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This paper presents the computation of three-level optimized pulse patterns (OPPs) that limit the common-mode voltage (CMV) and generate currents with low harmonic distortions. This is achieved by relaxing the symmetry properties of conventional OPPs and by reformulating the associated optimization problem accordingly. As demonstrated by the presented numerical results for a three-level converter driving a medium-voltage (MV) induction machine, the computed OPPs not only limit the CMV but also produce very low harmonic distortions, in some cases even lower than those of conventional OPPs. Experimental results based on a scaled-down, low-voltage (LV) drive system serve as a proof of concept, highlighting the benefits of the proposed OPPs.

This paper presents a control method for medium-voltage (MV) drive systems consisting of a three-level neutral-point-clamped (NPC) inverter and an induction machine. The proposed approach aims to achieve stator current reference tracking and balancing of the neutral point (NP) potential in one computational stage, without the help of additional control loops. To this end, a model predictive control (MPC) algorithm, designed as a multiple-input multiple-output (MIMO) controller, manipulates optimized pulse patterns (OPPs) in real time. As a result, minimal current harmonic distortions are produced, while the NP potential is kept balanced both during steady-state and transient operating conditions. The effectiveness of the proposed control approach is validated in a real-time system by simulating the MV drive of interest in a hardware-in-the-loop (HIL) setting.

This article proposes the computation of three-level optimized pulse patterns (OPPs) that achieve not only low harmonic load current distortions (load-friendly operation) but also low semiconductor losses (converter-friendly operation). To this end, the conduction and switching losses are modeled as a function of the OPP switching angles and the amplitude and phase of the converter current. By minimizing the current harmonics subject to an inequality constraint on the semiconductor losses, OPPs are derived that achieve minimal current distortions with a guaranteed upper bound on the semiconductor losses, thus ensuring the safe operation of the semiconductor switches within their thermal limits. Detailed numerical results for a medium-voltage system consisting of a neutral-point-clamped converter and an inductive load verify the benefits of this approach.

This article focuses on indirect model predictive control (MPC) for variable speed drives, such as induction and synchronous machine drives. The optimization problem underlying indirect MPC is typically written as a standard constrained quadratic programming (QP) problem, which requires a QP solver to find the optimal solution. Although many mature QP solvers exist, solving the QP problems in industrial real-time embedded systems in a matter of a few tens of microseconds remains challenging. Instead of using the complex general-purpose QP solvers, this article proposes a geometrical method for isotropic machine drives and an analytical method for anisotropic machine drives to find the optimal output voltage. This is done by examining and subsequently exploiting the geometry of the associated optimization problems. Both methods are simple, and easy to implement on industrial control platforms. The effectiveness of the proposed geometrical and analytical methods is demonstrated by experimental results for an induction machine drive and an interior permanent-magnet synchronous machine drive, respectively.

This article develops an observer-augmented multistep model predictive control strategy with finite-control-set principle to improve the robustness of the control loop against disturbances, including external disturbances, parameter mismatches, and model uncertainties. The influence of the parameter mismatches on the multistep finite-control-set model predictive control is first discussed via simulations and quantified by analyzing the probability of suboptimality. Furthermore, in order to compensate for these effects, the disturbances are included in the system model of the control problem as an extended state and estimated with a disturbance observer. The estimated disturbances as well as the system states are then delivered to the optimization problem of the current control and incorporated for the computation of the solution. The proposed method is then implemented on a dSPACE system and tested under several scenarios. The effectiveness of the proposal is validated with experimental results.

This article presents a direct model predictive control (MPC) scheme for drive systems consisting of a three-phase three-level neutral-point-clamped inverter and an induction machine. Even though the discussed MPC algorithm is a direct control strategy, it operates the inverter at a fixed switching frequency, while the output harmonic spectrum of the stator current is discrete, with harmonics at nontriplen, odd integer multiples of the fundamental frequency. As a result, the proposed method achieves similar or superior steady-state behavior than that of modulator-based control schemes. Moreover, thanks to its direct control nature, it exhibits the fast transient responses that characterize direct controllers due to the absence of an explicit modulator. Furthermore, the multiple control objectives of the system, i.e., stator current control and neutral-point potential balancing, are addressed in one computational stage, thus avoiding any additional control loops in a cascaded or parallel structure. This favorable control structure is facilitated by the adopted modeling approach, according to which the system behavior is described by the gradient of the system output. In doing so, not only a simple, versatile system model is derived, but also the direct MPC can be formulated as a constrained quadratic program, which can be easily solved in real time with an in-house solver. The effectiveness of the proposed control scheme is experimentally verified on a 4-kW drive system.

Model-predictive control (MPC) has emerged as a promising control method in power electronics, particularly for multiobjective control problems such as multilevel inverter (MLI) applications. Over the past two decades, improving the performance of MPC and tackling its technical challenges, such as computational load, modeling accuracy, cost function design, and weighting factor selection, have attracted great interest in power electronics. This article aims to discuss the current state of MPC strategies for MLI applications, describing the significance of each challenge with the reported effective solutions. Through this review, the MPC methods are categorized into two groups: direct MPC (without modulator) and indirect MPC (with modulator). The recent advances of each category are presented and analyzed, focusing on direct MPC as the most applied method for MLI topologies. In addition, some of the important concepts are experimentally validated through a case study and compared under the same operating conditions to evaluate the performance and highlight their features. Finally, the future trends of MPC for MLI applications are discussed based on the current state and reported developments.

Objectives: Data on COVID-19 in patients with interstitial lung disease are scarce and whether SARS-CoV-2 may trigger interstitial lung disease progression remains unknown. We aimed to analyze outcomes of COVID-19 in patients with systemic sclerosis–associated interstitial lung disease, including possible thoracic radiographic progression.Patients and Methods: All 43 patients with systemic sclerosis–associated interstitial lung disease followed in our center (mean ± SD, 55.2 ± 11.6 years, 36 female) with confirmed SARS-CoV2 infection up to 1 September 2022 were analyzed. Individual interstitial lung disease extent on high resolution CT (HRCT) performed before (up to 3 months) and after COVID-19 (2–5 months) was compared.Results: At SARS-CoV-2 infection, 9/43 patients were unvaccinated, whereas 5, 26, and 3 had received 2, 3, or 4 doses of an mRNA vaccine, respectively. Thirty-one patients were either on monotherapy with immunosuppressives (mycophenolate, n= 7; cyclophosphamide, n= 2; methotrexate, n= 10; tocilizumab, n= 7; rituximab, n= 1; etanercept, n= 1), or their combinations (n= 3). Eight patients (20%), of whom four unvaccinated, required hospitalization for pneumonia and three (7%) died of acute respiratory failure (n= 2, both unvaccinated) or cardiac arrest. Lack of vaccination was the only independent predictor for hospitalization (OR = 7.98, 95% CI: 1.25–51.09) and marginally for death (OR = 32.7, 95% CI: 0.97–1110.98), regardless of the presence of diffuse systemic sclerosis, interstitial lung disease extent greater than 20% or immunosuppressive treatment. In 22 patients with available HRCT pairs (vaccinated = 20), the interstitial lung disease extent before COVID-19 (20.4%± 17.8%) remained unchanged (22.4% ± 18.5%) in all but one patient.Conclusion: SARS-CoV-2 vaccination is of outmost importance for every systemic sclerosis patient with interstitial lung disease. COVID-19 does not seem to promote progression of systemic sclerosis–associated interstitial lung disease in vaccinated patients, but further studies are warranted.

Digital health interventions are effective for hypertension self-management, but a comparison of the effectiveness and implementation of the different modes of interventions is not currently available. This study aimed to compare the effectiveness of SMS, smartphone application, and website interventions on improving blood pressure in adults with hypertension, and to report on their reach, uptake, and feasibility.

Digital health interventions have shown promising results for the management of type 2 diabetes, but a comparison of the effectiveness and implementation of the different modes is not currently available. Therefore, this study aimed to compare the effectiveness of SMS, smartphone application, and website-based interventions on improving glycaemia in adults with type 2 diabetes and report on their reach, uptake, and feasibility.

This article investigates an innovative modulation technique for a predictive control applied to a synchronous reluctance motor (SyRM) drive. The new formulation of the duty cycles, in both linear and overmodulation regions, relies on the identified flux-versus-current characteristics. Furthermore, integral terms have been introduced in the predictive control to achieve satisfactory reference tracking performance with zero steady-state error, even under model parameters mismatches. Low current ripple with smooth and fast dynamic responses are achievable at fixed switching frequency over the whole current operating range. Simulations and experimental evidence show the effectiveness of the proposed controller against standard controllers such as field-oriented current control (FOC) and deadbeat current control (DBCC), guaranteeing low current ripple, robustness against parameters variations, and fast dynamic performance.

This article proposes a direct model predictive control (MPC) scheme for asymmetric six-phase permanent magnet synchronous machines (PMSMs), which combines control and modulation in one computation stage. By emulating the switching pattern of space vector modulation (SVM), the MPC problem is formulated as a 4-D current control problem where the switching sequences and instants are computed and directly applied to the inverters. This implicit modulation addresses the issue of a variable switching frequency and spread harmonic spectra of conventional direct MPC methods. Moreover, the effect of the modulation constraints and controller bandwidth on the system performance is investigated as well. To verify the effectiveness of the proposed control strategy, experiments are carried out with an asymmetric six-phase PMSM driven by two three-phase two-level inverters.

The steady increase in energy demands has led to ever-increasing “energy generation.” This, coupled with the need for higher efficiency, flexibility, and reliability, has boosted the use of power electronics in power and energy systems. Therefore, power electronics-based energy conversion systems (PEECSs) have become prominent in power generation, power transmission, and end user applications. Given the relevance of such systems, and by considering their trend of digitalization, it is crucial to establish digital and intelligent PEECSs. To this end, digital twins (DTs) can be adopted, as they integrate many cutting-edge information techniques to realize the life cycle management of complex systems by constructing real-time mappings of them. In this article, existing DT techniques for PEECSs are reviewed. The concept, system layers, and key technologies of DTs are described first. Some application cases of DTs are then elaborated. Finally, future trends and challenges of DTs are discussed to provide a valuable reference for subsequent research.

This paper proposes a long-horizon direct model predictive control (MPC) with reference tracking for medium-voltage (MV) drives that achieves favorable steady-state and transient behavior. However, as MPC is a model-based method, it is susceptible to parameter mismatches and variations of the machine. Moreover, even though a long prediction horizon significantly improves the steady-state behavior of the drive, it significantly increases the computational complexity of the direct MPC problem, rendering its real-time implementation a challenging—if not impossible—task. Motivated by these shortcomings of long-horizon direct MPC, this paper also aims to address them by enhancing the robustness of the developed control strategy, while keeping its computational complexity modest. To achieve the former, a prediction model suitable for MV drive systems is adopted that facilitates the effective estimation of the total leakage inductance of the machine. For the latter, the objective function of the MPC problem is formulated such that, even though the drive behavior is computed over a long prediction interval, only a few changes in the candidate switch positions are considered. The effectiveness of the proposed modeling, control, and estimation approaches is validated with hardware-in-the-loop (HIL) tests for an MV drive consisting of a three-level neutral point clamped (NPC) inverter and an induction machine (IM).

This paper investigates a finite-control set model-predictive control (FCS-MPC) algorithm to enhance the performance of a synchronous reluctance machine drive. Particular emphasis is placed on the definition of the cost function enabling a computationally light implementation while targeting good transient and steady-state performance. In particular, this work proposes the inclusion of an integral term into the cost function to ensure zero steady-state errors thus compensating for any model inaccuracies. A control effort term is also considered in the formulation of the cost function to achieve a high ratio between the sampling frequency and the average switching frequency. After a comprehensive simulation study showing the advantages of the proposed approach over the conventional FCS-MPC for a wide range of operating conditions, several experimental test results are reported. The effectiveness of the proposed control approach, including a detailed analysis of the effect of the load and speed variations, is thus fully verified providing useful guidelines for the design of a direct model predictive controller of synchronous reluctance motor drives.

The SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker.

Acute cholecystitis is a life-threatening emergency in elderly patients. This population-based cohort study aimed to evaluate the commonly used management strategies for elderly patients with acute cholecystitis as well as resulting mortality and re-admission rates. Data from all consecutive elderly patients (≥ 80 years) admitted with acute cholecystitis in England from 1997 to 2012 were captured from the Hospital Episode Statistics database. Influence of management strategies upon mortality was analyzed with adjustment for patient demographics and treatment year. 47,500 elderly patients were admitted as an emergency with acute cholecystitis. On the index emergency admission the majority of patients (n= 42,620, 89.7%) received conservative treatment, 3539 (7.5%) had cholecystectomy, and 1341 (2.8%) underwent cholecystostomy. In the short term, 30-day mortality was increased in the emergency cholecystectomy group (11.6%) compared to those managed conservatively (9.9%) (p< 0.001). This was offset by the long-term benefits of cholecystectomy with a reduced 1-year mortality [20.8 vs. 27.1% for those managed conservatively (p< 0.001)]. Management with percutaneous cholecystostomy had increased 30-day and 1-year mortality (13.4 and 35.0%, respectively). The annual proportion of cholecystectomies performed laparoscopically increased from 27% in 2006 to 59% in 2012. Within the cholecystectomy group, laparoscopic approach was an independent predictor of reduced 30-day mortality (OR 0.16, 95% CI 0.10–0.25). Following conservative management, there were 16,088 admissions with further cholecystitis. Only 11% of patients initially managed conservatively or with cholecystostomy received subsequent cholecystectomy. Acute cholecystitis is associated with significant mortality in elderly patients. Potential benefits of emergency cholecystectomy in selected elderly patients include reduced rate of readmissions and 1-year mortality. Laparoscopic approach for emergency cholecystectomy was associated with an 84% relative risk reduction in 30-day mortality compared to open surgery.

Background. High-flow nasal cannula (HFNC) is an oxygen delivery method shown to reduce the risk of intubation and mortality in patients with type 1 respiratory failure. The ROX-index score can predict HFNC failure. This study aims to evaluate sequential ROX-index assessments as predictors of HFNC failure and mortality. Methods. Prospective observational single-center study including all adult patients with positive SARS-CoV-2 PCR placed under HFNC from 1st November 2020 to 31st May 2021, and patients with hemodynamic instability or unable to tolerate HFNC were excluded. The primary endpoint was successful HFNC de-escalation. Results. In univariate analysis, HFNC de-escalation was associated with younger age (59.2 ± 14 vs. 67.7 ± 10.5 and p<0.001), lower levels of serum lactate (1.1 vs. 1.5 and p=0.013), and higher ROX-index at 12 hrs (5.09 vs. 4.13 and p<0.001). ROC curve analysis of ROX-index at 12 hrs yielded a c-statistic of 71.2% (95% CI 61.6–80.9 and p<0.001). ROX-index at 12 hrs and age retained significance in multivariate analysis. Using an optimal cutoff point of 4.43, we calculated a sensitivity of 64.5% and specificity of 69.6%. In univariate survival analysis, older age (68.8 ± 9.7 vs. 58.9 ± 13.9 and p<0.001), greater creatinine values (0.96 vs. 0.84 and p=0.022), greater SOFA score (p=0.039), and a lower 12 hrs ROX-index (4.22 vs. 4.95 and p=0.02) were associated with hospital mortality. The SOFA score and age retained significance in multivariate survival analysis. Conclusion. ROX-index is proven to be a valuable and easy-to-use tool for clinicians in the assessment of COVID-19 patients under HFNC.

Background: The value of normal C-reactive protein (CRP) in psoriatic arthritis (PsA) is debatable.Objectives: To test the hypothesis that CRP is frequently normal in contemporary real-world PsA patients, despite active disease.Design: In this cross-sectional study, patients were divided into two groups: CRP ⩽ 0.5 mg/dl (normal) and CRP > 0.5 mg/dl (increased). Having as dependent variable the CRP status, these groups were compared for disease-related features, including composite disease activity indices [clinical Disease Activity in PSoriatic Arthritis (cDAPSA) and minimal disease activity (MDA)] and patient-reported outcomes (PROs). Agreement between CRP status and cDAPSA/MDA scores was calculated (Cohen’s kappa).Methods: Data from consecutive PsA patients attending two outpatient rheumatology clinics (January 2019–June 2021) were analysed.Results: From 128 patients enrolled (51.6% females; mean ± standard deviation age: 53.4 ± 11.7 years; 23.4%, 48.4% and 64.1% treated with glucocorticoids, conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biologic DMARDs, respectively), two-thirds (66.4%, n= 85) had normal CRP values. CRP status was not associated with any of the disease-related parameters and PROs, but only with ESR [odds ratio: 1.04 (95% confidence interval: 1.01–1.06), p= 0.005]. Among patients with normal CRP, 45.9% (39/85) were on non-MDA state, while 21.2% (18/85) had cDAPSA-moderate and 5.9% (5/85) had cDAPSA-high disease activities. Conversely, 54.2% (39/72) of patients on non-MDA state and 52.3% (23/44) of those with cDAPSA-moderate or cDAPSA-high disease activity had normal CRP values. Cohen’s kappa between normal CRP and MDA, cDAPSA-remission, and cDAPSA-remission/low disease activity was –0.26, –0.21 and –0.22, respectively, displaying total disagreement.Conclusion: Normal CRP in PsA should not be used as surrogate marker of remission or low/MDA, therefore needs to be interpreted with caution in clinical decision-making.

Calcium channel blockers (CCBs) have a narrow therapeutic index, and their intake in excess is associated with a critical clinical presentation of sustained hypotension and non-cardiogenic pulmonary edema, which are difficult to treat. Unfortunately, the available treatments fail to resuscitate a significant number of patients poisoned by CCBs, rendering them the main cardiovascular drugs involved in death due to overdose. Importantly, in all cases reported until now in the literature, CCB intoxication was known at the time of patients' presentation and the medical challenge solely consisted of the therapeutic approach. In this case report, we describe our experience in treating a 72-year-old patient with recurrent episodes of sustained hypotension refractory to crystalloid and vasoconstrictor infusions. Prolonged pharmacologic support and intermittent sessions of hemofiltration induced stabilization and recovery. The results of an extensive diagnostic workup to elucidate the cause were unfruitful. The recurrent and paroxysmal nature of the clinical presentation along with its incidence after the patient left the protected setting of the hospital led the diagnostic approach to search for a possible external factor, which was shown to be, after toxicological investigation, unintentional amlodipine intoxication.

This paper introduces an approach to include a variable switching time point into predictive torque control (PTC). In PTC, the switching frequency is limited by the sampling frequency; its theoretical maximum value is half the sampling frequency. However, in reality the switching frequency is lower than this value, and thus, high current and torque ripples occur compared with modulator-based control methods. In order to overcome this, an optimization problem is formulated and solved in real time. Thereby, apart from the regulation of the torque and the flux magnitude to their references, an additional control objective should be met: the minimization of the torque ripple. To do so, the time point at which the switches of the inverter should change state is calculated. Further advantages of the proposed method include the design flexibility and great performance during transients. Experimental results that verify the performance of the presented control strategy are included.

A model predictive control (MPC) algorithm for dc–dc boost converters is proposed in this paper. The proposed control scheme is implemented as a current-mode controller. Two control loops are employed, with the inner loop being designed in the framework of MPC. Two different objective functions are formulated and investigated. The control objective, i.e., the regulation of the current to its reference, is achieved by directly manipulating the switch, thus a modulator is not required. As a prediction model, a hybrid model of the converter is used, which captures precisely the continuous and the discontinuous conduction modes. The proposed control strategy achieves very fast current regulation, while exhibiting only a modest computational complexity. Simulation and experimental results substantiate the effectiveness of the proposed approach.

To evaluate the rate of complications and the risk factors in relation to the extent of surgery in patients undergoing thyroidectomy in a tertiary university center. Data were collected retrospectively from 2,043 consecutive patients who underwent thyroid surgery for various thyroid diseases at the University Hospital of Patras, Greece, between January 1996 and December 2007. Recurrent laryngeal nerve palsy (RLNP) and hypoparathyroidism were set as the primary end points, while hematoma and wound infection were set as the secondary endpoints. Total, near-total and subtotal thyroidectomy was performed in 1,149, 777 and 117 patients, respectively. Transient RLNP occurred in 34 (1.6%) and permanent in 19 (0.9%) patients. Multivariate logistic regression analysis showed that extended resection (OR-odds ratio-1.6), Graves’ disease (OR 2.7), thyroiditis (OR 2.1), recurrent goiter (OR 2.3) and thyroid malignancy (OR 1.7) were all independent risk factors for transient RLNP, whereas Graves’ disease (OR 2.2) and recurrent goiter (OR 1.7) emerged as independent risk factors for permanent RLNP. The rates of transient and permanent hypoparathyroidism were 27.8% and 4.8%, respectively. Multivariate analysis for transient hypoparathyroidism revealed that the extent of surgical resection (OR 2.2), Graves’ disease (OR 2.1), recurrent goiter (OR 1.7), female gender (OR 1.5) and specimen weight (OR 1.6) were independent predictors.-However, the extent of surgical resection (OR 2.7), Graves’ disease (OR 1.8), recurrent goiter (OR 1.5) and malignant disease (OR 1.5) were independent risk factors for permanent hypoparathyroidism. Postoperative wound infection and hematoma occurred in 6 (0.3%) and 27 (1.3%) patients, respectively. No correlation was observed between wound infection or postoperative hemorrhage and the extent of surgery. Despite the higher morbidity, total thyroidectomy is emerging as an attractive surgical option even for benign thyroid disease due to the risk of subclinical (occult) malignancy, the possibility of goiter relapse as well as of the increased risk of complications following reoperation.

Laparoscopy has been widely accepted among surgeons for the diagnosis and management of acute abdominal conditions. In this study, we aim to evaluate and summarize the experience in laparoscopic procedures, both diagnostic and interventional, for emergency nontraumatic abdominal conditions, in a tertiary academic center.

Importance of the field:Among various human CYPs, CYP2E1 is of particular interest because of its involvement in the metabolic activation of many low molecular mass procarcinogens. CYP2E1 induction, which may be a consequence of genetic polymorphism or/and gene induction by xenobiotics, is the first step leading to the development of certain chemically-mediated cancers. The aim of this review is to outline the current knowledge on chemically-induced cancers through activation by CYP2E1, with emphasis on the association between polymorphisms of the CYP2E1 gene and incidence of different neoplasias.Areas covered in this review:Literature searches of MEDLINE (1966 to July 2009) for English articles in CYP2E1-induced carcinogenesis were conducted.What the reader will gain:CYP2E1 genetic polymorphisms leading to enhanced CYP2E1 gene transcription have been associated with increased risk of development of malignant tumours, through increased biotransformation of procarcinogens. Likewise, long-term intake of CYP2E1 inducers, such as ethanol, isoniazid, various solvents and chemicals, also increase the probability of developing malignancy, especially for carriers of certain CYP2E1 alleles.Take home message:Genetic screening for CYP2E1 ‘carcinogenic’ polymorphisms and CYP2E1 phenotype determination of susceptible subjects, as well as the development of effective CYP2E1 inhibitors, could be a future perspective towards prevention of CYP2E1-mediated cancers.

Disulfiram is used in the treatment of chronic alcoholism, because of the unpleasant symptoms it provokes after ethanol intake. The underlying mechanism is believed to be the accumulation of acetaldehyde in the blood, due to inhibition of the liver aldehyde dehydrogenases. In addition, it is known that disulfiram also has some neurotoxic properties. The aim of our study was to investigate the relationship between the pharmacological and neurotoxicological properties of disulfiram with respect to the doses applied. Increasing doses of disulfiram (25, 50, 75, 100 and 150 mg/kg) were administered intraperitoneally to Wistar rats and the hepatic enzyme activities of alcohol and aldehyde dehydrogenases were measured. Also, in two brain subregions (midbrain and hypothalamus) the levels of noradrenaline, dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid were determined. The higher dose of disulfiram (150 mg/kg) produced lethal effects in all treated animals. Aldehyde dehydrogenase activities were inhibited by disulfiram in a dose-dependent way, while alcohol dehydrogenase was not affected at all. Concerning the levels of brain biogenic amines, disulfiram produced a significant reduction in noradrenaline and an increase in dopamine levels in both structures of the brain, in a dose-dependent way. However, the lowest dose applied (25 mg/kg) had no effects on brain catecholamines. It is known that high doses of disulfiram may cause severe encephalopathy and peripheral neuropathy in humans, which could be attributed to the impairment of the metabolism of brain biogenic amines, due to inhibition of dopamine-β-hydroxylase. Our experimental data show that disulfiram affects the level of brain biogenic amines at dose levels higher than those inhibiting the activity of aldehyde dehydrogenase. Therefore, in clinical practice ‘disulfiram reaction’ could still be achieved with a low dosage regimen not producing neurotoxicity.

Male breast cancer represents approximately 1% of all breast cancer cases. Due to the low disease incidence, even the largest reported studies have included a limited number of cases. Therefore, there is a lack of extensive experience as far as the etiology, therapeutic modalities and prognosis of this disease are concerned.

Although a common cause of intestinal obstruction in children, intussusception is a rare event in the adult population living in temperate regions. It has long been known that various acquired immune deficiency syndrome related conditions of the bowel such as lymphoma, lymphoid hyperplasia, cytomegalovirus colitis and Kaposi's sarcoma can lead to intussusception. The diagnosis is particularly difficult in this population of patients due to the non-specific nature of the symptoms as well as the depressed immune response obscuring inflammation or ischemia. Though the reported acquired immune deficiency syndrome associated cases of intussusception refer to patients with known human immunodeficiency virus infection, in our case we present an intestinal intussusception as the first manifestation of human immunodeficiency virus infection.

The sensitivity of breast neoplasms to hormonal control provides the basis of novel investigational treatments with steroidal alkylators. An androsterone D-lactam steroidal ester, the 3β-hydroxy-13α-amino-13,17-seco- 5α-androstan-17-oic-13,17-lactam, p-bis(2-chloroethyl)amino phenyl acetate (lactandrate) was synthesized and tested for antitumor activity against six human breast cancer cell lines in vitroand against two murine and one xenograft mammary tumors in vivo. A docking study on the binding interactions of lactandrate with the ligand-binding domain (LBD) of estrogen receptor-alpha (ERα) was inquired. In vitrotesting of lactandrate cytostatic and cytotoxic activity was performed on T47D, MCF7, MDA-MB-231, BT-549, Hs578T, MDA-MB-435 breast adenocarcinoma human cell lines. In vivotesting was performed on two murine mammary tumors, the MXT tumor and CD8F1 adenocarcinoma, as well as on human mammary carcinoma MX-1 xenograft. Molecular modeling techniques were adopted to predict a possible location and interaction mode of the molecule into LBD. Lactandrate induced significantly high antitumor effect against all tested in vitroand in vivomodels. The cell lines with positive ER expression found to be significantly more sensitive to lactandrate. Moreover, lactandrate found to be positioned inside the binding cavity with its steroidal moiety, whilst the alkylating moiety protrudes out of receptor’s pocket. Lactandrate produced important anticancer activity on breast cancer in vitroand in vivo. Some correlation between ER and lactandrate effect was demonstrated. Docking studies provide the basis for the structure-based design of improved steroidal alkylating esters for the treatment of estrogen-related cancers.