Entrepreneurial orientation and international performance: the moderating effect of decision-making rationality

This research examines how entrepreneurial orientation (EO) influences international performance (IP) of the firm taking into account the moderating effect of decision-making rationality (DR) on the EO–IP association. Such an investigation is significant because it considers the interplay of strategic decision-making processes supported by the bounded rationality concept in the entrepreneurship field. Drawing from a study on activities of 216 firms in the United States and United Kingdom, the evidence suggests that DR positively moderates the EO–IP association. The findings suggest that managers can improve IP by combining EO with rational (analytical) processes in their strategic decisions

Therapeutic Management: When and What

Migraine is a widespread brain disease that is classified as the second most disabling condition and has the third highest prevalence of all medical conditions. Despite its non-emergent or life-threatening nature, migraine can progress to chronic type, a subform associated with significant morbidity and drug overuse. In the management of migraine, it is important therefore to introduce early prophylactic treatment in order to limit migraine chronification. In this chapter, we will go through all the treatment options, both acute and preventive, pharmaceutical and non-pharmaceutical following this flowchart: 1. Introduction; 2. General principles; 2.1 Symptomatic therapy; 2.2 Prophylactic management; 3. Pharmaceutical therapies; 3.1 Symptomatic; 3.1.1 Disease-specific; 3.1.2 No disease-specific; 3.2 Prophylactic; 3.2.1 Disease-specific; 3.2.2 No disease-specific; 3.3 Non-Pharmaceutical therapies; 3.4 Neuromodulation; 3.4.1 Invasive; 3.4.5 Non-invasive; 3.5 Nutrient (nutraceuticals); 3.6 Dietary interventions; 3.7 Acupuncture; 3.8 Physical therapy; 4. Cognitive behavioral therapies; 5. Patient centricity and patient education

The comparative effectiveness of migraine preventive drugs: a systematic review and network meta-analysis

OBJECTIVE: While there are several trials that support the efficacy of various drugs for migraine prophylaxis against placebo, there is limited evidence addressing the comparative safety and efficacy of these drugs. We conducted a systematic review and network meta-analysis to facilitate comparison between drugs for migraine prophylaxis. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov from inception to August 13, 2022, for randomized trials of pharmacological treatments for migraine prophylaxis in adults. Reviewers worked independently and in duplicate to screen references, extract data, and assess risk of bias. We performed a frequentist random-effects network meta-analysis and rated the certainty (quality) of evidence as either high, moderate, low, or very low using the GRADE approach. RESULTS: We identified 74 eligible trials, reporting on 32,990 patients. We found high certainty evidence that monoclonal antibodies acting on the calcitonin gene related peptide or its receptor (CGRP(r)mAbs), gepants, and topiramate increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo. We found moderate certainty evidence that beta-blockers, valproate, and amitriptyline increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, and low certainty evidence that gabapentin may not be different from placebo. We found high certainty evidence that, compared to placebo, valproate and amitriptyline lead to substantial adverse events leading to discontinuation, moderate certainty evidence that topiramate, beta-blockers, and gabapentin increase adverse events leading to discontinuation, and moderate to high certainty evidence that (CGRP(r)mAbs) and gepants do not increase adverse events. CONCLUSIONS: (CGRP(r)mAbs) have the best safety and efficacy profile of all drugs for migraine prophylaxis, followed closely by gepants.info:eu-repo/semantics/publishedVersio

Investigation of the effects of atmospheric pressure cold plasma on human cells and tissues

Atmospheric pressure cold plasma (APCP) is a novel tool in medicine for tissue disinfection. We recently reported that 2 minutes of APCP generated by a new portable device that ionizes a flow of helium gas exerted an antimicrobial effect, mainly due to the action of reactive oxygen species (ROS) (P. Brun et al., 2012). Since ROS induced DNA lesions that could lead to point mutations, before using plasma in medical treatment it is important to ascertain the safe usage of this device. In the study presented, we analysed the presence of ROS levels, pre-mutagenic 8-oxodeoxyguanosine (8-OHdG) and the expression of OGG1, a DNA glycosylase specific for the removal of 8-OHdG lesions in cell (fibroblasts and keratocytes) cultures. ROS levels in APCP-exposed microorganisms and keratocytes were detected by 2’,7’-dichlorofluorescein diacetate (HDCF-DA) fluorescence; the potential genotoxic effects of plasma were evaluated by analyses of cell cycle distribution, externalization of phosphatidylserine, HPLC determination of 8-OHdG expression, qRT-PCR and Western blotting of OGG1 gene and protein, at set time intervals. Our results demonstrated that APCP induced ROS formation in exposed human cells, a transient 8-OHdG expression and a consequent adaptative OGG1 response at the transcriptional and translational level. In conclusion, the short application of APCP to cells and tissues has a disinfection effect and leads to time-restricted ROS generation and to oxidative-stress related responses

a novel plasma source for sterilization of living tissues

A source for the production of low-power plasmas at atmospheric pressure, to be used for the nondamaging sterilization of living tissues, is presented. The source, powered by radiofrequency and working with a helium flow, has a specific configuration, studied to prevent the formation of electric arcs dangerous to living matter. It is capable of killing different types of bacteria with a decimal reduction time of 1?2?min; on the contrary, human cells such as conjunctival fibroblasts were found to be almost unharmed by the plasma. A high concentration of OH radicals, likely to be the origin of the sterilizing effect, is detected through their UV emission lines. The effect of the UV and the OH radicals on the fibroblasts was analysed and no significant effects were detected

Effect of laser treatment on the attachment and viability of mesenchymal stem cell responses on shape memory NiTi alloy

The objectives of this study were to investigate the effect of laser-induced surface features on the morphology, attachment and viability of mesenchymal stem cells (MSCs) at different periods of time, and to evaluate the biocompatibility of different zones: laser-melted zone (MZ), heat-affected zone (HAZ) and base metal (BM) in laser-treated NiTi alloy. The surface morphology and composition were studied by scanning electron microscope (SEM) and X-ray photoemission spectroscopy (XPS), respectively. The cell morphology was examined by SEM while the cell counting and viability measurements were done by hemocytometer and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. The results indicated that the laser-induced surface features, such as surface roughening, presence of anisotropic dendritic pattern and complete surface Ni oxidation were beneficial to improve the biocompatibility of NiTi as evidenced by the highest cell attachment (4 days of culture) and viability (7 days of culture) found in the MZ. The biocompatibility of the MZ was the best, followed by the BM with the HAZ being the worst. The defective and porous oxide layer as well as the coarse grained structure might attribute to the inferior cell attachment (4 days of culture) and viability (7 days of culture) on the HAZ compared with the BM which has similar surface morphology. © 2014 Elsevier B.V

In Vitro Generation of Cartilage-Carrier-Constructs on Hydroxylapatite Ceramics with Different Surface Structures

Tissue engineering approaches for healing cartilage defects are partly limited by the inability to fix cartilage to bone during implantation. To overcome this problem, cartilage can be - already in vitro - generated on a ceramic carrier which serves as bone substitute. In this study, the influence of a hydroxylapatite carrier and its surface structure on the quality of tissue engineered cartilage was investigated. Application of the carrier reduced significantly biomechanical and biochemical properties of the generated tissue. In addition, slight changes in the quality of the formed matrix, in the adhesive strength between cartilage and biomaterial and in attachment and proliferation of a chondrocyte monolayer could be observed for commercial grade carriers, with respect to modified topographies obtained by smooth grinding/polishing. These first results demonstrated an influence of the carrier and its surface structure, but further research is needed for explaining the described effects and for optimization of cartilage-carrier-constructs

Increased sporulation underpins adaptation of Clostridium difficile strain 630 to a biologically–relevant faecal environment, with implications for pathogenicity

Abstract Clostridium difficile virulence is driven primarily by the processes of toxinogenesis and sporulation, however many in vitro experimental systems for studying C. difficile physiology have arguably limited relevance to the human colonic environment. We therefore created a more physiologically–relevant model of the colonic milieu to study gut pathogen biology, incorporating human faecal water (FW) into growth media and assessing the physiological effects of this on C. difficile strain 630. We identified a novel set of C. difficile–derived metabolites in culture supernatants, including hexanoyl– and pentanoyl–amino acid derivatives by LC-MSn. Growth of C. difficile strain 630 in FW media resulted in increased cell length without altering growth rate and RNA sequencing identified 889 transcripts as differentially expressed (p < 0.001). Significantly, up to 300–fold increases in the expression of sporulation–associated genes were observed in FW media–grown cells, along with reductions in motility and toxin genes’ expression. Moreover, the expression of classical stress–response genes did not change, showing that C. difficile is well–adapted to this faecal milieu. Using our novel approach we have shown that interaction with FW causes fundamental changes in C. difficile biology that will lead to increased disease transmissibility

Fluid flow in the osteocyte mechanical environment : a fluid-structure interaction approach

Osteocytes are believed to be the primary sensor of mechanical stimuli in bone, which orchestrate osteoblasts and osteoclasts to adapt bone structure and composition to meet physiological loading demands. Experimental studies to quantify the mechanical environment surrounding bone cells are challenging, and as such, computational and theoretical approaches have modelled either the solid or fluid environment of osteocytes to predict how these cells are stimulated in vivo. Osteocytes are an elastic cellular structure that deforms in response to the external fluid flow imposed by mechanical loading. This represents a most challenging multi-physics problem in which fluid and solid domains interact, and as such, no previous study has accounted for this complex behaviour. The objective of this study is to employ fluid–structure interaction (FSI) modelling to investigate the complex mechanical environment of osteocytes in vivo. Fluorescent staining of osteocytes was performed in order to visualise their native environment and develop geometrically accurate models of the osteocyte in vivo. By simulating loading levels representative of vigorous physiological activity (3,000με compression and 300 Pa pressure gradient), we predict average interstitial fluid velocities (∼60.5μ m/s ) and average maximum shear stresses (∼11 Pa ) surrounding osteocytes in vivo. Interestingly, these values occur in the canaliculi around the osteocyte cell processes and are within the range of stimuli known to stimulate osteogenic responses by osteoblastic cells in vitro. Significantly our results suggest that the greatest mechanical stimulation of the osteocyte occurs in the cell processes, which, cell culture studies have indicated, is the most mechanosensitive area of the cell. These are the first computational FSI models to simulate the complex multi-physics mechanical environment of osteocyte in vivo and provide a deeper understanding of bone mechanobiology