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Regenerative medicine is a novel discipline that both excites undergraduates and may be used as a vehicle to expose students to scientific concepts and opportunities. The goal of this article is to describe the implementation of a National Science Foundation-funded Targeted Infusion Project in which underrepresented minority undergraduates are exposed to laboratory-bench skills and summer research opportunities that they may not have encountered otherwise. A 3-wk infusion of laboratory-bench and data presentation skills, in the context of a regenerative medicine/bioengineering project, aimed to engage students and expose them to opportunities as summer researchers and teaching assistants. The infusion aimed to assess the extent to which students improved 1) attitudes toward laboratory-bench-based techniques, using attitudes toward science as a proxy; 2) perceptions of scientific inquiry; 3) intentions to engage in undergraduate research; and 4) intentions to persist in science, technology, engineering, and mathematics (STEM)-related fields. Results indicate that the 3-wk infusion had no effect on science attitudes, but transcribed responses to structured interviews administered after the summer research experience indicated that students who completed summer research projects had positive experiences. Differences in intentions to engage in research were detected between groups of students in different STEM majors, in addition to differences in intentions to pursue a career in science. We describe the implementation of the infusion and briefly discuss quantitative outcomes. We conclude that infusion of laboratory-bench modules in the context of a regenerative medicine/bioengineering project may play a small but important role in increasing (minority) participation and persistence in the STEM pipeline.

Background: Many studies have identified health inequalities in childhood and adolescence. However, it is unclear how these have developed in recent years, particularly since the COVID-19 pandemic. Methods: Analyses are based on the German data from the international Health Behaviour in School-aged Children (HBSC) study from 2009/10 (n = 5,005), 2013/14 (n = 5,961), 2017/18 (n = 4,347), and 2022 (n = 6,475). A total of 21,788 students aged approximately between 11 and 15 years were included. Socioeconomic status (SES) was assessed using the Family Affluence Scale (FAS). Several health indicators were analysed stratified by gender using bivariate and multivariate analysis methods. Results: In 2022, there are clear socioeconomic inequalities in life satisfaction, self-rated health, fruit and vegetable consumption, and physical activity. These inequalities remained largely constant or increased between 2009/10 and 2022. Between 2017/18 and 2022, no significant changes in inequalities were found. Conclusions: Health inequalities are persistent and reduce the chances of growing up healthy. There is no evidence that inequalities in the analysed outcomes have changed during the pandemic period (between 2017/18 and 2022). Rather, the changes in the health indicators seem to affect all adolescents in a similar way.

Background: Health Behaviour in School-aged Children (HBSC) is one of the largest international studies on child and adolescent health and cooperates with the World Health Organization (WHO). In Germany, adolescents aged 11, 13 and 15 are surveyed every four years about their health, health behaviour and social conditions. This article describes the HBSC study and in particular the methodology of the current 2022 survey and prior surveys conducted between 2009/10 and 2017/18. Method: 174 schools with a total of 6,475 students participated in the 2022 survey. The survey was conducted using questionnaires and covered a wide range of topics (including mental health, physical activity, bullying experiences, social determinants of health and experiences related to COVID-19). The 2022 survey was complemented by a school principal survey (N = 160). In addition to the current sample, the samples of the three previous surveys with representative data for Germany are presented: 2009/10 (N = 5,005), 2013/14 (N = 5,961) and 2017/18 (N = 4,347).: Discussion The health of children and adolescents is of great public health importance. The HBSC study makes a substantial contribution by providing internationally comparable results, analysing trends, and providing stakeholders with comprehensive and representative health monitoring data.

Introduction The COVID-19 pandemic has shown the importance of resilient, modern, and well-equipped public health administrations from national to communal levels. In Germany, the surveillance, contact tracing, and local adaptions went through local health offices, revealing both their important role and also their lack of equipment and general preparation for health crises. Research on the mode of operation of the public health service (PHS), especially in a time of crisis, is rare. The present study aims to qualitatively and quantitatively assess problem areas, conflict potentials, and challenges that have become apparent for the PHS of Saxony-Anhalt during the pandemic. It focuses on the individual insight of employees of the PHS of Saxony-Anhalt and its 14 health offices to derive concrete needs and fields of action for increasing pandemic preparedness. Furthermore, the prospective personnel and resource-based requirements as well as the necessary structural and organisational changes of the public health departments are to be considered.Methods and analysis The study will follow a sequential mixed-methods approach. Introductory expert interviews (n=12) with leading staff of Saxony-Anhalt’s PHS will be conducted, followed by focus group interviews (n=4) with personnel from all departments involved in the pandemic response. Thereafter, a quantitative survey will be carried out to validate and complement the results of the qualitative phase.Ethics and dissemination Ethical approval was obtained by the Martin-Luther-Universität Halle-Wittenberg ethics commission (Ref number 2023-102). The authors will submit the results of the study to relevant peer-reviewed journals and give national and international oral presentations to researchers, members of the PHS, and policymakers.

This retrospective study aimed to evaluate the effects on the clinical signs of poisoning and adverse effects of intravenous lipid emulsion treatment in 82 animals (dogs and cats) with suspected poisonings over 18 months. Physical examination parameters and state of consciousness were documented every hour after the intravenous administration of a bolus of 2 ml/kg and 0.25 ml/kg/min over 60 minutes of a 20% intravenous lipid emulsion. The modified Glasgow coma scale and laboratory findings (blood gas analysis, triglyceride, lactate) were evaluated initially and three hours after discontinuing intravenous lipid emulsion administration. A statistical evaluation of the occurrence of adverse effects and the development of laboratory values was performed. A decrease in respiratory rate in the second control (8-12 hours) after ILE was observed. Three hours after completing of the intravenous lipid emulsion, triglyceride concentration increased about 10 times (p

In correlative light and electron microscopy (CLEM), the fluorescent images must be registered to the EM images with high precision. Due to the different contrast of EM and fluorescence images, automated correlation-based alignment is not directly possible, and registration is often done by hand using a fluorescent stain, or semi-automatically with fiducial markers. We introduce “DeepCLEM”, a fully automated CLEM registration workflow. A convolutional neural network predicts the fluorescent signal from the EM images, which is then automatically registered to the experimentally measured chromatin signal from the sample using correlation-based alignment. The complete workflow is available as a Fiji plugin and could in principle be adapted for other imaging modalities as well as for 3D stacks.

Abstract Covid-19 has been a global concern since 2019, crippling the world economy and health. Biological diagnostic tools have since been developed to identify the virus from bodily fluids and since the virus causes pneumonia, which results in lung inflammation, the presence of the virus can also be detected using medical imaging by expert radiologists. The success of each diagnostic method is measured by the hit rate for identifying Covid infections. However, the access for people to each diagnosis tool can be limited, depending on the geographic region and, since Covid treatment denotes a race against time, the diagnosis duration plays an important role. Hospitals with X-ray opportunities are widely distributed all over the world, so a method investigating lung X-ray images for possible Covid-19 infections would offer itself. Promising results have been achieved in the literature in automatically detecting the virus using medical images like CT scans and X-rays using supervised artificial neural network algorithms. One of the major drawbacks of supervised learning models is that they require enormous amounts of data to train, and generalize on new data. In this study, we develop a Swish activated, Instance and Batch normalized Residual U-Net GAN with dense blocks and skip connections to create synthetic and augmented data for training. The proposed GAN architecture, due to the presence of instance normalization and swish activation, can deal with the randomness of luminosity, that arises due to different sources of X-ray images better than the classical architecture and generate realistic-looking synthetic data. Also, the radiology equipment is not generally computationally efficient. They cannot efficiently run state-of-the-art deep neural networks such as DenseNet and ResNet effectively. Hence, we propose a novel CNN architecture that is 40% lighter and more accurate than state-of-the-art CNN networks. Multi-class classification of the three classes of chest X-rays (CXR), ie Covid-19, healthy and Pneumonia, is performed using the proposed model which had an extremely high test accuracy of 99.2% which has not been achieved in any previous studies in the literature. Based on the mentioned criteria for developing Corona infection diagnosis, in the present study, an Artificial Intelligence based method is proposed, resulting in a rapid diagnostic tool for Covid infections based on generative adversarial and convolutional neural networks. The benefit will be a high accuracy of lung infection identification with 99% accuracy. This could lead to a support tool that helps in rapid diagnosis, and an accessible Covid identification method using CXR images.

Abstract Eukaryotes may experience oxygen deprivation under both physiological and pathological conditions. Because oxygen shortage leads to a reduction in cellular energy production, all eukaryotes studied so far conserve energy by suppressing their metabolism. However, the molecular physiology of animals that naturally and repeatedly experience anoxia is underexplored. One such animal is the marine nematode Laxus oneistus. It thrives, invariably coated by its sulfur-oxidizing symbiont Candidatus Thiosymbion oneisti, in anoxic sulfidic or hypoxic sand. Here, transcriptomics and proteomics showed that, whether in anoxia or not, L. oneistus mostly expressed genes involved in ubiquitination, energy generation, oxidative stress response, immune response, development, and translation. Importantly, ubiquitination genes were also highly expressed when the nematode was subjected to anoxic sulfidic conditions, together with genes involved in autophagy, detoxification and ribosome biogenesis. We hypothesize that these degradation pathways were induced to recycle damaged cellular components (mitochondria) and misfolded proteins into nutrients. Remarkably, when L. oneistus was subjected to anoxic sulfidic conditions, lectin and mucin genes were also upregulated, potentially to promote the attachment of its thiotrophic symbiont. Furthermore, the nematode appeared to survive oxygen deprivation by using an alternative electron carrier (rhodoquinone) and acceptor (fumarate), to rewire the electron transfer chain. On the other hand, under hypoxia, genes involved in costly processes (e.g., amino acid biosynthesis, development, feeding, mating) were upregulated, together with the worm’s Toll-like innate immunity pathway and several immune effectors (e.g., bactericidal/permeability-increasing proteins, fungicides). In conclusion, we hypothesize that, in anoxic sulfidic sand, L. oneistus upregulates degradation processes, rewires the oxidative phosphorylation and reinforces its coat of bacterial sulfur-oxidizers. In upper sand layers, instead, it appears to produce broad-range antimicrobials and to exploit oxygen for biosynthesis and development.

BackgroundMental health is an increasing concern among vulnerable populations, including college students and veterans. ObjectiveThe purpose of this study was to determine if mobile health technology combined with health coaching can better enable a user to self-manage their mental health. MethodsThis study evaluated the mobile app “Biofeedback” that provided health coaching on stress self-management for college student veterans’ mental health concerns. Twenty-four college student veterans were recruited from a large public university in Texas during the spring 2020 semester, impacted by COVID-19. Ten participants were assigned to the intervention group where they used the mobile Biofeedback app on their smartphones and smartwatches, and 14 were assigned to the control group without the app; assignment was based on mobile phone compatibility. Both groups participated in one initial lab session where they learned a deep-breathing exercise technique. The intervention group was then asked to use the mobile Biofeedback app during their daily lives and a smartwatch, and the control group was asked to perform the breathing exercises on their own. Both groups filled out Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) self-assessments at 2-week intervals. At the end of the semester, both groups were given an exit interview to provide user experience and perceived benefits of health coaching via the mobile biofeedback app. ResultsThe deep-breathing exercise in the initial lab session reduced stress in both groups. Over the course of the study, the app recorded 565 coached breathing exercises with a significant decrease (approximately 3 beats per minute) in participants’ heart rate during the 6-minute time period immediately after conducting the breathing exercises (Spearman rank correlation coefficient –0.61, P

Abstract Chemotherapeutic drugs such as the alkylating agent Temozolomide (TMZ), in addition to reducing tumor mass, can also sensitize tumors to immune recognition by transient upregulation of multiple stress induced NKG2D ligands (NKG2DL). However, the potential for an effective response by innate lymphocyte effectors such as NK and γδ T cells that recognize NKG2DL is limited by the drug’s concomitant lymphodepleting effects. We have previously shown that modification of γδ T cells with a methylguanine DNA methyltransferase (MGMT) transgene confers TMZ resistance via production of O6-alkylguanine DNA alkyltransferase (AGT) thereby enabling γδ T cell function in therapeutic concentrations of TMZ. In this study, we tested this strategy which we have termed Drug Resistant Immunotherapy (DRI) to examine whether combination therapy of TMZ and MGMT-modified γδ T cells could improve survival outcomes in four human/mouse xenograft models of primary and refractory GBM. Our results confirm that DRI leverages the innate response of γδ T cells to chemotherapy-induced stress associated antigen expression and achieves synergies that are significantly greater than either individual approach.

Abstract Determination of treatment response to immunotherapy in glioblastoma multiforme (GBM) is a process which can take months. Detection of CD8+ T cell recruitment to the tumor with a noninvasive imaging modality such as positron emission tomography (PET) may allow for tumor characterization and early evaluation of therapeutic response to immunotherapy. In this study, we utilized 89Zr-labeled anti-CD8 cys-diabody-PET to provide proof-of-concept to detect CD8+ T cell immune response to oncolytic herpes simplex virus (oHSV) M002 immunotherapy in a syngeneic GBM model. Immunocompetent mice (n = 16) were implanted intracranially with GSC005 GBM tumors, and treated with intratumoral injection of oHSV M002 or saline control. An additional non-tumor bearing cohort (n = 4) receiving oHSV M002 treatment was also evaluated. Mice were injected with 89Zr-labeled anti-CD8 cys-diabody seven days post oHSV administration and imaged with a preclinical PET scanner. Standardized uptake value (SUV) was quantified. Ex vivo tissue analyses included autoradiography and immunohistochemistry. PET imaging showed significantly higher SUV in tumors which had been treated with M002 compared to those without M002 treatment (p = 0.0207) and the non-tumor bearing M002 treated group (p = 0.0021). Accumulation in target areas, especially the spleen, was significantly reduced by blocking with the non-labeled diabody (p

In correlative light and electron microscopy (CLEM), the fluorescent images must be registered to the EM images with high precision. Due to the different contrast of EM and fluorescence images, automated correlation-based alignment is not directly possible, and registration is often done by hand using a fluorescent stain, or semi-automatically with fiducial markers. We introduce “DeepCLEM”, a fully automated CLEM registration workflow. A convolutional neural network predicts the fluorescent signal from the EM images, which is then automatically registered to the experimentally measured chromatin signal from the sample using correlation-based alignment. The complete workflow is available as a Fiji plugin and could in principle be adapted for other imaging modalities as well as for 3D stacks.

Methodologies to assess stem cell differentiation in the culturing state are needed for regenerative medicine and tissue engineering techniques. In recent years, convolutional neural networks (CNNs), a class of deep neural networks, have made impressive advancements in image-based classification, recognition and detection tasks. CNNs have been introduced as a non-invasive cell characterization method by learning features directly from image data of unlabeled cells. Furthermore, this approach serves as a rapid and inexpensive methodology with high performance compared to traditional techniques that require complex laboratory procedures including antibody staining and gene expression analysis. Here, we studied the potential of the CNNs approach to recognize stem cell differentiation based on cell morphology utilizing phasecontrast microscopy images.We have examined the differentiation potential of bone marrow mesenchymal stem cells (BMSCs) into tenocytes, with the treatment of bone morphogenetic protein-12 (BMP-12). After treatment, the phase-contrast images of cells were obtained directly from cell culture flasks to train CNN and the differentiated phenotype of stem cells was characterized by immunostaining. CNN was able to classify the cells into three groups including non-stem cells (chondrocytes), stem cells (BMSCs) and differentiated stem cells (tenocytes) based on their morphology with 92.2 % accuracy. The presented study revealed that CNN performed faster and non-invasive cell classification task compared to traditional methodologies.

Today, medical technology manufacturers enter the service market through the development of digital service innovations. In the field of audiology, these developments increasingly shift the service capacities from audiologists to manufacturers and technical systems. However, the technology-driven developments of manufacturers lack acceptance of hearing device users and undermine the important role of audiologists within the service provision. By following a user-centered design approach in order to deal with the technological and social challenges of disruptive services, we aim to develop service innovations on an integrated service platform in the field of tele-audiology. To ensure the acceptance of technology-driven service innovations among hearing device users and audiologists, we systematically integrated these actors in a participatory innovation process. With qualitative and quantitative data we identified several requirements and preferences for different service innovations in the field of tele-audiology. According to the preferences of the different actors, we proposed a service platform approach based on a connected hearing device in three pillars of application: 1) one-to-one (1:1) service innovations based on a remote fitting concept directly improve the availability of services offered by audiologists without being physically present. Based on this, 2) one-to-many (1:N) service innovations allow the use of the connected hearing device as an indirect data source for training a machine learning algorithm that empowers users through the automation of service processes. A centralized server system collects the data and performs the training of this algorithm. The optimized algorithm is provided to the connected hearing devices to perform automatic acoustic scene classification. This in turn allows optimization of the hearing devices within each acoustic scene. After the user-centered development of the different service innovations which are designed to converge on an integrated service platform, we experimentally evaluated the functionality and applicability of the system as well as the associated role models between the technical system, the hearing device users and audiologists. As a future outlook, we show potentials to use the connected hearing device for 3) cross-industry (N:M) service innovations in contexts outside the healthcare domain and give practical implications for the market launch of successful service innovations in the field of tele-audiology.

Cell-free based approaches are introduced as a promising treatment method for articular cartilage. The success of this method requires cell colonisation from resident tissue into cell-free implants. The objective of our study is to promote the cell colonisation into cell-free collagen I based implants by mechanical stimulation. Therefore, a new in vitro cellular model consisting chondrocyte-seeded matrix and cell-free implants was developed in a polydimethylsiloxan (PDMS) mold. These constructs were cultured under dynamic and static culture conditions. For the dynamic culture, we have developed an in-house bioreactor system where both the load and the deformation applied to the specimen are recorded. Cyclic compression, with a strain of 5% and frequency of 0.1 Hz, was applied to constructs without any break. At the end of three days of dynamic and static cultivation, the cell-free implants were seperated from cell-seeded matrix and cultured in a petri dish three days long. Afterwards, they were analysed using fluoresence dyes. The microscopic assessment indicated that there was a cell migration into the cell-free implants which were cultured dynamically.

Abstract Patient-derived xenografts (PDXs) provide an opportunity to evaluate the effects of therapies in an environment that more closely resembles the human condition than that seen with long-term passage cell lines. In the current studies, we investigated the effects of FAK inhibition on two neuroblastoma PDXs in vitro. Cells were treated with two small molecule inhibitors of FAK, PF-573,228 (PF) and 1,2,4,5-benzentetraamine tetrahydrochloride (Y15). Following FAK inhibition, cell survival and proliferation decreased significantly and cell cycle arrest was seen in both cell lines. Migration and invasion assays were used to determine the effect of FAK inhibition on cell motility, which decreased significantly in both cell lines in the presence of either inhibitor. Finally, tumor cell stemness following FAK inhibition was evaluated with extreme limiting dilution assays as well as with immunoblotting and quantitative real-time PCR for the expression of stem cell markers. FAK inhibition decreased formation of tumorspheres and resulted in a corresponding decrease in established stem cell markers. FAK inhibition decreased many characteristics of the malignant phenotype, including cancer stem cell like features in neuroblastoma PDXs, making FAK a candidate for further investigation as a potential target for neuroblastoma therapy.

Objectives To understand attitudes towards infertility and willingness to pay (WTP) towards a publicly funded national assistive reproductive therapies (ART) programme.Design Attitudes survey with dichotomous and open-ended WTP questions.Setting Online survey administered in the USA, UK, Spain, Norway, Sweden, Finland, Denmark and China.Participants 7945 respondents, analysed by country. Nordic respondents were pooled into a regionally representative sample.Primary and secondary outcome measures Primary outcome measures were proportion of sample agreeing with different infertility-related and ART-related value statements and supporting a monthly contribution to fund a national ART programme, expressed in local currency. Secondary outcome measure was maximum WTP.Results Across the nationally representative samples, 75.5% of all respondents agreed with infertility as a medical condition and 82.3% and 83.7% with ART eligibility for anyone who has difficulty having a baby or a medical problem preventing them from having a baby, respectively. 56.4% of respondents supported a defined monthly contribution and 73.9% supported at least some additional contribution to fund a national ART programme. Overall, converting to euros, median maximum WTP was €3.00 and mean was €15.47 (95% CI 14.23 to 16.72) per month. Maximum WTP was highest in China and the USA and lowest in the European samples.Conclusions This large, multicountry survey extends our understanding of public attitudes towards infertility and fertility treatment beyond Europe. It finds evidence that a majority of the public in all sampled countries/regions views infertility as a treatable medical condition and supports the idea that all infertile individuals should have access to treatments that improve the chance of conception. There was also strong agreement with the idea that the desire for children is a basic human need. WTP questions showed that a majority of respondents supported a monthly contribution to fund a national ART programme, although there is some evidence of an acquiescence bias that may overstate support among specific samples.

Investigation of the mechanisms responsible for aggressive neuroblastoma and its poor prognosis is critical to identify novel therapeutic targets and improve survival. Enhancer of Zeste Homolog 2 (EZH2) is known to play a key role in supporting the malignant phenotype in several cancer types and knockdown of EZH2 has been shown to decrease tumorigenesis in neuroblastoma cells. We hypothesized that the EZH2 inhibitor, GSK343, would affect cell proliferation and viability in human neuroblastoma. We utilized four long-term passage neuroblastoma cell lines and two patient-derived xenolines (PDX) to investigate the effects of the EZH2 inhibitor, GSK343, on viability, motility, stemness and in vivo tumor growth. Immunoblotting confirmed target knockdown. Treatment with GSK343 led to significantly decreased neuroblastoma cell viability, migration and invasion, and stemness. GSK343 treatment of mice bearing SK-N-BE(2) neuroblastoma tumors resulted in a significant decrease in tumor growth compared to vehicle-treated animals. GSK343 decreased viability, and motility in long-term passage neuroblastoma cell lines and decreased stemness in neuroblastoma PDX cells. These data demonstrate that further investigation into the mechanisms responsible for the anti-tumor effects seen with EZH2 inhibitors in neuroblastoma cells is warranted.

Prostate cancer (PCa) is the most common cancer and the third most frequent cause of male cancer death in Germany. MicroRNAs (miRNA) appear to be involved in the development and progression of PCa. A diagnostic differentiation from benign prostate hyperplasia (BPH) is often only possible through transrectal punch biopsy. This procedure is described as painful and carries risks. It was investigated whether urinary miRNAs can be used as biomarkers to differentiate the prostate diseases above. Therefore urine samples from urological patients with BPH (25) or PCa (28) were analysed using Next-Generation Sequencing to detect the expression profile of total and exosomal miRNA/piRNA. 79 miRNAs and 5 piwi-interacting RNAs (piRNAs) were significantly differentially expressed (adjusted p-value < 0.05 and log2-Fc > 1 or < -1). Of these, 6 miRNAs and 2 piRNAs could be statistically validated (AUC on test cohort > = 0.7). In addition, machine-learning algorithms were used to identify a panel of 22 additional miRNAs, whose interaction makes it possible to differentiate the groups as well. There are promising individual candidates for potential use as biomarkers in prostate cancer. The innovative approach of applying machine learning methods to this kind of data could lead to further small RNAs coming into scientific focus, which have so far been neglected.

The hydrothermal vent tubeworm Riftia pachyptila hosts a single 16S rRNA phylotype of intracellular sulfur-oxidizing symbionts, which vary considerably in cell morphology and exhibit a remarkable degree of physiological diversity and redundancy, even in the same host. To elucidate whether multiple metabolic routes are employed in the same cells or rather in distinct symbiont subpopulations, we enriched symbionts according to cell size by density gradient centrifugation. Metaproteomic analysis, microscopy, and flow cytometry strongly suggest that Riftia symbiont cells of different sizes represent metabolically dissimilar stages of a physiological differentiation process: While small symbionts actively divide and may establish cellular symbiont-host interaction, large symbionts apparently do not divide, but still replicate DNA, leading to DNA endoreduplication. Moreover, in large symbionts, carbon fixation and biomass production seem to be metabolic priorities. We propose that this division of labor between smaller and larger symbionts benefits the productivity of the symbiosis as a whole.

Cryo-electron microscopy reveals how ubiquitination promotes the methylation of histone H3 by the histone-modifying complex COMPASS.

Studies concerning the mechanical properties of the human periodontal ligament under dynamic compression are rare. This study aimed to determine the viscoelastic properties of the human periodontal ligament under dynamic compressive loading. Ten human incisor specimens containing 5 maxillary central incisors and 5 maxillary lateral incisors were used in a dynamic mechanical analysis. Frequency sweep tests were performed under the selected frequencies between 0.05 Hz and 5 Hz with a compression amplitude that was 2% of the PDL's initial width. The compressive strain varied over a range of 4%-8% of the PDL's initial width. The storage modulus, ranging from 28.61 MPa to 250.21 MPa, increased with the increase in frequency. The loss modulus (from 6.00 MPa to 49.28 MPa) also increased with frequency from 0.05 Hz- 0.5 Hz but remained constant when the frequency was higher than 0.5 Hz. The tanδ showed a negative logarithmic correlation with frequency. The dynamic moduli and the loss tangent of the central incisor were higher than those of the lateral incisor. This study concluded that the human PDL exhibits viscoelastic behavior under compressive loadings within the range of the used frequency, 0.05 Hz- 5 Hz. The tooth position and testing frequency may have effects on the viscoelastic properties of PDL.

The maintenance and propagation of complex mixtures of cells in vitro in the form of native organs or engineered organoids has contributed to understanding mechanisms of cell and organ development and function which can be translated into therapeutic benefits. For example, allogeneic cultured postnatal human thymus tissue has been shown to support production of naïve recipient T cells when transplanted into patients with complete DiGeorge anomaly and other genetic defects that result in congenital lack of a thymus. Patients receiving such transplants typically exhibit reversal of their immunodeficiency and normalization of their peripheral blood T cell receptor V-beta repertoire, with long-term survival. This study was designed to assess the histopathologic changes that occur in postnatal human thymus slices when cultured according to protocols used for transplanted tissues. Results showed that as thymic organ cultures progressed from days 0 through 21, slices developed increasing amounts of necrosis, increasing condensation of thymic epithelium, and decreasing numbers of residual T cells. The architecture of the thymic epithelial network remained generally well-preserved throughout the 21 days of culture, with focal expression of cytokeratin 14, a putative biomarker of thymic epithelial cells with long-term organ-repopulating potential. All organ slices derived from the same donor thymus closely resembled one another, with minor differences in size, shape, and relative content of cortex versus medulla. Similarly, slices derived from different donors showed similar histopathologic characteristics when examined at the same culture time point. Taken together, these results demonstrate that diagnostic criteria based on structural features of the tissue identifiable via hematoxylin and eosin staining and cytokeratin immunohistochemistry can be used to evaluate the quality of slices transplanted into patients with congenital athymia.

It is widely known that tendon tissues are subjected to repeated cyclic mechanical load which influences cellular processes. The involvement of principles of mechanics in tissue engineering contributes to the investigations of the connection between mechanical and biological parameters in cellular processes and as well as to the development of new approaches for specific treatment methods. The healing process of injured tendons includes tenocyte migration which occurs from intact regions of tendon into the wound site. The aim of the present study is to investigate and enhance the migration characteristics of tenocytes under uniaxial mechanical stretching using an in-house tensile bioreactor system. Uniaxial mechanical stretching is applied to tenocyte-seeded silicone as well as collagen membranes, which possess different material properties. Tenocyte-seeded silicone membranes were investigated under three different loading conditions, including unstimulated (control), 3% and 5% strain, at frequency of 0.5 Hz. Tenocyte-seeded collagen membranes were investigated using three different frequencies, including unstimulated (control), 0.1 Hz and 0.5 Hz at strain of 4%. The main finding in this study is that uniaxially mechanical stretching at 3% strain enhances the cell migration more than 5% strain on silicone membranes.

In October 2016, an adolescent boy sought care for acute genital ulceration in Cologne, Germany. We presumed a sexually transmitted infection, but initial diagnostic procedures yielded negative results. He was hospitalized because swab samples from the lesion grew toxigenic Corynebacterium diphtheriae, leading to the diagnosis of possibly sexually transmitted cutaneous diphtheria.

BackgroundLow-grade gliomas cause significant neurological morbidity by brain invasion. There is no universally accepted objective technique available for detection of enlargement of low-grade gliomas in the clinical setting; subjective evaluation by clinicians using visual comparison of longitudinal radiological studies is the gold standard. The aim of this study is to determine whether a computer-assisted diagnosis (CAD) method helps physicians detect earlier growth of low-grade gliomas.Methods and findingsWe reviewed 165 patients diagnosed with grade 2 gliomas, seen at the University of Alabama at Birmingham clinics from 1 July 2017 to 14 May 2018. MRI scans were collected during the spring and summer of 2018. Fifty-six gliomas met the inclusion criteria, including 19 oligodendrogliomas, 26 astrocytomas, and 11 mixed gliomas in 30 males and 26 females with a mean age of 48 years and a range of follow-up of 150.2 months (difference between highest and lowest values). None received radiation therapy. We also studied 7 patients with an imaging abnormality without pathological diagnosis, who were clinically stable at the time of retrospective review (14 May 2018). This study compared growth detection by 7 physicians aided by the CAD method with retrospective clinical reports. The tumors of 63 patients (56 + 7) in 627 MRI scans were digitized, including 34 grade 2 gliomas with radiological progression and 22 radiologically stable grade 2 gliomas. The CAD method consisted of tumor segmentation, computing volumes, and pointing to growth by the online abrupt change-of-point method, which considers only past measurements. Independent scientists have evaluated the segmentation method. In 29 of the 34 patients with progression, the median time to growth detection was only 14 months for CAD compared to 44 months for current standard of care radiological evaluation (p < 0.001). Using CAD, accurate detection of tumor enlargement was possible with a median of only 57% change in the tumor volume as compared to a median of 174% change of volume necessary to diagnose tumor growth using standard of care clinical methods (p < 0.001). In the radiologically stable group, CAD facilitated growth detection in 13 out of 22 patients. CAD did not detect growth in the imaging abnormality group. The main limitation of this study was its retrospective design; nevertheless, the results depict the current state of a gold standard in clinical practice that allowed a significant increase in tumor volumes from baseline before detection. Such large increases in tumor volume would not be permitted in a prospective design. The number of glioma patients (n = 56) is a limitation; however, it is equivalent to the number of patients in phase II clinical trials.ConclusionsThe current practice of visual comparison of longitudinal MRI scans is associated with significant delays in detecting growth of low-grade gliomas. Our findings support the idea that physicians aided by CAD detect growth at significantly smaller volumes than physicians using visual comparison alone. This study does not answer the questions whether to treat or not and which treatment modality is optimal. Nonetheless, early growth detection sets the stage for future clinical studies that address these questions and whether early therapeutic interventions prolong survival and improve quality of life.

Synaptic vesicles (SVs) are a key component of neuronal signaling and fulfil different roles depending on their composition. In electron micrograms of neurites, two types of vesicles can be distinguished by morphological criteria, the classical "clear core" vesicles (CCV) and the typically larger "dense core" vesicles (DCV), with differences in electron density due to their diverse cargos. Compared to CCVs, the precise function of DCVs is less defined. DCVs are known to store neuropeptides, which function as neuronal messengers and modulators [1]. In C. elegans, they play a role in locomotion, dauer formation, egg-laying, and mechano- and chemosensation [2]. Another type of DCVs, also referred to as granulated vesicles, are known to transport Bassoon, Piccolo and further constituents of the presynaptic density in the center of the active zone (AZ), and therefore are important for synaptogenesis [3]. To better understand the role of different types of SVs, we present here a new automated approach to classify vesicles. We combine machine learning with an extension of our previously developed vesicle segmentation workflow, the ImageJ macro 3D ART VeSElecT. With that we reliably distinguish CCVs and DCVs in electron tomograms of C. elegans NMJs using image-based features. Analysis of the underlying ground truth data shows an increased fraction of DCVs as well as a higher mean distance between DCVs and AZs in dauer larvae compared to young adult hermaphrodites. Our machine learning based tools are adaptable and can be applied to study properties of different synaptic vesicle pools in electron tomograms of diverse model organisms.

Anaerobic thermophiles inhabit relic environments that resemble the early Earth. However, the lineage of these modern organisms co-evolved with our planet. Hence, these organisms carry both ancestral and acquired genes and serve as models to reconstruct early metabolism. Based on comparative genomic and proteomic analyses, we identified two distinct groups of genes in Thermovibrio ammonificans: the first codes for enzymes that do not require oxygen and use substrates of geothermal origin; the second appears to be a more recent acquisition, and may reflect adaptations to cope with the rise of oxygen on Earth. We propose that the ancestor of the Aquificae was originally a hydrogen oxidizing, sulfur reducing bacterium that used a hybrid pathway for CO2 fixation. With the gradual rise of oxygen in the atmosphere, more efficient terminal electron acceptors became available and this lineage acquired genes that increased its metabolic flexibility while retaining ancestral metabolic traits.