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In 20 patients with lymphoproliferative disease of granular lymphocytes (LDGL) the cytotoxic in vitro function of peripheral blood mononuclear cells was studied against both NK sensitive (K-562) and NK resistant target cells (Daudi). Cytotoxicity was analysed at resting conditions and after in vitro pre-incubation with recombinant α2-interferon, γ-interferon and interleukin 2. At resting conditions, a heterogeneous cytotoxic picture was observed against the K-562 targets, with 11 of the 20 patients showing a normal or increased NK activity, and nine an impaired function. Against the Daudi targets, unstimulated cells from all patients displayed a normal cytotoxic activity. Following in vitro stimulation, an increased lytic function against K-562 cells was demonstrated in six of the nine patients with low basal values, in three after boosting with all lymphokines tested and in three with interleukin 2. In three of these six patients incubation with interleukin 2 also produced an increased cytotoxic function against Daudi target cells; this phenomenon may be associated to the lymphokine-activated killer (LAK) system. The importance of investigating the cytotoxic in vitro function in LDGL patients to further characterize the biological features of GL and its relevance to better define the nature of this disease are discussed. [ABSTRACT FROM AUTHOR]

The synthesis of silver nanoparticles with controlled physicochemical properties is essential for governing their intended functionalities and safety profiles. However, synthesis process involves multiple parameters that could influence the resulting properties. This challenge could be addressed with the development of predictive models that forecast endpoints based on key synthesis parameters. In this study, we manually extracted synthesis-related data from the literature and leveraged various machine learning algorithms. Data extraction included parameters such as reactant concentrations, experimental conditions, as well as physicochemical properties. The antibacterial efficiencies and toxicological profiles of the synthesized nanoparticles were also extracted. In a second step, based on data completeness, we employed regression algorithms to establish relationships between synthesis parameters and desired endpoints and to build predictive models. The models for core size and antibacterial efficiency were trained and validated using a cross-validation approach. Finally, the features' impact was evaluated via Shapley values to provide insights into the contribution of features to the predictions. Factors such as synthesis duration, scale of synthesis and the choice of capping agents emerged as the most significant predictors. This study demonstrated the potential of machine learning to aid in the rational design of synthesis process and paves the way for the safe-by-design principles development by providing insights into the optimization of the synthesis process to achieve the desired properties. Finally, this study provides a valuable dataset compiled from literature sources with significant time and effort from multiple researchers. Access to such datasets notably aids computational advances in the field of nanotechnology., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

In recent years, multifunctional inorganic-organic hybrid materials have been widely investigated in order to determine their potential synergetic, antagonist, or independent effects in terms of reactivity. The aim of this study was to design and characterize a new hybrid material by coupling well-known photocatalytic TiO 2 nanoparticles with a mixture of lipopeptides (LP), to exploit its high binding affinity for metal cations as well as the ability to interact with bacterial membranes and disrupt their integrity. We used both chemical and colloidal synthesis methodologies and investigated how different TiO 2 :LP weight ratios affected colloidal, physicochemical, and functional properties. We discovered a clear breaking point between TiO 2 and LP single-component trends and identified different ranges of applicability by considering different functional properties such as photocatalytic, heavy metal sorption capacity, and antibacterial properties. At low LP contents, the photocatalytic properties of TiO 2 are preserved (conversion of organic dye = 99% after 40 min), and the hybrid system can be used in advanced oxidation processes, taking advantage of the additional antimicrobial LP properties. Around the breaking point (TiO 2 :LP 1:1), the hybrid material preserves the high surface area of TiO 2 (specific surface area around 180 m 2 /g) and demonstrates NOx depletion of up to 100% in 80 min, together with improved adhesion of hybrid antibacterial coating. The last design demonstrated the best results for the concurrent removal of inorganic, organic, and biological pollutants in water/soil remediation applications.

Numerous recent advances in robotics have been inspired by the biological principle of tensile integrity-or "tensegrity"-to achieve remarkable feats of dexterity and resilience. Tensegrity robots contain compliant networks of rigid struts and soft cables, allowing them to change their shape by adjusting their internal tension. Local rigidity along the struts provides support to carry electronics and scientific payloads, while global compliance enabled by the flexible interconnections of struts and cables allows a tensegrity to distribute impacts and prevent damage. Numerous techniques have been proposed for designing and simulating tensegrity robots, giving rise to a wide range of locomotion modes, including rolling, vibrating, hopping, and crawling. In this study, we review progress in the burgeoning field of tensegrity robotics, highlighting several emerging challenges, including automated design, state sensing, and kinodynamic motion planning.

We present Oncilla robot, a novel mobile, quadruped legged locomotion machine. This large-cat sized, 5.1 kg robot is one of a kind of a recent, bioinspired legged robot class designed with the capability of model-free locomotion control. Animal legged locomotion in rough terrain is clearly shaped by sensor feedback systems. Results with Oncilla robot show that agile and versatile locomotion is possible without sensory signals to some extend, and tracking becomes robust when feedback control is added (Ajallooeian, 2015). By incorporating mechanical and control blueprints inspired from animals, and by observing the resulting robot locomotion characteristics, we aim to understand the contribution of individual components. Legged robots have a wide mechanical and control design parameter space, and a unique potential as research tools to investigate principles of biomechanics and legged locomotion control. But the hardware and controller design can be a steep initial hurdle for academic research. To facilitate the easy start and development of legged robots, Oncilla-robot's blueprints are available through open-source. The robot's locomotion capabilities are shown in several scenarios. Specifically, its spring-loaded pantographic leg design compensates for overdetermined body and leg postures, i.e., during turning maneuvers, locomotion outdoors, or while going up and down slopes. The robot's active degree of freedom allow tight and swift direction changes, and turns on the spot. Presented hardware experiments are conducted in an open-loop manner, with little control and computational effort. For more versatile locomotion control, Oncilla-robot can sense leg joint rotations, and leg-trunk forces. Additional sensors can be included for feedback control with an open communication protocol interface. The robot's customized actuators are designed for robust actuation, and efficient locomotion. It trots with a cost of transport of 3.2 J/(Nm), at a speed of 0.63 m s-1 (Froude number 0.25). The robot trots inclined slopes up to 10°, at 0.25 m s-1. The multi-body Webots model of Oncilla robot, and Oncilla robot's extensive software architecture enables users to design and test scenarios in simulation. Controllers can directly be transferred to the real robot. Oncilla robot's blueprints are open-source published (hardware GLP v3, software LGPL v3)., (Copyright © 2018 Spröwitz, Tuleu, Ajallooeian, Vespignani, Möckel, Eckert, D'Haene, Degrave, Nordmann, Schrauwen, Steil and Ijspeert.)

The introduction of newer cytotoxic monoclonal antibodies and chimeric antigen receptor modified T cells is opening a new age in the management of B-lineage adult acute lymphoblastic leukemia. This therapeutic change must be very positively acknowledged because of the limits of intensive chemotherapy programs and allogeneic stem cell transplantation. In fact, with these traditional therapeutic tools the cure can be achieved in only 40-50% of the patients. The failure rates are particularly high in the elderly, in patients with post-induction persistence of minimal residual disease and especially in refractory/relapsed disease. The place of the novel immunotherapeutics in improving the outcome of adult patients with B-lineage acute lymphoblastic leukemia is reviewed.

Following the introduction of targeted therapy with tyrosine kinase inhibitors (TKI) at the beginning of the past decade, the outcome of patients with Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) has dramatically improved. Presently, the use of refined programs with first/second generation TKI's and chemotherapy together with allogeneic stem cell transplantation allow up to 50% of all patients to be cured. Further progress is expected with the new TKI ponatinib, overcoming resistance caused by T315I point mutation, other targeted therapies, autologous transplantation in molecularly negative patients, therapeutic monoclonal antibodies like inotuzumab ozogamicin and blinatumomab, and chimeric antigen receptor-modified T cells. Ph+ ALL could become curable in the near future even without allogeneic stem cell transplantation, minimizing the risk of therapy-related death and improving greatly the quality of patients' life.

This manuscript proposes a method to directly transfer the features of horse walking, trotting, and galloping to a quadruped robot, with the aim of creating a much more natural (horse-like) locomotion profile. A principal component analysis on horse joint trajectories shows that walk, trot, and gallop can be described by a set of four kinematic Motion Primitives (kMPs). These kMPs are used to generate valid, stable gaits that are tested on a compliant quadruped robot. Tests on the effects of gait frequency scaling as follows: results indicate a speed optimal walking frequency around 3.4 Hz, and an optimal trotting frequency around 4 Hz. Following, a criterion to synthesize gait transitions is proposed, and the walk/trot transitions are successfully tested on the robot. The performance of the robot when the transitions are scaled in frequency is evaluated by means of roll and pitch angle phase plots.

In this work we present a new mechatronic platform for measuring behavior of nonhuman primates, allowing high reprogrammability and providing several possibilities of interactions. The platform is the result of a multidisciplinary design process, which has involved bio-engineers, developmental neuroscientists, primatologists, and roboticians to identify its main requirements and specifications. Although such a platform has been designed for the behavioral analysis of capuchin monkeys (Cebus apella), it can be used for behavioral studies on other nonhuman primates and children. First, a state-of-the-art principal approach used in nonhuman primate behavioral studies is reported. Second, the main advantages of the mechatronic approach are presented. In this section, the platform is described in all its parts and the possibility to use it for studies on learning mechanism based on intrinsic motivation discussed. Third, a pilot study on capuchin monkeys is provided and preliminary data are presented and discussed.

Idarubicin-based induction programs in acute lymphoblastic leukemia (ALL) account for 75?-?85% of complete remission rate. A small amount of patients exhibit primary refractoriness, and approximately 60% of those achieving a remission eventually relapse. The present study aimed to review the outcome of patients relapsing after or resistant to an idarubicin-based, induction-consolidation regimen (with/without additional high dose cytarabine). The 'ABC' phase II trial consisted of mitoxantrone (50 mg/m(2) over 5 days) associated with high-dose methotrexate (1.5 g/m(2) over 24 h, followed by folinic acid rescue), high-dose methyl-prednisolone (125 mg b.i.d.) and vincristine, plus granulocyte colony-stimulating factor. Eligible patients were treated with two courses ('A' and 'B', the latter with reduced drug dosages), followed by allogeneic or autologous haematopoietic stem cell transplantation (HSCT, 'C'). Thirty-six patients (3 primary resistant, 33 at first marrow relapse) were evaluated. With 'A', 21 achieved a complete remission (CR), 10 were refractory and 5 died early. Eighteen patients received 'B' (with one more CR, for an overall CR rate of 61%) and, eventually, 12 patients had 'C' procedures (7 autologous, 5 allogeneic HSCT). WHO grade >or=3 treatment-related toxicity developed in 50% and 34% of 'A' and 'B' courses, respectively. The median duration of CR was 5.2 (range 0.5-19.7) months and median overall survival was 7.6 (range 0.5-20) months. In spite of 12 HSCTs, there was no long-term survivor. 'ABC' salvage proved feasible and comparable to reported rescue chemotherapic regimens, but the achievement of cure in refractory/relapsing ALL remains an outstanding clinical task.

Background and Objective: In a prior study, primary resistant acute lymphoblastic leukemia (RES-ALL) was observed in 11 of 176 (6%) adult patients treated with a four drug regimen (IVAP), its incidence being higher in T-cell or Philadelphia (Ph) chromosome/BCR-ABL rearrangement positive ALL cases with a blast cell count >25x10(9)/L (RES-ALL rate 19%, p=0.04). Aiming to minimize this percentage of resistant disease, fractionated cyclophosphamide (f-CY) was then added to the IVAP regimen., Design and Methods: Study 08-96 was a prospective, collaborative phase II trial carried out at eight general hospital centers specialized in the care of hematologic malignancies. Historical IVAP-treated patients served as a retrospective control group. All consecutive, untreated patients (>15 years) with a diagnosis of ALL or advanced-stage lymphoblastic lymphoma (LBL) were eligible. RES-ALL was defined as the persistence of >5% ALL cells in the bone marrow 28-40 days after the start of the IVAP regimen (idarubicin 10 mg/m(2)/d on days 1 and 2; vincristine 2 mg on days 1, 8 and 15; L-asparaginase 6,000 U/m(2) on alternate days 3 6 from day 8; prednisone 60 mg/m(2)/d on days 1-21). In the new study, two f-CY schedules were sequentially adopted: CY 150 or 75 mg/m(2)/bd, given for 4 consecutive days before IVAP (f-CY 1200 or 600, expressing total CY dose in mg/m(2))., Results: Eighty-eight patients were evaluable (age range 15-74 years, blast count 0-240x10(9)/L, 14 T-lineage, 74 B-lineage, 13 Ph/BCR-ABL+). The first 39 patients received the f-CY 1200 schedule, 22 patients received f-CY 600, and the last 27 patients were not given any f-CY. These changes were dictated by the results of interim analyses of the f-CY groups (RES-ALL rate not reduced, myelotoxicity increased). Altogether, compared with the historical IVAP and no f-CY groups, the incidence of RES-ALL was not decreased by the addition of f-CY 1200/600 in B-lineage ALL, regardless of Ph/BCR-ABL expression and blast count. However, none of 14 T-ALL cases in the new study had RES-ALL (8 in f-CY groups, 5 of whom with >25x10(9)/L blast cells), compared to 5/39 (13%, overall) or 4/21 (19%, with >25x10(9)/L blast cells) among the control cases. Owing to small sample size, this difference was not statistically significant., Interpretation and Conclusions: This preliminary experience suggests that T-ALL may be more sensitive than B-lineage ALL to an early therapy including f-CY. The hypothesis could be tested in a larger clinical trial.

In 1990 the Italian Non-Hodgkin's Lymphoma Cooperative Study Group (NHLSG) started a multicenter study on the role of interferon (IFN) in multiple myeloma (MM). The schedule of treatment was based on the assumption that melphalan plus prednisone (MP) would be better for good-prognosis patients, whereas poor-prognosis patients would benefit from polychemotherapy. Accordingly, IFN was included randomly for the induction treatment of good-prognosis patients and randomly as maintenance of the response achieved in both groups. Up to now 78 patients of the 124 enrolled have completed the induction treatment and are evaluable for response and response duration. The overall response rate was 59%. Sixty-two percent of good-prognosis patients obtained objective response, 9/14 (64%) with MP and 9/15 (60%) with MP+IFN. Up to now, with a median follow-up of 9 months from the evaluation of response, no difference has been recorded between the maintenance and no maintenance groups on relapse rate, neither in good- nor in poor-prognosis patients.

Background: We analyze here short- and long-term results in 49 patients with idiopathic thrombocytopenic purpura (ITP), consecutively treated with high-dose (h.d.) immunoglobulins (Ig) or anti-D Ig. The major aims of this study were to assess the prognostic power of some patient characteristics and to verify the possibility that repeated courses of treatment can induce a stable remission. Moreover, the relative efficacy and safety of these two treatments were compared., Patients and Methods: Group A included 28 patients with chronic ITP and 17 with ITP of recent onset who were receiving h.d. Ig; Group B included 5 patients with ITP of recent onset and 7 with chronic ITP treated with anti-D Ig. Eight cases, receiving both treatment, were included in both groups. Response to treatment was defined as any increase in platelet count above 30 x 10(9)/l, when the platelet count was less than 10 x 10(9)/l, or any doubling of the basal platelet count otherwise. Remission was defined as any platelet count higher than 100 x 10(9)/l lasting for 3 months or longer without therapy., Results and Conclusions: Cumulative response and remission rate was not statistically different in the two groups. Multivariate logistic regression analysis showed no influence of sex, previous therapy or duration of disease. Patients older than 60 years were definitely less responsive to h.d. Ig (58% vs 92%, p = 0.03). In Group A, two patients obtained remission after the first course of h.d. Ig. No additional remissions were obtained by repeated courses of h.d. Ig, apart from a single case of ITP of recent onset.(ABSTRACT TRUNCATED AT 250 WORDS)

To investigate the role of p55 and p75 chains of interleukin-2 receptor (IL-2R) on the activation of granular lymphocytes (GL) in patients with lymphoproliferative disease of granular lymphocytes (LDGL), the cells obtained from 11 LDGL patients (belonging to the CD3+ group) were studied for (a) the surface expression and (b) mRNA transcripts of the p55 and p75 IL-2R after activation with anti-CD3 monoclonal antibody (mAb) or interleukin-2 (IL-2). The effects of mAbs specifically blocking the p55 and p75 IL-2R on the generation of proliferative and cytotoxic functions were studied following anti-CD3 mAb stimulation. A significant difference was observed in the expression of p55 and p75 antigens on LDGL cells under resting conditions: a low number of p55 IL-2R+ (mean 1.2 +/- 0.4%) and high values of p75 IL-2R+ cells (54.9 +/- 7.4%). Accordingly, a barely detectable message for the p55 IL-2R and a strong signal for the p75 IL-2R mRNA were demonstrated. Following activation with anti-CD3 or IL-2, different patterns of IL-2R expression were observed. Anti-CD3 mAb induced an increase in the expression of the p55 IL-2R both at the mRNA and antigen level, whereas the p75 values remained consistently raised. In contrast, IL-2 induced the expression of p55 IL-2R mRNA associated with only a slight expression of this antigen. This finding was associated with a decrease in the cell expression of the p75 IL-2R, whereas the amount of p75 mRNA was unchanged. Both anti-CD3 mAb and IL-2 induced cell proliferation and cytotoxicity against the K-562 target cells. Anti-p55 IL-2R mAb did not affect the cytotoxic activity mediated by anti-CD3, but it markedly inhibited cell proliferation. Anti-p75 mAb did not inhibit either lytic function or cell proliferation mediated by anti-CD3 mAb, suggesting that only the high affinity IL-2R (p55 plus p75) is involved in anti-CD3 mediated cell activation in LDGL patients. This mechanism is different from that responsible for the IL-2 activation of CD3+ GL in LDGL patients, which is achieved through the p75 IL-2R alone. These results provide new insights into the pathophysiology of proliferating GL in LDGL patients and may also contribute to further characterization of the normal CD3+ GL population.

To clarify the mechanisms accounting for the hairy cell proliferation, in five patients with hairy cell leukemia (HCL), we evaluated the ability of neoplastic cells to proliferate in vitro in response to tumor necrosis factor-alpha (TNF-alpha), B-cell growth factor (BCGF), and interleukin 4 (IL-4). In addition, supernatants recovered from cultures of unstimulated hairy cells were tested for the capability to induce the proliferation of allogeneic hairy cells. We demonstrated that TNF-alpha and BCGF were able to induce the in vitro growth of hairy cells (stimulation index (SI) ranging, at different concentrations, from 1.6 to 10.7 and from 1.6 to 25.1 for TNF-alpha and BCGF, respectively). IL-4 did not show any proliferative effect on hairy cells. When unstimulated hairy cell supernatants were tested for the proliferative activity on allogeneic hairy cells, we demonstrated a low proliferative effect that was not inhibited by an anti-TNF-alpha antibody. Our findings demonstrate that unstimulated hairy cells proliferate in vitro in response to TNF-alpha and BCGF, thus suggesting that these cytokines could be involved in an autocrine model of cell proliferation.

The authors think that the sacral epidural anaesthesia effected with Mepivacaine 3%, 6 ml (180 mg) and Fentanyl 2 ml (100 mcg) is perfectly indicated for the proctologic surgery as it is of simple execution and presents a short latency (12 min.), good deepness and perfect haemodynamic stability. Besides, it does not endanger the lower limbs innervation. No urinary retention.