Biomaterials for the restoration of oral function are prone to biofilm formation, affecting oral health. Oral bacteria adhere to hydrophobic and hydrophilic surfaces, but due to fluctuating shear, ...little biofilm accumulates on hydrophobic surfaces in vivo. More biofilm accumulates on rough than on smooth surfaces. Oral biofilms mostly consist of multiple bacterial strains, but Candida species are found on acrylic dentures. Biofilms on gold and amalgam in vivo are thick and fully covering, but barely viable. Biofilms on ceramics are thin and highly viable. Biofilms on composites and glass-ionomer cements cause surface deterioration, which enhances biofilm formation again. Residual monomer release from composites influences biofilm growth in vitro, but effects in vivo are less pronounced, probably due to the large volume of saliva into which compounds are released and its continuous refreshment. Similarly, conflicting results have been reported on effects of fluoride release from glass-ionomer cements. Finally, biomaterial-associated infection of implants and devices elsewhere in the body is compared with oral biofilm formation. Biomaterial modifications to discourage biofilm formation on implants and devices are critically discussed for possible applications in dentistry. It is concluded that, for dental applications, antimicrobial coatings killing bacteria upon contact are more promising than antimicrobial-releasing coatings.
The acute respiratory distress syndrome (ARDS), a clinical complication of severe acute lung injury (ALI) in humans, is a leading cause of morbidity and mortality in critically ill patients. ALI is ...characterized by disruption of the lung alveolar-capillary membrane barrier and resultant pulmonary edema associated with a proteinaceous alveolar exudate. Current specific treatment strategies for ALI/ARDS are lacking. We hypothesized that mesenchymal stem cells (MSCs), with or without transfection with the vasculoprotective gene angiopoietin 1 (ANGPT1) would have beneficial effects in experimental ALI in mice.
Syngeneic MSCs with or without transfection with plasmid containing the human ANGPT1 gene (pANGPT1) were delivered through the right jugular vein of mice 30 min after intratracheal instillation of lipopolysaccharide (LPS) to induce lung injury. Administration of MSCs significantly reduced LPS-induced pulmonary inflammation, as reflected by reductions in total cell and neutrophil counts in bronchoalveolar lavage (BAL) fluid (53%, 95% confidence interval CI 7%-101%; and 60%, CI 4%-116%, respectively) as well as reducing levels of proinflammatory cytokines in both BAL fluid and lung parenchymal homogenates. Furthermore, administration of MSCs transfected with pANGPT1 resulted in nearly complete reversal of LPS-induced increases in lung permeability as assessed by reductions in IgM and albumin levels in BAL (96%, CI 6%-185%; and 74%, CI 23%-126%, respectively). Fluorescently tagged MSCs were detected in the lung tissues by confocal microscopy and flow cytometry in both naïve and LPS-injured animals up to 3 d.
Treatment with MSCs alone significantly reduced LPS-induced acute pulmonary inflammation in mice, while administration of pANGPT1-transfected MSCs resulted in a further improvement in both alveolar inflammation and permeability. These results suggest a potential role for cell-based ANGPT1 gene therapy to treat clinical ALI/ARDS.
Light, MeV-scale dark matter (DM) is an exciting DM candidate that is undetectable by current experiments. A germanium (Ge) detector utilizing internal charge amplification for the charge carriers ...created by the ionization of impurities is a promising new technology with experimental sensitivity for detecting MeV-scale DM. We analyze the physics mechanisms of the signal formation, charge creation, charge internal amplification, and the projected sensitivity for directly detecting MeV-scale DM particles. We present a design for a novel Ge detector at helium temperature (
∼
4 K) enabling ionization of impurities from DM impacts. With large localized E-fields, the ionized excitations can be accelerated to kinetic energies larger than the Ge bandgap at which point they can create additional electron–hole pairs, producing intrinsic amplification to achieve an ultra-low energy threshold of
∼
0.1 eV for detecting low-mass DM particles in the MeV scale. Correspondingly, such a Ge detector with 1 kg-year exposure will have high sensitivity to a DM-nucleon cross section of
∼
5
×
10
-
45
cm
2
at a DM mass of
∼
10 MeV/c
2
and a DM-electron cross section of
∼
5
×
10
-
46
cm
2
at a DM mass of
∼
1 MeV/c
2
.
Germanium (Ge) detectors with ability of measuring a single electron–hole (e–h) pair are needed in searching for light dark matter (LDM) down to the MeV scale. We investigate the feasibility of Ge ...detectors with amorphous-Ge (a-Ge) contacts to achieve the sensitivity of measuring a single e-h pair, which requires extremely low leakage current. Three Ge detectors with a-Ge contacts are used to study the charge barrier height for blocking electrons and holes. Using the measured bulk leakage current and the Döhler–Brodsky model, we obtain the values for charge barrier height and the density of localized energy states near the Fermi energy level for the top and bottom contacts, respectively. We predict that the bulk leakage current is extremely small and can be neglected at helium temperature (
∼
4 K). Thus, Ge detectors with a-Ge contacts possess the potential to measure a single e–h pair for detecting LDM particles.
Sepsis refers to the clinical syndrome of severe systemic inflammation precipitated by infection. Despite appropriate antimicrobial therapy, sepsis-related morbidity and mortality remain intractable ...problems in critically ill patients. Moreover, there is no specific treatment strategy for the syndrome of sepsis-induced multiple organ dysfunction.
We hypothesized that mesenchymal stem cells (MSCs), which have been shown to have immunomodulatory properties, would reduce sepsis-induced inflammation and improve survival in a polymicrobial model of sepsis.
Sepsis was induced in C57Bl/6J mice by cecal ligation and puncture (CLP), followed 6 hours later by an intravenous injection of MSCs or saline. Twenty-eight hours after CLP, plasma, bronchoalveolar lavage fluid and tissues were collected for analyses. Longer-term studies were performed with antibiotic coadministration to assess the effect of MSCs on survival.
MSC treatment significantly reduced mortality in septic mice receiving appropriate antimicrobial therapy. MSCs alone reduced systemic and pulmonary cytokine levels in mice with CLP-induced sepsis, preventing acute lung injury and organ dysfunction, despite the low levels of cell persistence. Microarray data highlighted an overall down-regulation of inflammation and inflammation-related genes (such as IL-10, IL-6) and a shift toward up-regulation of genes involved in promoting phagocytosis and bacterial killing. Finally, bacterial clearance was significantly greater in MSC-treated mice, in part due to enhanced phagocytotic activity of the host immune cells.
These data demonstrate that MSCs have beneficial effects on experimental sepsis, possibly by paracrine mechanisms, and suggest that immunomodulatory cell therapy may be an effective adjunctive treatment to reduce sepsis-related morbidity and mortality.
The detection of low-energy deposition in the range of sub-eV through ionization using germanium (Ge) with a bandgap of
∼
0.7 eV requires internal amplification of the charge signal. This can be ...achieved through high electric field that accelerates charge carriers, which can then generate more charge carriers. The minimum electric field required to generate internal charge amplification is derived for different temperatures. We report the development of a planar point contact Ge detector in terms of its fabrication and the measurements of its leakage current and capacitance as a function of applied bias voltage. With the determination of the measured depletion voltage, the field distribution is calculated using GeFiCa, which predicts that the required electric field for internal charge amplification can be achieved in proximity to the point contact. The energy response to an Am-241 source is characterized and discussed. We conclude that such a detector with internal charge amplification can be used to search for low-mass dark matter.
Incomplete reporting of study methods and results has become a focal point for failures in the reproducibility and translation of findings from preclinical research. Here we demonstrate that ...incomplete reporting of preclinical research is not limited to a few elements of research design, but rather is a broader problem that extends to the reporting of the methods and results. We evaluated 47 preclinical research studies from a systematic review of acute lung injury that use mesenchymal stem cells (MSCs) as a treatment. We operationalized the ARRIVE (Animal Research: Reporting of In Vivo Experiments) reporting guidelines for pre-clinical studies into 109 discrete reporting sub-items and extracted 5,123 data elements. Overall, studies reported less than half (47%) of all sub-items (median 51 items; range 37-64). Across all studies, the Methods Section reported less than half (45%) and the Results Section reported less than a third (29%). There was no association between journal impact factor and completeness of reporting, which suggests that incomplete reporting of preclinical research occurs across all journals regardless of their perceived prestige. Incomplete reporting of methods and results will impede attempts to replicate research findings and maximize the value of preclinical studies.
The Acute Respiratory Distress Syndrome (ARDS) is a devastating clinical condition that is associated with a 30-40% risk of death, and significant long term morbidity for those who survive. ...Mesenchymal stromal cells (MSC) have emerged as a potential novel treatment as in pre-clinical models they have been shown to modulate inflammation (a major pathophysiological hallmark of ARDS) while enhancing bacterial clearance and reducing organ injury and death. A systematic search of MEDLINE, EMBASE, BIOSIS and Web of Science was performed to identify pre-clinical studies that examined the efficacy MSCs as compared to diseased controls for the treatment of Acute Lung Injury (ALI) (the pre-clinical correlate of human ARDS) on mortality, a clinically relevant outcome. We assessed study quality and pooled results using random effect meta-analysis. A total of 54 publications met our inclusion criteria of which 17 (21 experiments) reported mortality and were included in the meta-analysis. Treatment with MSCs, as compared to controls, significantly decreased the overall odds of death in animals with ALI (Odds Ratio 0.24, 95% Confidence Interval 0.18-0.34, I2 8%). Efficacy was maintained across different types of animal models and means of ALI induction; MSC origin, source, route of administration and preparation; and the clinical relevance of the model (timing of MSC administration, administration of fluids and or antibiotics). Reporting of standard MSC characterization for experiments that used human MSCs and risks of bias was generally poor, and although not statistically significant, a funnel plot analysis for overall mortality suggested the presence of publication bias. The results from our meta-analysis support that MSCs substantially reduce the odds of death in animal models of ALI but important reporting elements were sub optimal and limit the strength of our conclusions.
The ovary is perhaps the most dynamic organ in the human body, only rivaled by the uterus. The molecular mechanisms that regulate follicular growth and regression, ensuring ovarian tissue ...homeostasis, remain elusive. We have performed single-cell RNA-sequencing using human adult ovaries to provide a map of the molecular signature of growing and regressing follicular populations. We have identified different types of granulosa and theca cells and detected local production of components of the complement system by (atretic) theca cells and stromal cells. We also have detected a mixture of adaptive and innate immune cells, as well as several types of endothelial and smooth muscle cells to aid the remodeling process. Our results highlight the relevance of mapping whole adult organs at the single-cell level and reflect ongoing efforts to map the human body. The association between complement system and follicular remodeling may provide key insights in reproductive biology and (in)fertility.
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