A new vector, based on the PolII promoter for the U1 snRNA gene, for the expression of siRNAs in mammalian cells

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Therapeutic Education and Physical Activity to Support Self-management of Cancer-related Fatigue in Hematologic Cancer Patients: Protocol of a Feasibility Randomized Controlled Trial

Introduction: Hematologic malignancies account for nearly 8% of new cancer diagnosis in Italy. Cancer-related fatigue (CRF) is one of the most distressing symptoms reported by patients with cancer. As CRF has a multifactorial etiology, physical activity and therapeutic education may be beneficial for managing CRF, both during and after cancer treatment. However, there is a lack of evidence specific to hematologic malignancies. This paper describes the protocol of a feasibility study on Therapeutic Education and Physical Activity (TEPA) intervention to support self-management of CRF in patients with hematologic malignancies. Methods: TEPA was addressed to newly diagnosed adult individuals with hematologic malignancy able to take part in a rehabilitation programme at the AUSL-IRCCS of Reggio Emilia. The protocol was developed in 2 phases. Phase I was an observational cohort study involving a convenience sample of 10 participants with the aim to evaluate the feasibility of the assessment schedule and to register longitudinal clinical data regarding CRF (FACIT-F), psychologic distress (NCCN Distress Thermometer), QoL (EORTC QLQ-C30), physical performance (TUG and 6MWT) and habitual level of physical activity during first months after diagnosis. Phase II (underway) is a feasibility randomized controlled trial (TEPA) involving a convenience sample of 40 participants and comparing 2 parallel active interventions (Therapeutic Education versus Therapeutic Education and Physical Activity) on top of usual care. The primary aim is to estimate the feasibility of TEPA, measured by the adherence rate to the intervention. Secondary aims are: to estimate the effect size of TEPA in terms of changes in CRF, psychological distress, QoL, physical performance and habitual level of physical activity (measured as in Phase I); to collect patient satisfaction, perception of usefulness of the TEPA intervention and data on long-term adherence to an active lifestyle. Data are collected in both phases at the time of diagnosis and then at 1-, 3- (completion of intervention) and 7-month follow-up. Discussion: Data on feasibility and effect size of TEPA will be analyzed upon completion of Phase II, allowing us to design a large, adequately powered RCT to verify the effectiveness of this intervention on CRF management in patients with hematologic cancer. Trial registration: clinicaltrials.gov; Trial registration number: NCT0340307

Therapeutic education and physical activity are feasible and safe in hematologic cancer patients referred to chemotherapy: results of a randomized controlled trial

Purpose: Although over 60% of patients with hematologic cancer report distressing fatigue, they often do not receive recommendations on fatigue management strategies. The aim of this pilot study was to estimate the feasibility of therapeutic education and physical activity (TEPA) by measuring the patients’ adherence to this multidimensional intervention. The secondary aim was to estimate the impact of TEPA on clinical outcomes. Methods: Patients with hematologic cancer participated in this single-center, open-label, randomized controlled trial. The control group (CG) received two educational group sessions on fatigue and physical activity. The experimental group (EG) received the two educational sessions plus six weekly individual sessions aimed at implementing a personalized physical exercise program. Follow-ups were at 1, 3, and 7 months. Results: Forty-six patients referred to chemotherapy were included, corresponding to 54% of recruitment rate. Adherence reached 90% in the EG and 68% in the CG. Most patients (65% in EG and 64% in CG) attended a minimum of 80% of the planned sessions. Overall retention rate was 87% (85% in EG and 91% in CG). No adverse events were registered. No between-group differences were detected in fatigue (FACIT-F), psychological distress (NCCN Distress Thermometer), QoL (EORTC QLQ-C30), or functional exercise capacity (TUG test and 6MWT). Adherence to an active lifestyle, measured by a semi-structured interview, increased from 56.5 to 84% in the EG at 7 months (p = 0.02), whereas it decreased slightly in the CG (from 47.8 to 42.9%). Conclusion: Multidimensional rehabilitation interventions are feasible and safe in this population, and larger trials should focus on the efficacy of such approaches on clinically relevant outcomes. Trial registration: ClinicalTrials.gov Identifier: NCT03403075

Data segmentation based on the local intrinsic dimension

One of the founding paradigms of machine learning is that a small number of variables is often sufficient to describe high-dimensional data. The minimum number of variables required is called the intrinsic dimension (ID) of the data. Contrary to common intuition, there are cases where the ID varies within the same data set. This fact has been highlighted in technical discussions, but seldom exploited to analyze large data sets and obtain insight into their structure. Here we develop a robust approach to discriminate regions with different local IDs and segment the points accordingly. Our approach is computationally efficient and can be proficiently used even on large data sets. We find that many real-world data sets contain regions with widely heterogeneous dimensions. These regions host points differing in core properties: folded versus unfolded configurations in a protein molecular dynamics trajectory, active versus non-active regions in brain imaging data, and firms with different financial risk in company balance sheets. A simple topological feature, the local ID, is thus sufficient to achieve an unsupervised segmentation of high-dimensional data, complementary to the one given by clustering algorithms

Optical trapping calculations for metal nanoparticles. Comparison with experimental data for Au and Ag spheres.

We calculate the optical forces on Au and Ag nanospheres through a procedure based on the Maxwell stress tensor. We compare the theoretical and experimental force constants obtained for gold and silver nanospheres finding good agreement for all particles with r < 80 nm. The trapping of the larger particles recently demonstrated in experiments is not foreseen by our purely electromagnetic theory based on fixed dielectric properties. Since the laser power produces a heating that may be large for the largest spheres, we propose a model in which the latter particles are surrounded by a steam bubble. This model foresees the trapping of these particles and the results turn out to be in reasonable agreement with the experimental data

Efficacy of a Copper-Calcium-Hydroxide Solution in Reducing Microbial Plaque on Orthodontic Clear Aligners: A Case Report

The aim of this study was to investigate the ability of a copper-calcium-hydroxide-based compound to remove microbial plaque naturally produced onto orthodontic clear aligners. A commercially available dental paste, named Cupral, based on copper-calcium-hydroxide, was used. A healthy volunteer (female, 32 years old), undergoing orthodontic treatment with thermoplastic clear aligners was enrolled. By conventional/confocal microscopy and colony-forming unit (CFU) assay, 2-week used aligners were examined for microbial plaque, prior and following exposure to Cupral. Confocal microscopy revealed abundant plaque irregularly distributed onto the aligner surface. Following Cupral treatment, a drastic decrease occurred in plaque thickness and matrix presence. As assessed by the CFU assay, total microbial load approached 10 9 CFUs/aligner, with slight differences in aerobiosis and anaerobiosis culture conditions; six macroscopically different types of colonies were detected and identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Following Cupral treatment, microbial load dropped to undetectable levels, irrespectively of the conditions considered. Exposure of clear aligners to Cupral results in the elimination of contaminating microorganisms; the antimicrobial activity is retained up to 1.25% concentration. Overall, our data describe a novel use of Cupral, a copper-calcium-hydroxide-based compound, in daily hygiene practices with promising results

HIV-1 co-infection does not reduce exposure to rifampicin, isoniazid, and pyrazinamide in South African tuberculosis outpatients

There are contrasting data in the literature about antituberculosis plasma drug concentrations in HIV-1-coinfected patients. We report the pharmacokinetics of rifampin, isoniazid, and pyrazinamide in a cohort of patients being treated for active tuberculosis, the majority of whom were coinfected with HIV-1 and had commenced antiretroviral therapy within 2 months of starting antituberculosis treatment. We also examined the association between antituberculosis drug concentrations and reported drug side effects at the 2-month clinical review. One hundred patients with pulmonary tuberculosis (65% coinfected with HIV-1) were intensively sampled to determine rifampin, isoniazid, and pyrazinamide plasma concentrations after 7 to 8 weeks of a daily quadruple-therapy regimen dosed according to World Health Organization (WHO) weight bands. Pharmacokinetic parameters were determined for each patient by using nonlinear mixed-effects models. HIV-1-coinfected patients had lower clearance rates for rifampin (21% decrease) and isoniazid (23% decrease) than HIV-1-uninfected patients, with resulting higher areas under the concentration-time curve from 0 to 24 h (AUC0–24) and maximum concentrations of drug in serum (Cmax). Antiretroviral therapy (ART) that included double-standard-dose lopinavir/ritonavir further lowered rifampin clearance, by 46%, and increased the AUC0–24. The current uniform dosing (per kilogram of body weight) across WHO weight bands was associated with a trend of decreased pharmacokinetic exposures for the lowest weight band. Use of fat-free mass as opposed to total body weight for allometric scaling of clearance significantly improved the model. Ambulant HIV-1-coinfected patients, the majority of whom were coprescribed ART, did not have reduced antituberculosis drug concentrations compared to HIV-1-uninfected patients

Beads for Cell Immobilization: Comparison of Alternative Additive Manufacturing Techniques

The attachment or entrapment of microbial cells and enzymes are promising solutions for various industrial applications. When the traps are beads, they are dispersed in a fluidized bed in a vessel where a pump guarantees fresh liquid inflow and waste outflow without washing out the cells. Scientific papers report numerous types of cell entrapment, but most of their applications remain at the laboratory level. In the present research, rigid polymer beads were manufactured by two different additive manufacturing (AM) techniques in order to verify the economy, reusability, and stability of the traps, with a view toward a straightforward industrial application. The proposed solutions allowed for overcoming some of the drawbacks of traditional manufacturing solutions, such as the limited mechanical stability of gel traps, and they guaranteed the possibility of producing parts of constant quality with purposely designed exchange surfaces, which are unfeasible when using conventional processes. AM proved to be a viable manufacturing solution for beads with complex shapes of two different size ranges. A deep insight into the production and characteristics of beads manufactured by AM is provided. The paper provides biotechnologists with a manufacturing perspective, and the results can be directly applied to transit from the laboratory to the industrial scale