Introduction/objectives
The review systematically explored in vivo or in situ studies investigating the efficacy of nano-hydroxyapatite (nHA) to reduce initiation of or to remineralize initial caries ...lesions.
Data
Prospective controlled (non-)randomized clinical trials investigating the efficacy of a nHA compared to any other (placebo) treatment or untreated/standard control.
Sources
Three electronic databases (Central Cochrane, PubMed-MEDLINE, Ovid EMBASE) were screened. Outcomes were, e.g., ICDAS score, laser fluorescence, enamel remineralization rate, mineral loss, and lesion depth. No language or time restrictions were applied. Risk of bias and level of evidence were graded using the Risk of Bias 2.0 tool and GRADE profiler.
Study selection/results
Five in vivo (and 5 in situ) studies with at least 633 teeth (1031 specimens) being assessed in more than 420 (95) patients were included. No meta-analysis could be performed for in vivo studies due to the high heterogeneity of the study designs and the variety of outcomes. In situ studies indicate that under demineralization conditions, NaF was able to hinder demineralization, whereas nHA did not; simultaneously, nHA did not differ from the fluoride-free control. In contrast, under remineralizing conditions, nHA and NaF show the same remineralizing potential. However, the level of evidence was very low. Furthermore, six studies showed a high risk of bias, and six studies were funded/published by the manufacturers of the tested products.
Conclusion
The low number of clinical studies, the relatively short follow-up periods, the high risks of bias, and the limiting grade of evidence do not allow for conclusive evidence on the efficacy of nHA.
Clinical relevance
No conclusive evidence on the efficacy of nHA could be obtained based on the low number of clinical studies, the relatively short follow-up periods, the high risks of bias, the limiting grade of evidence, and study conditions that do not reflect the everyday conditions.
Zika virus (ZIKV) has emerged as a cause of congenital brain anomalies and a range of placenta-related abnormalities, highlighting the need to unveil the modes of maternal-fetal transmission. The ...most likely route of vertical ZIKV transmission is via the placenta. The earliest events of ZIKV transmission in the maternal decidua, representing the maternal uterine aspect of the chimeric placenta, have remained unexplored. Here, we show that ZIKV replicates in first-trimester human maternal-decidual tissues grown ex vivo as three-dimensional (3D) organ cultures. An efficient viral spread in the decidual tissues was demonstrated by the rapid upsurge and continued increase of tissue-associated ZIKV load and titers of infectious cell-free virus progeny, released from the infected tissues. Notably, maternal decidual tissues obtained at midgestation remained similarly susceptible to ZIKV, whereas fetus-derived chorionic villi demonstrated reduced ZIKV replication with increasing gestational age. A genome-wide transcriptome analysis revealed that ZIKV substantially upregulated the decidual tissue innate immune responses. Further comparison of the innate tissue response patterns following parallel infections with ZIKV and human cytomegalovirus (HCMV) revealed that unlike HCMV, ZIKV did not induce immune cell activation or trafficking responses in the maternal-fetal interface but rather upregulated placental apoptosis and cell death molecular functions. The data identify the maternal uterine aspect of the human placenta as a likely site of ZIKV transmission to the fetus and further reveal distinct patterns of innate tissue responses to ZIKV. Our unique experimental model and findings could further serve to study the initial stages of congenital ZIKV transmission and pathogenesis and evaluate the effect of new therapeutic interventions.
In view of the rapid spread of the current ZIKV epidemic and the severe manifestations of congenital ZIKV infection, it is crucial to learn the fundamental mechanisms of viral transmission from the mother to the fetus. Our studies of ZIKV infection in the authentic tissues of the human maternal-fetal interface unveil a route of transmission whereby virus originating from the mother could reach the fetal compartment via efficient replication within the maternal decidual aspect of the placenta, coinhabited by maternal and fetal cells. The identified distinct placental tissue innate immune responses and damage pathways could provide a mechanistic basis for some of the placental developmental abnormalities associated with ZIKV infection. The findings in the unique model of the human decidua should pave the way to future studies examining the interaction of ZIKV with decidual immune cells and to evaluation of therapeutic interventions aimed at the earliest stages of transmission.
We aimed at demonstrating non-inferiority of bortezomib/cyclophosphamide/dexamethasone (VCD) compared to bortezomib/doxorubicin/dexamethasone (PAd) induction therapy with respect to very good partial ...response rates or better (⩾VGPR) in 504 newly diagnosed, transplant-eligible multiple myeloma patients. VCD was found to be non-inferior to PAd with respect to ⩾VGPR rates (37.0 versus 34.3%, P=0.001). The rates of progressive disease (PD) were 0.4% (VCD) versus 4.8% (PAd; P=0.003). In the PAd arm, 11 of 12 patients with PD had either renal impairment (creatinine ⩾2 mg/dl) at diagnosis or the cytogenetic abnormality gain 1q21, whereas no PD was observed in these subgroups in the VCD arm. Leukocytopenia/neutropenia (⩾3°) occurred more frequently in the VCD arm (35.2% versus 11.3%, P<0.001). Neuropathy rates (⩾2°) were higher in the PAd group (14.9 versus 8.4%, P=0.03). Serious adverse events, both overall and those related to thromboembolic events, were higher in the PAd group (32.7 versus 24.0%, P=0.04 and 2.8 versus 0.4%, P=0.04). Stem cell collection was not impeded by VCD. VCD is as effective as PAd in terms of achieving ⩾VGPR rates with fewer PD and has a favorable toxicity profile. Therefore, VCD is preferable to PAd as induction therapy.
Density‐functional theory calculations of (TiO2)n clusters (n = 1–5) in the gas phase and adsorbed on pristine graphene as well as graphene quantum dots are presented. The cluster adsorption is found ...to be dominated by van der Waals forces. The electronic structure and in particular the excitation energies of the bare clusters and the TiO2/graphene composites are found to vary largely in dependence on the size of the respective constituents. This holds in particular for the energy and the spatial localization of the highest occupied and lowest unoccupied molecular orbitals. In addition to a substantial gap narrowing, a pronounced separation of photoexcited electrons and holes is predicted in some instances. This is expected to prolong the lifetime of photoexcited carriers. Altogether, TiO2/graphene composites are predicted to be promising photocatalysts with improved electronic and photocatalytic properties compared to bulk TiO2.
Local, hybrid, and constrained DFT are used to explore the potential of graphene and graphene quantum dots for photosensitizing titania clusters. The electronic structure and excitation energies of the bare clusters and composite material are found to vary largely in dependence on the size of the respective constituents. In addition to a red‐shifted absorption, also a spatial separation of photoexcited charge carriers is predicted to contribute to an enhanced photocatalysis in specific cases.
•First insights into communication in MTCs with patient participation.•Patients’ negative emotions were expressed indirectly during their case discussion.•Emotions were mostly linked to diagnosis, ...treatment and possible side effects.•Active patient participation depends on patient characteristics and hospital setting.
To investigate (a) how many questions and negative emotions (cues/concerns) breast and/or gynecologic cancer patients and companions express during their case discussion in multidisciplinary tumor conferences (MTCs), (b) with which topics the emotions are linked, and (c) which patient- and context-related characteristics determine patients’ communicative behavior.
This observational study included audio/video recordings of MTCs with patient participation in three breast and gynecological cancer centers. Using the Verona Coding Definitions of Emotional Sequences, patients’ and companions’ questions and negative emotions expressed were analyzed. Multiple regression analyses were used to determine associations between communicative behavior and patient- and context-related characteristics.
We identified 607 questions and 230 cues/concerns expressed by patients/companions in 82 case discussions in MTCs. The number of questions was significantly associated with the hospital. In case discussions with patients who had need for psychological support and who were accompanied, more questions were asked by patients/companions.
The results show that active patient participation does not depend only on patient characteristics, but also on the hospital setting.
If cancer centers want to enable patient participation in MTCs, they must define the role of the patient before. Subsequently, conditions must be created to enable this role expectation.
Objective
Patients' participation is part of patient‐centeredness, but it is so far unclear whether providers in multidisciplinary tumor conferences (MTCs) with patient participation communicate in a ...patient‐centered way. Our aim is to explore (a) to what extent providers ask questions to breast and gynecological cancer patients during case discussion in MTCs, (b) how providers respond to patients' expressions of emotions during case discussions, and (c) which patient‐ and context‐related characteristics and responses are associated with patients' trust in the treatment team after the case discussion.
Methods
This observational study included survey data and audio recordings of MTCs with patient participation at three breast and gynecological cancer centers. Providers' questions to patients and responses to patients' emotional expressions were coded using the Verona Coding Definitions of Emotional Sequences. The response can be explicitly or non‐explicitly related to the emotion and space‐reducing or space‐providing. Multiple linear regression analysis was used to determine associations between providers' responses, patient‐ and context‐related characteristics, and patients' trust in the treatment team after the case discussion.
Results
We analyzed 82 case discussions (77 breast, 5 breast and gynecological cancer patients). Providers asked a total of 646 questions, of which 86% were polar (yes/no). Providers gave 303 responses to a total of 230 emotional expressions by patients. Non‐explicit responses were associated with more trust when they were space‐providing, but with less trust when space‐reducing.
Conclusions
The frequency of providers' closed questions and space‐reducing responses to emotions shows that patient‐centered communication rarely takes place in MTCs with patient participation.
To evaluate frequency, biologic features, and clinical relevance of RUNX1 mutations in acute myeloid leukemia (AML).
Diagnostic samples from 945 patients (age 18 to 60 years) were analyzed for RUNX1 ...mutations. In a subset of cases (n = 269), microarray gene expression analysis was performed.
Fifty-nine RUNX1 mutations were identified in 53 (5.6%) of 945 cases, predominantly in exons 3 (n = 11), 4 (n = 10), and 8 (n = 23). RUNX1 mutations clustered in the intermediate-risk cytogenetic group (46 of 640, 7.2%; cytogenetically normal, 34 of 538, 6.3%), whereas they were less frequent in adverse-risk cytogenetics (five of 109, 4.6%) and absent in core-binding-factor AML (0 of 77) and acute promyelocytic leukemia (0 of 61). RUNX1 mutations were associated with MLL-partial tandem duplications (P = .0007) and IDH1/IDH2 mutations (P = .03), inversely correlated with NPM1 (P < .0001), and in trend with CEBPA (P = .10) mutations. RUNX1 mutations were characterized by a distinct gene expression pattern; this RUNX1 mutation-derived signature was not exclusive for the mutation, but also included mostly adverse-risk AML eg, 7q-, -7, inv(3), or t(3;3). RUNX1 mutations predicted for resistance to chemotherapy (rates of refractory disease 30% and 19%, P = .047, for RUNX1-mutated and wild-type patients, respectively), as well as inferior event-free survival (EFS; P < .0001), relapse-free survival (RFS, P = .022), and overall survival (P = .051). In multivariable analysis, RUNX1 mutations were an independent prognostic marker for shorter EFS (P = .007). Explorative subgroup analysis revealed that allogeneic hematopoietic stem-cell transplantation had a favorable impact on RFS in RUNX1-mutated patients (P < .0001).
AML with RUNX1 mutations are characterized by distinct genetic properties and are associated with resistance to therapy and inferior outcome.
Herpes simplex virus 1 (HSV1) is a ubiquitous human pathogen that utilizes variable mechanisms to evade immune surveillance. The glycosylphosphatidylinositol (GPI) anchoring pathway is a multistep ...process in which a myriad of different proteins are covalently attached to a GPI moiety to be presented on the cell surface. Among the different GPI-anchored proteins there are many with immunological importance. We present evidence that the HSV1-encoded miR H8 directly targets PIGT, a member of the protein complex that covalently attaches proteins to GPI in the final step of GPI anchoring. This results in a membrane down-modulation of several different immune-related, GPI-anchored proteins, including ligands for natural killer-activating receptors and the prominent viral restriction factor tetherin. Thus, we suggest that by utilizing just one of dozens of miRNAs encoded by HSV1, the virus can counteract the host immune response at several key points.
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•HSV1 miR H8 targets PIGT of the GPI anchoring pathway•Expression of the anti-viral protein tetherin is reduced and viral spread enhanced•Expression of GPI-anchored activating NK cell ligands is reduced•Recognition and elimination by NK cells decrease
Herpes simplex virus 1 is a ubiquitous human pathogen and the cause of several ailments. Enk et al. found that the HSV1-encoded miR H8 targets the GPI anchoring pathway, reducing expression of several immune-modulating proteins, thus enhancing viral spread and enabling evasion of natural killer cell elimination.
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