Tranexamic Acid (TXA) for the Hemostatic Treatment of Post-Partum Hemorrhage (PPH): What Key Points Have We Learnt After All These Years?

Post-partum bleeding or post-partum hemorrhage (PPH) is often defined as the loss of more than 500 mL of blood after vaginal delivery or 1000 mL of blood after cesarean section following the delivery of a child [...]

Comparative chondrogenesis of human cells in a 3D integrated experimental/computational mechanobiology model

We present an integrated experimental–computational mechanobiology model of chondrogenesis. The response of human articular chondrocytes to culture medium perfusion, versus perfusion associated with cyclic pressurisation, versus non-perfused culture, was compared in a pellet culture model, and multiphysic computation was used to quantify oxygen transport and flow dynamics in the various culture conditions. At 2 weeks of culture, the measured cell metabolic activity and the matrix content in collagen type II and aggrecan were greatest in the perfused+ pressurised pellets. The main effects of perfusion alone, relative to static controls, were to suppress collagen type I and GAG contents, which were greatest in the non-perfused pellets. All pellets showed a peripheral layer of proliferating cells, which was thickest in the perfused pellets, and most pellets showed internal gradients in cell density and matrix composition. In perfused pellets, the computed lowest oxygen concentration was 0.075mM (7.5% tension), the maximal oxygen flux was 477.5 nmol/m2/s and the maximal fluid shear stress, acting on the pellet surface, was 1.8mPa (0.018 dyn/cm2). In the non-perfused pellets, the lowest oxygen concentration was 0.003mM (0.3% tension) and the maximal oxygen flux was 102.4nmol/m2/s.Alocal correlationwas observed, between the gradients in pellet properties obtained from histology, and the oxygen fields calculated with multiphysic simulation. Our results showup-regulation of hyalinematrix protein production by human chondrocytes in response to perfusion associated with cyclic pressurisation. These results could be favourably exploited in tissue engineering applications

Laser production of gas phase complexes of metal α-aminophosphonic acid mixtures and their role in chiral recognition

Clusters between first-group metal ions and chiralα-aminophosphonic acids have been readily generated by Pulsed Laser Ablation (PLA) and by Electrospray Ionization (ESI) and their fragmentation investigated by mass spectrometry. The complexes studied have the general formula[Me(I)Cl2]+, where Me(I) is H, Li, Na, or K, C is (R)-(—)-(1-aminoethyl) phosphonic acid(ER)and (S)-(+)-(1-aminoethyl) phosphonic acid(ES),(1R)-(+)-(1-amino-2-methylpropyl) phosphonic acid(PR)and (1S)-(—)-(1-amino-2-methylpropyl) phosphonic acid(PS),(1R)-(-)-(1-amino-hexyl) phosphonic acid (HR) and (1S)-(+)-(1-amino-hexyl) phosphonic acid (HS), o-phospho-L-serine (SS)ando-phospho-D-serine(SR), and L is a referenceα-aminophosphonic acid (E, P, H or S) of defined configuration. Collision induced dissociation (CID) of diastereomeric[Me(I)Cl2]+complexes leads to fragmentation patterns characterized by[Me(I)Cl]+/[Me(I)L2]+abundance ratios which depend upon the configuration of solute C. These different spectral features were correlated to the different stability of the diastereomeric[Me(I)CRL]+and[Me(I)CSL]+complexes in the gas phase

Novel Mechanisms of Cell Uptake in Lipid-Mediated Gene Delivery

The mechanism of cell uptake in lipid mediated gene delivery was investigated in NIH3T3 and CHO cell lines. We show that different endocytic pathways are activated by shape coupling between lipoplex and membrane lipids. Our results suggest that tailoring the lipoplex lipid composition to the patchwork-like plasma membrane profile could be a successful machinery of coordinating the endocytic pathway activities and the subsequent intracellular processing. Transfection experiments performed at 4C, when endocytosis does not take place, show that a novel class of highly efficient multicomponent lipoplexes enter cells by a temperature-independent fusion-like mechanism. In vivo, plasma proteins bind to lipoplex surface and create a rich ‘protein corona’ that is recognized by cells and other biological structures. The ‘protein corona’ associated to lipoplexes after interaction with human plasma was found to be much richer in basic immunoglobulins gamma proteins (Ig-Gs) than that of pure lipid vesicles in the absence of DNA. Because surface properties of lipoplexes may determine their interaction with cells and tissues, an accurate knowledge of lipoplex surface properties may be important for predicting biological responses. These findings also suggest the existence of hybrid structures made of multilamellar complexes either stuck together by DNA or coexisting with DNA loaded intact vesicles

Epigenetic and genetic landscape of uterine leiomyomas: a current view over a common gynecological disease

Purpose: Despite the numerous studies on the factors involved in the genesis and growth of uterine leiomyomas, the pathogenesis of these tumors remains unknown. Intrinsic abnormalities of the myometrium, abnormal myometrial receptors for estrogen, and hormonal changes or altered responses to ischemic damage during the menstrual period may be responsible for the initiation of (epi)genetic changes found in these tumors. Considering these elements, we aimed to offer an overview about epigenetic and genetic landscape of uterine leiomyomas. Methods: Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. Results: Several studies showed that leiomyomas have a monoclonal origin. Accumulating evidence converges on the risk factors and mechanisms of tumorigenesis: the translocation t (12;14) and deletion of 7q were found in the highest percentages of recurrence; dysregulation of the HMGA2 gene has been mapped within the critical 12q14-q15 locus. Estrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental estrogens has been poorly explored. The growth factors with mitogenic activity, such as transforming growth factor-β3, fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I are elevated in fibroids and may have a role as effectors of the tumor promotion. Conclusion: The new clues on genetics and epigenetics, as well as about the growth factors that control normal and pathological myometrial cellular biology may be of great help for the development of new effective and less invasive therapeutic strategies in the near future

Factors Determining the Superior Performance of Lipid/DNA/Protammine Nanoparticles over Lipoplexes.

The utility of using a protammine/DNA complex coated with a lipid envelope made of cationic 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) for transfecting CHO (Chinese hamster ovary cells), HEK293 (human embryonic kidney cells), NIH 3T3 (mouse embryonal cells), and A17 (murine cancer cells) cells was examined. The widely used DOTAP/DNA lipoplex was employed as a reference. In all the tested cell lines lipid/protamine/DNA (LPD) nanoparticles were more e!cient in transfecting cells than lipoplexes even though the lipid composition of the lipid envelope was the same in both devices. Physical!chemical properties were found to control the ability of nanocarriers to release DNA upon interaction with cellular membranes. LPD complexes easily release their DNA payload, while lipoplexes remain largely intact and accumulate at the cell nucleus. Collectively, these data explain why LPD nanoparticles often exhibit superior performances compared to lipoplexes in trasfecting cells and represent a promising class of nanocarriers for gene delivery

Motivation, Perception, and Behavior of the Adult Orthodontic Patient: A Survey Analysis

Purpose. The article is aimed at improving the understanding of the sociocultural profile of adult orthodontic patients and their expectations. In particular, it addresses three main aspects: the motivation and needs that underpin the decision to start orthodontic treatment, how it influences the patients’ daily life, and the different oral hygiene demands. Materials and Methods. An online survey was completed by 276 patients undergoing orthodontic treatment with different techniques. The questions asked concerned gender, age, type of appliance, any previous orthodontic treatments, type of any previous retainers, reasons for therapy, satisfaction, pain, problems in eating, daily number of teeth brushings and flossings before and during the treatment, perception of cost, sensation of visibility of the appliance, and if they would recommend orthodontic treatment. Results. A significant role within our sample is played by gender; 87.94% consisted of female patients out of which 72.57% wanted to improve their aesthetics, while only 54.84% of male patients cited the same reason. Invisible aligners were preferred by 67.70% of the patients due to them being considered the least painful, causing the fewest problems with eating, and the least visible. Metal braces were perceived as the less expensive treatment. Over a third of the patients (33.85%) had previously undergone orthodontic treatment, among them 54.05% wore a mobile retainer, 31.08% a fixed one, and 14.86% both. Daily tooth brushing and flossing increased during therapy with clear aligners by 48.94% and 126.39%, respectively. Conclusions. The greatest demand for orthodontic treatments comes from women, as they pay more attention to aesthetics, which makes the clear aligners the most common choice. The relapse after orthodontic treatment seems to cause a higher demand for retreatment, and oral hygiene habits significantly improve during orthodontic treatment, especially with the clear aligners

The impact of COVID-19 quarantine on patients with dementia and family caregivers: a nation-wide survey.

Quarantine for COVID-19 is associated with an acute worsening of clinical symptoms in patients with dementia as well as increase of caregivers’ burden. These findings emphasize the importance to implement new strategies to mitigate the effects of quarantine in patients with dementia

How to survey displaced workers in Switzerland ? Sources of bias and ways around them

Studying career outcomes after job loss is challenging because individually displaced worker form a self-selected group. Indeed, the same factors causing the workers to lose their jobs, such as lack of motivation, may also reduce their re-employment prospects. Using data from plant closures where all workers were displaced irrespective of their individual characteristics offers a way around this selection bias. There is no systematic data collection on workers displaced by plant closure in Switzerland. Accordingly, we conducted our own survey on 1200 manufacturing workers who had lost their job 2 years earlier. The analysis of observational data gives rise to a set of methodological challenges, in particular nonresponse bias. Our survey addressed this issue by mixing data collection modes and repeating contact attempts. In addition, we combined the survey data with data from the public unemployment register to examine the extent of nonresponse bias. Our analysis suggests that some of our adjustments helped to reduce bias. Repeated contact attempts increased the response rate, but did not reduce nonresponse bias. In contrast, using telephone interviews in addition to paper questionnaires helped to substantially improve the participation of typically underrepresented subgroups. However, the survey respondents still differ from nonrespondents in terms of age, education and occupation. Interestingly, these differences have no significant impact on the substantial conclusion about displaced workers' re-employment prospects