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BackgroundThe increasing application of generative artificial intelligence large language models (LLMs) in various fields, including dentistry, raises questions about their accuracy. ObjectiveThis study aims to comparatively evaluate the answers provided by 4 LLMs, namely Bard (Google LLC), ChatGPT-3.5 and ChatGPT-4 (OpenAI), and Bing Chat (Microsoft Corp), to clinically relevant questions from the field of dentistry. MethodsThe LLMs were queried with 20 open-type, clinical dentistry–related questions from different disciplines, developed by the respective faculty of the School of Dentistry, European University Cyprus. The LLMs’ answers were graded 0 (minimum) to 10 (maximum) points against strong, traditionally collected scientific evidence, such as guidelines and consensus statements, using a rubric, as if they were examination questions posed to students, by 2 experienced faculty members. The scores were statistically compared to identify the best-performing model using the Friedman and Wilcoxon tests. Moreover, the evaluators were asked to provide a qualitative evaluation of the comprehensiveness, scientific accuracy, clarity, and relevance of the LLMs’ answers. ResultsOverall, no statistically significant difference was detected between the scores given by the 2 evaluators; therefore, an average score was computed for every LLM. Although ChatGPT-4 statistically outperformed ChatGPT-3.5 (P=.008), Bing Chat (P=.049), and Bard (P=.045), all models occasionally exhibited inaccuracies, generality, outdated content, and a lack of source references. The evaluators noted instances where the LLMs delivered irrelevant information, vague answers, or information that was not fully accurate. ConclusionsThis study demonstrates that although LLMs hold promising potential as an aid in the implementation of evidence-based dentistry, their current limitations can lead to potentially harmful health care decisions if not used judiciously. Therefore, these tools should not replace the dentist’s critical thinking and in-depth understanding of the subject matter. Further research, clinical validation, and model improvements are necessary for these tools to be fully integrated into dental practice. Dental practitioners must be aware of the limitations of LLMs, as their imprudent use could potentially impact patient care. Regulatory measures should be established to oversee the use of these evolving technologies.

Background: Toll-like-receptors (TLRs) provide a critical link between innate and adaptive immune responses. It has been shown that TLR5 ligand Flagellin can enhance the suppressive capacity of regulatory T-cells (Treg), but can also functions as an adjuvant. The immune response in atherosclerosis is characterized by an imbalance of pro- and anti-atherogenic T-cells. We aimed to establish if the TLR5/Flagellin axis is involved in the immune response of atherosclerosis. Methods: We first assessed the effect of Flagellin exposure on macrophage maturation and T-cell polarization. Next, we created TLR5-/-/LDLr-/- chimeras to study the TLR5/Flagellin axis in atherosclerosis. Results: Flagellin exposure to primary macrophages did not result in clear polarization differences, but we did observe a less migratory phenotype (decreased MCP-1, CCR2 expression) in TLR5-/- macrophages. Interestingly, expression of the T-cell polarizing cytokine IL-6 was induced by Flagellin exposure, a phenomenon not observed in TLR5-/- macrophages. Next, we assessed potential T cell polarizing properties of Flagellin. Flagellin can induce expansion of regulatory T-cells, however this induction is completely overruled when Flagellin is used as an adjuvant. Hematopoietic absence of TLR5 significantly attenuates atherosclerotic lesion formation by 25% (1.03±0.06×106 μm2 vs 0.79±0.06 ×106 μm2 in TLR5-/-, p = 0.01). This was accompanied by a decrease in macrophage area (-46%, p = 0.01) and necrotic core size (-32%, p<0.05) while collagen content was similar between groups. Interestingly, plasma levels of IL-6 were significantly lower in TLR5-/- chimeras (40.2±6.3 in WT vs. 15.1±2.7 pg/ml in TLR5-/-, p=0.003). Concomitantly, TLR5-/- chimeras displayed defective T-cell responsiveness, as seen by impaired proliferation and decreased splenic T cell content. In conclusion, hematopoietic TLR5 deficiency inhibits atherosclerotic lesion formation by attenuated macrophage accumulation and defective T cell responsiveness. [ABSTRACT FROM AUTHOR]

Introduction: Gliptins are a relatively recent class of oral antidiabetic agents used in the treatment of type 2 diabetes. The aim of this study is to identify the adverse effects of gliptins in patients with type 2 diabetes, compare the tolerability of these drugs with data from the literature, and determine patients' behavior in the face of these adverse effects with a view to optimizing their management., Methods: Our study is cross-sectional, descriptive, and analytical, involving 100 patients aged over 20 years, followed at the Endocrinology Department of the Military Hospital Mohammed V., Results: The average age of the patients was 63 years, with a sex ratio F/H of 1.13. The median age of diabetes in the patients was 13 years, with an average blood glucose level of 1.64 and an average hemoglobin A1c of 8.26. The comorbidities were 30% cardiovascular disease, 25% hypertension, and 14% dyslipidemia, and 30% of patients had no comorbidities. Forth-six percent of patients reported adverse events and 54% did not report any adverse event. Twenty-eight percent of the adverse events were gastrointestinal, 18% skin disorders, 14% urinary tract infections, 12% hypoglycemia, 12% nervous system disorders, 8% airway infections, and 8% general disorders., Conclusion: This study shows that gliptins remain a safe option as the side effects seem fairly well tolerated by patients. Adverse events may impact patient compliance and pose a problem of adherence to treatment. Thus, it would be advantageous to develop therapeutic education for diabetic patients to detect and manage adverse effects., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)

Tuberculous dactylitis can cause osteomyelitis, which is a rare extrapulmonary manifestation of tuberculosis, often misdiagnosed due to its nonspecific presentation and resemblance to other conditions like neoplasms. A 15-year-old male patient reported to our clinic with a 1-year history of left index finger pain and swelling following a football-related injury. Despite conservative management, the symptoms had progressively worsened over the past few months. Clinical examination revealed deformity and swelling of the middle phalanx, along with induced pain on range of motion. Bacteriological analysis indicated polymorphic nuclear cells and the presence of coagulase-negative Staphylococcus ( Staphylococcus hominis ). Radiographic evaluation, including x-ray and magnetic resonance imaging, revealed medullary expansion, trabecular thinning, and focal soft tissue swelling. Magnetic resonance imaging displayed extensive soft tissue and bone marrow involvement, raising concerns of a tumor. An open biopsy was performed, yielding unexpected findings of necrotizing and suppurative granulomatous inflammation, strongly suggesting an ongoing infectious process. The subsequent Quantiferon TB Gold Test confirmed tuberculosis infection. Treatment encompassed debridement, synovectomy, and initiation of an antituberculosis regimen. The patient showed significant improvement after treatment. Timely diagnosis and treatment of tuberculous dactylitis are crucial, as highlighted by the patient's positive response to combined surgical and pharmacological intervention, despite initial diagnostic challenges., Competing Interests: The authors declare no financial interests or commercial associations that could pose or create a real or perceived bias in relation to the content of this article. Specifically, the authors have no employment, stock ownership, consultancy roles, honoraria, patents, or funding related to the subject of this article. All potential conflicts of interest for the author group have been disclosed and no new conflicts have arisen since submission., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Skin can be damaged by intense and prolonged exposure to ultraviolet (UV) radiation. Photoaging and acute damage from sun exposure result in collagen degradation and enzymatic activity decline in the skin. Fucoidan (FUC) exhibits potential antiaging properties, including collagen synthesis promotion and enzyme activity inhibition. However, FUC's limited ability to penetrate the skin layers due to its large molecular weight makes it a challenge for topical application. In this study, we successfully developed a new approach by integrating thermoresponsive gel (TRG) containing FUC with solid microneedles (SMNs) as a delivery system. TRG is formulated using a combination of Pluronic F127 (PF127) and Pluronic F68 (PF68) polymers, while SMNs are made from a mixture of poly(vinyl alcohol) (PVA) and poly(vinylpyrrolidone) (PVP) polymers with a variety of cross-linkers. Based on the results of ex vivo testing, it was shown that more than 80% of FUC can be delivered using the optimized formula. Furthermore, the results of the in vitro blood hemolytic test showed that TRG-FUC-SMNs were relatively biocompatible. In vivo antiaging activity tests using a rat model exposed to UV for 14 days showed that histological assessment, skin elasticity measurement, wrinkle evaluation, and skin moisture content had no significant differences ( p < 0.05) compared to the positive control group. In contrast, a significant difference ( p < 0.05) was observed when comparing the TRG-FUC-SMNs group with the group that received only TRG-FUC without pretreatment and negative controls. These findings suggest that FUC has potential to be delivered using the TRG system in combination with SMNs to harness its antiaging properties.

Skin aging occurs naturally as essential skin components gradually decline, leading to issues such as fine lines, wrinkles, and pigmentation. Fucoidan, a natural bioactive compound, holds potential for addressing these age-related concerns. However, its hydrophilic nature and substantial molecular weight hinder its absorption into the skin. In this study, we utilized polyvinyl pyrrolidone K30 (PVP) and polyvinyl alcohol (PVA) as polymers to fabricate dissolving microneedles loaded with fucoidan (DMN-F). The DMN-F formulations were examined for physical characteristics, stability, permeability, toxicity, and efficacy in animal models. These formulations exhibited consistent polymer blends with a conical structure and uniform cone-shaped design. Microneedle structure and penetration capability gradually decreased with increasing fucoidan concentration, with storage recommended at approximately 33 % relative humidity (RH). Ex vivo studies showed that DMN-F efficiently delivered up to 95.03 ± 2.36 % of the total fucoidan concentration into the skin. In vivo investigations revealed that DMN-F effectively reduced wrinkles, improved skin elasticity, maintained moisture levels, and increased epidermal thickness. Histological images provided additional evidence of DMN-F's positive effects on these aging parameters. The results confirm that the DMN-F formulation effectively delivers fucoidan into the skin, allowing it to treat and mitigate signs of aging., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: This study aimed to explore the experiences of young adult cancer patients within the Tunisian context. Methods: A total of 104 patients between the ages of 20 and 40, undergoing treatment for various types and stages of cancer, participated in a questionnaire-based survey. The survey encompassed topics related to the socioeconomic and psychological impacts of cancer, coping mechanisms, relationships, sexuality, and future aspirations. Results: Of the participants, 78 were women (75%) and 26 were men (25%), with an average age of 33 years. Financial difficulties were reported by 60 patients (57.7%). The most common emotional responses to the diagnosis were sadness (54.8%), followed by denial (18.3%) and anger (5.8%). Thirteen patients (12.5%) choose not to receive information about the stage of their disease. In addition, 42 patients (40.4%) experienced a decrease in perceived physical attractiveness, while negative effects on sexuality were observed in 44.2% of cases. The primary concerns reported by patients were the fear of recurrence or progression (48%) and infertility (48%). Furthermore, 43 patients (41.3%) expressed a decrease in self-confidence, notably influenced by financial difficulties (OR: 2.77 [95% CI: 1.12-6.87]), physical alterations (OR: 0.18 [95% CI: 0.07-0.45]), and sexual issues (OR: 0.17 [95% CI: 0.06-0.48]). Notably, 78 patients (75%) continued to make future plans, particularly those under 30 years of age (OR: 0.2 [95% CI: 0.04-0.96]). Moreover, 47.1% of patients expressed an inclination toward immigration to developed countries, primarily due to perceived superior health care systems (61.5%). Conclusions: Young cancer patients face a range of social and psychological challenges, suggesting the necessity for a specialized care approach.

Objectives: Adjunctive rifampicin for implant-associated infections is controversial. This study investigated the clinical outcomes of rifampicin combination therapy compared with monotherapy in treating prosthetic joint infection (PJI) or prosthetic valve endocarditis (PVE) due to staphylococci and streptococci., Methods: A systematic search was performed from inception to 13 June 2022 in Embase, MEDLINE, Cochrane and Web of Science to investigate the clinical outcomes of rifampicin combination therapy compared with monotherapy in treating staphylococcal and streptococcal PJI or PVE. Randomised controlled trials (RCTs) and observational studies were included in the systematic review and meta-analysis., Results: Fourteen studies were included. A moderate quality of evidence was found in favour of rifampicin in patients with staphylococcal PJI who underwent a debridement, antibiotics and implant retention (DAIR) procedure [odds ratio = 2.49, 95% confidence interval (CI) 1.93-3.23]. Including the two RCTs only, adding rifampicin to the antibiotic regimen after DAIR was also in favour of rifampicin, but this was not statistically significant (risk ratio = 1.27, 95% CI 0.79-2.04; n = 126). Pooling data for patients with staphylococcal PJI who underwent a two-stage procedure showed that adding rifampicin was not associated with therapeutic success. Limited evidence was found for the use of rifampicin for PVE caused by staphylococci., Conclusions: Adding rifampicin in the treatment of staphylococcal PJI treated by DAIR clearly increased the likelihood for therapeutic success. The clinical benefit of adjunctive rifampicin in the treatment of other staphylococci and streptococci implant-associated infections is still unclear., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This article focuses on the design of a sensor system for a non-planar surface, in particular a cylindrical shape, such as a kayak paddle. The main objective is to develop a piezoresistive sensor system to measure the pressure exerted by the hand on the shaft. The study begins with static characterization of the sensors, including dispersion analysis to assess their sensitivity, linearity and measurement range. A calibration process is carried out using a dedicated test bench, and an inverse viscoelastic model is used to establish an accurate relationship between the measured resistance and the corresponding pressure. The sensor system is connected to a data acquisition board equipped with an analog-to-digital converter (ADC) that enables the direct conversion of analog data into digital resistance values. Furthermore, Bluetooth Low Energy (BLE) wireless communication is employed to facilitate data transfer to a computer, enabling a detailed pressure mapping of the kayak paddle and real-time data collection. The calibrated sensors are then tested and validated on the kayak paddle, facilitating the mapping of pressure zones on the paddle surface. This mapping provides information for locating areas of high pressure exertion during kayaker movements.

Background: The COVID-19 pandemic caused extraordinary changes in dental practices, including evidence-based dentistry (EBD). Despite dental practitioners' positive attitudes toward EBD, implementation has been limited. This study aimed to investigate the knowledge, attitudes, and practices of EBD among dental professionals in Saudi Arabia and explore the COVID-19 pandemic impacts on perceptions of EBD., Methods: A cross-sectional study was conducted using a questionnaire that was distributed electronically to dentists and dental students in Saudi Arabia. Multiple linear regression and descriptive statistics were used for data analysis., Results: The mean knowledge score was 48.33 ± 13.63 out of 70 points, with 37.31% to 60.45% awareness of EBD components. Only 37% were aware of the Cochrane Collaboration. Specialist/consultants and participants from the central region had significantly better knowledge scores. Lack of time (75.60%) was the most significant barrier to EBD. Only 36.60% of participants used EBD for treatment procedures. Most (72.4%-80.6%) believed the pandemic increased EBD's importance, 67.70% believed that EBD should be mandatory, and 62.90% believed all decisions in dental clinics will follow EBD in the future. However, 53.50% reported that EBD material was difficult to follow during COVID-19., Conclusions: The level of knowledge about EBD among dental professionals in Saudi Arabia is relatively acceptable. It is difficult to put EBD to practice due to the overwhelming flow of information. More educational and organizational efforts should be implemented to advocate for EBD., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Pharmacy and Bioallied Sciences.)

Twenty-five B-cell-depleted patients (24 following anti-CD19/20 therapy) diagnosed with coronavirus disease 2019 had been symptomatic for a median of 26 days but remained antibody negative. All were treated with convalescent plasma with high neutralizing antibody titers. Twenty-one (84%) recovered, indicating the potential therapeutic effects of this therapy in this particular population., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies and is the third cause of cancer-related death worldwide. Surgery is the optimal treatment for early HCC; however, the majority of cases are not suitable for curative resection at the time of diagnosis. Surgical resection difficulties may be related to size, site, number of tumors, extrahepatic involvement, and patient general condition. Exophytic tumors were considered as relative contraindication for thermal ablation because of the risk of incomplete ablation or major complications as hemorrhage and seeding., Aim of This Study: to evaluate the safety and efficacy of microwave ablation (MWA) of exophytic HCC in comparison with non-exophytic HCC., Methods: Prospective comparative study carried on 30 patients having 30 exophytic (six of those patients had another non-exophytic lesion) and 32 patients having 44 non-exophytic HCC lesions (22 had single lesion, 8 patients had 2 lesions, and 2 patients had 3 lesions) within Milan criteria. All patients were child A or B, they were subjected to full clinical assessment, laboratory investigations, and radiological investigations. Laparoscopic assisted percutaneous MWA was the procedure of choice in our study for all patients either having exophytic or non-exophytic lesions using no-touch wedge technique for exophytic lesions and direct puncture for non-exophytic lesions., Results: Technical success was 100% in both groups, all lesions were completely ablated as confirmed by LIOUS. There were no major complications or perioperative mortality and low incidence of local tumor progression in both exophytic and non-exophytic groups., Conclusion: Laparoscopic assisted MWA of exophytic HCC is safe and effective with comparable results to non-exophytic HCC. Exophytic HCC is not contraindication for MWA with proper technique selection., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The classic chest CT imaging features of COVID-19 pneumonia have low specificity due to their similarity with a number of other conditions. So, the goal of the present study is to learn from the pathophysiology of COVID-19 clinical features, laboratory results, and high-resolution CT manifestations in different stages of disease severity to provide significant reference values for diagnosis, prevention, and treatment., Methods: This was a multicentered study that included 128 patients. Demographic, clinical, and laboratory data, in addition to chest HRCT findings, were evaluated. According to chest HRCT features, radiologic scoring were grade 1 and 2 for mild grades of the disease, 3 and 4 for moderate grades of the disease, and 5 and 6 for severe grades of the disease., Results: Patient clinical symptoms ranged between fever, dry cough, muscle ache (myalgia)/fatigue, dyspnea, hyposomia, sore throat, and diarrhea. Lymphocytes and WBCs were significantly lower in patients with severe COVID-19. A significant negative correlation was found with WBCs (r = - 0.245, P = 0.005), lymphocytes% (r = - 0.586, P < 0.001), RBCs (r = - 0.2488, P = 0.005), Hb (gm/dl) (r = - 0.342, P < 0.001), and HCT (r = - 0.377, P < 0.001). Transferrin and CRP were significantly higher in moderate and severe COVID-19 than mild degree and showed a significant positive correlation with CT score (r = 0.356, P < 0.001) and (r = 0.429, P < 0.001), respectively. The most common CT features were peripheral pulmonary GGO and air space consolidation., Conclusion: Clinical features, laboratory assessment, and HRCT imaging had their characteristic signs and performances. Correlating them can make it possible for physicians and radiologists to quickly obtain the final diagnosis and staging of the COVID-19 pneumonia.

Rickets are abnormalities of mineralization that can lead to bone fractures and deformities. Vitamin-resistant rickets is defined as any rickets not prevented by regular, early and prolonged administration of vitamin D and not cured by a sufficient total dose. The aim of our work is to describe the clinical, paraclinical and therapeutic aspects of X-linked hypophosphatemic rickets (XLHR), which is the most common cause of hereditary rickets and on the other hand to highlight the interest not only of the early care but also the regular long-term monitoring of these children.

A 61-year-old Ghanaian woman presented with dizziness and low oxygen saturations whereupon a methaemoglobin level of 24.9% was obtained. Initially it was thought to be caused by an unknown toxin. However, failure to normalise spontaneously and a short recurrence following administration of methylene blue suggested a congenital cause. Subsequently a novel variant in the CYB5R3 gene, coding for Cytochrome b5 reductase, was demonstrated. Absence of polycythaemia prompted additional analysis for a concomitant haemoglobinopathy.

C1 esterase inhibitor (C1-INH) can inhibit multiple pathways (complement, contact-kinin, coagulation, and fibrinolysis) that are all implicated in the pathophysiology of asthma. We explored the effect of human plasma-derived C1-INH on allergic lung inflammation in a house dust mite (HDM) induced asthma mouse model by daily administration of C1-INH (15 U) during the challenge phase. NaCl and HDM exposed mice had comparable plasma C1-INH levels, while bronchoalveolar lavage fluid (BALF) levels were increased in HDM exposed mice coinciding with slightly reduced activation of complement (C5a). C1-INH treatment reduced Th2 response and enhanced HDM-specific IgG1. Influx of eosinophils in BALF or lung, pulmonary damage, mucus production, procoagulant response or plasma leakage in BALF was similar in both groups. In conclusion, C1-INH dampens Th2 responses during HDM induced allergic lung inflammation.

Klebsiella pneumoniae is a common cause of pneumonia. Previous studies have documented an important role for Toll-like receptors (TLRs) expressed by myeloid cells in the recognition of K. pneumoniae and the initiation of a protective immune response. Lung epithelial cells also express TLRs and can participate in innate immune defense. The aim of this study was to examine the role of the common TLR adaptor protein myeloid-differentiation factor (MyD) 88 in lung epithelium during host defense against K. pneumoniae-induced pneumonia. To this end, we first crossed mice expressing cre recombinase under the control of the surfactant protein C (SftpCcre) or the club cell 10 kD (CC10cre) promoter with reporter mice to show that SftpCcre mice mainly express cre in type II alveolar cells, whereas CC10cre mice express cre almost exclusively in bronchiolar epithelial cells. We then generated mice with cell-targeted deletion of MyD88 in type II alveolar (SftpCcre-MyD88-lox) and bronchiolar epithelial (CC10cre-MyD88-lox) cells, and infected them with K. pneumoniae via the airways. Bacterial growth and dissemination were not affected by the loss of MyD88 in SftpCcre-MyD88-lox or CC10cre-MyD88-lox mice compared with control littermates. Furthermore, inflammatory responses induced by K. pneumoniae in the lung were not dependent on MyD88 expression in type II alveolar or bronchiolar epithelial cells. These results indicate that MyD88 expression in two distinct lung epithelial cell types does not contribute to host defense during pneumonia caused by a common human gram-negative pathogen.

Toll-like receptors (TLR) provide a critical link between innate and adaptive immunity, both important players in atherosclerosis. Since evidence for the role of TLR5 is lacking, we aimed to establish this in the immune axis of atherosclerosis. We assessed the effect of the TLR5-specific ligand Flagellin on macrophage maturation and T-cell polarisation. Next, we generated TLR5 -/- LDLr -/- chimeras to study the effect of hematopoietic TLR5 deficiency on atherosclerosis formation. Flagellin stimulation did not influence wildtype or TLR5 -/- macrophage maturation. Only in wildtype macrophages, Flagellin exposure increased MCP-1 and IL6 expression. Flagellin alone reduced T-helper 1 proliferation, which was completely overruled in the presence of T-cell receptor activation. In vivo, hematopoietic TLR5 deficiency attenuated atherosclerotic lesion formation by ≈25% (1030*10 3  ± 63*10 3 vs. 792*10 3  ± 61*10 3 μm 2 ; p = 0.013) and decreased macrophage area (81.3 ± 12.0 vs. 44.2 ± 6.6 μm 2 ; p = 0.011). In TLR5 -/- chimeric mice, we observed lower IL6 plasma levels (36.4 ± 5.6 vs. 15.1 ± 2.2 pg/mL; p = 0.003), lower (activated) splenic CD4 + T-cell content (32.3 ± 2.1 vs. 21.0 ± 1.2%; p = 0.0018), accompanied by impaired T-cell proliferative responses. In conclusion, hematopoietic TLR5 deficiency inhibits atherosclerotic lesion formation by attenuated macrophage accumulation and defective T-cell responsiveness.

Asthma is a highly prevalent chronic allergic inflammatory disease of the airways affecting people worldwide. House dust mite (HDM) is the most common allergen implicated in human allergic asthma. HDM-induced allergic responses are thought to depend upon activation of pathways involving Toll-like receptors and their adaptor protein myeloid differentiation factor 88 (MyD88). We sought here to determine the role of MyD88 in myeloid and type II lung epithelial cells in the development of asthma-like allergic disease using a mouse model. Repeated exposure to HDM caused allergic responses in control mice characterized by influx of eosinophils into the bronchoalveolar space and lung tissue, lung pathology and mucus production and protein leak into bronchoalveolar lavage fluid. All these responses were abrogated in mice with a general deficiency of MyD88 but unaltered in mice with MyD88 deficiency, specifically in myeloid or type II lung epithelial cells. We conclude that cells other than myeloid or type II lung epithelial cells are responsible for MyD88-dependent HDM-induced allergic airway inflammation., (© 2016 British Society for Immunology.)

Pseudomonas aeruginosa is a flagellated pathogen frequently causing pneumonia in hospitalized patients and sufferers of chronic lung disease. Here we investigated the role of the common Toll-like receptor (TLR) adaptor myeloid differentiation factor (MyD)88 in myeloid vs. lung epithelial cells in clearance of P. aeruginosa from the airways. Mice deficient for MyD88 in lung epithelial cells (Sftpccre-MyD88-lox mice) or myeloid cells (LysMcre-MyD88-lox mice) and bone marrow chimeric mice deficient for TLR5 (the receptor recognizing Pseudomonas flagellin) in either parenchymal or hematopoietic cells were infected with P. aeruginosa via the airways. Sftpccre-MyD88-lox mice demonstrated a reduced influx of neutrophils into the bronchoalveolar space and an impaired early antibacterial defense after infection with P. aeruginosa, whereas the response of LysMcre-MyD88-lox mice did not differ from control mice. The immune-enhancing role of epithelial MyD88 was dependent on recognition of pathogen-derived flagellin by epithelial TLR5, as demonstrated by an unaltered clearance of mutant P. aeruginosa lacking flagellin from the lungs of Sftpccre-MyD88-lox mice and an impaired bacterial clearance in bone marrow chimeric mice lacking TLR5 in parenchymal cells. These data indicate that early clearance of P. aeruginosa from the airways is dependent on flagellin-TLR5-MyD88-dependent signaling in respiratory epithelial cells., (Copyright © 2016 the American Physiological Society.)

Introduction: Magnetic resonance cholangiopancreatography (MRCP) has achieved widespread success as a diagnostic tool for hepatobiliary lesions. MRCP offers an effective method of hepatobiliary diagnosis that is safer than the use of invasive procedures, namely endoscopic retrograde cholangiopancreatography, and is more accurate than ultrasound., Aim: The aim of the study was to assess the diagnostic quality and overall accuracy of MRCP for the evaluation of hepatobiliary lesions., Patients and Methods: Eighty patients (42 male, 38 female; mean age, 38.3 years) suspected for hepatobiliary lesions were enrolled in this study. MRCP protocols applied for imaging of the hepatobiliary system were T2-weighted fast spin echo sequence on axial and coronal planes; three-dimensional, fat suppressed, heavily T2-weighted fast spin echo sequence with multislab acquisition mode; two-dimensional thick single slab projectional images, and three-dimensional reconstruction algorithms., Results: Among the patients, jaundice and biliary colic were the commonest clinical complaints. MRCP has detected different pathologic entities among congenital anomalies, inflammatory conditions, neoplastic disorders, and postoperative and post-traumatic complications. The MRCP diagnosis was compared with the final diagnosis reached by endoscopic retrograde cholangiopancreatography, surgical, or histopathologic data. MRCP has a high overall diagnostic accuracy of 97%, sensitivity of 98%, and specificity of 93%., Conclusions: MRCP provides a safe, noninvasive, accurate diagnostic tool in detection of the presence and level of biliary obstruction and also denotes its cause with high accuracy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Klebsiella pneumoniae is among the most common Gram-negative bacteria that cause pneumonia. Gp96 is an endoplasmic reticulum chaperone that is essential for the trafficking and function of Toll-like receptors (TLRs) and integrins. To determine the role of gp96 in myeloid cells in host defence during Klebsiella pneumonia, mice homozygous for the conditional Hsp90b1 allele encoding gp96 were crossed with mice expressing Cre-recombinase under control of the LysM promoter to generate LysMcre-Hsp90b1-flox mice. LysMcre-Hsp90b1-flox mice showed absence of gp96 protein in macrophages and partial depletion in monocytes and granulocytes. This was accompanied by almost complete absence of TLR2 and TLR4 on macrophages. Likewise, integrin subunits CD11b and CD18 were not detectable on macrophages, while being only slightly reduced on monocytes and granulocytes. Gp96-deficient macrophages did not release pro-inflammatory cytokines in response to Klebsiella and displayed reduced phagocytic capacity independent of CD18. LysMcre-Hsp90b1-flox mice were highly vulnerable to lower airway infection induced by K. pneumoniae, as reflected by enhanced bacterial growth and a higher mortality rate. The early inflammatory response in Hsp90b1-flox mice was characterized by strongly impaired recruitment of granulocytes into the lungs, accompanied by attenuated production of pro-inflammatory cytokines, while the inflammatory response during late-stage pneumonia was not dependent on the presence of gp96. Blocking CD18 did not reproduce the impaired host defence of LysMcre-Hsp90b1-flox mice during Klebsiella pneumonia. These data indicate that macrophage gp96 is essential for protective immunity during Gram-negative pneumonia by regulating TLR expression., (Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Klebsiella pneumoniae is an important cause of sepsis. The common Toll-like receptor adapter myeloid differentiation primary response gene (MyD)88 is crucial for host defense against Klebsiella. Here we investigated the role of MyD88 in myeloid and endothelial cells during Klebsiella pneumosepsis. Mice deficient for MyD88 in myeloid (LysM-Myd88(-/-)) and myeloid plus endothelial (Tie2-Myd88(-/-)) cells showed enhanced lethality and bacterial growth. Tie2-Myd88(-/-) mice reconstituted with control bone marrow, representing mice with a selective MyD88 deficiency in endothelial cells, showed an unremarkable antibacterial defense. Myeloid or endothelial cell MyD88 deficiency did not impact on lung pathology or distant organ injury during late stage sepsis, while LysM-Myd88(-/-) mice demonstrated a strongly attenuated inflammatory response in the airways early after infection. These data suggest that myeloid but not endothelial MyD88 is important for host defense during gram-negative pneumonia derived sepsis.

MR cholangiopancreatography (MRCP) is still a rapidly evolving technique, but it has been already accepted as clinically useful and is widely used to evaluate biliary or pancreatic diseases. The advantages of this technique are that it does not use contrast media or ionizing radiation, it is noninvasive and complication free, and the examination is relatively short. MRCP has high sensitivity and specificity for diagnosing biliary dilatation and for determining the site and cause of stenosis. With further improvements of hardware and technique, MRCP is expected to replace diagnostic endoscopic retrograde cholangiopancreatography to examine the biliary and pancreatic ducts in the near future. The other applications include evaluation of primary sclerosing cholangitis, stenosis after liver transplantation, and bilioenteric anastomoses. This article reviews the current applications of MRCP in the evaluation of the pancreas and the biliary system., (© 2013 Published by Elsevier Inc.)

Background: Enthesopathy is an evolving area for applied clinical research. MRI is the gold standard in the diagnosis of elbow joint pathology, but recent reports indicate that ultrasound imaging is more sensitive and accurate than MRI in detecting enthesopathy of the heels and knees. Too many patients are under-diagnosed and/or misdiagnosed because the early pathological changes of enthesitis in the different types of seronegative arthropathies are not detected., Objectives: This study was undertaken to describe the ultrasound features of elbow enthesitis in patients with seronegative arthropathies., Methods: We studied 38 diseased elbows in 38 patients with spondyloarthropathies (26 men and 12 women, mean age 32 years). All had elbow enthesopathy without typical conventional radiographic findings. Patients with histories of degenerative changes and/or local steroid injections were excluded. An HDI 3000 ATL ultrasound machine was used with a 5-12 MHz linear transducer to examine the affected elbow joints. The elbows of 10 normal healthy individuals were examined as normal controls. The patients were examined in the supine position with the elbow flexed 30°-50°. Longitudinal and transverse scans were obtained of the radiohumeral joint, the ulnahumeral joint, and the olecranon fossa. Two independent observers unaware of the clinical diagnosis read the ultrasound images and assessed the collateral ligaments, intratendinous echogenicity, tendon calcification, tendon thickness, presence of fluid, synovial proliferation, and bony changes. The reliability of the sonographic images was assessed by review of video recordings of the ultrasound examinations., Results: Ultrasound revealed loss of the fibrillar echopattern (100 %), lack of a homogenous pattern with loss of the tightly packed echogenic dots (100 %), peritendinous edema with flaring of the tendon margins (84.2 %), irregular fusiform tendon thickening (100 %), and hyperechoic intratendinous lesions with ill-defined focal defects (18.4 %). Ultrasound also detected intratendinous calcifications of both the common extensor and common flexor tendons (52.6 %). Bony erosions were seen at the tendon insertions into the lateral epicondyles (13.15 %)., Conclusion: Ultrasonographic features of elbow enthesitis differed from those described in knee and heel enthesitis. Ultrasound clearly showed early signs of tendon calcification, tendon edema, peritendinitis, and bony entheseal erosions. However, in elbow enthesitis the early bone erosion was associated with bone marrow edema, and the common extensor tendon was diffusely thickened. Ultrasound is a reliable, reproducible bedside imaging procedure. It improves the documentation of disease activity, progression, and treatment responses in patients with spondyloarthropathies. We recommend its use for the diagnosis and post-treatment follow-up of patients with enthesitis and seronegative spondyloarthropathies.

Background: Ovarian cancer has the highest mortality of all gynecologic malignancies. FDG-PET/CT was proven to be accurate for identification of primary ovarian tumors, regional lymph nodes, and distant metastases., Purpose: To evaluate ovarian masses at FDG-PET/CT in correlation with histopathologic findings., Material and Methods: Ninety-eight patients underwent whole body FDG-PET/CT examination. Eighty-six patients with primary ovarian cancer and 12 patients with metastatic disease to the ovaries were included., Results: PET/CT imaging was true-positive in 87/94 patients with malignant tumors. In 4/4 patients with benign tumors, PET/CT results were true-negative, with sensitivity of 92.6%, specificity 100%, total test accuracy 92.9%. Fifty-seven patients were diagnosed as stage IV ovarian cancer with distant metastasis., Conclusion: The anatomical/functional examination by FDG-PET/CT was proven to be valuable in increasing the diagnostic accuracy that can help improve patient management.

Background: Recognition of lipopolysaccharide (LPS) is required for effective defense against invading gram-negative bacteria. Recently, in vitro studies revealed that CD14 is required for activation of the myeloid differentiation factor (MyD)88-dependent Toll-like receptor (TLR)4 signaling pathway by smooth (S)-LPS, but not by rough (R)-LPS. The present study investigated the role of CD14 in induction of lung inflammation in mice by these different LPS chemotypes., Methodology/results: Neutrophil accumulation and tumor necrosis factor (TNF) release in bronchoalveolar lavage fluid were determined 6 hours after intranasal treatment of wild type (WT) and CD14 knock-out (KO) mice with different doses S-LPS or R-LPS. The contribution of CD14 to lung inflammation induced by S-LPS or R-LPS depended on the LPS dose. At low doses, S-LPS and R-LPS induced neutrophil influx in a CD14-dependent manner. Low dose S-LPS-induced cytokine release also depended on CD14. Strikingly, neutrophil influx and TNF release induced by high dose S-LPS or R-LPS was diminished in the presence of CD14. Intranasal administration of sCD14 to CD14 KO mice treated with S-LPS partially reversed the inflammatory response to the response observed in WT mice., Conclusions: In conclusion, CD14 modulates effects of both S-LPS and R-LPS within the lung in a similar way. Except for R-LPS-induced TNF release, S-LPS and R-LPS at low dose induced acute lung inflammation in a CD14-dependent manner, while the inflammatory response triggered by high dose S-LPS or R-LPS was diminished by CD14.

Sepsis is a very heterogeneous clinical syndrome broadly defined as the systemic host response to an infection. Until very recently, the prevailing concept of the pathogenesis of sepsis was that mortality is the consequence of an uncontrolled hyperinf lammatory response of the host. The disappointing results of nearly 40 years of anti-inflammatory strategies and the development of animal models that more closely mimic clinical sepsis have led to the reconsideration of the pathophysiology of sepsis. Sepsis is now considered a misbalance between proinflammatory reactions (designed to kill invading pathogens but at the same time responsible for tissue damage) and anti-inflammatory responses (designed to limit excessive inflammation, but at the same time making the host more vulnerable for secondary infections). This review discusses key components of the pro- and anti-inflammatory response to sepsis, listing potential novel interventional strategies along the way.

Background: Malignant breast lesions usually are differentiated by FDG-PET with a semiquantitative FDG standardized uptake value (SUV) of 2.5. However, the frequency of breast cancer with an SUV of less than or equal to 2.5 is noteworthy, and often present diagnostic challenges. This study was undertaken to evaluate the accuracy of dual-time point FDG-PET/CT with FDG standardized uptake value (SUV) calculation in the characterization of such breast tumors., Methods: Forty-nine female patients with newly diagnosed breast cancer were found to have primary breast cancer with minimally increased FDG uptake and met the criteria for inclusion in this study by having borderline levels of increased FDG uptake (SUV max less than or equal to 2.5) in the initial FDG-PET/CT images. Consequently, they underwent further delayed phase FDG-PET/CT scan for better evaluation of the disease., Results: Of the 49 cancer lesions; the majority were found to have rising or unvarying dual-time changes in SUV max (75.5%). The median value of SUV max increases by 25% between the early and delayed scan. The means+/-S.D. of the SUV max1, the SUV max2, and the Delta SUV max% were 1.2+/-0.6%, 1.3+/-0.9%, and 5.1+/-22.4%, respectively. The receiver-operating-characteristic (ROC) analysis proved that the highest accuracy for characterization of malignant breast lesions was obtained when a Delta SUV max% cut-off value 0.0% was used as criteria for malignant FDG uptake-change over time with sensitivity 75.5%, and false-positive rate 20.4%., Conclusion: These results suggested that dual-time FDG-PET/CT imaging with standardized uptake value (SUV) estimation can improve the accuracy of the test in the evaluation of breast cancer with low FDG uptake.

The frequency of malignancy with low FDG uptake is significant and often presents diagnostic challenges. The usefulness of dual-time point FDG-PET/CT imaging (including early "after 45 minutes" and delayed "after 100 minutes," phases after radionuclide administration) for detection of such tumors has been documented. The authors present 2 cases of pathologically proven breast cancer with minimally increased FDG uptake on the initial scan (maximum standardized uptake value; SUVmax <2.5). Detection was improved by performing a dynamic PET study with early and delayed scans. Patients with a poorly visualized breast lesion due to minimal FDG uptake on the initial FDG-PET images should not be considered as benign and deserves further delayed phase imaging.

Background: Despite the high complete necrosis rate of radiofrequency ablation (RFA), tumor recurrence, either local tumor recurrence or new tumor formation, remains a significant problem. Purpose of this study is to evaluate the pattern and risk factors for intrahepatic recurrence after percutaneous RFA for hepatocellular carcinoma (HCC)., Methods: We studied 40 patients with 48 HCCs (< or = 3.5 cm) who were treated with percutaneous RFA. The mean follow-up period was 24.1 +/- 15.7 months. We evaluated the cumulative disease-free survival of overall intrahepatic recurrence, local tumor progression (LTP) and intrahepatic distant recurrence (IDR). Thirty host, tumoral and therapeutic risk factors were reviewed for significant tie-in correlation with recurrence: age; gender; whether RFA was the initial treatment for HCC or not; severity of liver disease; cause of liver cirrhosis; contact of tumor to major hepatic vessels and liver capsule; degree of approximation of tumor to the liver hilum; ablation time; degree of benign pre-ablational enhancement; sufficient safety margin; tumor multinodularity; tumor histological differentiation; tumor segmental location; maximum tumor diameter; degree of tumor pre-ablational enhancement at arterial phase CT, MRI or CT-angiography; and laboratory markers pre- and post-ablation (AFP, PIVKA II, TP, AST, ALT, ALP and TB)., Results: The incidence of overall recurrence, LTP and IDR was 65, 23 and 52.5%, respectively. The cumulative disease-free survival rates were 54.6, 74.8 and 78.3% at 1 year, 27.3, 71.9 and 46.3% at 2 years and 20, 71.9 and 29.4 at 3 years, respectively. Univariate and multivariate analysis showed that the significant risk factors for LTP were: tumor size > or = 2.3 cm, insufficient safety margin, multinodular tumor, tumors located at segments 8 and 5, and patient's age > 65 years (P < 0.05). No significant risk factor relationship for IDR could be detected., Conclusion: Our results would have clinical implications for advance warning and appropriate management of patients scheduled for RFA. Patients at risk of LTP should be closely monitored in the first year. Furthermore, regular long-term surveillance is essential for early detection and eradication of IDR.

Unlabelled: Several studies have shown that low body mass index (BMI) is associated with low BMD and fractures. However, the results that have been published from studies on reproductive factors and BMD are extremely controversial, with some demonstrating a beneficial effect, while others show a detrimental impact of these factors on bone mass., Objective: To study the influence of several gynecological factors (years since menopause (YSM), age at menarche and gynecological age or reproductive life) simultaneously with anthropometric factors as determinants of bone mineral density (BMD) in healthy women older than 40., Methods: BMD was determined by dual energy X-ray absorptiometry (DXA) at the lumbar spine and femurs in women aged >40 randomly chosen from the population of Rabat with a cluster sampling method., Results: Four hundred and twenty-two healthy women older than 40 years were included in the study. The mean age was 57.2 years (8.4) [40-79] and the mean number of parities was 4.42 (2.9) [0-14]. Osteoporosis according to the classification of WHO (T-score

Bone mineral density (BMD) measurements using dual-energy X-ray absorptiometry (DXA) are widely used to diagnose osteoporosis and assess its severity. Previous studies show the necessity to establish reference data for bone mass measurements for each particular population. Such data are lacking for the Moroccan population. The aim of this study was to determine spine and femur BMD reference values for the Moroccan female population and to compare them with values from western and other Arab countries. A cross-sectional study of 569 Moroccan women, (randomly selected in the area of Rabat, the capital of Morocco, aged between 20 and 79 yr) was carried out to establish reference values of BMD. Measurements were taken at the lumbar spine and proximal femurs using DXA (Lunar Prodigy Vision, GE). The data were compared with published normative data taken by United States (U.S.), European, Kuwaiti, Lebanese, and Saudi women over 6 decades of age. The percentage of osteoporosis in postmenopausal women using our reference curve was compared to that observed when the other curves (US, European and Arab) implemented in the Lunar machine was used. Our results showed that the Moroccan women showed the expected decline in BMD at both sites with age after peaking at 20-29 years of age. Moroccan females have lower BMD at the spine than U.S., Europeans, and Kuwaitis (approximately 10-12% for patients older than 50 yr). The BMD values of the total femur in Moroccan females were close to western (European and American), and Kuwaitis, but higher than Lebanese and Saudis. Using our reference database, 37.9% of postmenopausal women had spine osteoporosis vs. 39.6% and 23.4% using US/European and Arabic Lunar reference values respectively. At the femurs, 6.7% had osteoporosis vs. 2.5% using the Arabic Lunar reference values. In conclusion, our study emphasizes the importance of using population-specific reference values for BMD measurements to avoid over or underdiagnosis of osteoporosis.