A pragmatic benchmarking study of an evidence-based personalised approach in 1938 adolescents with high-risk idiopathic scoliosis

Combining evidence-based medicine and shared decision making, current guidelines support an evidence-based personalised approach (EBPA) for idiopathic scoliosis in adolescents (AIS). EBPA is considered important for adolescents\u2019 compliance, which is particularly difficult in AIS. Benchmarking to existing Randomised Controlled Trials (RCTs) as paradigms of single treatments, we aimed to check the effectiveness and burden of care of an EBPA in high-risk AIS. This study\u2019s design features a retrospective observation of a prospective database including 25,361 spinal deformity patients < 18 years of age. Participants consisted of 1938 AIS, 11\u201345\u25e6 Cobb, Risser stage 0\u20132, who were studied until the end of growth. EBPA included therapies classified for burdensomeness according to current guidelines. Using the same inclusion criteria of the RCTs on exercises, plastic, and elastic bracing, out of the 1938 included, we benchmarked 590, 687, and 884 participants, respectively. We checked clinically significant results and burden of care, calculating Relative Risk of success (RR) and Number Needed to Treat (NNT) for efficacy (EA) and intent-to-treat analyses. At the end of growth, 19% of EBPA participants progressed, while 33% improved. EBPA showed 2.0 (1.7\u20132.5) and 2.9 (1.7\u20134.9) RR of success versus Weinstein and Coillard\u2019s studies control groups, respectively. Benchmarked to plastic or elastic bracing, EBPA had 1.4 (1.2\u20131.5) and 1.7 (1.2\u20132.5) RR of success, respectively. The EBPA treatment burden was greater than RCTs in 48% of patients, and reduced for 24% and 42% versus plastic and elastic bracing, respectively. EBPA showed to be from 40% to 70% more effective than benchmarked individual treatments, with low NNT. The burden of treatment was frequently reduced, but it had to be increased even more frequently

A systematic review opens the black box of “usual care” in stroke rehabilitation control groups and finds a black hole

INTRODUCTION: In experimental trials, new methods are tested against the “best” or “usual” care. To appraise control group (CG) interventions provided as “usual care,” we focused on stroke as a leading cause of disability demanding rehabilitation as a complex intervention. EVIDENCE ACQUISITION: For this methodological appraisal, we conducted a systematic review of RCTs without timespan limitation. The PICO included stroke survivors, rehabilitation, control group intervention, lower limb function. To assess the risk of bias, we used the Cochrane risk of bias tool (RoB). we identified the terminology describing the CG Program (CGP), performed a knowledge synthesis and conducted a frequency analysis of provided interventions. EVIDENCE SYNTHESIS: we included 155 publications. 13.6% of the articles did not describe the CG, and 11.6% indicated only the professionals involved. In the remaining 116 studies, three studies provided an intervention according to specific guidelines, 106 different “usual care” CGPs were detected, with nine proposed twice and two between four and five times. The most adopted terminology to state “usual care” was “conventional physiotherapy.” CONCLUSIONS: This study shows that usual care in CG does not actually exist, as both specific terminology and consistency within CGP contents are missing. Reporting guidelines should give better assistance on this issue. These results should be verified in other fields

Prostasome-like particles in stallion semen.

Human semen contains membranous vesicles called prosta- somes. They are secreted by the prostate gland and contain large amounts of cholesterol, sphingomyelin, and Ca2. Prostasomes enhance the motility of ejaculated spermatozoa and are in- volved in a number of additional biological functions. No prostasome-like vesicles have been described in horse se- men up to now. We have demonstrated the presence of pros- tasome-like vesicles in the equine semen and characterized them as to size, morphology, and lipid composition; we have found that they are similar to human prostasomes in many re- spects. We propose that these vesicles might be important for the fecundity of horse semen. This is of interest since the success of artificial insemination is limited by the fact that stallion sperm barely survive cryopreservation

Cancer Stem Cells (CSCs), Circulating Tumor Cells (CTCs) and Their Interplay with Cancer Associated Fibroblasts (CAFs): A New World of Targets and Treatments

The importance of defining new molecules to fight cancer is of significant interest to the scientific community. In particular, it has been shown that cancer stem cells (CSCs) are a small sub-population of cells within tumors with capabilities of self-renewal, differentiation, and tumorigenicity; on the other side, circulating tumor cells (CTCs) seem to split away from the primary tumor and appear in the circulatory system as singular units or clusters. It is becoming more and more important to discover new biomarkers related to these populations of cells in combination to define the network among them and the tumor microenvironment. In particular, cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment with different functions, including matrix deposition and remodeling, extensive reciprocal signaling interactions with cancer cells and crosstalk with immunity. The settings of new markers and the definition of the molecular connections may present new avenues, not only for fighting cancer but also for the definition of more tailored therapies

"3D tumor spheroid models for in vitro therapeutic screening: a systematic approach to enhance the biological relevance of data obtained"

The potential of a spheroid tumor model composed of cells in different proliferative and metabolic states for the development of new anticancer strategies has been amply demonstrated. However, there is little or no information in the literature on the problems of reproducibility of data originating from experiments using 3D models. Our analyses, carried out using a novel open source software capable of performing an automatic image analysis of 3D tumor colonies, showed that a number of morphology parameters affect the response of large spheroids to treatment. In particular, we found that both spheroid volume and shape may be a source of variability. We also compared some commercially available viability assays specifically designed for 3D models. In conclusion, our data indicate the need for a pre-selection of tumor spheroids of homogeneous volume and shape to reduce data variability to a minimum before use in a cytotoxicity test. In addition, we identified and validated a cytotoxicity test capable of providing meaningful data on the damage induced in large tumor spheroids of up to diameter in 650 micron by different kinds of treatments

Combining preclinical tools and models to unravel tumor complexity: Jump into the next dimension

Tumors are complex and heterogeneous diseases characterized by an intricate milieu and dynamically in connection with surrounding and distant tissues. In the last decades, great efforts have been made to develop novel preclinical models able to recapitulate the original features of tumors. However, the development of an in vitro functional and realistic tumor organ is still utopic and represents one of the major challenges to reproduce the architecture of the tumor ecosystem. A strategy to decrypt the whole picture and predict its behavior could be started from the validation of simplified biomimetic systems and then proceed with their integration. Variables such as the cellular and acellular composition of tumor microenvironment (TME) and its spatio-temporal distribution have to be considered in order to respect the dynamic evolution of the oncologic disease. In this perspective, we aim to explore the currently available strategies to improve and integrate in vitro and in vivo models, such as three-dimensional (3D) cultures, organoids, and zebrafish, in order to better understand the disease biology and improve the therapeutic approaches

A conservative coupling algorithm between a compressible flow and a rigid body using an Embedded Boundary method

This paper deals with a new solid-fluid coupling algorithm between a rigid body and an unsteady compressible fluid flow, using an Embedded Boundary method. The coupling with a rigid body is a first step towards the coupling with a Discrete Element method. The flow is computed using a Finite Volume approach on a Cartesian grid. The expression of numerical fluxes does not affect the general coupling algorithm and we use a one-step high-order scheme proposed by Daru and Tenaud [Daru V,Tenaud C., J. Comput. Phys. 2004]. The Embedded Boundary method is used to integrate the presence of a solid boundary in the fluid. The coupling algorithm is totally explicit and ensures exact mass conservation and a balance of momentum and energy between the fluid and the solid. It is shown that the scheme preserves uniform movement of both fluid and solid and introduces no numerical boundary roughness. The effciency of the method is demonstrated on challenging one- and two-dimensional benchmarks

Anti-tumor efficacy assessment of the sigma receptor pan modulator RC-106. A promising therapeutic tool for pancreatic cancer

Introduction: Pancreatic cancer (PC) is one of the most lethal tumor worldwide, with no prognosis improvement over the past 20-years. The silent progressive nature of this neoplasia hampers the early diagnosis, and the surgical resection of the tumor, thus chemotherapy remains the only available therapeutic option. Sigma receptors (SRs) are a class of receptors proposed as new cancer therapeutic targets due to their over-expression in tumor cells and their involvement in cancer biology. The main localization of these receptors strongly suggests their potential role in ER unfolded protein response (ER-UPR), a condition frequently occurring in several pathological settings, including cancer. Our group has recently identified RC-106, a novel pan-SR modulator with good in vitro antiproliferative activities toward a panel of different cancer cell lines. In the present study, we investigated the in vitro properties and pharmacological profile of RC-106 in PC cell lines with the aim to identify a potential lead candidate for the treatment of this tumor. Methods: Pancreatic cancer cell lines Panc-1, Capan-1, and Capan-2 have been used in all experiments. S1R and TMEM97/S2R expression in PC cell lines was quantified by Real-Time qRT-PCR and Western Blot experiments. MTS assay was used to assess the antiproliferative effect of RC-106. The apoptotic properties of RC-106 was evaluated by TUNEL and caspase activation assays. GRP78/BiP, ATF4, and CHOP was quantified to evaluate ER-UPR. Proteasome activity was investigated by a specific fluorescent-based assay. Scratch wound healing assay was used to asses RC-106 effect on cell migration. In addition, we delineated the in vivo pharmacokinetic profile and pancreas distribution of RC-106 in male CD-1 mice. Results: Panc-1, Capan-1, and Capan-2 express both SRs. RC-106 exerts an antiproliferative and pro-apoptotic effect in all examined cell lines. Cells exposure to RC-106 induces the increase of the expression of ER-UPR related proteins, and the inhibition of proteasome activity. Moreover, RC-106 is able to decrease PC cell lines motility. The in vivo results show that RC-106 is more concentrated in pancreas than plasma. Conclusion: Overall, our data evidenced that the pan-SR modulator RC-106 is an optimal candidate for in vivo studies in animal models of PC

Кінетика сумісного виділення цинку і нікелю з розбавлених електролітів

Досліджені закономірності виділення цінку, нікелю і цинк-нікелевого сплаву з розведених електролітів, що містять в якості лігандів амінокислоту та аміак. Найкращі технологічні параметри та якість покрить отримані при спільному вмісті у розчині обох лігандів. Запропонований електроліт характеризується високою стабільністю, є технологічним та екологічно безпечним.The mechanisms of zinc, nickel and zinc-nickel alloy deposition from diluted electrolytes, containing amino acid or ammonia as a ligand, were investigated. The very technological characteristics and coatings quality were obtained if the electrolyte contained both of the ligands. The suggested electrolyte is characterized by high stability, processibility and it is ecologically safe

In vitro irradiation system for radiobiological experiments

Background: Although two-dimensional (2-D) monolayer cell cultures provide important information on basic tumor biology and radiobiology, they are not representative of the complexity of three-dimensional (3-D) solid tumors. In particular, new models reproducing clinical conditions as closely as possible are needed for radiobiological studies to provide information that can be translated from bench to bedside. Methods: We developed a novel system for the irradiation, under sterile conditions, of 3-D tumor spheroids, the in vitro model considered as a bridge between the complex architectural organization of in vivo tumors and the very simple one of in vitro monolayer cell cultures. The system exploits the same equipment as that used for patient treatments, without the need for dedicated and highly expensive instruments. To mimic the passage of radiation beams through human tissues before they reach the target tumor mass, 96-multiwell plates containing the multicellular tumor spheroids (MCTS) are inserted into a custom-built phantom made of plexiglass, the material most similar to water, the main component of human tissue. Results: The system was used to irradiate CAEP- and A549-derived MCTS, pre-treated or not with 20 \u3bcM cisplatin, with a dose of 20 Gy delivered in one session. We also tested the same treatment schemes on monolayer CAEP and A549 cells. Our preliminary results indicated a significant increment in radiotoxicity 20 days after the end of irradiation in the CAEP spheroids pre-treated with cisplatin compared to those treated with cisplatin or irradiation alone. Conversely, the effect of the radio- chemotherapy combination in A549-derived MCTS was similar to that induced by cisplatin or irradiation alone. Finally, the 20 Gy dose did not affect cell survival in monolayer CAEP and A549 cells, whereas cisplatin or cisplatin plus radiation caused 100% cell death, regardless of the type of cell line used. Conclusions: We set up a system for the irradiation, under sterile conditions, of tumor cells grown in 3-D which allows for the use of the same dose intensities and schedules utilized in clinical practice. This irradiation system, coupled with 3-D cell cultures, has the potential to generate information that could be used to individually tailor radiotherap