Trichothecenes NIV and DON modulate the maturation of murinedendritic cells

Nivalenol (NIV) and Deoxynivalenol (DON), mycotoxins of the trichothecene family are considered very common food contaminants. In this work, we investigated whether the immunotoxic effects ascribed to these trichothecenes may be mediated by perturbations in the activity of dendritic cells (DCs). Murine bone marrow-derived DCs were used to evaluate the effects of NIV and DON on the LPS-induced maturation process.We found that the expression of the class II MHC and of the accessory CD11c molecules, but not of the costimulatory CD86 marker, was down-regulated by NIV and DON exposure in LPS-treated DCs, as well as nitric oxide (NO) production. Interestingly, NIV, but not DON, induced DC necrosis. Moreover, the analysis of the cytokine pattern showed that IL-12 and IL-10 expressions induced by LPS exposure were suppressed by both trichothecenes in a dose-dependent fashion. On the other hand, the secretion of the proinflammatory cytokine TNFa was increased as a direct consequence of DON and NIV exposure. Taken together, our data indicated that the immunotoxicity of NIV and DON was related to the capacity of both trichothecenes to interfere with phenotypic and functional features of maturing DCs

Layered Na0.71CoO2: a powerful candidate for viable and high performance Na-batteries

The present study reports on the synthesis and the electrochemical behavior of Na0.71CoO2, a promising candidate as cathode for Na-based batteries. The material was obtained in two different morphologies by a double-step route, which is cheap and easy to scale up: the hydrothermal synthesis to produce Co3O4 with tailored and nanometric morphology, followed by the solid-state reaction with NaOH, or alternatively with Na2CO3, to promote Na intercalation. Both products are highly crystalline and have the P2-Na0.71CoO2 crystal phase, but differ in the respective morphologies. The material obtained from Na2CO3 have a narrow particle length (edge to edge) distribution and 2D platelet morphology, while those from NaOH exhibit large microcrystals, irregular in shape, with broad particle length distribution and undefined exposed surfaces. Electrochemical analysis shows the good performances of these materials as a positive electrode for Na-ion half cells. In particular, Na0.71CoO2 thin microplatelets exhibit the best behavior with stable discharge specific capacities of 120 and 80 mAh g-1 at 5 and 40 mA g-1, respectively, in the range 2.0–3.9 V vs. Na+/Na. These outstanding properties make this material a promising candidate to construct viable and high-performance Na-based batteries

A case of bilateral luxatio erecta

Luxatio erecta is an uncommon form of glenohumeral dislocation. Cases of bilateral inferior shoulder dislocation (luxatio erecta) are very rare, and only ten cases have been described in literature. We describe a case of a woman with bilateral luxatio erecta of the shoulders treated with close reduction, immobilization and rehabilitation. The patient had fallen downstairs while clinging to both lateral banisters

Combinations of QT-prolonging drugs: towards disentangling pharmacokinetic and pharmaco-dynamic effects in their potentially additive nature.

Background: Whether arrhythmia risks will increase if drugs with electrocardiographic (ECG) QT-prolonging properties are combined is generally supposed but not well studied. Based on available evidence, the Arizona Center for Education and Research on Therapeutics (AZCERT) classification defines the risk of QT prolongation for exposure to single drugs. We aimed to investigate how combining AZCERT drug categories impacts QT duration and how relative drug exposure affects the extent of pharmacodynamic drug–drug interactions. Methods: In a cohort of 2558 psychiatric inpatients and outpatients, we modeled whether AZCERT class and number of coprescribed QT-prolonging drugs correlates with observed rate-corrected QT duration (QTc) while also considering age, sex, inpatient status, and other QTc-prolonging risk factors. We concurrently considered administered drug doses and pharmacokinetic interactions modulating drug clearance to calculate individual weights of relative exposure with AZCERT drugs. Because QTc duration is concentration-dependent, we estimated individual drug exposure with these drugs and included this information as weights in weighted regression analyses. Results: Drugs attributing a ‘known’ risk for clinical consequences were associated with the largest QTc prolongations. However, the presence of at least two versus one QTc-prolonging drug yielded nonsignificant prolongations [exposure-weighted parameter estimates with 95% confidence intervals for ‘known’ risk drugs + 0.93 ms (–8.88;10.75)]. Estimates for the ‘conditional’ risk class increased upon refinement with relative drug exposure and coadministration of a ‘known’ risk drug as a further risk factor. Conclusions: These observations indicate that indiscriminate combinations of QTc-prolonging drugs do not necessarily result in additive QTc prolongation and suggest that QT prolongation caused by drug combinations strongly depends on the nature of the combination partners and individual drug exposure. Concurrently, it stresses the value of the AZCERT classification also for the risk prediction of combination therapies with QT-prolonging drugs

L’utilizzo del denosumab nel tumore a cellule giganti e relativi effetti sul trattamento chirurgico

Background. Dopo l’introduzione del denosumab nel trattamento del Tumore a Cellule Giganti (TCG) diversi autori ne hanno descritto l’utilizzo, mentre meno sono i lavori che correlano l’utilizzo del farmaco associato all’intervento chirurgico valutandone in particolare tempistica chirurgica, tipo di intervento e tasso complessivo di morbilità. Riportiamo l’esperienza dell’Ortopedia Oncologica dell’AOUC Firenze agli effetti sul trattamento chirurgico nei pazienti trattati con denosumab pre- e postoperatorio. Obiettivi. Scopo di questo studio è la valutazione della casisitica di pazienti dell’Ortopedia Oncologica dell’AOU Careggi con TCG trattati con denosumab e il relativo effetto sul trattamento chirurgico. Materiali e metodi. Dal 2010 al 2014 abbiamo trattato 91 pazienti con TCG, 25 di questi sono stati trattati con denosumab 120 mg. Lo schema di trattamento ha previsto denosumab 120 mg nel preoperatorio 1 fl sc ogni 4 settimane per una media di 3,9 mesi (con un minimo di 3 e un massimo di 6) e a seguire denosumab postoperatorio ogni 4 settimane per 6 mesi. 6 pazienti hanno effettuato un trattamento neoadiuvante, 6 adiuvante, 12 neoadiuvante e adiuvante, 1 paziente trattato alla recidiva. La tempistica dell’intervento chirurgico è stata decisa basandosi sulla clinica e valutando la diagnostica per immagini per la valutazione della risposta alla terapia (in accordo con i criteri RECIST). Risultati. Tutti i pazienti erano valutabili, 12 donne e 13 uomini con età media di 35 anni (range 19-72); per la maggior parte la localizzazione del TCG era agli arti inferiori (n = 7 femori distali, n = 1 femori prossimali, n = 3 tibie distali, n = 3 tibie prossimali, n = 2 peroni prossimali, n = 1 rotula, n = 1 calcagno), 5 nell’arto superiore (n = 1 omero distale, n = 2 radio distale, n = 1 radio prossimale, n = 1 dito mano), 1 nel sacro e 1 nell’ala iliaca. 24 pazienti sono stati trattati per lesione primitiva ed un paziente alla recidiva. Tutti i pazienti sono stati trattati chirurgicamente, 19 con curettage (76%), 5 con la resezione (20%), 1 con escissione tessuti molli (4%). conclusioni. Il denosumab si è mostrato efficace nella pratica clinica riducendo le dimensioni delle lesioni, rendendo possibile una procedura chirurgica meno invasiva e una buona preservazione della funzionalità articolare. Nonostante i risultati incoraggianti c’è da tener presente che il farmaco cambia la tecnica chirurgica con la necessità di una chirurgia “paziente specifica” e che le indicazioni di utilizzo del farmaco sono ancora confuse rendendo necessari studi in cieco e a lungo termine per confermare i tempi del trattamento e le possibili complicazioni nel lungo periodo riguardo l’utilizzo del farmaco

Optimal hysteresis control via a queueing system with two heterogeneous energy-consuming servers

A queueing system having two different servers is under study. Demands enter the system according to a Markov Arrival Process. Service times have phase-type distribution. Service of demands is possible only if the fixed number of energy units, probably different for two servers, is available in the system at the potential service beginning moment. Energy units arrive in the system also according to a Markov Arrival Process and are stored in a stock (battery) of a finite capacity. Leakage of energy units from the stock can occur. Demands waiting in the infinite buffer are impatient and can leave the buffer after an exponentially distributed waiting time. One server is the main one and permanently provides service when the buffer is not empty and the required number of energy units is available. The second server is the assistant server and is switched on or off depending on the availability of energy units and queue length according to the hysteresis strategy defined by two thresholds. The assistant server is switched on when the queue length is not less than the greater threshold and is switched off when the queue length becomes smaller than the smaller threshold. The use of the assistant server has to be paid. Thus, the problem of the optimal selection of the thresholds defining the control strategy naturally arises. To solve this problem, the study of the behavior of the system under any fixed values of the parameters of the control strategy is necessary. Such a study is given in this paper. Numerical results are presented. They illustrate the feasibility of computer realization of the developed algorithms for computation of the stationary distribution of the system states and the main key performance indicators as well as the result of solving one of the possible optimization tasks

Analysis of a retrial queue with group service of impatient customers

A single-server retrial queue with a MAP flow, PH service times and a pool of finite capacity for accumulation of the customers and their group service is considered. Service to the next group is not provided until the number of customers in the pool will reach a certain predefined threshold value. The service time of a group depends on its size and it is less than the sum of the individual service times. The dependencies of the basic performance measures of the system on the capacity of the pool and the threshold are obtained. Numerical results are presented. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature

Disuse osteoporosis and hip prosthesis: Surgical implications, a case report

In this paper, the authors present a case of osteo-arthtritis of the hip secondary to a septic event which was surgically treated with a hip prosthesis and complicated by intraoperative fracture due to a localized disuse osteoporosis. Disuse osteoporosis is an induced rapid bone loss in human skeleton that occurs mostly after a cord injury or muscle paralysis. Hypodynamia can also be a risk factor for osteoporosis. In this case the author describe the onset of a femoral intraoperative fragility fracture in a 58 year old woman affected by an erosive septic osteoarthritis. Our case suggest that disuse osteoporosis presence should be diagnosed and treated before surgery to help prevent major surgical or post-operative complications beginning a pharmacological antiresorptive treatment before the surge