Computed tomography and magnetic resonance imaging of congenital thoracic systemic venous anomalies.

We present the imaging findings of thoracic systemic venous anomalies diagnosed by computed tomography and magnetic resonance imaging. Persistent left superior vena cava is the commonest anomaly of the thoracic systemic veins encountered either incidentally as an isolated finding or associated with congenital heart disease. Inferior vena cava (IVC) interruption with azygos continuation is the second most common anomaly, which may also be isolated or be associated with left isomerism syndrome. The article will also discuss other rarer systemic venous anomalies including retroaortic brachiocephalic vein and IVC drainage into the left atrium. Finally, the impact of pre-procedure reporting of thoracic systemic venous anomalies on the choice of intervention and patient outcome will be addressed.

Whole-body diffusion-weighted imaging with background body signal suppression and quantitative apparent diffusion coefficient in the detection, staging, and grading of non-Hodgkin lymphoma.

Purpose: Assess reproducibility of detection, staging, and grading of non-Hodgkin lymphoma (NHL) using whole-body diffusion-weighted imaging with background body signal suppression (WB-DWIBS). Material and methods: Thirty NHL patients underwent WB-DWIBS, divided into 2 groups according to staging and grading. Image analysis and apparent diffusion coefficient (ADC) measurement of the largest lymph node in each group were performed by 2 observers. Inter-observer agreement was performed. Results: Overall inter-observer agreement for detection of NHL was excellent (k = 0.843; 92.05%) with excellent inter-observer agreement of nodal disease (cervical, thoracic and abdominal) (k = 0.783, 0.769, and 0.856; 96.67%, 90.0%, and 93.3% respectively), extra-nodal disease (k = 1; 100%), and splenic involvement (k = 0.67; 83.3%). The overall inter-observer agreement of DWIBS in staging of NHL was excellent (k = 0.90; 94.9%) with excellent inter-observer agreement for stage I (k = 0.93; 96.4%), stage II (k = 0.90; 94.8%), stage III (k = 0.89; 94.6%), and stage IV (k = 0.88; 94.0%). There was significant difference between ADC in stage I, II (0.77 ± 0.13, 0.85 ± 0.09 × 10-3 mm2/s), and stage III, IV (0.63 ± 0.08, 0.64 ± 0.11 × 10-3 mm2/s, p < 0.002, < 0.001). Interclass correlation showed almost perfect agreement for ADC measurement in staging and grading groups (r = 0.96 and r = 0.85, respectively, p < 0.001). There was significant difference between ADC in aggressive lymphoma (0.65 ± 0.1, 0.67 ± 0.13 × 10-3 mm2/s) and indolent lymphoma (0.76 ± 0.14, 0.84 ± 0.09 × 10-3 mm2/s, p < 0.028, < 0.001). Conclusion: DWIBS is reproducible for detection and staging of nodal and extra-nodal involvement in patients with NHL. ADC can quantitatively participate in the staging and grading of NHL.

Ultrastable Conjugated Microporous Polymers Containing Benzobisthiadiazole and Pyrene Building Blocks for Energy Storage Applications.

In recent years, conjugated microporous polymers (CMPs) have become important precursors for environmental and energy applications, compared with inorganic electrode materials, due to their ease of preparation, facile charge storage process, π-conjugated structures, relatively high thermal and chemical stability, abundance in nature, and high surface areas. Therefore, in this study, we designed and prepared new benzobisthiadiazole (BBT)-linked CMPs (BBT-CMPs) using a simple Sonogashira couplings reaction by reaction of 4,8-dibromobenzo(1,2-c;4,5-c')bis(1,2,5)thiadiazole (BBT-Br2) with ethynyl derivatives of triphenylamine (TPA-T), pyrene (Py-T), and tetraphenylethene (TPE-T), respectively, to afford TPA-BBT-CMP, Py-BBT-CMP, and TPE-BBT-CMP. The chemical structure and properties of BBT-CMPs such as surface areas, pore size, surface morphologies, and thermal stability using different measurements were discussed in detail. Among the studied BBT-CMPs, we revealed that TPE-BBT-CMP displayed high degradation temperature, up to 340 °C, with high char yield and regular, aggregated sphere based on thermogravimetric analysis (TGA) and scanning electron microscopy (SEM), respectively. Furthermore, the Py-BBT-CMP as organic electrode showed an outstanding specific capacitance of 228 F g-1 and superior capacitance stability of 93.2% (over 2000 cycles). Based on theoretical results, an important role of BBT-CMPs, due to their electronic structure, was revealed to be enhancing the charge storage. Furthermore, all three CMP polymers featured a high conjugation system, leading to improved electron conduction and small bandgaps.

Prevalence of diabetes distress and depression and their association with glycemic control in adolescents with type 1 diabetes in Dubai, United Arab Emirates.

OBJECTIVE: Diabetes distress and depression have been shown to be prevalent among adolescents with type 1 diabetes and screening for these parameters should be a routine part of diabetes care. To assess the prevalence of diabetes distress and depression and their association with glycemic control in a sample of adolescents with type 1 diabetes attending a diabetes center in Dubai, United Arab Emirates. All adolescents aged 13 to 18 years with type 1 diabetes that were seeking treatment at the Dubai Diabetes Center from the period of September 1, 2018 to May 1, 2019. A total of 72 participants completed the study. RESEARCH DESIGN AND METHODS: Adolescents were asked to fill in questionnaires assessing diabetes distress and depression. Multivariate linear regression analysis was used to assess the relationships between the subsets of socio-demographic and clinical characteristics, and the scores of the questionnaires. RESULTS: The mean HbA1c of the study sample was 9.61% [82 mmol/mol] with higher levels found in females as compared with males (p<0.05). Females showed significantly greater levels of distress as compared with males. Although adolescents with HbA1c≥7.5% scored higher for diabetes distress and depression, the difference was not statistically significant to those with an HbA1c of <7.5%. Higher levels of diabetes distress were highly correlated with depressive symptoms, with distress and depression both being significant predictors of one another. CONCLUSIONS: Our results highlight the importance of implementing and sustaining psycho-educational interventions to aid in alleviating diabetes distress and depression in this subgroup of the population.

Heat stress affects some physiological and productive variables and alters metabolism in dairy ewes.

Heat stress (HS) has a significant economic impact on the global dairy industry. However, the mechanisms by which HS negatively affects metabolism and milk synthesis in dairy ewes are not well defined. This study evaluated the production and metabolic variables in dairy ewes under controlled HS conditions. Eight Lacaune ewes (75.5 ± 3.2 kg of body weight; 165 ± 4 d of lactation; 2.31 ± 0.04 kg of milk per day) were submitted to thermoneutral (TN) or HS conditions in a crossover design (2 periods, 21 d each, 6-d transition). Conditions (day-night, 12-12 h; relative humidity; temperature-humidity index, THI) were: TN (15-20°C; 50 ± 5%; THI = 59-65) and HS (28-35°C; 45 ± 5%; THI = 75-83). Ewes were fed ad libitum and milked twice daily. Rectal temperature, respiratory rate, feed intake, water consumption, and milk yield were recorded daily. Milk and blood samples were collected weekly. Additionally, TN and HS ewes were exposed to glucose tolerance test, insulin tolerance test, and epinephrine challenge. Heat stress reduced feed intake (-11%), and increased rectal temperature (+0.77°C), respiratory rate (+90 breaths/min), and water consumption (+28%). Despite the reduced feed intake, HS ewes produced similar milk to TN ewes, but their milk contained lower fat (-1.7 points) and protein (-0.86 points). Further, HS milk tended to contain more somatic cells (+0.23 log points). Blood creatinine was greater in HS compared with TN, but no differences in blood glucose, nonesterified fatty acids, or urea were detected. When glucose was infused, TN and HS had similar insulin response, but higher glucose response (+85%) was detected in HS ewes. Epinephrine infusion resulted in lower nonesterified fatty acids response (-215%) in HS than TN ewes. Overall, HS decreased feed intake, but milk production was not affected. Heat stress caused metabolic adaptations that included increased body muscle degradation and reduced adipose tissue mobilization. These adaptations allowed ewes to spare glucose and to avoid reductions in milk yield.

Sensing solutions for improving the performance, health and wellbeing of small ruminants.

Diversity of production systems and specific socio-economic barriers are key reasons explaining why the implementation of new technologies in small ruminants, despite being needed and beneficial for farmers, is harder than in other livestock species. There are, however, helpful peculiarities where small ruminants are concerned: the compulsory use of electronic identification created a unique scenario in Europe in which all small ruminant breeding stock became searchable by appropriate sensing solutions, and the largest small ruminant population in the world is located in Asia, close to the areas producing new technologies. Notwithstanding, only a few research initiatives and literature reviews have addressed the development of new technologies in small ruminants. This Research Reflection focuses on small ruminants (with emphasis on dairy goats and sheep) and reviews in a non-exhaustive way the basic concepts, the currently available sensor solutions and the structure and elements needed for the implementation of sensor-based husbandry decision support. Finally, some examples of results obtained using several sensor solutions adapted from large animals or newly developed for small ruminants are discussed. Significant room for improvement is recognized and a large number of multiple-sensor solutions are expected to be developed in the relatively near future.

Mechanisms of action of metformin with special reference to cardiovascular protection.

Management guidelines continue to identify metformin as initial pharmacologic antidiabetic therapy of choice for people with type 2 diabetes without contraindications, despite recent randomized trials that have demonstrated significant improvements in cardiovascular outcomes with newer classes of antidiabetic therapies. The purpose of this review is to summarize the current state of knowledge of metformin's therapeutic actions on blood glucose and cardiovascular clinical evidence and to consider the mechanisms that underlie them. The effects of metformin on glycaemia occur mainly in the liver, but metformin-stimulated glucose disposal by the gut has emerged as an increasingly import site of action of metformin. Additionally, metformin induces increased secretion of GLP-1 from intestinal L-cells. Clinical cardiovascular protection with metformin is supported by three randomized outcomes trials (in newly diagnosed and late stage insulin-treated type 2 diabetes patients) and a wealth of observational data. Initial evidence suggests that cotreatment with metformin may enhance the impact of newer incretin-based therapies on cardiovascular outcomes, an important observation as metformin can be combined with any other antidiabetic agent. Multiple potential mechanisms support the concept of cardiovascular protection with metformin beyond those provided by reduced blood glucose, including weight loss, improvements in haemostatic function, reduced inflammation, and oxidative stress, and inhibition of key steps in the process of atherosclerosis. Accordingly, metformin remains well placed to support improvements in cardiovascular outcomes, from diagnosis and throughout the course of type 2 diabetes, even in this new age of improved outcomes in type 2 diabetes.

Finite Field Method for Nonlinear Optical Property Prediction Using Rational Function Approximants.

The finite field (FF) method is a quick, easy-to-implement tool for the prediction of nonlinear optical properties. Here, we present and explore a novel variant of the FF method, which uses a rational function to fit a molecule's energy with respect to an electric field. Similarly to previous FF methods, factors crucial for the method's accuracy were tuned. These factors include the number of terms in the function, the distribution of fields used to construct the approximation, and the initial field in the approximation. It was found that the approximant form that best fits the energy has four numerator terms and three denominator terms. To determine a reasonable field distribution, the common ratio of a geometric progression was optimized to √2. Finally, an algorithm for determining a good initial field guess was devised. The optimized FF method was used to compute the polarizability and second hyperpolarizability for a set of 121 molecules and the first hyperpolarizability for a set of 91 molecules. The results from this were compared to a previous polynomial-based FF method. It was found that using a rational function gives higher errors compared to the polynomial model. However, unlike the polynomial model, no subsequent refinement steps were needed to obtain usable results. An overall comparison of the behavior of the two methods also shows that the rational function is less sensitive to the chosen initial field, making it a good choice for new quantum chemistry codes.

A non-invasive method to produce pressure ulcers of varying severity in a spinal cord-injured rat model.

STUDY DESIGN: Experimental study. OBJECTIVES: The objective of this study was to establish a non-invasive model to produce pressure ulcers of varying severity in animals with spinal cord injury (SCI). SETTING: The study was conducted at the Johns Hopkins Hospital in Baltimore, Maryland, USA. METHODS: A mid-thoracic (T7-T9) left hemisection was performed on Sprague-Dawley rats. At 7 days post SCI, rats received varying degrees of pressure on the left posterior thigh region. Laser Doppler Flowmetry was used to record blood flow. Animals were killed 12 days after SCI. A cardiac puncture was performed for blood chemistry, and full-thickness tissue was harvested for histology. RESULTS: Doppler blood flow after SCI prior to pressure application was 237.808±16.175 PFUs at day 7. Following pressure application, there was a statistically significant decrease in blood flow in all pressure-applied groups in comparison with controls with a mean perfusion of 118.361±18.223 (P<0.001). White blood cell counts and creatine kinase for each group were statistically significant from the control group (P=0.0107 and P=0.0028, respectively). CONCLUSIONS: We have created a novel animal model of pressure ulcer formation in the setting of a SCI. Histological analysis revealed different stages of injury corresponding to the amount of pressure the animals were exposed to with decreased blood flow immediately after the insult along with a subsequent marked increase in blood flow the next day, conducive to an ischemia-reperfusion injury (IRI) and a possible inflammatory response following tissue injury. Following ischemia and hypoxia secondary to microcirculation impairment, free radicals generate lipid peroxidation, leading to ischemic tissue damage. Future studies should be aimed at measuring free radicals during this period of increased blood flow, following tissue ischemia.

Assessment of awareness, perception and utilization of health services among patients attending clinic at the Muslim Ummah Hospital, Kisi, South-west, Nigeria.

BACKGROUND: Health has been a prime concern of humanity since the dawn of history. People aspire to improve their health and also that of their household and communities. Healthcare utilization by the community is greatly influenced by their awareness and perception. METHODOLOGY: A descriptive study of the Awareness, Perception and Utilization of the Muslim Ummah Hospital, Kisi was carried out using a structured, interviewer administered questionnaire. Three hundred and eighty (380) participated in the study. A systematic sampling technique was utilized in sample selection. RESULT: The mean age of respondent was 36.9 + 2.95 years. Female respondents constituted 58.92% while the male counterpart were 41.08%. Awareness among the respondents is quite encouraging, as 198 (52%) of women respondents showed knowledge of the presence of the health center. A total of 38.1% (145) believed the service is very good while only 6.5% (25) considered it to be poor. On utilization profile 56.7% (215) had one time or the other attended the Outpatient Department; 43 (11.3%) for General Surgery, 7.4% (28) immunization, 15.4% (59) Delivery service and 9.2% (35) for Antenatal care. CONCLUSION: Health service utilization of the Muslim Ummah Comprehensive Hospital was shown to be greatly influenced by the community awareness of the service provided and their perception of the quality of service.

Drug release by pH-responsive molecular tweezers: atomistic details from molecular modeling.

pH-responsive molecular tweezers have been proposed as an approach for targeting drug-delivery to tumors, which tend to have a lower pH than normal cells. We performed a computational study of a pH-responsive molecular tweezer using ab initio quantum chemistry in the gas-phase and molecular dynamics (MD) simulations in solution. The binding free energy in solution was calculated using steered MD. We observe, in atomistic detail, the pH-induced conformational switch of the tweezer and the resulting release of the drug molecule. Even when the tweezer opens, the drug molecule remains near a hydrophobic arm of the molecular tweezer. Drug release cannot occur, it seems, unless the tweezer is in a hydrophobic environment with low pH.

Application of variation theory in STEM education: A comprehensive guideline for STEM teachers.

Incorporating appropriate pedagogical strategies has been instrumental in the development of a favorable learning environment for holistic learning, particularly in Science, Technology, Engineering, and Mathematics (STEM) education. However, there is growing evidence of the need to advance the existing methods, through more robust and comprehensive fieldwork grounded in design study. It has been shown that the lack of guidance in lesson planning using variation theory is also thought to require particular attention, as the accuracy of the student learning relies significantly on the planning of the lesson. However, little research has outlined the strategy to be followed for incorporating variation theory. This article proposes a method of preparing lesson plans to systematically implement the variation theory in STEM classrooms. The method seeks to design and implement current techniques as follows:•According to variation theory, teachers must create the necessary conditions for learning for the students to recognize what they are expected to learn.•To create the necessary conditions for learning, teachers define the key aspects of the topic to be covered and use different patterns of variations in teaching those contents, such as contrast, separation, generalization, and fusion.•Finally, teachers focus on the key aspects one by one or simultaneously to grab students' attention.

Solvatochromism of new tetraphenylethene luminogens: integration of aggregation-induced emission and conjugation-induced rigidity for emitting strongly in both solid and solution state.

In this study, we synthesized and characterized four tetraphenylethene (TPE) analogs, investigated their photophysical properties, and conducted quantum chemical calculations. Some molecules exhibited aggregation-induced emission enhancement behavior and showed efficient emission in both solid and solution states. Solvatochromism was observed in particular derivatives, with solvent polarity influencing either a bathochromic or hypsochromic shift, indicating the occurrence of photoinduced intramolecular charge transfer (ICT) processes. Quantum chemical calculations confirmed that variations in molecular packing and rigidity among the TPE analogs contributed to their diverse behavior. The study showcases aggregation in luminophores without significant impact on the excited state and highlights how minor alterations in terminal substituents can lead to unconventional behavior. These findings have implications for the development of luminescent materials. Furthermore, the synthesized compounds exhibited biocompatibility, suggesting their potential for cell imaging applications.

Real-World Study on Effectiveness of Insulin Glargine U300 After Oral Antidiabetic Drug Failure in Patients with Type 2 Diabetes in the Gulf Region.

INTRODUCTION: The effectiveness and safety of long-acting insulin glargine U300 (Gla-300), in patients with type 2 diabetes mellitus (T2DM) requiring insulin, has not been reported in the Gulf region. METHODS: Insulin-naïve patients with T2DM, uncontrolled on OADs, and prescribed Gla-300 were followed up in a 12-month prospective observational study. Gla-300 was titrated to glycemic targets. The primary endpoint (achieving glycemic targets) was evaluated at month 6 of treatment. The need for treatment intensification, safety, and patient-reported outcomes (PRO) were also reported. RESULTS: The study included 412 patients (61.7% men; age 52.2 ± 11.1 years and T2DM duration 10.7 ± 6.8 years). Almost 50% were on more than 3 OADs, mostly biguanides, sulfonylureas, and dipeptidyl-peptidase-4 inhibitors. Baseline HbA1c level was 9.2% ± 1.1% and targets were set at 6.9% ± 0.4%. Baseline fasting plasma glucose was 11.5 ± 3.8 mmol/l. Fifty-seven patients (13.8%) achieved glycemic targets at month 6, hindered by baseline HbA1c ≥ 10%, frequent co-morbidities, older age, suburban/rural residence, and full-time employment. Levels of HbA1c dropped progressively by 0.96% ± 0.07% (month 3), 1.29% ± 0.08% (month 6), and 1.76% ± 0.06% (month 12). Gla-300 dose was 17.0 ± 9.0 IU/day at baseline, 24.6 ± 9.6 IU/day at month 3, 28.5 ± 9.9 IU/day at month 6, and 30.7 ± 10.7 IU/day at month 12. Three patients experienced non-severe hypoglycemia and a slight decrease in body weight and PROs improved. CONCLUSIONS: In the Gulf, Gla-300 in patients with T2DM uncontrolled on OADs improved glycemic control, with low rates of hypoglycemia and improved PROs. Gla-300 dose up-titration from baseline to month 6 did not, however, result in a vast proportion of patients achieving their pre-determined HbA1c targets. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03703869.

Combination of HIF-1α gene transfection and HIF-1-activated bone marrow-derived angiogenic cell infusion improves burn wound healing in aged mice.

Impaired burn wound healing in the elderly represents a major clinical problem. Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator that orchestrates the cellular response to hypoxia. Its actions in dermal wounds promote angiogenesis and improve healing. In a murine burn wound model, aged mice had impaired wound healing associated with reduced levels of HIF-1. When gene therapy with HIF-1 alone did not correct these deficits, we explored the potential benefit of HIF-1 gene therapy combined with the intravenous infusion of bone marrow-derived angiogenic cells (BMDACs) cultured with dimethyloxalylglycine (DMOG). DMOG is known to reduce oxidative degradation of HIF-1. The mice treated with a plasmid DNA construct expressing a stabilized mutant form of HIF-1α (CA5-HIF-1α)+BMDACs had more rapid wound closure. By day 17, there were more mice with completely closed wounds in the treated group (χ(2), P=0.05). The dermal blood flow measured by laser Doppler showed significantly increased wound perfusion on day 11. Homing of BMDACs to the burn wound was dramatically enhanced by CA5-HIF-1α gene therapy. HIF-1α mRNA expression in the burn wound was increased after transfection with CA5-HIF-1α plasmid. Our findings offer insight into the pathophysiology of burns in the elderly and point to potential targets for developing new therapeutic strategies.

Finding optimal finite field strengths allowing for a maximum of precision in the calculation of polarizabilities and hyperpolarizabilities.

The finite field method, widely used for the calculation of static dipole polarizabilities or the first and second hyperpolarizabilities of molecules and polymers, is thoroughly explored. The application of different field strengths and the impact on the precision of the calculations were investigated. Borders could be defined and characterized, establishing a range of feasible field strengths that guarantee reliable numerical results. The quality of different types of meshes to screen the feasible region is assessed. Extrapolation schemes are presented that reduce the truncation error and allow to increase the precision of finite field calculations by one to three orders of magnitude.

Rationale and design of the Cardiovascular Inflammation Reduction Trial: a test of the inflammatory hypothesis of atherothrombosis.

BACKGROUND: Inflammation plays a fundamental role in atherothrombosis. Yet, whether direct inhibition of inflammation will reduce the occurrence of adverse cardiovascular outcomes is not known. DESIGN: The Cardiovascular Inflammation Reduction Trial (CIRT) (ClinicalTrials.govNCT01594333) will randomly allocate 7,000 patients with prior myocardial infarction (MI) and either type 2 diabetes or the metabolic syndrome to low-dose methotrexate (target dose 15-20 mg/wk) or placebo over an average follow-up period of 3 to 5 years. Low-dose methotrexate is a commonly used anti-inflammatory regimen for the treatment of rheumatoid arthritis and lacks significant effects on lipid levels, blood pressure, or platelet function. Both observational and mechanistic studies suggest that low-dose methotrexate has clinically relevant antiatherothrombotic effects. The CIRT primary end point is a composite of nonfatal MI, nonfatal stroke, and cardiovascular death. Secondary end points are all-cause mortality, coronary revascularization plus the primary end point, hospitalization for congestive heart failure plus the primary end point, all-cause mortality plus coronary revascularization plus congestive heart failure plus the primary end point, incident type 2 diabetes, and net clinical benefit or harm. CIRT will use standardized central methodology designed to ensure consistent performance of all dose adjustments and safety interventions at each clinical site in a manner that protects the blinding to treatment but maintains safety for enrolled participants. SUMMARY: CIRT aims to test the inflammatory hypothesis of atherothrombosis in patients with prior MI and either type 2 diabetes or metabolic syndrome, conditions associated with persistent inflammation. If low-dose methotrexate reduces cardiovascular events, CIRT would provide a novel therapeutic approach for the secondary prevention of heart attack, stroke, and cardiovascular death.

Nutritional rehabilitation of malnourished children detected by Screening Tool for Assessment of Malnutrition in Pediatric: Urban versus rural settings.

BACKGROUND: Malnutrition presents a major global health burden. In Egypt, it remains an important issue in children under 5 years especially in rural communities. AIM OF THE STUDY: The aim of the study was to screen 2-5 years old children enrolled from Egyptian hospitals in rural and urban areas for the risk of malnutrition using Screening Tool for Assessment of Malnutrition in Pediatric (STAMP) and to evaluate the effectiveness of nutritional intervention programs. SUBJECTS AND METHODS: This cross-sectional study was conducted on 90 patients recruited from two hospitals in urban and rural Cairo, Dietary history and anthropometric measurements were assessed. Patients at intermediate and severe risk of malnutrition according to STAMP were given tailored nutritional programs. RESULTS: In the rural hospital, 4.4% of the screened children were underweight, 22.2% were marginally underweight, and 73.3% had normal weight. Regarding the urban hospital, 15.6% were marginally underweight, 84.4% had normal weight and no underweight patients. Among the rural group 35.6% were at high risk according to STAMP score results compared to 20% in the urban group. Nevertheless, the only significant differences were the more stunting and higher BMI in rural hospital patients. After nutritional intervention, high-risk category patients decreased in both groups coupled by significant improvement in the anthropometric parameters and nutrition data with no significant differences between them. CONCLUSION: Nutritional education and prompt implementation of nutritional rehabilitation program for malnourished children detected by screening tools result in improvement in their nutritional status disregards their location whether urban or rural.

Endothelial Insulin Resistance Exacerbates Experimental Periodontitis.

Epidemiological studies suggest that the severity of periodontitis is higher in people with diabetes than in healthy individuals. Insulin resistance might play a crucial role in the pathogenesis of multiple diabetic complications and is reportedly induced in the gingiva of rodents with type 2 diabetes; however, the molecular mechanisms underlying the pathogenesis of diabetes-related periodontitis remain unclear. Therefore, we aimed to investigate whether endothelial insulin resistance in the gingiva may contribute to the pathogenesis of periodontitis as well as elucidate its underlying molecular mechanisms. We demonstrated that insulin treatment downregulated lipopolysaccharide (LPS)-induced or tumor necrosis factor α (TNFα)-induced VCAM1 expression in endothelial cells (ECs) via the PI3K/Akt activating pathway, resulting in reduced cellular adhesion between ECs and leukocytes. Hyperglycemia-induced selective insulin resistance in ECs diminished the effect of insulin on LPS- or TNFα-stimulated VCAM1 expression. Vascular endothelial cell-specific insulin receptor knockout (VEIRKO) mice exhibited selective inhibition of the PI3K/Akt pathway in the gingiva and advanced experimental periodontitis-induced alveolar bone loss via upregulation of Vcam1, Tnfα, Mcp-1, Rankl, and neutrophil migration into the gingiva compared with that in the wild-type (WT) mice despite being free from diabetes. We also observed that insulin-mediated activation of FoxO1, a downstream target of Akt, was suppressed in the gingiva of VEIRKO and high-fat diet (HFD)-fed mice, hyperglycemia-treated ECs, and primary ECs from VEIRKO. Further analysis using ECs transfected with intact and mutated FoxO1, with mutations at 3 insulin-mediated phosphorylation sites (T24A, S256D, S316A), suggested that insulin-mediated regulation of VCAM1 expression and cellular adhesion of ECs with leukocytes was attenuated by mutated FoxO1 overexpression. These results suggest that insulin resistance in ECs may contribute to the progression of periodontitis via dysregulated VCAM1 expression and cellular adhesion with leukocytes, resulting from reduced activation of the PI3K/Akt/FoxO1 axis.

Solid-State Luminescent Materials Containing Both Indole and Pyrimidine Moieties: Design, Synthesis, and Density Functional Theory Calculations.

Heterocyclic compounds with effective solid-state luminescence offer a wide range of uses. It has been observed that combining pyrimidine and indole moieties in a single molecule can enhance material behavior dramatically. Here, different heterocyclic compounds with indole and pyrimidine moieties have been synthesized effectively, and their structures have been validated using NMR, IR, and mass spectroscopy. The photoluminescence behavior of two substances was investigated in powder form and solutions of varying concentrations. After aggregation, one molecule displayed a redshifted luminescence spectrum, whereas another homolog showed a blueshift. Thus, density functional theory calculations were carried out to establish that introducing a terminal group allows modifying of the luminescence behavior by altering the molecular packing. Because of the non-planarity, intermolecular interactions, and tiny intermolecular distances within the dimers, the materials demonstrated a good emission quantum yield (Φem) in the solid state (ex. 25.6%). At high temperatures, the compounds also demonstrated a stable emission characteristic.