The effect of placebo and neurophysiological involvements

Placebo and placebo effect are important issues related to the drug therapy for clinical and scientific meanings. The rates of placebo may get as many as 50% for analgesic drugs in headache. The high answer to placebo brings questions on pathophysiology of headache. Answers may offer a new strategy in the implementation of trials and new insight in neurophysiology of headache. Current knowledge on placebo and placebo effect will be analysed and dicussed looking for new direction in headache field

Experimental characterization of SLM and EBM cubic lattice structures for lightweight applications

This study carries out an experimental characterization of lattice structures that are based on cubic cells fabricated through selective laser melting (SLM) and electron beam melting (EBM). The lattice failure under compressive load is studied as a function of the process typology, material properties, and dimensional parameters of the unit cell. The bulk material is first characterized to evaluate the process stability. Three main failure modes of the lattice are identified, depending on the response of ductile/brittle material and the direction of crack propagation. The relationship between lattice geometrical parameters and mechanical strength is observed. The results of the modeling and experiments are suitable to validate the design of lightweight components built with AM processes. The structural performances related to geometrical features, material properties and technological constraints are well explained for further applications in structural design. The equivalent Young’s module of lattice samples with different cell size has been measured and compared with numerical simulations based on the homogenization method

A scalable human iPSC-based neuromuscular disease model on suspended biobased elastomer nanofiber scaffolds

Many devastating neuromuscular diseases currently lack effective treatments. This is in part due to a lack of drug discovery platforms capable of assessing complex human neuromuscular disease phenotypes in a scalable manner. A major obstacle has been generating scaffolds to stabilise mature contractile myofibers in a multi-well assay format amenable to high content image analysis (HCI). This study describes the development of a scalable human iPSC-neuromuscular disease model, whereby suspended elastomer nanofibers support long-term stability, alignment, maturation, and repeated contractions of iPSC-myofibers, innervated by iPSC-motor neurons in 96-well assay plates. In this platform, optogenetic stimulation of the motor neurons elicits robust myofiber-contractions, providing a functional readout of neuromuscular transmission. Additionally, HCI provides rapid and automated quantification of axonal outgrowth, myofiber morphology, and neuromuscular synapse number and morphology. By incorporating amyotrophic lateral sclerosis (ALS)-related TDP-43G298S mutant motor neurons and CRISPR-corrected controls, key neuromuscular disease phenotypes are recapitulated, including weaker myofiber contractions, reduced axonal outgrowth, and reduced number of neuromuscular synapses. Treatment with a candidate ALS drug, the receptor-interacting protein kinase-1 (RIPK1)-inhibitor necrostatin-1, rescues these phenotypes in a dose-dependent manner, highlighting the potential of this platform to screen novel treatments for neuromuscular diseases

In vitro characterization of adipose stem cells non-enzymatically extracted from the thigh and abdomen

Autologous fat grafting is a surgical technique in which adipose tissue is transferred from one area of the body to another, in order to reconstruct or regenerate damaged or injured tissues. Before reinjection, adipose tissue needs to be purified from blood and cellular debris to avoid inflammation and preserve the graft viability. To perform this purification, different enzymatic and mechanical methods can be used. In this study, we characterized in vitro the product of a closed automatic device based on mechanical disaggregation, named Rigenera\uae, focusing on two sites of adipose tissue harvesting. At first, we optimized the Rigenera\uae operating timing, demonstrating that 60 s of treatment allows a higher cellular yield, in terms of the cell number and growth rate. This result optimizes the mechanical disaggregation and it can increase the clinical efficiency of the final product. When comparing the extracted adipose samples from the thigh and abdomen, our results showed that the thigh provides a higher number of mesenchymal-like cells, with a faster replication rate and a higher ability to form colonies. We can conclude that by collecting adipose tissue from the thigh and treating it with the Rigenera\uae device for 60 s, it is possible to obtain the most efficient product

Two Multicenter Surveys on Equine Back-Pain 10 Years a Part

Despite back-pain being a common cause of poor performance in sport horses, a tailored diagnostic workflow and a consolidated therapeutic approach are currently lacking in equine medicine. The aim of the study was to assess the evolution in the veterinarian approach to diagnose and treat back-pain over a 10 years period. To investigate this topic, two surveys were addressed to equine veterinarians working in practice throughout Europe 10 years apart (2006 and 2016). The answers were organized in an Excel dataset and analyzed. There were 47 respondents in 2006 and 168 in 2016, from 8 European Countries. The main reasons for examining horses with back-pain were poor performance (76%), behavioral issues (68%), and lameness (50%). When assessing back pain, 97% of respondents applied careful digital pressure over paravertebral muscles, 90% of them used digital back mobilization, and 69% was detecting areas of localized heat. The use of diagnostic analgesia to confirm the source of pain was rarely employed. Radiography and ultrasonography were the most frequent diagnostic imaging modalities used to investigate the causes of back-pain in both surveys. Obtaining a definitive diagnosis in horses with back-pain is considered challenging due to the reduced accessibility of the area and the variability in the pain manifestations. Corticosteroids injections were used for local treatments by 80% of respondents in 2006 and 92% in 2016. Recently, ultrasonography has been extensively used during the injections of the vertebral articular facets and sacroiliac joints region. The use of complementary therapies was restricted to a low percentage of respondents in the first survey (20%) but it increased over the decade. In 2016, a wider percentage of respondents considered osteopathy (40%), kinesiotherapy (29%), and acupuncture (22%) when treating back disorders compared to 2006. The structural differences of the two surveys did not enable a direct data comparison. Based on the results of this surveys, however, veterinarians should be sensitized to the back-pain problems and seek to integrate findings from clinical research studies in their daily practice

Management of unscheduled tetanus prophylaxis in Emergency Departments: Point-of-Care implementation as a rapid tool for the evaluation of anti-tetanus antibodies

Background and aim: Each analytical activity, including those carried out in Point of Care (POCT) must be, at law, under the control of Laboratory Medicine. Before the implementation of the rapid tetanus quick stick (TQS) test for the evaluation of the specific tetanus immunisation, a multi-disciplinary and multi-professional group was created. The aim of this study was to evaluate the ability of Emergency Department (ED) staff to manage and correctly understand the result of TQS test in POCT. Materials and Methods: This analysis took into consideration 152 patients admitted to ED with traumatic wounds; information on the state of tetanus immunisation at their arrival wasn't recorded. Blood sample analysis was performed twice. The Laboratory confirmed a 100% concordance between their results and ELISA test (standard criterion). Study design consisted of 2 phases: the first one (50 test) to preliminarily evaluate if any corrective action or improvement of procedures is required, and the second one (102 tests) to confirm the quality of corrective actions. Results: The concordance of results between TQS test in Laboratory and POCT test in ED was 80% in the first phase and 95% in the second one.Conclusions: The use of the rapid TQS test is a valuable tool; however, to avoid serious mistakes of interpretation, periodic checks on the quality of the results must be arranged

When a Friend Becomes Your Enemy: Natural Killer Cells in Atherosclerosis and Atherosclerosis-Associated Risk Factors

Atherosclerosis (ATS), the change in structure and function of arteries with associated lesion formation and altered blood flow, is the leading cause of cardiovascular disease, the number one killer worldwide. Beyond dyslipidemia, chronic inflammation, together with aberrant phenotype and function of cells of both the innate and adaptive immune system, are now recognized as relevant contributors to atherosclerosis onset and progression. While the role of macrophages and T cells in atherosclerosis has been addressed in several studies, Natural Killer cells (NKs) represent a poorly explored immune cell type, that deserves attention, due to NKs’ emerging contribution to vascular homeostasis. Furthermore, the possibility to re-polarize the immune system has emerged as a relevant tool to design new therapies, with some succesfull exmples in the field of cancer immunotherapy. Thus, a deeper knowledge of NK cell pathophysiology in the context of atherosclerosis and atherosclerosis-associated risk factors could help developing new preventive and treatment strategies, and decipher the complex scenario/history from “the risk factors for atherosclerosis” Here, we review the current knowledge about NK cell phenotype and activities in atherosclerosis and selected atherosclerosis risk factors, namely type-2 diabetes and obesity, and discuss the related NK-cell oriented environmental signals

Multibody Computer Model of the Entire Equine Forelimb Simulates Forces Causing Catastrophic Fractures of the Carpus during a Traditional Race

Simple Summary Palios are traditional horseraces held in the main square of few Italian cities. Due to peculiar features of such circuits, adapted to the square architecture and thus characterized by tight curves and unconventional footing surface, horses involved are at particular risk of accidents. Prevention of catastrophic musculoskeletal injuries is a significant issue and matter of debate during these events. In particular, the negotiation of the curves in the city circuits is a significative concern. An experiment was set up to build a model of entire forelimb at the point of failure in the context of a turn comparable to that in a Palio circuit. The model was informed by live data and the output compared to post-mortem findings obtained from a horse that sustained a catastrophic fracture of the carpus during this competition. The objective of this study is to determine the magnitude and distribution of internal forces generated across the carpus under which the catastrophic injury has occurred and describe related post-mortem findings. A catastrophic fracture of the radial carpal bone experienced by a racehorse during a Palio race was analyzed. Computational modelling of the carpal joint at the point of failure informed by live data was generated using a multibody code for dynamics simulation. The circuit design in a turn, the speed of the animal and the surface characteristics were considered in the model. A macroscopic examination of the cartilage, micro-CT and histology were performed on the radio-carpal joint of the limb that sustained the fracture. The model predicted the points of contact forces generated at the level of the radio-carpal joint where the fracture occurred. Articular surfaces of the distal radius, together with the proximal articular surface of small carpal bones, exhibited diffuse wear lines, erosions of the articular cartilage and subchondral bone exposure. Even though the data in this study originated from a single fracture and further work will be required to validate this approach, this study highlights the potential correlation between elevated impact forces generated at the level of contact surfaces of the carpal joint during a turn and cartilage breakdown in the absence of pre-existing pathology. Computer modelling resulted in a useful tool to inversely calculate internal forces generated during specific conditions that cannot be reproduced in-vivo because of ethical concerns