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Psoriasis is an increasingly common chronic immune-mediated skin disease recognized for its systemic effects that extend beyond the skin and include various cardiovascular diseases, neurological diseases, type 2 diabetes, and metabolic syndrome. This study aimed to explore the complex relationship between psoriasis and metabolic syndrome by analyzing clinical, biochemical, and immunological parameters in patients with psoriasis alone and in patients combining psoriasis and metabolic syndrome. A total of 150 patients were enrolled, 76 with psoriasis only (PSO) and 74 with psoriasis and metabolic syndrome (PSO–MS). Data collected included anthropometric measurements, blood tests, and inflammatory markers. Statistical analysis was performed using the independent t-test, Mann–Whitney U test, Kruskal–Wallis test, and chi-square test to compare the two groups. Patients in the PSO–MS group had a significantly higher body weight, abdominal circumference, BMI, and inflammatory markers compared to patients with PSO. In addition, increased levels of IL-17A, cholesterol, triglycerides, and glucose were observed in the PSO–MS group. This study highlights the increased metabolic risk and exacerbated systemic inflammation associated with the coexistence of psoriasis and metabolic syndrome. These findings demonstrate the need for a comprehensive therapeutic approach and early intervention to manage metabolic complications in patients with psoriasis and metabolic syndrome.

Introduction: Dental occlusion refers to the static and dynamic relationships that are established between the teeth of the two arches and is an important factor in the homeostasis of the dento-maxillary system. The objective of the present study was to compare two digital occlusal analysis systems: the T-Scan III system and the Medit I600 intraoral scanner. Materials and Methods: The study was carried out on 20 students from the Faculty of Dental Medicine Craiova, whose dental occlusion was assessed with the T-Scan III system and with the Medit I600 intraoral scanner. Dental occlusion was assessed in the maximum intercuspation position, the edge-to-edge protrusion position, and the edge-to-edge position in right and left laterotrusion. The images of the 2D occlusal contact areas obtained by both methods were converted to .jpeg format and then transferred to Adobe Photoshop CS6 2021 (Adobe Systems, San Jose, CA, USA) for comparison. The recorded data were statistically processed. Results: Analyzing the data provided by the two digital occlusal analysis systems, it was found that the T-Scan III system provided data related to the amplitude of the occlusal forces, the surface on which they were distributed (the contact surface), the dynamics of the occlusal contacts, and the proportion in which they were distributed at the level of the two hemiarches, and the Medit I600 intraoral scanner performed an evaluation of the occlusal interface of the two arches, highlighting the extent of the contact areas with the degree of overlapping of the occlusal components. Although both methods of occlusal analysis recorded the highest values for the maximum intercuspation position, the results could not be compared. Conclusions: The two digital systems provide different data in occlusal analysis. As the T-Scan III system is considered the gold standard for occlusal analysis, more studies are needed to understand the data provided by the Medit I600 intraoral scanner and their significance.

Background: Over time, numerous surgical procedures and biomaterials have been proposed for the reconstruction of post-extraction bone defects, each with their advantages and disadvantages. The main objective of this study was to evaluate dimensional changes in the alveolar bone 3 months after tooth extraction, before implant planning, comparing alveolar ridge preservation (ARP) with spontaneous healing. Methods: A total of 84 patients with non-restorable molars were included in the study. Forty-two patients received ARP with advanced platelet-rich fibrin (A-PRF) and spontaneous healing was evaluated in these patients. Cone beam computed tomography (CBCT) analysis performed before and after surgical intervention was used to determine the changes in vertical and horizontal bone dimensions produced after tooth extraction. Results: CBCT measurements showed reduction in both vertical and horizontal alveolar bone size in both groups. For the study group, the alveolar parameters (height, width) were higher compared to the control group. The percentage variations between dimensional differences from the two groups were 38.58% for height, and for width were 36.88% at 0 mm, 35.56% at 3 mm, 36.61% at 5 mm, and 38.73% at 7 mm. The differences were statistically significant (p ˂ 0.0005). Conclusions: The results obtained after ARP with A-PRF showed a reduced loss of bone volume compared to spontaneous healing.

Colorectal cancer is one of the most widespread types of cancer that still causes many deaths worldwide. The development of new diagnostic and prognostic markers, as well as new therapeutic methods, is necessary. The calcitonin gene-related peptide (CGRP) neuropeptide alongside its receptor calcitonin receptor-like receptor (CRLR) could represent future biomarkers and a potential therapeutic target. Increased levels of CGRP have been demonstrated in thyroid, prostate, lung, and breast cancers and may also have a role in colorectal cancer. At the tumor level, it acts through different mechanisms, such as the angiogenesis, migration, and proliferation of tumor cells. The aim of this study was to measure the level of CGRP in colorectal cancer patients’ serum by enzyme-linked immunosorbent assay (ELISA) and determine the level of CGRP and CRLR at the tumor level after histopathological (HP) and immunohistochemical (IHC) analysis, and then to correlate them with the TNM stage and with different tumoral characteristics. A total of 54 patients with newly diagnosed colorectal adenocarcinoma were evaluated. We showed that serum levels of CGRP, as well as CGRP and CRLR tumor level expression, correlate with the TNM stage, with local tumor extension, the presence of lymph node metastasis, and distant metastasis, and also with the tumor differentiation degree. CGRP is present in colorectal cancer from the incipient TNM stage, with levels increasing with the stage, and can be used as a diagnostic and prognostic marker and may also represent a potentially new therapeutic target.

Malocclusions have a continuously increasing prevalence from one generation to another as a result of climate change, soil, atmosphere, and water pollution. All of these aspects have unfavorable consequences for the nutritional scheme. Thus, nutrition, together with other etiopathogenic factors, contributes to complex alterations in the somatic development of the entire organism and, implicitly, of the cephalic extremity. The study group included 4147 children from randomly selected schools from Vâlcea County, Romania. The aim of this study is to determine the prevalence of malocclusions in schoolchildren in Vâlcea County, Romania, according to the three main classes of malocclusions (according to Angle’s classification), age groups (from 6 to 10 years old and from 11 to 14 years old), gender (male and female), and place of origin (rural and urban). For Angle class I malocclusions, we recorded the highest prevalence (48.78% of the total number of schoolchildren with malocclusions), followed by Angle class II malocclusions (45.85% of the total number of schoolchildren with malocclusions), and for Angle class III malocclusions we found the lowest prevalence (5.37% of the total number of schoolchildren with malocclusions). According to gender, we found the highest prevalence in the female gender (29.90% of the total number of female subjects), while in the male gender, we recorded a prevalence of 27.70% of the total number of male subjects. Regarding the place of origin, there is a higher prevalence of malocclusions in urban areas (29.16%). The study subgroup included 140 children randomly selected from the total number of subjects in the study group. They were included in a more advanced study. The aim is to find potential associations between the presence of malocclusions and various oral variables. Categorical variables were expressed as numerical values and percentages, and their association was evaluated with either the Chi-square test of association or homogeneity, or the Fisher Exact test. The acquired data were incorporated into a binomial logistic regression model to assess the likelihood of developing malocclusions in relation to the following variables: defective phonation, bruxism, frequency of teeth brushing, onychophagia, oral respiration, infantile deglutition, placing objects between the maxillaries, thumb sucking, and salivary aspects. It is also aimed at comparing the results obtained with similar ones from the specialized literature.

Colorectal cancer (CRC) remains one of the most important global health problems, being in the top 3 neoplasms in terms of the number of cases worldwide. Although CRC develops predominantly from the adenoma–adenocarcinoma sequence through APC gene mutations, in recent years, studies have demonstrated the role of chronic inflammation in this neoplasia pathogenesis. Cytokines are important components of chronic inflammation, being some of the host regulators in response to inflammation. The pro-inflammatory cytokines IL-1β, IL-6, and TNF-α are involved in tumor cell proliferation, angiogenesis, and metastasis and seem to strengthen each other’s mode of action, these being stimulated by the same mediators. In our study, we collected data on 68 patients with CRC and 20 healthy patients from the Gastroenterology Department of Craiova County Emergency Clinical Hospital, who were assessed between January 2022 and February 2023. The main purpose of this study was to investigate the correlation between increased plasma levels of the cytokines and the extent of the tumor, lymph nodes, and metastasis—(TNM stage), as well as the patients’ prognoses. We also compared the plasma levels of cytokines and acute inflammatory markers, namely, the erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and fibrinogen, along with the tumor markers, carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA 19.9), in CRC patients. We showed that all the pro-inflammatory cytokines studied had higher levels in patients with CRC in comparison with the control group. We also showed that the acute inflammatory markers of erythrocyte sedimentation rate, C-reactive protein, and fibrinogen, and the tumor markers of CEA and CA 19.9 can be useful in diagnosis and prognosis in patients with CRC. Considering the association between pro-inflammatory cytokines and CRC, the development of new targeted therapies against IL-1β, IL-6, and TNF-α can improve patient care and the CRC survival rate.

Composite materials used in dental restorations are considered resistant, long-lasting and aesthetic. As the wear of restorations is an important element in long-term use, the aim of this study was to evaluate the surface condition of nanohybrid and microfilled composite resins, after being subjected to the erosive action of dental bleaching protocols. This paper reflects a comparative study between one nanofilled composite and three microfilled composites used in restorations. For each composite, three sets of samples (under the form of composite discs) were created: a control group, an “office bleach” group with discs bleached with 40% hydrogen peroxide gel, and a “home bleach” group with discs bleached with 16% carbamide peroxide gel. Wear was numerically determined as the trace and the coefficients of friction obtained using a tribometer, the ball-on-disk test method, and two balls: alumina and sapphire. For all composite groups, there were statistically significant differences between the wear corresponding to the control and bleaching groups, for both testing balls. Regarding the composite type, the largest traces were recorded for GC Gradia direct anterior, for all groups, using the alumina ball. In contrast, for the sapphire ball, 3M ESPE Filtek Z550 was characterized by the largest traces. With respect to the friction coefficients, the “office bleach” group recorded the largest values, no matter the composite or the ball type used. The 3M ESPE Valux Plus composite recorded the largest friction coefficients for the alumina ball, and 3M ESPE Filtek Z550 for the sapphire ball. Overall, the “office bleach” group was characterized by higher composite wear, compared to the “home bleach” protocol or control group. Nanofilled composite resins showed superior wear resistance to microfilled resins after undergoing a bleaching protocol.

Impairment of the immune response in MRONJ (medication-related osteonecrosis of the jaws) is one of the still unclear etiopathogenic mechanisms of this condition encountered in cancer patients treated with bisphosphonates, with negative effects on the patient’s quality of life. The aim of the present study was to correlate the immune response with etiopathogenic factors via immunohistochemical evaluation of the maxillary tissues in zoledronic acid osteonecrosis. The retrospective study included a group of 51 patients with various types of cancers, diagnosed with stage 2 or 3 MRONJ at zoledronic acid and treated surgically. Immunohistochemical expressions of αSMA, CD3, CD4, CD8, CD20, CD79α, CD68, CD204, and tryptase were evaluated. Immunohistochemical markers expressions were statistically analyzed according to the duration of the treatment, the trigger factor, the location of the MRONJ, and the healing status. Analysis of the immune response included T lymphocytes, B lymphocytes, plasma cells, macrophages, and mast cells. The duration of treatment significantly influenced the immunohistochemical expression of most markers (p < 0.05). For an increasing trend in treatment duration, a decreasing trend in marker score was observed, suggesting an inverse correlation. The expression of the markers was different depending on the trigger factor, on MRONJ localization (maxilla/mandible), and the healing status, being more intense in patients cured per primam compared to those who had relapses. The patient’s immune response was negatively influenced by the duration of the treatment, the trigger factor, the location of the lesion in the mandible, and the recurrence of MRONJ.

The success of endodontic treatment is dependent on the removal of bacteria. A modern strategy to reduce bacterial load is laser irradiation. During this procedure, there is a local increase in temperature with possible side effects. The aim of this study was to determine the thermal behavior of a maxillary first molar when performing the conventional irradiation technique using a diode laser. For this study, a 3D virtual model of a maxillary first molar was created. The preparation of the access cavity, the rotary instrumentation of the palatal root canal and the laser irradiation protocol were simulated. The model was exported in a finite element analysis program where the temperature and heat flux were studied. Temperature and heat flux maps were obtained, and the temperature increase on the internal wall of the root canal was analyzed. The maximum temperature value exceeded 400 °C and was maintained for less than 0.5 s. The obtained temperature maps support the bactericidal effect of diode laser and the limitation of damage to surrounding tissues. On internal root walls, the temperature reached several hundred degrees Celsius, but for very short durations. Conventional laser irradiation is an adjuvant method of decontamination of the endodontic system.

The purpose of this study is to identify and quantify preclinical changes with the help of optical coherence tomography angiography (OCTA) within the retinal microcirculation of young type 1 diabetes (T1D) patients without clinical signs of diabetic retinopathy (DR) and to compare these results with those obtained from healthy age-matched subjects. OCTA is currently used for monitoring diabetic retinopathy; however, there is no current consensus on which OCTA parameter alterations predict the first clinical signs of diabetic retinopathy. The main challenge that young patients with T1D face during the course of the disease is that they can rapidly progress to the development of DR, especially during adolescence. Moreover, they also present an increased risk of rapid progression toward advanced stages of DR and vision loss compared to type 2 diabetes patients, indicating the importance of early diagnosis and intervention. The limitations of the currently used screening procedures that led to the conceptualization of our study are the difficulties in performing fluorescein angiography tests for diagnosing the clinical signs of DR on young patients, namely the invasive procedure of dye injection, the risk of allergic reactions and the long duration of the examination. Moreover, given the long life expectancy of young T1D patients, it is essential to identify the preclinical changes in retinal microvasculature before reaching the first clinical signs quantifiable by FFA. The clinical study enrolled 119 subjects aged between 4 and 30 years old with a mean age of 13 years old, comprising 61 T1D patients with a mean duration of the disease of 4 years and 8 months and 58 healthy age-matched subjects for the control group. OCTA scans were performed using the RevoNX 130 OCTA device (Optopol) to evaluate the following retinal parameters: foveal avascular zone (FAZ) area, perimeter and circularity, overall foveal thickness, and superficial and deep vessel densities. Statistically significant differences between the two groups were identified for the following parameters: the FAZ area in the T1D group (0.42 ± 0.17) was larger than the control group (0.26 ± 0.080), the FAZ circularity (0.41 ± 0.11) was decreased compared to the control group (0.61 ± 0.08) and the FAZ perimeter was larger (3.63 ± 0.97) compared to the control group (2.30 ± 0.50). The overall foveal thickness was decreased in the T1D group (222.98 ± 17.33) compared to the control group (230.64 ± 20.82). The total vessel density of the superficial capillary plexus (SCP) on an investigated area of 6 X 6 mm centered around the fovea was decreased in the T1D group (37.4164 ± 2.14) compared to the control group (38.0241 ± 2.44). Our data suggest that specific imaging biomarkers such as FAZ perimeter, area and circularity, decreased overall foveal thickness and decreased vessel density in the SCP precede the clinical diagnosis of DR in young T1D patients and represent useful parameters in quantifying capillary nonperfusion in T1D patients without clinical signs of DR.

Background: Developmental defects of enamel (DDE) are frequently encountered in primary and permanent teeth, yet their etiology is not completely known. Enamel hypoplasia is considered a predisposing factor for early caries. The objective of this study was the evaluation of several risk factors potentially causing DDE and the possible association between DDE and dental caries. Methods: This study was performed on a group of 213 rural children from Romania. It combined a thorough dental examination for all children, and a questionnaire filled in by their mothers, regarding the evolution of their pregnancy and the child’s health status in the first years of life. Results: There was no statistically significant association between DDE presence and data regarding the evolution of pregnancy, mothers’ health status or children’s conditions during early childhood. There was a significant association between the use of amoxicillin, ibuprofen, and cephalosporin during the period of formation of permanent teeth, and one environmental factor (water source), and the presence of DDE (Chi Square, p < 0.05). Also, DDEs were associated with the presence of caries (Fisher, p = 0.001). Conclusions: Children who consumed water from private wells and children who received medication during early childhood developed more enamel defects, presenting a higher risk of caries development.

Background and objectives: Occlusal overloads produce a series of manifestations in teeth, especially attrition and non-carious cervical lesions (NCCL). Optical Coherence Tomography (OCT) can highlight and evaluate tooth lesions. The aim of this study was to examine the changes of dental hard tissues in the cervical area because of occlusal overload by macroscopic examination and using in vitro Swept Source OCT examination. Materials and Methods: The study was performed on 21 extracted teeth with occlusal trauma. After macroscopic and OCT examination, the 2D OCT images were transformed into 3D images using ImageJ software. Statistical analysis of macroscopic and OCT images was performed with Statistical Package for Social Sciences. Results: On 21 teeth, 88 cervical lesions (cracks) were identified. Upper premolars with an occlusal Smith and Knight tooth wear score of 2 had the most NCCL. Statistical analysis revealed significant differences in the median widths of cervical lesions between teeth with score 1 and score 3. Additionally, we obtained statistically significant differences in median widths between the buccal and oral surfaces. Conclusions: These cracks can be considered precursors of NCCL. NCCL can be located on dental surfaces in the cervical area other than the buccal one. A 3D reconstruction of OCT images emphasized that cracks are located especially at enamel level, evolving towards the enamel–dentin junction, with multiple ramifications.

The Hepatitis C Virus (HCV) infection often associates medical and mental health conditions which lead to increased levels of distress. Our study aimed at assessing the level of perceived stress on a sample of 90 HCV infected patients treated with Direct-Acting Antiviral (DAA) agents for 12 weeks, and its possible correlations with clinical and evolutionary elements. The evaluation was conducted in three phases: before administration of the DAAs (BSL), at the End of the Treatment (EOT), and 24 weeks after the BSL (Sustained Viral Response—SVR). The perceived stress was measured using the Perceived Stress Scale (PSS). The efficiency of the DAA treatment reduced the levels of stress (98.99% moderate and high stress at BSL to 70.00% at SVR). It was observed, for the entire study period (BSL to SVR), that the decrease in the perceived stress severity was significantly associated with demographic items such as gender (p < 0.01), urban environment (p < 0.001), the age of the subjects (p < 0.05), and clinical data such as F4 degree of fibrosis (p = 0.001) and overweight or obesity class II (p < 0.01). The perceived stress is directly associated with the severity of the HCV infection, and it could be significantly lowered by an efficient therapeutic approach, as DAAs are nowadays.

Developmental defects of enamel (DDEs) are deviations from the normal appearance in terms of the quantity and quality of tooth enamel. They may be genetic or acquired. The most important DDEs are hypomineralization and hypoplasia. The aim of this study was to produce “in vivo” DDE in Wistar rats by administering amoxicillin to pregnant females and to highlight these lesions after sacrifice of the pups by macroscopic and microscopic examination and optical coherence tomography (OCT). Amoxicillin (100 mg/kg) was administered to two pregnant Wistar female rats for the production of DDEs. When the pups were 2 months old, they were sacrificed, and their jaws were harvested together with their teeth. The jaws were examined macroscopically, microscopically, and by OCT. Following the macroscopic and microscopic examination, it was established that four pups had a total of 42 DDE lesions. At the OCT examination, the hypomineralization was characterized by an intense, inhomogeneous OCT signal, and the hypoplasia was characterized by the absence of the signal. Administration of amoxicillin to pregnant females of Wistar rats resulted in DDEs in their offspring. The OCT examination confirmed the presence of these lesions in the teeth of rat pups.

The experimental investigation of a prototypical set-up simulating a loss of flow accident in a helium-cooled breeding blanket first wall mock-up under typical heat load conditions is presented. The experimental campaign reproduces the expected DEMO thermal-hydraulics conditions during normal and off-normal situations and aims at providing some insight into the fast transients associated with the loss of flow in the blanket first wall. The experimental set-up and the definition of the experimental matrix are discussed, including pre-test analysis performed in support of these activities. The major experimental results are discussed, and a procedure of using the acquired data for validating and calibrating the RELAP-3D model of the mock-up is introduced. All these activities contributed to the creation of a relevant theoretical and practical experience that can be used in further studies concerning incidental transients in real-plant scenarios in the framework of DEMO plant fusion safety activities.

The validation of numerical tools employed in the analysis of incidental transients in a fusion reactor is a topic of main concern. KIT is taking part in this task providing both experimental data and by performing numerical analysis in support of the main codes used for the safety analyses of the Helium Cooled Pebble Bed (HCPB) blanket concept. In recent years, an experimental campaign has been performed in the KIT-HELOKA facility to investigate the behavior of a First Wall Mock-Up (FWMU) under Loss Of Flow Accident (LOFA) conditions. The aim of the experimental campaign was twofold: to check the expected DEMO thermal-hydraulics conditions during normal and off-normal conditions and to provide robust data for code validation. The present work is part of these validation efforts, and it deals with the analysis of the LOFA experimental campaign with the system code MELCOR 1.8.6 for fusion. A best-estimate methodology has been used in support of this analysis to ease the distinction between user’s assumptions and code limitations. The numerical analyses are here described together with their goals, achievements, and lesson learnt.

The development and the validation of old and new software in relevant DEMO reactor conditions have been exploited in the latest years within the EUROfusion Consortium. The aim was to use—if possible—the software already validated for fission reactors and to fill the gaps with new ad-hoc software. As contribution to this effort, the Karlsruhe Institute of Technology (KIT) developed and tested a novel software to apply the Best-Estimate Model Calibration and Prediction through Experimental Data Assimilation methodology to the system codes RELAP5-3D, MELCOR 1.8.6, and MELCOR 2.2. This software is called Best-estimate for SYstem Codes (BeSYC), and it is developed as a MATLAB App. The application is in charge of applying the mathematical framework of the methodology, writing and executing the code runs required by the methodology, and printing the obtained results. The main goal of BeSYC is to wrap up the methodology in a software suitable to be used by any user through a simple graphical user interface. Albeit developed in the fusion research context, BeSYC can be applied to any reactor/scenario type supported by the specific system code. The goals of BeSYC, the mathematical framework, the main characteristics, and the performed verification and validation activities are described in this paper.

The 2019 novel coronavirus, known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), is causing a global pandemic. The virus primarily affects the upper and lower respiratory tracts and raises the risk of a variety of non-pulmonary consequences, the most severe and possibly fatal of which are cardiovascular problems. Data show that almost one-third of the patients with a moderate or severe form of COVID-19 had preexisting cardiovascular comorbidities such as diabetes mellitus, obesity, hypertension, heart failure, or coronary artery disease. SARS-CoV2 causes hyper inflammation, hypoxia, apoptosis, and a renin–angiotensin system imbalance in a variety of cell types, primarily endothelial cells. Profound endothelial dysfunction associated with COVID-19 can be the cause of impaired organ perfusion that may generate acute myocardial injury, renal failure, and a procoagulant state resulting in thromboembolic events. We discuss the most recent results on the involvement of endothelial dysfunction in the pathogenesis of COVID-19 in patients with cardiometabolic diseases in this review. We also provide insights on treatments that may reduce the severity of this viral infection.

Recent preclinical studies in our laboratory have shown that the bile acid profile is altered during diabetes development and such alteration has been linked to the diabetes-associated inflammatory profile. Hence, this study aimed to investigate if the first-line antidiabetic drug metformin will alter the bile acid profile and diabetes-associated inflammation in a murine model of pre-type 2 diabetes. C57 mice were randomly allocated into three equal groups of eight. Group One was given a low-fat diet (LFD), Group Two was given a high-fat diet (HFD), and Group Three was given an HFD and, upon prediabetes confirmation, daily oral metformin for one month. Blood glucose, glycated haemoglobin, drug concentrations in tissues and faeces, and the inflammatory and bile acid profiles were measured. Metformin showed wide tissue distribution and was also present in faeces. The bile acid profile showed significant alteration due to prediabetes, and although metformin did not completely normalize it, it did exert significant effects on both the bile acid and the inflammatory profiles, suggesting a direct and, to some extent, positive impact, particularly on the diabetes-associated inflammatory profile.

Fast and strong interacting systems are hard to control from both performance and control effort points of view. Moreover, multiple objective functions or objectives with various identifiers of varying weights can hold unfeasible solutions at times. A novel cost objective function is proposed here to overcome both feasibility set limitations and computational burdens. An application example is used to illustrate its added value, which is a fast and strong interacting multivariable system: a landscape office lighting regulatory problem. New lighting technology and an intelligent control system have been produced to improve control accuracy and reduce power consumption. While optimizing the hardware of the lighting system, the energy consumption can be further reduced by applying advanced control strategy in the lighting system. This paper designed a fractional order distributed model predictive control (FOMPC) scheme to realize the reference tracking and stability control of multiple illuminations at the same time. In order to test the efficiency of the control strategy, an experiment was carried out on the lighting setup based on the dSPACE control system. The FOMPC scheme was analyzed through simulation and lighting experiments based on the dSPACE control system. Through a comparison with the mode predictive control (MPC) scheme, the superiority of the FOMPC scheme for the dynamic behavior and control performance of multiple lighting systems was verified. The research results provide a basis for multiple lighting control and its application.

Bile acids (BA)s are known surfactants and well-documented to play a major role in food digestion and absorption. Recently, potential endocrinological and formulation-stabilisation effects of BAs have been explored and their pharmacological effects on supporting cell survival and functions have gained wide interest. Hence, this study aimed to explore the hyper-glycaemic dependent dose-effect of the BA chenodeoxycholic acid (CDCA) when encapsulated with pancreatic β-cells, allowing assessment of CDCA’s impacts when encapsulated. Four different concentrations of the BA were prepared, and viable cells were encapsulated and incubated for 2 days. Multiple analyses were carried out including confocal imaging, glucose-induced cellular mitochondrial viability indices, insulin production, inflammatory biomarker analyses and cellular bioenergetics measurements. There was a significant dose-effect with different concentrations of the BA, affecting cellular viability and antioxidant activities, cell functions and insulin release, inflammatory biomarkers, and cellular-bioenergetics at different oxidative stress levels. The results demonstrate that, when encapsulated, the BA CDCA exerts positive pharmacological effects at the cellular level, and such effects are concentration dependent.

A recent study showed an association between diabetes development and the bile acid lithocholic acid (LCA), while another study demonstrated positive biological effects of the conjugated bile acid, taurocholic acid (TCA), on pancreatic cells. Thus, this study aimed to encapsulate TCA with primary islets (graft) and study the biological effects of the graft, post-transplantation, in diabetic mice, including effects on LCA concentrations. Sixteen mature adult mice were made diabetic and randomly divided into two equal groups, control and test (transplanted encapsulated islets without or with TCA). Graft pharmaceutical features pre-transplantation, and biological effects including on LCA concentrations post-transplantation, were measured. TCA-microcapsules had an oval shape and similar size compared with the control. The treatment group survived longer, showed improved glucose and interleukin-6 concentrations, and lower LCA concentrations in plasma, large intestine, faeces, liver and spleen, compared with control. Results suggest that TCA incorporation with islets encapsulated graft exerted beneficial effects, but there was no direct and significant dependency between concentrations of interleukin-6 and LCA.

Biguanides, particularly the widely prescribed drug metformin, have been marketed for many decades and have well-established absorption profiles. They are commonly administered via the oral route and, despite variation in oral uptake, remain commonly prescribed for diabetes mellitus, typically type 2. Studies over the last decade have focused on the design and development of advanced oral delivery dosage forms using bio nano technologies and novel drug carrier systems. Such studies have demonstrated significantly enhanced delivery and safety of biguanides using nanocapsules. Enhanced delivery and safety have widened the potential applications of biguanides not only in diabetes but also in other disorders. Hence, this review aimed to explore biguanides’ pharmacokinetics, pharmacodynamics, and pharmaceutical applications in diabetes, as well as in other disorders.

Pancreatic β-cell loss and failure with subsequent deficiency of insulin production is the hallmark of type 1 diabetes (T1D) and late-stage type 2 diabetes (T2D). Despite the availability of parental insulin, serious complications of both types are profound and endemic. One approach to therapy and a potential cure is the immunoisolation of β cells via artificial cell microencapsulation (ACM), with ongoing promising results in human and animal studies that do not depend on immunosuppressive regimens. However, significant challenges remain in the formulation and delivery platforms and potential immunogenicity issues. Additionally, the level of impact on key metabolic and disease biomarkers and long-term benefits from human and animal studies stemming from the encapsulation and delivery of these cells is a subject of continuing debate. The purpose of this review is to summarise key advances in this field of islet transplantation using ACM and to explore future strategies, limitations, and hurdles as well as upcoming developments utilising bioengineering and current clinical trials.

Introduction: Bile acid-based drug encapsulation for oral delivery has been recently explored in our laboratory and has shown to be beneficial in terms of drug-targeted delivery and release profile, but stability at various temperatures has not previously been examined; hence, this is the aim of this study. Methods: Various types of bile acid-based microcapsules containing the drug metformin were produced and tested for accelerated temperature-controlled profiles, as well as morphology, elemental composition, drug content, resilience, floatability, wettability and release profiles at various pH values. Results: Accelerated temperature-controlled analysis showed negligible effects on morphology, size, or shape at very low temperatures (below 0 °C), while higher temperatures (above 25 °C) caused alterations. Drug contents, morphology and elemental composition remained similar, while wettability and the release profiles showed formulation-dependent effects. Discussion and Conclusion: Results suggest that bile acid-based microcapsules containing metformin are affected by temperature; hence, their shelf life is likely to be affected by storage temperature, all of which have a direct impact on drug release and stability profiles.

Introduction. Several studies have shown that different biomaterials and hydrogels comprising various bile acids such as chenodeoxycholic acid (CDCA), as well as excipients such as poly-(styrene)-sulphonate (PSS) and poly-(allyl)-amine (PAA), exhibited positive biological effects on encapsulated viable pancreatic β-cells. Hence, this study aimed to investigate whether incorporating CDCA with PSS and PAA will optimise the functions of encapsulated pancreatic islets post-transplantation in Type 1 diabetes (T1D). Methods. Mice were made T1D, divided into two equal groups, and transplanted with encapsulated islets in PSS-PAA (control) or with CDCA-PSS-PAA (treatment) microcapsules. The effects of transplanted microcapsules on blood glucose, inflammation and the bile acid profile were measured post-transplantation. Results and Conclusion. Compared with control, the treatment group showed better survival rate, improved glycaemic control, and lower inflammatory profile, illustrated by ↓ interleukin 1-β, interleukin-6, interleukin-12, and tumour-necrosis factor-α, and ↓ levels of the bile acid, as well as lithocholic acid in the plasma, liver, large intestine and faeces. The results suggest that CDCA incorporation with PSS-PAA microcapsules exerted beneficial effects on encapsulated islets and resulted in enhanced diabetes treatment, post-transplantation, at the local and systemic levels.

Introduction. Primary bile acids (PBAs) are produced and released into human gut as a result of cholesterol catabolism in the liver. A predominant PBA is chenodeoxycholic acid (CDCA), which in a recent study in our laboratory, showed significant excipient-stabilizing effects on microcapsules carrying insulinoma β-cells, in vitro, resulting in improved cell functions and insulin release, in the hyperglycemic state. Hence, this study aimed to investigate the applications of CDCA in bio-encapsulation and transplantation of primary healthy viable islets, preclinically, in type 1 diabetes. Methods. Healthy islets were harvested from balb/c mice, encapsulated in CDCA microcapsules, and transplanted into the epididymal tissues of 6 syngeneic diabetic mice, post diabetes confirmation. Pre-transplantation, the microcapsules’ morphology, size, CDCA-deep layer distribution, and physical features such as swelling ratio and mechanical strength were analyzed. Post-transplantation, animals’ weight, bile acids’, and proinflammatory biomarkers’ concentrations were analyzed. The control group was diabetic mice that were transplanted encapsulated islets (without PBA). Results and Conclusion. Islet encapsulation by PBA microcapsules did not compromise the microcapsules’ morphology or features. Furthermore, the PBA-graft performed better in terms of glycemic control and resulted in modulation of the bile acid profile in the brain. This is suggestive that the improved glycemic control was mediated via brain-related effects. However, the improvement in graft insulin delivery and glycemic control was short-term.

Probucol (PB) is a highly lipophilic drug with potential protective effects on pancreatic β-cells from inflammation and oxidation. PB has poor bioavailability and solubility, and despite many attempts, significant improvement in antidiabetic effects or absorption has yet to be discovered. Recently, the role of bile acids has been established in significant drug formulation stabilisation effects and as cell-penetrating agents. Promising results in pharmaceutical formulation studies on drug stability and release patterns when lithocholic acid (LCA) is conjugated with PB and sodium alginate (SA) have been demonstrated. Thus, this study aimed to develop and characterise PB microcapsules incorporating LCA and examine the biological effects of the microcapsules in vitro and in vivo. PB/LCA microcapsules were prepared using an encapsulation method, ionic gelation vibrational jet flow technology. LCA incorporation in PB microcapsules showed positive effects on β-cells with improved insulin release, antioxidant activity, and PB intracellular uptake. Diabetic mice gavaged LCA-PB microcapsules showed a significant reduction in diabetes signs and symptoms, better survival rate, reduced blood glucose levels, and pro-inflammatory cytokines, with an increase PB level in blood and tissues suggesting a potential therapy for treating diabetes mellitus.

Introduction. A major obstacle in islet transplantation and graft survival pre and post transplantation is islet apoptosis due to mainly inflammatory bio molecules released during islet harvesting and post graft transplantation and hence, subsequent graft fibrosis and failure. This study aimed to investigate if incorporation of the anti-inflammatory anti-hyperlipidaemic drug probucol (PB) would improve islet-graft survival and function, post transplantation in Type 1 diabetes (T1D). Methods. T1D was induced in mice, and biological profiles of the diabetic mice transplanted PB-microencapsulated islets harvested from healthy syngeneic mice were measured. Results and Conclusion. Compared with sham (no PB), the treated group showed significant reduction in serum levels of interleukin-1β, interleukin-6, interleukin-12, interleukin-17, and tumour necrosis factor-α, accompanied by a 3-fold increase in survival duration, which suggests PB islet-protective effects, post transplantation.

The utilisation of bioartificial organs is of significant interest to many due to their versatility in treating a wide range of disorders. Microencapsulation has a potentially significant role in such organs. In order to utilise microcapsules, accurate characterisation and analysis is required to assess their properties and suitability. Bioartificial organs or transplantable microdevices must also account for immunogenic considerations, which will be discussed in detail. One of the most characterized cases is the investigation into a bioartificial pancreas, including using microencapsulation of islets or other cells, and will be the focus subject of this review. Overall, this review will discuss the traditional and modern technologies which are necessary for the characterisation of properties for transplantable microdevices or organs, summarizing analysis of the microcapsule itself, cells and finally a working organ. Furthermore, immunogenic considerations of such organs are another important aspect which is addressed within this review. The various techniques, methodologies, advantages, and disadvantages will all be discussed. Hence, the purpose of this review is providing an updated examination of all processes for the analysis of a working, biocompatible artificial organ.

Aging is considered a contributing factor to many diseases such as cardiovascular disease, Alzheimer’s disease, and hearing loss. Age-related hearing loss, also termed presbycusis, is one of the most common sensory impairments worldwide, affecting one in five people over 50 years of age, and this prevalence is growing annually. Associations have emerged between presbycusis and detrimental health outcomes, including social isolation and mental health. It remains largely untreatable apart from hearing aids, and with no globally established prevention strategies in the clinical setting. Hence, this review aims to explore the pathophysiology of presbycusis and potential therapies, based on a recent advancement in bile acid-based bio-nanotechnologies. A comprehensive online search was carried out using the following keywords: presbycusis, drugs, hearing loss, bile acids, nanotechnology, and more than 150 publications were considered directly relevant. Evidence of the multifaceted oxidative stress and chronic inflammation involvement in cellular damage and apoptosis that is associated with a loss of hair cells, damaged and inflamed stria vascularis, and neuronal signalling loss and apoptosis continues to emerge. New robust and effective therapies require drug delivery deeper into the various layers of the cochlea. Bile acid-based nanotechnology has gained wide interest in its permeation-enhancing ability and potential for numerous applications in treating presbycusis.

For complex systems, it is not easy to obtain optimal designs for the hardware architecture and control configurations. Every design aspect influences the final performance, and often the interactions of the different components cannot be clearly determined in advance. In this work, a novel co-design optimization method was applied that allows the optimal placement and selection of actuators and sensors to be performed simultaneously with the determination of the control architecture and associated controller tuning parameters. This novel co-design method was applied to a state-space model of a downscaled active car suspension laboratory setup. This setup mimics a car driving over a specific road surface while active components in the suspension have to increase the driver’s comfort by counteracting unwanted vibrations. The result of this co-design optimization methodology is a Pareto front that graphically represents the trade-off between the maximum performance and the total implementation cost; the co-design results were validated with measurements of the physical active car suspension setup. The obtained controller tuning parameters are compared herein with existing controller tuning methods to demonstrate that the co-design method is able to determine optimal controller tuning parameters.

Bile acids have recently been studied for potential applications as formulation excipients and enhancers for drug release; however, some bile acids are not suitable for this application. Unconjugated lithocholic acid (ULCA) has recently shown drug formulation-stabilizing and anti-inflammatory effects. Lipophilic drugs have poor gut absorption after an oral dose, which necessitates the administration of high doses and causes subsequent side effects. Probucol (PB) is a highly lipophilic drug with poor oral absorption that resulted in restrictions on its clinical prescribing. Hence, this study aimed to design new delivery systems for PB using ULCA-based matrices and to test drug formulation, release, temperature, and biological effects. ULCA-based matrices were formulated for PB oral delivery by applying the jet-flow microencapsulation technique using sodium alginate as a polymer. ULCA addition to new PB matrices improved the microcapsule’s stability, drug release in vitro (formulation study), and showed a promising effect in ex vivo study (p < 0.05), suggesting that ULCA can optimize the oral delivery of PB and support its potential application in diabetes treatment.

This paper presents a calibration approach of a manipulator robot controller using an auto-tuning technique. Since the industry requires machines to run with increasing speed and precision, an optimal controller is too demanding. Even though the robots make use of an internal controller, usually, this controller does not fulfill the user specification with respect to their applications. Therefore, in order to overcome the user requirements, an auto-tuning method based on a single sine test is employed to obtain the optimal parameters of the proportional–integral–derivative PID controller. This approach has been tested, validated and implemented on a UR10 robot. The experimental results revealed that the performances of the robot increased when the designed controller, using the auto-tuning technique, was employed.