Destructive Damage Research Articles

INTERDISCIPLINARITY IN COMPLEX THERAPEUTIC APPROACH OF PSYCHIATRIC PATIENTS WITH DYSFUNCTIONAL SYNDROME OF THE STOMATOGNATED SYSTEM

Diseases in the maxillofacial sphere and especially the dysfunctional syndrome of the stomatognathic system have many connections and interferences with the psychiatric pathology and, last, but not least, the appearance and aesthetics have an impact on social life and success. On the other hand, there has been a significant increase in the use of antipsychotics in recent decades. The negative impact on oral health has also increased. The ability to diagnose mental illness is essential due to the social stigma associated with these disorders and a correct differential diagnose as well. This paper describes an oro-dental rehabilitation in one case, psychiatrically treated, with mandibular and maxilla missing teeth and dental destruction and prosthetic damage, temporomandibular disorders pathology due to the disbalanced occlusion and depression and anxiety, with specific medication, fixed and removable hybrid prosthesis and intra oral complex rehabilitation.

Excessive Apoptosis in Ulcerative Colitis: Crosstalk Between Apoptosis, ROS, ER Stress, and Intestinal Homeostasis

Ulcerative colitis (UC), an etiologically complicated and relapsing gastrointestinal disease, is characterized by the damage of mucosal epithelium and destruction of the intestinal homeostasis, which has caused a huge social and economic burden on the health system all over the world. Its pathogenesis is multifactorial, including environmental factors, genetic susceptibility, epithelial barrier defect, symbiotic flora imbalance, and dysregulated immune response. Thus far, although immune cells have become the focus of most research, it is increasingly clear that intestinal epithelial cells play an important role in the pathogenesis and progression of UC. Notably, apoptosis is a vital catabolic process in cells, which is crucial to maintain the stability of intestinal environment and regulate intestinal ecology. In this review, the mechanism of apoptosis induced by reactive oxygen species and endoplasmic reticulum stress, as well as excessive apoptosis in intestinal epithelial dysfunction and gut microbiology imbalance are systematically and comprehensively summarized. Further understanding the role of apoptosis in the pathogenesis of UC may provide a novel strategy for its therapy in clinical practices and the development of new drugs.

The Influence of Temperature and Host Gender on Bacterial Communities in the Asian Citrus Psyllid.

Simple SummaryDiaphorina citri is an important natural vector for the Huanglongbing pathogen, which causes destructive damage to citrus production. The temperature and gender are critical abiotic and biotic factors affecting insect physiology as well as the symbiont abundance. Nevertheless, how temperature and gender affect the bacterial communities present in D. citri is still unclear. This study used high-throughput sequencing of 16S ribosomal RNA amplicons to identify amplicon sequence variants in D. citri. The dominant phylum was Proteobacteria, and Candidatus Profftella and Wolbachia were the dominant taxa in all groups. Furthermore, under a high-temperature treatment, Profftella was the prevalent symbiont in females, but Wolbachia had a higher abundance in males. In males, Profftella was more abundant under low-temperature treatments than high-temperature treatments. In contrast, Wolbachia showed a higher abundance under high-temperature treatments than under low-temperature treatments. The results will provide a new vision for understanding the co-adaptation of D. citri and its symbionts to environmental stresses.The Asian citrus psyllid, D. citri Kuwayama is the primary vector for Candidatus Liberibacter asiaticus (CLas), which causes a destructive disease in citrus plants. Bacterial symbionts are important determinants of insect physiology, and they can be impacted by many external factors. Temperature is an important abiotic factor affecting insect physiology, and it is also known that differences in symbiont proportions may vary in different insect genders. To date, it is unclear how the symbionts of D. citri are affected by temperature and gender. This study used high-throughput sequencing of 16S ribosomal RNA amplicons to determine how temperature and gender affect the bacterial communities present in D. citri. We identified 27 amplicon sequence variants (ASVs) belonging to 10 orders, seven classes, and five phyla. The dominant phylum was Proteobacteria (99.93%). Other phyla, including Firmicutes, Bacteroidota, Deinococcota, Cyanobacteria, and Actinobacteriota, were less abundant (<0.1%). Profftella (71.77–81.59%) and Wolbachia (18.39–28.22%) were the predominant taxa in all samples. Under high-temperature treatment, Profftella was more common in females, while Wolbachia had a higher abundance in males. In males, Profftella was more abundant under low-temperature treatments than under high-temperature treatments. In contrast, Wolbachia showed a higher abundance under high-temperature treatments than under low-temperature treatments. An RT-qPCR (quantitative real-time PCR) approach confirmed the results obtained with high-throughput DNA sequencing. Our results provide a basis for understanding the co-adaptation of D. citri and its symbionts to environmental temperature stress.

Real-time monitoring the interfacial dynamic processes at model cell membranes: Taking cell penetrating peptide TAT as an example

A real-time and molecule-level monitoring of the interfacial dynamic interactions between molecules and a cell membrane is of vital importance. Herein, taking TAT, one of the most representative cell penetrating peptides, as an example, a photo-voltage transient technique and a dynamic giant bistratal vesicle (GBV) leakage method were combined with the traditional giant unilamellar vesicle (GUV) leakage assays, to provide a molecule-level understanding of the dynamic membrane interaction process performed in a low ionic strength and neutral pH condition. The photo-voltage test based on supported phospholipid bilayers showed a quick disturbance (<1 min) followed by a continuous reconstruction of the membrane by peptides, leading to a slight destruction (at TAT concentrations lower than 1 μg mL−1, i.e., 0.64 μM) or strong damage (e.g. at 10 μg mL−1, i.e., 6.4 μM) of the bilayer structure. The GUV/GBV leakage assays further demonstrated the TAT-induced membrane deformation and transmembrane diffusion of dyes, which occurred in an immediate, linear, and TAT-concentration dependent manner. Moreover, the flux of dye across the substrate-immobilized membranes was approximately three times of that across the substrate-free ones. This work gives information on time and molecular mechanism of the TAT-membrane interactions, demonstrates the different permeabilizing effects of TAT on immobilized and free membranes. Overall, it provides useful strategies to investigate the nano-bio interfacial interactions in a simple, global and real-time way.

GBT021601, a Next Generation HbS Polymerization Inhibitor: Results of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Adults Living with Sickle Cell Disease and Healthy Volunteers

Background: Sickle cell disease (SCD) is caused by polymerization of sickle hemoglobin (HbS), resulting in red blood cell (RBC) sickling, RBC destruction, vaso-occlusion and end-organ damage. GBT021601 is an oral, small molecule, next-generation HbS polymerization inhibitor. Similar to voxelotor, the first generation HbS polymerization inhibitor, GBT021601 increases hemoglobin-oxygen (Hb-O2) affinity and stabilizes hemoglobin (Hb) in the oxy-hemoglobin (oxyHb) state, thereby inhibiting polymerization of HbS in RBCs. The fraction of Hb bound to drug - (Hb occupancy) approximates the oxyHb molecules per RBC. Compared to voxelotor, GBT021601 has the potential to achieve higher Hb occupancies. GBT021601 achieves greater exposures per dose and is more potent as measured by improvements in hematological parameters in an in vivo SCD mouse model (Dufu, Kobina 2020). We hypothesized that GBT021601 would achieve a substantial reduction in RBC hemolysis and increase in hemoglobin while maintaining a favorable safety profile. We therefore explored safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) in healthy volunteer participants (HVs) and adults living with SCD.Methods: Two studies are in progress: 1) the first in human (FIH), randomized, double-blind, placebo-controlled, parallel group phase 1 study for HVs ages 18-55 years; and 2) a single arm, intrapatient single dose and multiple ascending dose study in homozygous HbSS SCD patients ages 18-60 years with baseline Hb levels ≥5.5 g/dL and ≤10.5 g/dL and without vaso-occlusive crisis or transfusion within 30 days of screening. The HV study tests single ascending doses (SAD) with a 6:2 randomization ratio. Doses administered to HV cohorts ranged from 50 mg to 2200 mg. The SCD patient study tests a single dose (100 mg) followed by multiple ascending doses of the study drug in the same patients to reach a % Hb occupancy of >20-30% over 7 weeks. The primary endpoints for both studies are safety and tolerability. Secondary endpoints include PK and PD. For the patient study, additional secondary endpoints are confirmation of the relationship between time matched GBT021601 concentrations and the change from baseline of clinical measures of anemia and hemolysis. Hb occupancy is calculated as a percentage of the molar ratio of drug concentrations in RBCs to the estimated Hb concentrations (using MCHC) in RBCs.Results: As of July 22, 2021, 63 HVs and 6 adults with SCD were enrolled. Thirty-nine HVs completed the study; one discontinued due to moving to a new geographical area and 23 were in follow-up. GBT021601 was generally well-tolerated, most adverse events (AE) were Grade 1 and 2, there were no deaths, and there was one serious adverse event in a HV that was not related to the study drug. There were no AEs indicative of tissue hypoxia. GBT021601 showed linear PK, high partitioning into RBCs, and a dose dependent increase in percent hemoglobin occupancy in HVs (Figure 1). From single doses of 50 to 1400 mg, the mean preliminary % Hb occupancy ranged from 0.88 to 25%, respectively, exceeding the Hb occupancies reported for HV receiving single doses of voxelotor over a similar range (Putz, 2017).Six adults with SCD have received a single 100 mg dose of GBT021601 and the dose has been well tolerated. Multiple-dose data in adults will be presented.Conclusions: Single doses of GBT021601 are well tolerated in HV and adults with SCD. Given its drug exposure, GBT021601 has the capacity to achieve a targeted Hb occupancy and attain the desired hematological effect at low doses, therefore reducing pill burden and improving clinical outcomes for individuals living with SCD. Forthcoming multiple-dose data will help to evaluate GBT021601's potential as a best-in-class, oral, disease-modifying therapy for SCD.Funding: This study was supported by Global Blood Therapeutics. [Display omitted] DisclosuresBrown: Pfizer: Research Funding; Imara: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Forma Therapeutics: Research Funding; Novo Nordisk: Consultancy; Global Blood Therapeutics: Consultancy, Research Funding. Redfern: Eisai: Other: Advisory Board; Linear Clinical Research: Current Employment; Pfizer: Other: Advisory Board; Novartis: Other: Advisory Board; Astra Zeneca: Other: Advisory Board; Roche: Other: Advisory Board. Lisbon: Global Blood Therapeutics: Current Employment. Washington: Global Blood Therapeutics: Consultancy. Agodoa: Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Smith-Whitley: Global Blood Therapeutics: Current Employment.

Distribution record of the invasive drywood termite Cryptotermes domesticus (Haviland) in Riau Province, Sumatra Island, Indonesia

The domestic drywood termite, Cryptotermes domesticus (Haviland), has been referred to in past literature as a native species originating in the Southeast Asia region. The species come to prominence due to its destructive damage to a dried wood log by creating passages and nests inside the wood. Its economic importance makes the species one of the monitored species in inter-island transport as part of a biosecurity initiative by the Indonesian Government. In the present study, we collected drywood termites’ specimens from four locations in Riau Province, Sumatra Island, and conducted morphological identification. In the end, we verify the presence of C. domesticus in all four sites studied. This finding establishes the continued presence of the species in Sumatra, one of the areas reported as the native distribution of the species other than Java and Kalimantan following the Holmgren reports in 1913. We believe this report can be an addition to the current status of C. domesticus in Sumatra and also be an addition to the biosecurity initiative list of monitored species regarding the C. domesticus native range in Indonesia.

Interdisciplinary approach to the management of a patient with Sjogren’s syndrome: a clinical case

Dryness of the mucous membranes (in mouth, nose, genitals in women) and skin are the most common complaints of patients with Sjogren’s disease — a multisystem immune‑mediated disorder that causes anxiety and concern associated with the difficulties of initial diagnosis. The authors present a clinical case of a patient with primary Sjogren’s syndrome, a large number of symptoms of digestive diseases, complaints of dryness of mucous membranes, in particular the oral cavity. The diagnosis was confirmed by allied specialists such as ophthalmologist, gynecologist, rheumatologist, dentist. Detailed dental examination revealed the main dental complaints (constant dry mouth, galitos, changes in taste), clinical condition (dryness of the red border of the lips, swelling of the oral mucosa, changes in the relief of the gums), decreased secretory activity and significant reduction of unstimulated salivation with a moderate level of stimulated salivation. It is noted that a significant decrease in sialometry (0.01 ml per minute) and functional activity of the small salivary glands (up to 18) confirms the presence of true xerostomia. Micro‑crystallization of saliva revealed disorganization of irregularly shaped structures, as well as a significant number of organic inclusions, which indicates a violation of homeostasis in the oral cavity. Given the results of ultrasound examination of the large salivary glands and the absence of enlargement and swelling of the glands during clinical examination, we can assume that the destructive damage to the glands is not so pronounced, evacuation function of the gland is not reduced, but the amount of secretion is significantly reduced. To provide medical aid to patients with Sjogren’s syndrome, the accessibility of the qualified consultation is important and required, with conduction of comprehensive examinations by allied specialists, including a dentist.&#x0D;

Storm damage risk assessment for offshore cage culture

This study establishes a practical methodology for storm damage risk assessment and zoning for offshore cage culture by superimposing the vulnerability theory onto hydrodynamic modeling. The peak significant wave height is statistically correlated to the normalized fatigue load criteria at specified loading cycles to classify the destruction duration and damage state during storm events. The yield damage of the flotation pipe under cyclical wave oscillations was identified as the major failure mechanism of the sea cage. The structural failure risk would significantly decrease to 4.5-m waves, which is much lower than the manufacturing standard due to cumulative damage in a relatively short operation time. The wave-circulation model was applied to hindcast 112 high-impact typhoon scenarios in the study area for the return period analysis of the storm wave field. The damage risk distribution of the cage culture was mapped across the landscape to increase storm strength according to the vulnerability classification. The effectiveness of island shielding was explicitly revealed, and the leeward side was overall less risky as the return period increased, with the safe area shrinking inshore. For extreme conditions over a 100-year return period, the shield performance of leeward bays varied significantly due to the shoreline profile differences. Some existing cage deployment locations are at-risk relative to the structural resistance capability, whereas other unrecognized areas might be suitable for cage culture. These findings imply the necessity of storm risk assessment before proactive prevention measures and deployment zoning. The methodology may also be adapted to storm risk predictions for other facilities in the coastal ocean.

Toxicity effects of size fractions of incinerated sewage sludge bottom ash on human cell lines

Sewage sludge bottom ash (SSBA) from the incineration plant used for the production of construction materials possibly possess heavy metals which might cause a negative impact on human health. Considering biosafety, we investigated the toxicity effects of 0.5–2 mm (aggregate substitute) and < 0.075 mm (cement substitute) in its solid and leachate form on human lung fibroblast cells (MRC-5) and human skin epidermal cells (HaCaT) on exposure through contact. MTS assay revealed the cellular responses of lung and skin cell lines to the leachates showing that the skin cells, which often interact with the external environment displayed better tolerance than the lung cells, whereas solid ash showed a concentration and size-dependent toxicity. Solid ash was found to downregulate the intracellular glutathione/superoxide dismutase activities and upregulate lactate dehydrogenase/lipid peroxidation activities thus inducing oxidative stress to the cell and subsequently resulting in the cell membrane leakage, destructive mitochondrial membrane potential (Δψm), apoptosis, and DNA damage, which is nearly 7-fold higher than the negative control. At a high concentration, DNA damage index of 1.09 and 1.29 was observed for the 0.5–2 mm sized ash leachate on skin cells and lung cells respectively, whereas for ash (<0.075 mm size) leachate, this fraction was 1.29 and 2.96, respectively. Overall, the ash leachate is found to be safer/biocompatible if they come in contact with humans as compared to SSBA in its solid form.

Curcumin-containing Silver Nanoparticles Prevent Carbon Tetrachloride- induced Hepatotoxicity in Mice.

Hepatotoxicity remains an important clinical challenge. Hepatotoxicity observed in response to toxins and hazardous chemicals may be alleviated by delivery of the curcumin in silver nanoparticles (AgNPs-curcumin). In this study, we examined the impact of AgNPs-curcumin in a mouse model of carbon tetrachloride (CCl4)-induced hepatic injury. Male C57BL/6 mice were divided into three groups (n=8 per group). Mice in group 1 were treated with vehicle control alone, while mice in Group 2 received a single intraperitoneal injection of 1 ml/kg CCl4 in liquid paraffin (1:1 v/v). Mice in group 3 were treated with 2.5 mg/kg AgNPs-curcumin twice per week for three weeks after the CCl4 challenge. Administration of CCL4 resulted in oxidative dysregulation, including significant reductions in reduced glutathione and concomitant elevations in the level of malondialdehyde (MDA). CCL4 challenge also resulted in elevated levels of serum aspartate transaminase (AST) and alanine transaminase (ALT); these findings were associated with the destruction of hepatic tissues. Treatment with AgNPs-curcumin prevented oxidative imbalance, hepatic dysfunction, and tissue destruction. A comet assay revealed that the CCl4 challenge resulted in significant DNA damage as documented by a 70% increase in nuclear DNA tail-length; treatment with AgNPscurcumin inhibited the CCL4-mediated increase in nuclear DNA tail-length by 34%. Administration of AgNPs-curcumin resulted in significant anti-oxidant activity in vivo. This agent has the potential to prevent hepatic tissue destruction and DNA damage that results from direct exposure to CCL4.

A Mitochondria‐Targeted Fluorescence Probe for Visualizing Detection of Hypochlorite in Living Cells

AbstractRheumatoid arthritis (RA) is an extremely common inflammatory disease that can lead to joint destruction and irreversible damage. Establishing a reliable and simple analytical method is essential for the early assessment of RA. Hypochlorous acid (HClO) serves as a biomarker, and patients with inflammatory diseases often have abnormal levels of HClO. A novel mitochondria‐targeted fluorescent probe ((E)‐2‐(2‐(6‐((dimethylcarbamothioyl)oxy)naphthalen‐2‐yl)vinyl)‐1‐ethyl‐3,3‐dimethyl‐3H‐indol‐1‐ium, Hcy‐HClO) has been designed with the purpose of monitoring HClO level fluctuations in biological systems. In the presence of HOCl, intramolecular charge transfer fluorescence is triggered, and the probe exhibits a clear change in the fluorescence signal under simulated physiological conditions. The probe features a fast response (5 s), high selectivity and sensitivity, and a lower detection limit towards HOCl. In addition, the probe exhibits great biocompatibility and low cytotoxicity. More importantly, the probe can effectively aggregate mitochondria and be applied to the imaging of intracellular HClO. It is possible that the developed probe is able to act as a powerful tool to diagnose and monitor various inflammatory diseases, including RA.

Archeological Traces of Sixth Century Earthquakes in İstanbul Küçükçekmece Lake Basin (Bathonea) Excavations

Located 20 km west of the Bosporus, the Bathonea ancient port settlement on the Avcılar / Firuzköy Peninsula northwest of Küçükçekmece Lagoon Lake has been the subject of archeological excavations with a multidisciplinary team since 2010. Excavations determined two separate structures with intense and destructive damage and studies were performed about whether or not this damage was caused by destructive earthquakes in the region. A church structure with an apse had most pronounced intense damage and skeletons belonging to two hugging individuals were identified under the stones of a collapsed dome. Additionally, coins dated to 550 and other archeological materials reveal the destructive earthquake occurred after 550 in the period of the Emperor Justinian (527-565). If it had occurred during the reign of a different emperor, the coins would have been out of circulation. Strong destructive traces were identified in other structures spread over a large area in the excavation site, apart from the apse structure. In the north of the peninsula nearly 600 m from the church structure, visible offsets and collapsed walls were revealed in the walls of a great water cistern. Deformation offsets and fractures observed in this cistern and in tunnels bringing water to the cistern provide evidence of earthquakes in the 6th century. After the structure became unusable, bricks and stones used for construction of other structures in the 7-8th centuries provide important data to date the earthquake. Excavations supporting geophysical studies continue. The results from the excavation confirm some historical earthquakes occurring in Istanbul and mentioned by ancient and medieval writers with archeological evidence for the first time.

Transfer of ownership on the basis of a sales agreement: some legal nuances

The publication is devoted to the analysis of some legal nuances of the transfer of ownership under a sales contract. First, the article describes the general characteristics of contracts aimed at the transfer of ownership and determines the place of a sales contract in their system. It is further established that the moment of transfer of ownership on the basis of a sales contract is not always tied to the time of the contract conclusion.&#x0D; Some special norms on the transfer of ownership, which are contained in the general provisions on purchase and sale, are analyzed and their limitations and superficiality are revealed. The absence of special legal regulation stipulated an appeal to the General Part of the Civil Code of Ukraine, where the general rule enshrines the practice of recognizing the moment of acquisition of ownership at the time of transfer for all contracts. Therefore, the paper further analyzes the requirement that the seller’s obligation to transfer the thing is considered fulfilled, which raised doubts about the success of the legislator to give such importance to the transfer while investing only one-sided meaning. Since the position is expressed and substantiated that the transfer of ownership cannot occur at the time of transfer of the goods by the seller, but in case of non-acceptance by the buyer. An important argument in favor of the latter thesis is the legislator’s diverge of the provisions on the transfer of ownership and the transfer of the risk of accidental destruction or accidental damage to goods in certain rules, correctly assuming the possibility of mismatch of the above moments.&#x0D; The publication emphasizes that even taking into account the moment of acceptance of the goods by the buyer when determining the moment of transfer of ownership is not always able to solve practical problems that may arise during the transfer of ownership under a sales contract, therefore, a conclusion is formulated on the need to revise the general legislative approach to determining the moment of transfer of ownership and its binding not to a unilateral act (transfer of the thing), but to the moment of action by the other party to the contract aimed at its goal achieving. Given that a sales contract is paid, it is determined that the moment of transfer of ownership should be considered the moment of receipt of counter-satisfaction by the counterparty under the contract (the buyer’s payment of the price for the purchased thing).

UAVs in Disaster Management: Application of Integrated Aerial Imagery and Convolutional Neural Network for Flood Detection

Floods have been a major cause of destruction, instigating fatalities and massive damage to the infrastructure and overall economy of the affected country. Flood-related devastation results in the loss of homes, buildings, and critical infrastructure, leaving no means of communication or travel for the people stuck in such disasters. Thus, it is essential to develop systems that can detect floods in a region to provide timely aid and relief to stranded people, save their livelihoods, homes, and buildings, and protect key city infrastructure. Flood prediction and warning systems have been implemented in developed countries, but the manufacturing cost of such systems is too high for developing countries. Remote sensing, satellite imagery, global positioning system, and geographical information systems are currently used for flood detection to assess the flood-related damages. These techniques use neural networks, machine learning, or deep learning methods. However, unmanned aerial vehicles (UAVs) coupled with convolution neural networks have not been explored in these contexts to instigate a swift disaster management response to minimize damage to infrastructure. Accordingly, this paper uses UAV-based aerial imagery as a flood detection method based on Convolutional Neural Network (CNN) to extract flood-related features from the images of the disaster zone. This method is effective in assessing the damage to local infrastructures in the disaster zones. The study area is based on a flood-prone region of the Indus River in Pakistan, where both pre-and post-disaster images are collected through UAVs. For the training phase, 2150 image patches are created by resizing and cropping the source images. These patches in the training dataset train the CNN model to detect and extract the regions where a flood-related change has occurred. The model is tested against both pre-and post-disaster images to validate it, which has positive flood detection results with an accuracy of 91%. Disaster management organizations can use this model to assess the damages to critical city infrastructure and other assets worldwide to instigate proper disaster responses and minimize the damages. This can help with the smart governance of the cities where all emergent disasters are addressed promptly.

Versatile gadolinium(III)-phthalocyaninate photoagent for MR/PA imaging-guided parallel photocavitation and photodynamic oxidation at single-laser irradiation

Current light-mediated photodynamic therapy (PDT) is far underutilized in clinical cancer treatment due to its low pharmacological effect. We herein proposed a new gadolinium(III)-phthalocyanine (GdPc)-enabled phototherapeutics, photoacoustic/dynamic therapy (PADT), towards in vivo solid tumors via parallel-produced photocavitation and photodynamic oxidation with excitation by a single pulsed laser. We demonstrated that pulsed irradiation of GdPc could simultaneously produce an intense acoustic effect and a high-level 1O2 quantum yield to afford mitochondrial damage and initiate programmed cell death. Under the guidance of magnetic resonance/photoacoustic dual-modal imaging, the mechanical oxygen-independent destruction of acoustic cavitation and the chemical damage of 1O2 were validated to afford combinatorial inhibition of tumors under either normal or hypoxic conditions after the agent delivered into the cancer cells by a pH-sensitive nanomicelle. The single-laser initiated PADT using GdPc as a versatile photoagent maximizes the use of light energy to minimize the dose requirement of oxygen and agent towards high therapeutic efficacy, surpassing dramatically over conventional PDT.

Monocyte Differentiation into Destructive Macrophages on In Vitro Administration of Gingival Crevicular Fluid from Periodontitis Patients.

Background: Periodontitis is an inflammatory condition of the tooth-supporting structures initiated and perpetuated by pathogenic bacteria present in the dental plaque biofilm. In periodontitis, immune cells infiltrate the periodontium to prevent bacterial insult. Macrophages derived from monocytes play an important role in antigen presentation to lymphocytes. However, they are also implicated in causing periodontal destruction and bystander damage to the host tissues. Objectives: The objective of the present study was to quantify the cytokine profile of gingival crevicular fluid (GCF) samples obtained from patients with periodontitis. The study further aimed to assess if GCF of periodontitis patients could convert CD14+ monocytes into macrophages of destructive phenotype in an in vitro setting. The secondary objectives of the study were to assess if macrophages that resulted from GCF treatment of monocytes could affect the synthetic properties, stemness, expression of extracellular matrix proteins, adhesion molecules expressed by gingival stem cells, gingival mesenchymal stromal cells, and osteoblasts. Methods: GCF, blood, and gingival tissue samples were obtained from periodontitis subjects and healthy individuals based on specific protocols. Cytokine profiles of the GCF samples were analyzed. CD14+ monocytes were isolated from whole blood, cultured, and treated with the GCF of periodontitis patients to observe if they differentiated into macrophages. Further, the macrophages were assessed for a phenotype by surface marker analysis and cytokine assays. These macrophages were co-cultured with gingival stem cells, epithelial, stromal cells, and osteoblasts to assess the effects of the macrophages on the synthetic activity of the cells. Results: The GCF samples of periodontitis patients had significantly higher levels of IFN gamma, M-CSF, and GM-CSF. Administration of the GCF samples to CD14+ monocytes resulted in their conversion to macrophages that tested positive for CD80, CD86, and CD206. These macrophages produced increased levels of IL-1β, TNF-α, and IL-6. Co-culture of the macrophages with gingival stem cells, epithelial cells, and stromal cells resulted in increased cytotoxicity and apoptotic rates to the gingival cells. A reduced expression of markers related to stemness, extracellular matrix, and adhesion namely OCT4, NANOG, KRT5, POSTN, COL3A1, CDH1, and CDH3 were seen. The macrophages profoundly affected the production of mineralized nodules by osteoblasts and significantly reduced the expression of COL1A1, OSX, and OCN genes. Conclusion: In periodontitis patients, blood-derived monocytes transform into macrophages of a destructive phenotype due to the characteristic cytokine environment of their GCF. Further, the macrophages affect the genotype and phenotype of the resident cells of the periodontium, aggravate periodontal destruction, as well as jeopardize periodontal healing and resolution of inflammation.

SEL VƏ DAŞQIN AXINLARINDA DAĞ ÇAYLARI MƏCRASININ YUYULMA DƏRİNLİYİNİN TƏYİNİ

Abstract. The article is dedicated to the determination of the wash depth of mountain rivers in floods and overflows. As well-known, hydrotechnical equipment is exposed to destructive damages of the floods and overflows. The undersurface of bridge basement and coast guards are washed away, the surface of drainage devices in water supply and dams (Düker) at river crossings are opened up. Therefore, the protection of the equipment against the destructive damage of the floods and overflows should be ensured. To this aim, first of all, the depth of the fortification of the equipment basement in riverbeds and the width through which the river can flow should be determined and the works of installing coast guards should be accordingly implemented. Since the flow regime of rivers due to floods in the course of mountain riverbeds dramatically changes, the width, depth, roughness and cross-sectional area of the riverbed also changes. To that reason, in the smallest case, calculation formulas includes the average width and wash depth of the riverbed in the course of the floods and overflows, average diameter of undersurface soils, the slope of the location of hydrotechnical structures, velocity due to the average diameter of the riverbed soils and so on. The article contains the analyses of theoretical and practical materials about the floods and overflows in mountain rivers. For the rivers flowing through the southern hills of Great Caucasus Mountains, the expressions for determining the riverbed parameters and hydrological parameters of rivers are used. According to the expressions, average width due to non-washing of the riverbed in floods in accordance with flood flow and slope of the studied part of the riverbed, the average depth of the riverbed crossing the flood, the average velocity of the flow and the wash depth in accordance with them are determined. basing on all these, the determining method of the wash depth of mountain riverbeds in floods have been worked out and determining the wash depth have been recorded. The studied methodology can be used in determining the riverbed parameters in floods and overflows. Keywords: Flood, riverbed deformation, mountain river, wash depth, average diameter of undersurface sediments, riverbed stability, flood velocity

Post-disaster effect on radiation safety in multihospital radiological unit: a one-year post-earthquake observation report in Lombok

A series of earthquakes that hit Lombok, Nusa Tenggara Barat, in the span of August - September 2018 had caused a massive destruction and major damage especially in the structure of buildings including the radiological unit in the hospitals around the Lombok island. The damage in radiological unit building structures could cause a radiation leak in the surrounding areas and endanger the radiation safety of the hospital personnel. Many efforts were taken from the hospital itself and the government to immediately repair the damages in the structure. This study aimed to reports analysis the damage caused by the earthquake to the building structure and the efforts that were taken to repair the damages one year after the events. The measurements of exposure around the buildings were also performed to assess the results of the building renovation. The results were then compared with the radiation exposure measurements report prior to the events. A series of recommendations was then offered based on the results analysis regarding the enhancement of the shielding.

Microscopic changes in the neurocytes of the cerebellar cortex in dynamics under conditions of experimental thermal injuryc

Summary. Thermal injury as a stress factor of exogenous origin, in which the development of multiple organ failure and dysfunction of organs and systems of the body occur. The nervous system is one of the first to perceive and respond to pain impulses. It is important to reorganize all the structural components of the microcirculatory tract and neurons as a result of endogenous intoxication, which develops during thermal trauma. The target of lesions is the cerebellum, as a multifunctional organ of the central nervous system. The aim of the study – to establish the microscopic reorganization of neurocytes of the cerebellar cortex in the dynamics under conditions of experimental thermal trauma to the skin. Materials and Methods. The experimental study was performed on 24 adult white male rats weighing 180–200 g. Simulation of third-degree burns was performed with copper plates heated in boiled water to a temperature of 97–100º on the epilated surface of the skin of animal bodies under thiopental sodium. The size of the affected areas was 18–20 % of the body of rats. Collection of material for microscopic examination was performed in accordance with generally accepted methods. Histological sections obtained on a sled microtome 5–6 μm thick were stained with hematoxylin and eosin, toluidine blue by the method of Nissl. Semi-thin sections made on an ultramicrotome LKB-3 were stained with methylene blue. The micropreparations were studied using a MICROmed SEO SCAN light microscope and photo-documented using a Vision CCD Camera with a histological image output system. Results. Microscopic studies have shown an interdependence between the duration of the experiment and abnormalities in the structural components of neurons in all layers of the cerebellar cortex. In the early stages of the experiment there are reactive changes, which are adaptive-compensatory in nature with initial destructive damage. On day 14, and especially after 21 days, polymorphism is observed, significant cell degeneration, manifested by pycnosis of the nuclei, the development of intra- and pericellular edema in neurons of the granular, ganglionic and granular layers of the cerebellar cortex

Treatment of collagen-induced arthritis rat model by using Notch signalling inhibitor.

BackgroundThe Notch signalling pathway has been reported to play a key role in rheumatoid arthritis (RA) development. Thus, inhibition of the activation of this signalling pathway may be a promising approach to the treatment of RA. In this study, the Notch signalling inhibitor LY411575, which can inhibit both Notch1 and Notch3, was used for the treatment of collagen-induced arthritis (CIA) rats.MethodsWistar rats were immunised with bovine type II collagen (CII) to establish rats CIA model. The inhibitory effects of LY411575 on Notch1 intracellular domain (N1ICD) and Notch3 intracellular domain (N3ICD) protein was verified by western blot (WB) in vitro. CIA rats were treated with different doses of LY411575 for 15 and 28 days, respectively. Methotrexate and sodium carboxymethyl cellulose (CMC-Na) were used as positive and negative (vehicle) control respectively. Destruction of the rat ankle joint and the bone loss on the periarticular side were evaluated by micro-computed tomography (Micro-CT). In addition, destruction of the ankle articular cartilage and the osteoclast numbers were determined by histology. Expression of N1ICD and N3ICD in the ankle joint was detected by immunohistochemistry.ResultsLY411575 could significantly inhibit the expression of N1ICD and N3ICD in vitro. Micro-CT test showed that the ankle joint destruction significantly improved after treatment with LY411575 (5 ​mg/kg and 10 ​mg/kg, respectively). The bone quality in the LY411575 (5 ​mg/kg and 10 ​mg/kg, respectively) groups were improved compared with the vehicle group. Histological analysis showed that LY411575 (5 ​mg/kg and 10 ​mg/kg, respectively) treatment reduced the severity of ankle joint inflammation in CIA rats (including ankle joint destruction, pannus formation, and cartilage damage) and reduced the expression of N1ICD and N3ICD in CIA rats ankle joints significantly.ConclusionThe inhibitor of Notch signalling LY411575 is an effective treatment for CIA.The translational potential of this articleOur study provides new evidence to support the potential clinical application of Notch signalling pathway inhibitor LY411575 as a drug candidate for the treatment of RA.