the establishment of a way to retrieve the implanted encapsulated cells in case the treatment needs to be halted or when cells need to be renewed is still a big challenge. The combination of micro and macroencapsulation approaches could provide the requirements to achieve a proper immunoisolation, while maintaining the cells localized into the body. We present the development and characterization of a porous implantable macrocapsule device for the loading of microencapsulated cells. The device was fabricated in polyamide by selective laser sintering (SLS), with controlled porosity defined by the design and the sintering conditions. Two types of microencapsulated cells were tested in order to evaluate the suitability of this device; erythropoietin (EPO) producing C 2 C 12 myoblasts and Vascular Endothelial Growth Factor (VEGF) producing BHK fibroblasts. Results showed that, even if the metabolic activity of these cells decreased over time, the levels of therapeutic protein that were produced and, importantly, released to the media were stable.

The interconnection of different tissue-tissue interfaces may extend organ-on-chips to a new generation of sophisticated models capable of recapitulating more complex organ-level functions. Single interfaces are largely recreated in organ-on-chips by culturing the cells on opposite sides of a porous membrane that splits a chamber in two or by connecting the cells of two adjacent compartments through microchannels. However, it is difficult to interconnect more than one interface using these approaches. To address this challenge, we present a novel microfluidic device where cells are arranged in parallel compartments and are highly interconnected through a grid of microgrooves, which facilitates paracrine signaling and heterotypic cell-cell contact between multiple tissues. In addition, the device includes electrodes on the substrate for the measurement of transepithelial electrical resistance (TEER). Unlike conventional methods for measuring the TEER where electrodes are on each side of the cell barrier, a method with only electrodes on the substrate has been validated. As a proof-of-concept, we have used the device to mimic the structure of the blood-retinal barrier by co-culturing primary human retinal endothelial cells (HREC), a human neuroblastoma cell line (SH-SY5Y), and a human retinal pigment epithelial cell line (ARPE-19). Cell barrier formations were assessed by a permeability assay, TEER measurements, and ZO-1 expression. These results validate the proposed microfluidic device with microgrooves as a promising in vitro tool for the compartmentalization and monitoring of barrier tissues.

Aims: Alcohol abuse has long been known as a disease with social and economic burden to society. Given the complex nature of alcohol treatment, it is worthwhile to examine the change over time of patients admitted to residential alcohol abuse rehabilitation units., Methods: The data were collected from two Italian projects on alcoholics performed in the mid-1990s (ASSALT) and in 2009 (CORRAL), respectively. Categorical variables were considered in terms of absolute and relative frequencies. Comparisons of relative frequencies between groups were assessed by means of Fisher's exact test. Mixed logistic regression models were fitted to CORRAL data to identify the predictors of the probability of being a polysubstance abuser or having a dual diagnosis. The association estimates were reported as adjusted odds ratios and relative 95% confidence intervals., Results: Compared to the mid-1990s, in 2009 patients were older (P= 0.0003), with a higher level of education (P= 0.0204), with fewer comorbidities (liver disease except cirrhosis, P < 0.0001; polyneuropathy, P= 0.0001), more frequently polysubstance abusers (P < 0.0001), affected by dual diagnosis (P < 0.0001). In 2009, the probability of being a polysubstance abuser was higher in younger and in patients with dual psychiatric diagnosis. Female gender and polysubstance abuse were positively associated to the probability of being affected by dual psychiatric diagnosis., Conclusions: The increment of patients admitted to residential programs for alcohol dependence with polysubstance abuse and/or dual psychiatric diagnoses suggests the need to pay more attention to both psychological/psychiatric interventions and internal medicine/physical rehabilitation., Short Summary: The results of this study suggest that further research is needed to identify the best treatment strategy that is safe and effective for the new population of alcoholics., (© The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Gait analysis is recognized as a useful assessment tool in the field of human movement research. However, doubts remain on its real effectiveness as a clinical tool, i.e. on its capability to change the diagnostic-therapeutic practice. In particular, the conditions in which evidence of a favorable cost-benefit ratio is found and the methodology for properly conducting and interpreting the exam are not identified clearly. To provide guidelines for the use of Gait Analysis in the context of rehabilitation medicine, SIAMOC (the Italian Society of Clinical Movement Analysis) promoted a National Consensus Conference which was held in Bologna on September 14th, 2013. The resulting recommendations were the result of a three-stage process entailing i) the preparation of working documents on specific open issues, ii) the holding of the consensus meeting, and iii) the drafting of consensus statements by an external Jury. The statements were formulated based on scientific evidence or experts' opinion, when the quality/quantity of the relevant literature was deemed insufficient. The aim of this work is to disseminate the consensus statements. These are divided into 13 questions grouped in three areas of interest: 1) General requirements and management, 2) Methodological and instrumental issues, and 3) Scientific evidence and clinical appropriateness. SIAMOC hopes that this document will contribute to improve clinical practice and help promoting further research in the field., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

The visual system is extremely efficient at detecting events across time even at very fast presentation rates; however, discriminating the identity of those events is much slower and requires attention over time, a mechanism with a much coarser resolution [Cavanagh, P., Battelli, L., & Holcombe, A. O. Dynamic attention. In A. C. Nobre & S. Kastner (Eds.), The Oxford handbook of attention (pp. 652-675). Oxford: Oxford University Press, 2013]. Patients affected by right parietal lesion, including the TPJ, are severely impaired in discriminating events across time in both visual fields [Battelli, L., Cavanagh, P., & Thornton, I. M. Perception of biological motion in parietal patients. Neuropsychologia, 41, 1808-1816, 2003]. One way to test this ability is to use a simultaneity judgment task, whereby participants are asked to indicate whether two events occurred simultaneously or not. We psychophysically varied the frequency rate of four flickering disks, and on most of the trials, one disk (either in the left or right visual field) was flickering out-of-phase relative to the others. We asked participants to report whether two left-or-right-presented disks were simultaneous or not. We tested a total of 23 right and left parietal lesion patients in Experiment 1, and only right parietal patients showed impairment in both visual fields while their low-level visual functions were normal. Importantly, to causally link the right TPJ to the relative timing processing, we ran a TMS experiment on healthy participants. Participants underwent three stimulation sessions and performed the same simultaneity judgment task before and after 20 min of low-frequency inhibitory TMS over right TPJ, left TPJ, or early visual area as a control. rTMS over the right TPJ caused a bilateral impairment in the simultaneity judgment task, whereas rTMS over left TPJ or over early visual area did not affect performance. Altogether, our results directly link the right TPJ to the processing of relative time.

Electroconvulsive therapy (ECT) is effective in treatment-resistant depression (TRD). It may act through intracellular process modulation, but its exact mechanism is still unknown. Animal research supports a neurotrophic effect for ECT. We aimed to investigate the association between changes in serum brain-derived neurotrophic factor (sBDNF) levels and clinical improvement following ECT in patients with TRD. Twenty-one patients with TRD (2 men, 19 women; mean age, 63.5 years; S.D., 11.9) were assessed through the Hamilton Depression Rating Scale (HDRS), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Impressions scale, Severity (CGIs) before and after a complete ECT cycle. At the same time-points, patients underwent blood withdrawal for measuring sBDNF levels. ECT significantly reduced HDRS, BPRS, and CGIS scores, but not sBDNF levels. No significant correlation was found between sBDNF changes, and each of HDRS, BPRS, and CGIs score changes. sBDNF levels in TRD patients were low both at baseline and post-ECT. Our results do not support that improvements in TRD following ECT are mediated through increases in sBDNF levels., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Mitochondrial myopathies (MMs) often present with leukoencephalopathy and psychiatric symptoms, which do not respond to or worsen with psychiatric drugs., Case Report: A 67-year-old woman with a 10-year history of probable chronic progressive external ophthalmoplegia, an MM, had drug-resistant, anxious-depressive symptoms. Since she had never had seizures, we proposed 20 sessions of deep transcranial magnetic stimulation (dTMS) for her depression. Surprisingly, besides the expected improvement of depression, we observed marked improvement of movement disorder that lasted as long as the patient was undergoing dTMS. She also improved her performance on neuropsychological tests of executive function and cognitive speed. Depressive symptom improvement was persistent, while anxiety symptoms recurred after the end of the sessions., Conclusions: dTMS may be an alternative antidepressant strategy in patients with MMs, provided that they are free from seizures. The mechanism of improvement of motor disturbance may relate to dorsolateral prefrontal cortex stimulation and improved executive function and needs further investigation., (Copyright © 2015. Published by Elsevier Inc.)

Introduction: Co-occurrence of Major Depressive (MDD) and Alcohol Use Disorders (AUDs) is frequent, causing more burden than each disorder separately. Since the dorsolateral prefrontal cortex (DLPFC) is critically involved in both mood and reward and dysfunctional in both conditions, we aimed to evaluate the effects of dTMS stimulation of bilateral DLPFC with left prevalence in patients with MDD with or without concomitant AUD., Methods: Twelve MDD patients and 11 with concomitant MDD and AUD (MDD+AUD) received 20 dTMS sessions. Clinical status was assessed through the Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impressions severity scale (CGIs), craving through the Obsessive Compulsive Drinking Scale (OCDS) in MDD+AUD, and functioning with the Global Assessment of Functioning (GAF)., Results: There were no significant differences between the two groups in sociodemographic (age, sex, years of education and duration of illness) and baseline clinical characteristics, including scores on assessment scales. Per cent drops on HDRS and CGIs scores at the end of the sessions were respectively 62.6% and 78.2% for MDD+AUD, and 55.2% and 67.1% for MDD (p<0.001). HDRS, CGIs and GAF scores remained significantly improved after the 6-month follow-up. HDRS scores dropped significantly earlier in MDD+AUD than in MDD LIMITATIONS: The small sample size and factors inherent to site and background treatment may have affected results., Conclusions: High frequency bilateral DLPFC dTMS with left preference was well tolerated and effective in patients with MDD, with or without AUD. The antidepressant effect of dTMS is not affected by alcohol abuse in patients with depressive episodes. The potential use of dTMS for mood modulation as an adjunct to treatment in patients with a depressive episode, with or without alcohol abuse, deserves further investigation., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: The purpose of this literature database search-based review was to critically consider and evaluate the findings of literature focusing on efficacy and safety of 5-HT3 antagonists in the treatment of obsessive-compulsive disorder (OCD), so as to test whether preclinical data match clinical therapeutic trials., Design: The PubMed database has been searched for papers on 5-HT3 antagonists and OCD in humans and for animal models of OCD and 5-HT3 receptors., Results: Of the clinically tested 5-HT3 receptor antagonists, ondansetron has been used to treat OCD in five therapeutic studies, whereas granisetron only in one recent trial. Both showed some efficacy in open studies and superiority to placebo in double-blind studies, along with fair safety. No animal OCD model directly implicated 5-HT3 receptors., Conclusions: Overall, results indicate some utility, but the available literature is too scanty to allow for valid conclusions to be drawn. The mismatch between animal models of obsessive-compulsive disorder and clinical data with 5-HT3 antagonists needs more clinical data to ensure that it is not an artefact., (Copyright © 2015 John Wiley & Sons, Ltd.)

Introduction: Deep transcranial magnetic stimulation (dTMS) is a new form of TMS allowing safe stimulation of deep brain regions. The objective of this preliminary study was to assess the role of dTMS maintenance sessions in protecting patients with bipolar disorder (BD) or recurrent major depressive disorder (MDD) from developing depressive or manic relapses in a 12-month follow-up period., Methods: Twenty-four drug-resistant patients with a current depressive episode and a diagnosis of MDD or BD have been enrolled in the study. All the participants underwent daily dTMS sessions for 4 weeks. One group (maintenance - M group) received additional maintenance dTMS sessions weekly or twice a week., Results: After the first dTMS cycle, a significant reduction of Hamilton Depression Rating Scale (HDRS) scores was observed in all participants. Subsequently, the HDRS mean scores did not significantly change over time in the M group, while it significantly increased in the non-M-group after 6 and 12 months., Discussion: This study confirms previous evidence of a positive therapeutic effect of dTMS on depressive symptoms and suggests that, after recovery from acute episodes, maintenance dTMS sessions may be helpful in maintaining euthymia in a 12-month follow-up period.

Postpartum psychosis, which rarely presents with Capgras syndrome (delusional misidentification), requires rapid symptom resolution. First-line drugs have important drawbacks, such as delayed onset of clinical response and secretion in breast milk. In this report, we report successful treatment of a treatment-resistant woman presenting with treatment-resistant Capgras syndrome, with onset during postpartum. A 36-year-old woman had presented with Capgras syndrome during postpartum. For more than five years, she believed her son and other family members were substituted by impostors. All adequately administrated treatments were unsuccessful. We suggested electroconvulsive therapy to overcome treatment resistance. After six electroconvulsive therapy sessions, delusions of doubles subsided and other symptoms improved. She was discharged two weeks later with a mood stabilizer and low-dose atypical antipychotic combination and is well at the one-and-a-half-year follow-up. Electroconvulsive therapy followed by a mood stabilizer-antipsychotic drug combination showed rapid, permanent, and effective control of long-standing Capgras syndrome in a young woman., (© The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Several questions arise from the recent use of behavioral genetic research data in the courtroom. Ethical issues concerning the influence of biological factors on human free will, must be considered when specific gene patterns are advocated to constrain court's judgment, especially regarding violent crimes. Aggression genetics studies are both difficult to interpret and inconsistent, hence, in the absence of a psychiatric diagnosis, genetic data are currently difficult to prioritize in the courtroom. The judge's probabilistic considerations in formulating a sentence must take into account causality, and the latter cannot be currently ensured by genetic data., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The treatment of premenstrual dysphoric disorder (PMDD) is far from satisfactory, as there is a high proportion of patients who do not respond to conventional treatment. The antidiuretic sulfonamide, acetazolamide, inhibits carbonic anhydrase and potentiates GABAergic transmission; the latter is putatively involved in PMDD. We therefore tried acetazolamide in a series of women with intractable PMDD. Here, we describe a series of eight women diagnosed with DSM-IV-TR PMDD, five of whom had comorbidity with a mood disorder and one with an anxiety disorder, who were resistant to treatment and responded with symptom disappearance after being added-on 125 mg/day acetazolamide for 7-10 days prior to menses each month. Patients were free from premenstrual symptoms at the 12-month follow-up. We suggest that acetazolamide may be used to improve symptoms of PMDD in cases not responding to other treatments. GABAergic mechanisms may be involved in counteracting PMDD symptoms.

A 24-year-old man experiencing comorbid body dysmorphic disorder since age 16 years, complicated in recent months by a major depressive episode with psychotic features, showed resistance to various drug and psychotherapy combinations. We suggested electroconvulsive therapy (ECT) to overcome treatment resistance. After 1 ECT cycle, mood and anxiety symptoms improved significantly, delusional interpretations and ideas of reference subsided, and dysmorphophobic symptoms improved as well. Six months later, the patient was doing well with a mood stabilizer/antipsychotic combination. Electroconvulsive therapy may improve symptoms of comorbid body dysmorphic disorder along with mood improvement in treatment-resistant depressive disorder.

A 41-year-old man with comorbid binge-eating disorder, severe obesity, and bipolar disorder since the age of 20 years, resistant to drug and psychotherapy combinations, worsened progressively. Relentless weight gain forced him to immobility and dependence on others. He was hospitalized for a mixed-mood episode with anxiety, mystical delusions, and auditory hallucinations. To overcome treatment resistance, we suggested electroconvulsive therapy. After 1 electroconvulsive therapy cycle, psychological symptoms promptly improved. He received clozapine and lithium. After 2 years, he reached normal weight and fair psychopathological compensation.

Primary Objective: Early treatment of epilepsy is warranted to avoid possible severe consequences. This study aimed to assess the value of treatment in a patient who developed epilepsy after major brain surgery., Design: Case description. A 51 years-old man had a history of putative petit mal seizures since adolescence and left frontotemporal lobectomy after a major traffic accident at age 17. He subsequently developed quickly generalizing partial complex seizures, associated with severe behavioural alterations and personality changes; the condition was left untreated. A further seizure-related loss of consciousness led to another traffic accident at age 47., Methods and Procedures: The patient was administered 200 mg/day topiramate, 600 mg/day quetiapine, 1000 mg/day valproate, 1200 mg/day gabapentin and 800 mg/day carbamazepine., Main Outcomes and Results: The instituted anti-epileptic treatment reduced seizure frequency and severity, but did not affect psychiatric symptomatology, which even worsened. An association between anti-epileptic drugs with mood stabilizing properties and an atypical anti-psychotic dramatically improved psychiatric symptoms, but did not prevent the patient from needing long-term healthcare., Conclusions: Long-term untreated epilepsy may expose to accident proneness and further psychiatric deterioration. Early diagnosis and treatment of epilepsy may help in avoiding a potentially lethal vicious circle.

A young woman with bipolar I disorder and comorbid catatonia on enteral nutrition from several months, developed a form of near-lethal catatonia with weight loss, pressure sores, muscle atrophy, electrolyte imbalance, and depression of vital signs. A compulsory treatment was necessary, and informed consent was obtained from her mother for electroconvulsive therapy (ECT). After 7 ECT sessions, the patient recovered and resumed feeding. ECT may save the life of a patient with catatonia provided that legal obstacles are overcome. Clinicians should carefully evaluate patients with near-lethal catatonia, taking into account the risk of pulmonary embolism and other fatal events. The medical-legal issues, which vary across state regulations, should be addressed in detail to avoid unnecessary and potentially harmful delay in intervention.

In this work a methodology to fabricate carbon nanotube based electrodes using plasma enhanced chemical vapour deposition has been explored and defined. The final integrated microelectrode based devices should present specific properties that make them suitable for microelectrode arrays applications. The methodology studied has been focused on the preparation of highly regular and dense vertically aligned carbon nanotube (VACNT) mat compatible with the standard lithography used for microelectrode arrays technology.

Toscana virus (TOSV) infection may often cause symptomatic meningitides and encephalitides. These usually subside in few days and their sequelae do not last for more than few weeks. We here report the case of a 49-year-old man who developed encephalitis after being bitten by phlebotomi in a region near southern Tuscany, where TOSV is endemic, and who developed postencephalitic seizures and subsequently, persistent personality alterations, characterized by sexually dissolute behavior and aggressiveness. One year after infection, the patient needs a combination of an SSRI antidepressant and a mood stabilizer/anticonvulsant to obtain less than optimal symptom improvement. This points to the need of establishing better preventive measures in Tuscany and nearby regions.

Hepatic steatosis is a widespread condition of high prevalence in Western populations, and its asymptomatic nature represents a hefty problem in liver surgery and transplantation. Current diagnostic methods rely mainly on biopsy and blood tests, and are thus time consuming and expensive. Here we report the use of direct impedance measurements on liver tissue as a promising alternative to conventional diagnostic methods in surgery and transplantation. Working on a dual Zucker Fat (ZF), Zucker Lean (ZL) rat experimental model, we show that certain parameters extracted from multi-frequency impedance measurements correlate well with the presence of steatosis and that these results can be adequately approximated with bi-frequency measurements extracting the impedance modulus at 1 kHz and the impedance phase angle at 5.7 kHz. We further support our findings on a theoretical model of tissue impedance, and the simulations carried out suggest a possible mechanism to expound the negative effect of steatosis in post-transplant graft function.

It has been established in animal tests that this monitoring can be used as a reliable indicator of organ viability prior to implantation. The complete system has an easy-to-use interface, integrates seamlessly in a transport cool-box and conducts continuous, minimally invasive monitoring of the organ, making it a suitable tool for its intended clinical application. The system constitutes the starting point of a new line of equipment that, using custom multiprobe microsensors as core elements, will prompt the path towards new biomedical application niches in the field of microsystems.