The structure of research questions in randomized-controlled trials in rehabilitation field

Objective The aim of this study is to assess whether and how PICO format is described to frame research questions in randomized controlled trials (RCTs) looking at effectiveness of rehabilitation interventions. Design A methodological study was conducted. RCTs in the rehabilitation field, published between July 1st, 2019 and December 31st, 2019 were included. The framing of the primary research question (RQ) from each trial was evaluated. Results Ninety-seven RCTs were included in the analysis. The most frequent framing of the primary RQ was as an \u201cobjective\u201d statement (55%) and in 33% of the articles this was stated as an \u201cobjective\u201d together with a \u201chypothesis\u201d description. All PICO elements were present in 55% of RQ, but only 49% have used the statement suggested by Cochrane. The results showed that the most frequent framing of primary RQ was \u201cobjective\u201d using all PICO elements, but few articles followed the statement suggested by Cochrane to describe them. Conclusion: our findings suggest that a specific item about the \u201cresearch question\u201d and the rationale that drove to the proposed design following the form suggested by Cochrane is included in the RCTRACK checklist

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

Microscopic Polyangiitis With Selective Involvement of Central and Peripheral Nervous System : A Case Report

Background: Microscopic polyangiitis (MPA) is a necrotizing vasculitis that affects predominantly small-sized vessels in many organ systems. The disease generally causes glomerulonephritis, pulmonary damage, arthritis, and neuropathy. An exclusive involvement of both central nervous system (CNS) and peripheral nervous system (PNS) is extremely rare. Case Presentation: A 62-year-old woman was admitted to our hospital with a 3 months history of right foot drop, recently complicated by intense myalgia, arthralgia, and allodynia to tactile, vibratory, and pressure stimuli. Since blood tests revealed elevated inflammatory indexes, we suspected either infectious or immune-mediated disorders. Chest radiograph, blood culture series, and echocardiogram revealed normal findings, while urinalysis showed a bacterial infection that was successfully treated. The neurophysiological findings were compatible with multiple mononeuritis, and a brain MRI evidenced ischemic lesions of both basal ganglia and thalamus. A wide-spectrum autoantibody assay revealed the presence of high-titer perinuclear anti-neutrophil cytoplasmic antibodies specific for myeloperoxidase (MPO-ANCA). According to these findings, the diagnosis of MPA was made, and the patient was successfully treated with intravenous (IV) methylprednisolone, followed by two doses of rituximab. Conclusions: An assessment of both CNS and PNS should be included in the diagnostic evaluation of MPA. The involvement of the PNS may raise the risk of a relapsing course and treatment failure, therefore it should be considered in the choice of induction and maintenance therapy

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

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

The Effectiveness of Behavioral Interventions in Adults with Post-Traumatic Stress Disorder during Clinical Rehabilitation: A Rapid Review

Background: This review examined the effectiveness of behavioral interventions for adults with post-traumatic stress disorder (PTSD) triggered by physical injury or medical trauma. It discusses implications in support of rehabilitation management for COVID-19 survivors diagnosed with PTSD. Methods: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Interim Guidance from the Cochrane Rapid Reviews Methods Group. The authors searched for randomized control trials in PubMed, Embase, and CENTRAL databases up to 31 March 2021. Results: Five studies (n = 459) met the inclusion criteria. Each study measured a different comparison of interventions. The certainty of the evidence was judged to be very low for all outcomes. Post-traumatic stress disorder symptom reduction was found to be in favor of trauma-focused cognitive-behavioral therapy, cognitive therapy, and cognitive-behavioral therapy. Cognitive function improvements were observed in favor of the cognitive processing therapy control intervention. Conclusions: Overall, there is uncertainty about whether behavioral interventions are effective in reducing PTSD symptoms and improving functioning and quality of life when the disorder is triggered by a physical or medical trauma rather than a psychological trauma. Further research should investigate their efficacy in the context of rehabilitation management and gather evidence on this populatio

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

Stochastic Eulerian Lagrangian Methods for Fluid-Structure Interactions with Thermal Fluctuations

We present approaches for the study of fluid-structure interactions subject to thermal fluctuations. A mixed mechanical description is utilized combining Eulerian and Lagrangian reference frames. We establish general conditions for operators coupling these descriptions. Stochastic driving fields for the formalism are derived using principles from statistical mechanics. The stochastic differential equations of the formalism are found to exhibit significant stiffness in some physical regimes. To cope with this issue, we derive reduced stochastic differential equations for several physical regimes. We also present stochastic numerical methods for each regime to approximate the fluid-structure dynamics and to generate efficiently the required stochastic driving fields. To validate the methodology in each regime, we perform analysis of the invariant probability distribution of the stochastic dynamics of the fluid-structure formalism. We compare this analysis with results from statistical mechanics. To further demonstrate the applicability of the methodology, we perform computational studies for spherical particles having translational and rotational degrees of freedom. We compare these studies with results from fluid mechanics. The presented approach provides for fluid-structure systems a set of rather general computational methods for treating consistently structure mechanics, hydrodynamic coupling, and thermal fluctuations.Comment: 24 pages, 3 figure

The influence of bias in randomized controlled trials on rehabilitation intervention effect estimates: what we have learned from meta-epidemiological studies

This study aimed to synthesize evidence from studies that addressed the influence of bias domains in randomized controlled trials on rehabilitation intervention effect estimates and discuss how these findings can maximize the trustworthiness of an RCT in rehabilitation. We screened studies about the influence of bias on rehabilitation intervention effect estimates published until June 2023. The characteristics and results of the included studies were categorized based on methodological characteristics and summarized narratively. We included seven studies with data on 227,806 RCT participants. Our findings showed that rehabilitation intervention effect estimates are likely exaggerated in trials with inadequate/unclear sequence generation and allocation concealment when using continuous outcomes. The influence of blinding was inconsistent and different from the rest of medical science, as meta-epidemiological studies showed overestimation, underestimation, or neutral associations for different types of blinding on rehabilitation treatment effect estimates. Still, it showed a more consistent pattern when looking at patient-reported outcomes. The impact of attrition bias and intention to treat has been analyzed only in two studies with inconsistent results. The risk of reporting bias seems to be associated with overestimation of treatment effects. Bias domains can influence rehabilitation treatment effects in different directions. The evidence is mixed and inconclusive due to the poor methodological quality of RCTs and the limited number and quality of studies looking at the influence of bias and treatment effects in rehabilitation. Further studies about the influence of bias in RCTs on rehabilitation intervention effect estimates are needed