Supporting Function Research Articles

IL-1β Induces a Proinflammatory Fibroblast Microenvironment that Impairs Lung Progenitors' Function.

Chronic obstructive pulmonary disease (COPD) is characterized by a persistent inflammatory state in the lungs and defective tissue repair. Although the inflammatory response in patients with COPD is well characterized and known to be exaggerated during exacerbations, its contribution to lung injury and abnormal repair is still unclear. In this study, we aimed to investigate how the inflammatory microenvironment affects the epithelial progenitors and their supporting mesenchymal niche cells involved in tissue repair of the distal lung. We focused on IL-1β, a key inflammatory mediator that is increased during exacerbations of COPD, and used an organoid model of lung epithelial cells and fibroblasts to assess the effect of IL-1β treatment on these cells' transcriptome and secreted factors. Whereas direct treatment of the lung organoids with IL-1β promoted organoid growth, this switched toward inhibition when it was added as fibroblast pretreatment followed by organoid treatment. We then investigated the IL-1β-driven mechanisms in the fibroblasts and found an inflammatory response related to (C-X-C motif) ligand (CXCL) chemokines; we confirmed that these chemokines were responsible for the impaired organoid growth and found that targeting their C-X-C chemokine receptors 1/2 (CXCR1/2) receptors or the IL-1β intracellular signaling reduced the proinflammatory response and restored organoid growth. These data demonstrate that IL-1β alters the fibroblasts' state by promoting a distinct inflammatory response, switching their supportive function on epithelial progenitors toward an inhibitory one in an organoid assay. These results imply that chronic inflammation functions as a shift toward inhibition of repair, thereby contributing to chronic inflammatory diseases like COPD.

Modern approaches in the surgical treatment of infectious complications of diabetic foot syndrome

The study analyzed modern Russian and foreign scientific publications devoted to infectious complications in patients with diabetes mellitus and diabetic foot syndrome. The data of the International Diabetes Federation, the state register of patients with diabetes mellitus, demonstrate that the actual prevalence of diabetes mellitus is much higher than the registered data, which predisposes to large annual economic costs for the prevention, diagnosis, and treatment of diabetes mellitus, taking into account the treatment of complications and monitoring the morbidity of the global population. In the treatment of infectious complications in these patients, classical purulent surgeries are widely used, including opening abscesses and phlegmon and drainage of anatomical spaces of the foot. The classifications of infectious complications of diabetic foot syndrome has evolved. Modern surgical methods of treatment of infectious complications in these patients are highlighted. The classical approach to surgical opening and drainage of purulent foci is highly traumatic owing to impaired blood supply and innervation, prolonged postoperative period, and impaired supporting function of the limb, which is irreversible, at least during inpatient stay. The paper also described the use of minimally invasive approaches, including the use of endovide support, for the drainage of deep plantar phlegmon and the performance of staged rehabilitation, including additional treatment methods such as ultrasound cavitation, local application of negative pressure, and ozone therapy.

Assessment of Burden in Family Caregivers of Chronic Hemodialysis and Peritoneal Dialysis Patients During the Pandemic Period of COVID-19.

In Greece, patients undergoing hemodialysis (HD) usually go to dialysis centers two or three times a week for three/four hours per session because the treatment for home is unavailable; therefore, caregivers should perform supportive transportation and care functions. This study was designed to assess the burden and quality of life in caregivers of patients undergoing hemodialysis and peritoneal dialysis (PD) and to record their attitude toward Coronavirus Disease-2019 (COVID-19). We studied caregivers of patients undergoing hemodialysis and peritoneal dialysis. A total of 80 caregivers took part (30 caregivers of patients of PD and 50 caregivers of patients of HD). The final form of the questionnaire was based on the Quality-of-Life Scale (SF-12) and the Zarit Scale, in order to record the scale of burden and the effect on them throughout the process. The Fear Due to COVID-19 Scale (FCV-19S) contributed to recording the caregivers' fear toward the pandemic of COVID-19. Most of the caregivers were women with an average age of about 60years and 6-10 were the patient's wife or partners. The prevalence of the moderate or severe burden of the patients was found at 18.7%, and the few or no burden at all at 33.8%. The prevalence of fear toward COVID-19 was at very high levels, reaching 82.5% in all caregivers. During the pandemic period of COVID-19, the role of the caregivers of the patients, both who follow the PD method and those who have joined the HD, is particularly important. Their quality of life has been partially affected in all dimensions.

Homeostasis of carbohydrates and reactive oxygen species is critically changed in the brain of middle-aged mice: Molecular mechanisms and functional reasons

The brain is an organ that consumes a lot of energy. In the brain, energy is required for synaptic transmission, numerous biosynthetic processes and axonal transport in neurons, and for many supportive functions of glial cells. The main source of energy in the brain is glucose and to a lesser extent lactate and ketone bodies. ATP is formed at glucose catabolism via glycolysis and oxidative phosphorylation in mitochondrial electron transport chain (ETC) within mitochondria being the main source of ATP. With age, brain's energy metabolism is disturbed, involving a decrease in glycolysis and mitochondrial dysfunction. The latter is accompanied by intensified generation of reactive oxygen species (ROS) in ETC leading to oxidative stress. Recently, we have found that crucial changes in energy metabolism and intensity of oxidative stress in the mouse brain occur in middle age with minor progression in old age. In this review, we analyze the metabolic changes and functional causes that lead to these changes in the aging brain.

Glia Cell Morphology Analysis Using the Fiji GliaMorph Toolkit.

Glial cells are the support cells of the nervous system. Glial cells typically have elaborate morphologies that facilitate close contacts with neighboring neurons, synapses, and the vasculature. In the retina, Müller glia (MG) are the principal glial cell type that supports neuronal function by providing a myriad of supportive functions via intricate cell morphologies and precise contacts. Thus, complex glial morphology is critical for glial function, but remains challenging to resolve at a sub-cellular level or reproducibly quantify in complex tissues. To address this issue, we developed GliaMorph as a Fiji-based macro toolkit that allows 3D glial cell morphology analysis in the developing and mature retina. As GliaMorph is implemented in a modular fashion, here we present guides to (a) setup of GliaMorph, (b) data understanding in 3D, including z-axis intensity decay and signal-to-noise ratio, (c) pre-processing data to enhance image quality, (d) performing and examining image segmentation, and (e) 3D quantification of MG features, including apicobasal texture analysis. To allow easier application, GliaMorph tools are supported with graphical user interfaces where appropriate, and example data are publicly available to facilitate adoption. Further, GliaMorph can be modified to meet users' morphological analysis needs for other glial or neuronal shapes. Finally, this article provides users with an in-depth understanding of data requirements and the workflow of GliaMorph. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Download and installation of GliaMorph components including example data Basic Protocol 2: Understanding data properties and quality 3D-essential for subsequent analysis and capturing data property issues early Basic Protocol 3: Pre-processing AiryScan microscopy data for analysis Alternate Protocol: Pre-processing confocal microscopy data for analysis Basic Protocol 4: Segmentation of glial cells Basic Protocol 5: 3D quantification of glial cell morphology.

Recent strategies for constructing hierarchical multicomponent nanoparticles/metal-organic framework hybrids and their applications.

Hybrid nanoparticles with unique tailored morphologies and compositions can be utilized for numerous applications owing to their combination of inherent properties as well as the structural and supportive functions of each component. Controlled encapsulation of nanoparticles within nanospaces (NPNSs) of metal-organic frameworks (MOFs) (denoted as NPNS@MOF) can generate a large number of hybrid nanomaterials, facilitating superior activity in targeted applications. In this review, recent strategies for the fabrication of NPNS@MOFs with a hierarchical architecture, tailorability, unique intrinsic properties, and superior catalytic performance are summarized. In addition, the latest and most important examples in this sector are emphasized since they are more conducive to the practical applicability of NPNS@MOF nanohybrids.

An assessment of the effectiveness of supervision in preventive healthcare institutions under the purview of the Regional Directorate of Health Services, Kalutara

Background: Supervision is an essential element in primary healthcare. It is not only the number that matters but the quality and effectiveness of supervision as well. Ineffective supervision is a cause of poor performance that can lead to sub-optimal health outcomes.Objective: To assess the effectiveness of supervision in preventive healthcare institutions under the administrative purview of the Regional Directorate of Health Services (RDHS), Kalutara.Method: A descriptive cross-sectional study was designed and carried out in all preventive sector healthcare institutions under the administrative purview of the RDHS, Kalutara. The entire population of the supervisors (Regional Director and Deputy Regional Director of Health Services, Consultant Community Physician, Medical Officer-Maternal & Child Health, Regional Epidemiologist, District Dental Surgeon, Supervisory Public Health Nursing Officers, Supervisory Public Health Inspector, Medical Officers of Health, Additional Medical Officers of Health, Supervisory Public Health Inspectors, Public Health Nursing Sisters, and Supervisory Public Health Midwives) and supervisees (Public Health Inspectors and School Dental Therapists) in the RDHS division except the Public Health Midwives (PHMs) was included in the study as their actual numbers are low. The selection of PHMs, the major category of supervisees, was subjected to random sampling. Self-administered questionnaires, focus group discussions, and observatory visits were used to collect the data. Data were analyzed both quantitatively and qualitatively. The effectiveness of supervision was assessed utilizing Manchester Clinical Supervision Scale (MCSS-26). Knowledge, attitudes, and practices of supervisors were assessed through a self-administered questionnaire and to some extent through observations.Results: The overall response rate was 67.8%. The knowledge related to supportive supervision among the supervisors was moderate. The level of knowledge was not significantly different among the different categories of supervisors. The level of attitudes towards supervision was also moderate. However, it was significantly different among the supervisory categories. As per the scale devised through the questionnaire, the supervisory practice was moderate as well, but it was not significantly different among the different categories of supervisors. The mean score of MCSS-26 was 65.67 indicating that overall supervision was ineffective by its threshold limit of 73. Apart from the administrative function of supervision, the supportive and educational functions were largely ineffective.Conclusion and recommendations: The effectiveness of supervision was suboptimal in preventive care health institutions of the RDHS division Kalutara. Appropriate measures that focused on enhancing supportive and educational functions of supervision are therefore required to improve the effectiveness of supervision among different categories of supervisors in the division. Designing and implementing more focused training and development activities to improve knowledge, attitude, and practices in supportive supervision; facilitating, encouraging, and empowering the supervisors to implement their post-supervisory recommendations; and utilizing the MCSS-26 as a tool of measuring supervisory effectiveness for the purpose of monitoring and evaluating the supervisory activities, are therefore recommended to improve the effectiveness of supervision in the division.

Robust trajectory-constrained frequency control for microgrids considering model linearization error

Grid supportive modes integrated within inverter-based resources can improve the frequency response of renewable-rich microgrids. The synthesis of grid supportive modes to guarantee frequency trajectory constraints under a predefined disturbance set is challenging but essential. To tackle this challenge, a numerical optimal control (NOC)-based control synthesis methodology is proposed. Without loss of generality, a wind-diesel fed microgrid is studied, where we aim to design grid supportive functions in the wind turbine. In the control design, linearized models are used, and the linearization-induced errors are quantitatively analyzed by reachability and interval arithmetics and represented in the form of interval uncertainties. Then, the NOC problem can be formulated into a robust mixed-integer linear program. The control structure is strategically configured into two levels to realize online deployment. The proposed control is verified on the modified 33-node microgrid with a full-order three-phase nonlinear model in Simulink. The simulation results show the effectiveness of the proposed control paradigm and the necessity of considering linearization-induced uncertainty.

Applying Deep Learning-based concepts for the detection of device misconfigurations in power systems

The electrical energy system is undergoing major changes due to the necessity for more sustainable energy generation and the following increased integration of novel grid-connected devices, such as inverters or electric vehicle supply equipment. To operate reliably in novel circumstances, as created by the decentralization of generation, power systems usually need grid supportive functions provided by these devices. These functions include control mechanisms such as reactive power dispatch used for voltage control or active power reduction depending on the voltage. As the main contribution of this work, an approach for the development of the detection of misconfigured (e.g., wrongly parameterized control curve) grid devices using solely operational data is proposed. By generating and analyzing operational data of power distribution grids, a Deep Learning-based approach is applied to the detection problem given. An end-to-end framework is used to synthesize and process the data as well as to apply machine learning techniques to it. The results offer insights into the applicability and possible ways to improve the proposed solution and how it could be employed by grid operators. The findings show that DL methods, in contrast to traditional machine learning, can be used for the problem at hand and that the framework developed offers the necessary tools to fine-tune and scale the solution for broader usage.

Out of the Shadow: Blue Light Exposure Induces Apoptosis in Müller Cells

Awareness toward the risks of blue light (BL) exposure is rising due to increased use of BL-enriched LEDs in displays. Short-wave BL (400-500 nm) has a high photochemical energy, leading to the enhanced production of reactive oxygen species (ROS). BL potentially plays a role in causing dry eye, cataracts, and age-related macular degeneration (AMD). The effect of BL on retinal pigment epithelium cells (RPEs) or photoreceptors has been extensively investigated. In contrast, only a few studies have investigated the effects of BL exposure on Müller cells (MCs). This is mainly due to their lack of photosensitive elements and the common assumption that their reaction to stress is only secondary in disease development. However, MCs perform important supportive, secretory, and immune functions in the retina, making them essential for retinal survival. Increased oxidative stress is a key player in many retinal diseases such as AMD or glaucoma. We hypothesize that increased oxidative stress can also affect MCs. Thus, we simulated oxidative stress levels by exposing primary porcine MCs and human MIO-M1 cells to BL. To confirm the wavelength-specificity, the cells were further exposed to red (RL), purple (PL), and white light (WL). BL and WL exposure increased ROS levels, but only BL exposure led to apoptosis in primary MCs. Thus, BL accounted for the harmful part of WL exposure. When cells were simultaneously exposed to BL and RL (i.e., PL), cell damage due to BL could be partly prevented, as could the inhibition of p53, demonstrating the protective effect of RL and p53 dependency. In contrast, BL hardly induced apoptosis in MIO-M1 cells, which is likely due to the immortalization of the cells. Therefore, enhanced oxidative stress levels can significantly harm MC function, probably leading to decreased retinal survival and, thus, further enhancing the progression of retinal diseases. Preventing the cell death of these essential retinal cells represents a promising therapy option to enhance retinal survival.

High MN1 Expression Is Associated with an Lspc-Enriched Phenotype and Glycolysis Representing a New Vulnerability in Acute Myeloid Leukemia

Despite a steady increase in the number of targeted therapies over the past decades, the 5-year overall survival (OS) rate remains poor in acute myeloid leukemia (AML). Currently, high expression of the oncogenic Meningioma 1 (MN1) is associated with poor OS in AMLs with normal karyotype, and we correlated its expression with a more immature cellular composition in AML samples. Hence, we hypothesized that supplementation of AML cells that usually fail to engraft in xenograft models, such as acute promyelocytic leukemia (APL), with MN1 would promote in vivo expansion in mice allowing the study of potential therapeutic vulnerabilities. The in vitro experiments were performed in human AML cell lines, primary AML cells (n=39), and isolated healthy CD34+ cells. MN1-overexpression (OE) was lentivirally performed. Bioenergetic profiles were evaluated by a Seahorse analyzer. Gene expression was measured by RNA-sequencing/qPCR. Protein levels were measured by immunofluorescence microscopy. Viability and surface protein expression was evaluated by flow cytometry. For in vivo studies, eight-weeks old female NSGS mice were transplanted with MN1-OE primary APL blast cells, and mice were followed for 12 weeks. Cells from the mouse organs were isolated, analyzed, and sorted for human APL blasts (CD45+CD117+CD33+) for ex vivo studies. We show that genetic MN1-OE in APL cells resulted in increased cell survival upon cytotoxic therapy, and decreased sensitivity to ATRA-induced terminal differentiation in short and long term cultures (3/8 days). In healthy CD34+ cells, we observed that MN1-OE was able to increase cell proliferation and stemness properties in CMP-sorted (CD34+CD38+CD123+CD45RA-) but not in GMP-sorted cells (CD34+CD38+CD123+CD45RA+), showing in human models the results from Heuser et al., 2011 in murine MN1-model. Co-expression of MN1+PML-RARα in healthy CD34+ cells resulted in superior expansion with retention of the CD34 marker, in comparison with the single hits. At the molecular level, APL cells with MN1high displayed transcriptional programs associated with "HYPOXIA"/"HSC-UP", whereas MN1low levels correlated with "OXPHOS-UP"/"GMP-UP". Despite no evident differences in Seahorse analysis, MN1-OE cells exhibited increased levels of the glycolytic enzyme PDK1. Functionally, MN1-OE cells were more sensitive to glycolytic inhibitors 2,2-dichloroacetophenone (a PDK1 inhibitor) and 2-deoxyglucose, revealing glycolysis as a metabolic vulnerability in MN1high AMLs, which was further validated in primary AML samples. These data are in line with our previous report indicating that more immature AML subtypes typically display a more glycolytic metabolic profile (Erdem et al, 2022). MN1 is an intrinsically disordered protein containing a long polyQ-stretch that is required for transformation (Riedel et al, 2021). We questioned whether the expression of chaperone proteins would be necessary for the appropriate functioning of MN1. We observed that expression of the DNAJB6 isoform 2 (DNAJB6b) correlated with MN1 expression across a large panel of genetic subtypes of AML, including more immature AML subtypes, such as the TP53-mutant AML but also in APL. shRNA-induced knockdown in AML cells of DNAJB6b resulted in cytosolic retention of MN1, associated with reduced cell survival. In vivo, the patient-derived xenograft model showed engraftment of APL samples upon MN1-OE, with the colonization of secondary organs and splenomegaly, which was not observed in the control. Flow cytometry analysis revealed that MN1-engrafted mice displayed increased levels of APL blasts in comparison with control, which had a large proportion of mature myeloid cells (CD33+CD11b+). Ex vivo screen of engrafted cells revealed increased resistance to ATRA-induced differentiation in MN1-OE sorted blasts. We provide further evidence to support the role of MN1 as an oncogenic hit allowing in vivo studies of difficult-to-engraft AML subtypes. Functionally, high MN1 expression resulted in decreased differentiation, retention of stem-like properties, and metabolic shift towards a more glycolytic state. We demonstrated that DNAJB6b controls the cellular localization of MN1, with its downregulation associated with the loss of MN1 supportive functions. Finally, our findings suggest that targeting glycolysis can be leveraged as a therapeutically actionable mechanism for driving cell death in MN1high AMLs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

SIRT3 alleviates mitochondrial dysfunction induced by recurrent low glucose and improves the supportive function of astrocytes to neurons.

Hypoglycemia is an independent risk factor of cognitive impairment in patients with diabetes. Our previous study indicated that dysfunction of astrocytic mitochondria induced by recurrent low glucose (RLG) may account for hypoglycemia-associated neuronal injury and cognitive decline. Sirtuin 3 (SIRT3) is a key deacetylase for mitochondrial proteins and has recently been demonstrated to be an important regulator of mitochondrial function. However, whether mitochondrial dysfunction due to hypoglycemia is associated with astrocytic SIRT3 remains unclear, and few studies have focused on the impact of astrocytic SIRT3 on neuronal survival. In the present work, primary mouse cortical astrocytes cultured in normal glucose (5.5mM) and high glucose (16.5mM) were treated with five rounds of RLG (0.1mM). The results showed that RLG suppressed SIRT3 expression in a glucose-dependent manner. High-glucose culture considerably increased the vulnerability of SIRT3 to RLG, leading to disrupted mitochondrial morphology in astrocytes. Overexpression of SIRT3 markedly improved astrocytic mitochondrial function and reduced RLG-induced oxidative stress. Moreover, SIRT3 suppressed a shift towards a neuroinflammatory A1-like reactive phenotype of astrocytes in response to RLG with reduced IL-1β, IL-6, and TNFα levels. Furthermore, it elevated brain-derived neurotrophic factor (BDNF) levels and promoted neurite growth by activating BDNF/TrkB signaling in the co-cultured neurons. The present study reveals the probable crosstalk between neurons and astrocytes after hypoglycemic exposure and provides a potential target in treating hypoglycemia-associated neuronal injury.

Environmental perception and control of gastrointestinal immunity by the enteric nervous system.

The enteric nervous system (ENS) forms a versatile sensory system along the gastrointestinal tract that interacts with most cell types in the bowel. Herein, we portray host-environment interactions at the intestinal mucosal surface through the lens of the enteric nervous system. We describe local cellular interactions as well as long-range circuits between the enteric, central, and peripheral nervous systems. Additionally, we discuss recently discovered mechanisms by which enteric neurons and glia respond to biotic and abiotic environmental changes and how they regulate intestinal immunity and inflammation. The enteric nervous system emerges as an integrative sensory system with manifold immunoregulatory functions under both homeostatic and pathophysiological conditions.

Social Support, Coping, and Cancer-Related Health Burden in Long-term Survivors Treated with Hematopoietic Stem Cell Transplantation as Adolescents or Young Adults.

Purpose: Long-term adolescent and young adult hematopoietic stem cell transplantation (HCT) survivors face complex physical and psychological treatment effects that contribute to cancer-related health burden. We aimed to identify the role of social support and coping strategies on cancer-related health burden. Methods: This cross-sectional analysis included HCT recipients from the INSPIRE trial [NCT00799461], who received their first transplant between ages 15 and 39. As our primary outcome, we used the health burden subscale of the Cancer and Treatment Distress measure. We assessed correlates using the Short Form-36v2 physical component summary, brief Coping Orientation to Problems Experienced (COPE), and ENRICHD Social Support Inventory. We used hierarchical multivariable linear regression to identify factors associated with cancer-related health burden, with the first step including sociodemographic and clinical factors, the second step adding physical function, and the third step including social support and coping. Results: Participants (N = 293) were 52% male and 93% white, non-Hispanic, with a mean age of 30.2 (standard deviation 6.6) at first transplant. In step one, sex accounted for ∼3% of the variance (p = 0.006). Adding physical function explained an additional 33% of the variance (p = <0.001). Social support and coping strategies explained 11% of the variance (p = <0.001). The final model explained 47% of the variance; better physical function, more social support, and active coping were associated with lower cancer-related health burden, while female sex, venting, and distraction were associated with higher cancer-related health burden. Conclusion: Supporting physical function and fostering social support and active coping may help mitigate cancer-related health burden in this population. Clinical Trial Registration: NCT00799461.

The Role of Implementation of IDSR Strategy on Indicators of the Core and Supportive Surveillance Functions at the Head of Localities

Background: Disease surveillance is a cornerstone of outbreak detection and control. The evaluation of a disease surveillance system is important to ensure its performance over time.&#x0D; Objectives: The role of implementation; of IDSR strategy on indicators of the core and supportive surveillance functions at the head of localities.&#x0D; Materials and methods: An intervention approach (one group pre-test post-test design) was conducted and baseline data of communicable diseases surveillance was obtained from selected Kassala state, four localities, and 60 health facilities. After implementing an integrated disease surveillance and response (IDSR) strategy for six months to evaluate core and support functions. The same questionnaire (WHO- guided modified and tested questionnaire) that was used in the baseline was applied.&#x0D; Results: The study showed that indicators of the supportive at the head of locality was improved at the head of four localities in terms of standards and guidelines, training, supervision and resources which witnessed significant improvement during pre and post intervention more than 90%.&#x0D; Conclusion: Improvements in indicators of core and support functions at the locality and state levels are inextricably linked to the quality of activities carried out at health facility levels. This was noticed when the value of intervention-supported functions increased, which may also be justified by the technique of computation technique, which is based on the aggregate of indicators of health facilities.

Article Retracted

Background: Disease surveillance is a cornerstone of outbreak detection and control. The evaluation of a disease surveillance system is important to ensure its performance over time.&#x0D; Objectives: The role of implementation; of IDSR strategy on indicators of the core and supportive surveillance functions at the head of localities.&#x0D; Materials and methods: An intervention approach (one group pre-test post-test design) was conducted and baseline data of communicable diseases surveillance was obtained from selected Kassala state, four localities, and 60 health facilities. After implementing an integrated disease surveillance and response (IDSR) strategy for six months to evaluate core and support functions. The same questionnaire (WHO- guided modified and tested questionnaire) that was used in the baseline was applied.&#x0D; Results: The study showed that indicators of the supportive at the head of locality was improved at the head of four localities in terms of standards and guidelines, training, supervision and resources which witnessed significant improvement during pre and post intervention more than 90%.&#x0D; Conclusion: Improvements in indicators of core and support functions at the locality and state levels are inextricably linked to the quality of activities carried out at health facility levels. This was noticed when the value of intervention-supported functions increased, which may also be justified by the technique of computation technique, which is based on the aggregate of indicators of health facilities.

Ultra-small molybdenum-based nanodots as an antioxidant platform for effective treatment of periodontal disease.

Periodontal disease (PD) is a local inflammatory disease with high morbidity, manifesting tissue destruction results from inflammation of the host immune response to bacterial antigens and irritants. The supportive function of connective tissue and skeletal tissue can be jeopardized without prompt and effective intervention, representing the major cause of tooth loss. However, traditional treatments exhibited great limitations, such as low efficacies, causing serious side effects and recurrent inflammatory episodes. As a major defense mechanism, reactive oxygen species (ROS) play important roles in the pathological progression of PD. Antioxidant therapy is widely believed to be an effective strategy for ROS-triggered diseases, including oxidative stress-induced PD. Most antioxidants can only scavenge one or a few limited kinds of ROS and cannot handle all kinds. In addition, current antioxidant nanomaterials present limitations associated with toxicity, low stability, and poor biocompatibility. To this end, we develop ultra-small molybdenum-based nanodots (MoNDs) with strong ROS in oxidative stress-induced PD. To the best of our knowledge, this is the first time that MoNDs have been used for PD. In the present study, MoNDs have shown extremely good therapeutic effects as ROS scavengers. Spectroscopic and in vitro experiments provided strong evidence for the roles of MoNDs in eliminating multiple ROS and inhibiting ROS-induced inflammatory responses. In addition, the mouse model of PD was established and demonstrated the feasibility of MoNDs as powerful antioxidants. It can alleviate periodontal inflammation by scavenging multiple ROS without obvious side effects and exhibit good biocompatibility. Thus, this newly developed nanomedicine is effective in scavenging ROS and inhibiting M1 phenotypic polarization, which provides promising candidates for the treatment of PD.

A Framework for Developing Educational Industry 4.0 Activities and Study Materials

The advent of Industry 4.0 is changing the role of human labour towards a more supportive function in the production system, requiring new digital-, technical-, interdisciplinary-, collaborative- and communicative competencies. This challenges educational institutions to develop new teaching activities and materials to address ever emerging needs. To address this, this paper presents an Educational Framework to support educators in developing new teaching activities and study material for Industry 4.0. The model distinguishes itself from other educational design models by combining an iterative approach toward problem-solving, with the concept of authentic task design, as the core elements. Based on 14 pilot cases, it is concluded that educational framework have increased the educational activities in the areas in focus.

Impaired supporting function of the feet in adolescents with congenital cleft lip and palate with a mesial ratio of dentition

BACKGROUND: Impaired occlusal relationships of dental rows can cause adaptive changes in the entire musculoskeletal system, including the feet. Thus, studying the biomechanics of the feet with the possibility of changing the medical rehabilitation program of patients with dentomaxillofacial anomalies of various geneses is important.&#x0D; AIM: To investigate the plantographic characteristics of the feet in adolescents with congenital cleft lip and palate and combined dentomaxillofacial anomaly with a mesial ratio of dental rows and analyze patterns of distribution of plantar pressure before and after reconstructive operations on the jaws and restoration of facial harmony.&#x0D; MATERIALS AND METHODS: The study included 31 patients of both sexes aged 1517 years, who were divided into two groups. The first group consisted of 15 patients with congenital cleft lip and palate after the early stages of reconstructive surgery (cheilorhinoplasty and uranoplasty) and developed a combined dentomaxillofacial anomaly. The second group, with milder lesion, included 16 patients with combined dentomaxillofacial anomaly and do not have congenital cleft lip and palate. Patients had skeletal forms of mesial ratios of dental rows. To correct the bite and restore the aesthetics of the face, all patients underwent simultaneous bone reconstructive (orthognathic) surgery on the upper and lower jaws, including genioplasty in some of them, to restore the normal relationship of the jaw bones and harmonize the face. The plantographic characteristics of the feet were studied in patients before surgery and 16 months after surgery. The results of these two groups were compared with a pantographic examination of 18 healthy children (control group) without these pathologies in the maxillofacial region and without impairment of the supporting function of the foot.&#x0D; RESULTS: The first and second groups had a significant decrease in the indices of support on both feet before surgery: t, up to 85 (normal, 96); m, up to 16 (normal, 23); and s, up to 20 (normal, 24), which indicate a decrease in the spring function of the transverse and longitudinal arches and impairment of the supporting function of the feet. It was most pronounced in patients with congenital cleft lip and palate. Deviations in the magnitude of the Clark angle were multidirectional on the left and right feet, which indicated an abnormally high asymmetry of the load distribution between the feet. Functional relationships between the foot arches were pathologically enhanced to values of rs = 0.83 (normal, rs = 0.14), which indicated a formed pathological support strategy of the feet. After reconstructive operations on the jaws, the biomechanics of the feet in patients with combined dentomaxillofacial anomaly (without congenital cleft lip and palate) tended to normalize.&#x0D; CONCLUSIONS: It is necessary to consider the possible aggravating effect of the feet with a modified support strategy on the condition of the dentofacial area. Moreover, the comprehensive diagnosis plan of adolescents with congenital cleft lip and palate and combined dentomaxillofacial anomaly and combined dentomaxillofacial anomaly (without congenital cleft lip and palate) should include a study of the supporting function of the feet, considering rehabilitation measures to correct the distribution of plantar pressure.

Benzalkonium Chloride, Even at Low Concentrations, Deteriorates Intracellular Metabolic Capacity in Human Conjunctival Fibroblasts.

The objective of this study was to clarify the effects of benzalkonium chloride (BAC) on two-dimensional (2D) and three-dimensional (3D) cultures of human conjunctival fibroblast (HconF) cells, which are in vitro models replicating the epithelial barrier and the stromal supportive functions of the human conjunctiva. The cultured HconF cells were subjected to the following analyses in the absence and presence of 10−5% or 10−4% concentrations of BAC; (1) the barrier function of the 2D HconF monolayers, as determined by trans-endothelial electrical resistance (TEER) and FITC dextran permeability, (2) real-time metabolic analysis using an extracellular Seahorse flux analyzer, (3) the size and stiffness of 3D HconF spheroids, and (4) the mRNA expression of genes that encode for extracellular matrix (ECM) molecules including collagen (COL)1, 4 and 6, and fibronectin (FN), α-smooth muscle actin (α-SMA), ER stress related genes including the X-box binding protein-1 (XBP1), the spliced XBP1 (sXBP1) glucose regulator protein (GRP)78, GRP94, and the CCAAT/enhancer-binding protein homologous protein (CHOP), hypoxia inducible factor 1α (HIF1α), and Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α). In the presence of BAC, even at low concentrations at 10−5% or 10−4%, the maximal respiratory capacity, mitochondrial respiratory reserve, and glycolytic reserve of HconF cells were significantly decreased, although the barrier functions of 2D HconF monolayers, the physical properties of the 3D HconF spheroids, and the mRNA expression of the corresponding genes were not affected. The findings reported herein highlight the fact that BAC, even such low concentrations, may induce unfavorable adverse effects on the cellular metabolic capacity of the human conjunctiva.