Background
Viral pathogen–associated molecular patterns, such as dsRNA, disrupt airway tolerance to inhaled allergens. Specifically, the Th2 and Th17 cell responses are induced by low‐dose dsRNA and ...the Th1‐dominant response by high‐dose dsRNA.
Objective
In this model, we evaluate the role of TNF‐α in the development of adaptive immune dysfunction to inhaled allergens induced by airway sensitization with dsRNA‐containing allergens.
Methods
A virus‐associated asthma mouse model was generated via simultaneous airway administration of ovalbumin (OVA) and low (0.1 μg) or high (10 μg) doses of polyinosine–polycytidylic acid (polyI:C). The effect of TNF‐α on Th2 airway inflammation was evaluated using TNF‐α‐deficient mice and recombinant TNF‐α.
Results
TNF‐α production was enhanced by airway exposure to low and high doses of polyI:C. After airway sensitization with OVA plus low‐dose polyI:C, TNF‐α‐deficient mice exhibited less OVA‐induced airway inflammation than did wild‐type (WT) mice. However, this did not occur upon sensitization with high‐dose polyI:C. In terms of T‐cell response, the production of IL‐4 from lung T cells after OVA challenge was enhanced by airway sensitization with OVA plus low‐dose polyI:C in WT mice, and this phenotype was inhibited by the absence of TNF‐α. Moreover, the Th2 cell response induced by sensitization with OVA plus low‐dose polyI:C, which was abolished in TNF‐α‐deficient mice, was restored in these mice upon addition of recombinant TNF‐α.
Conclusion
The results of this study suggest that TNF‐α produced by airway exposure to low‐dose dsRNA is a key mediator in the development of Th2 cell response to inhaled allergens.
Summary
Background
Many bacterial components in indoor dust can evoke inflammatory pulmonary diseases. Bacteria secrete nanometre‐sized vesicles into the extracellular milieu, but it remains to be ...determined whether bacteria‐derived extracellular vesicles in indoor dust are pathophysiologically related to inflammatory pulmonary diseases.
Objective
To evaluate whether extracellular vesicles (EV) in indoor air are related to the pathogenesis of pulmonary inflammation and/or asthma.
Methods
Indoor dust was collected from a bed mattress in an apartment. EV were prepared by sequential ultrafiltration and ultracentrifugation. Innate and adaptive immune responses were evaluated after airway exposure of EV.
Results
Repeated intranasal application of indoor‐dust‐induced neutrophilic pulmonary inflammation accompanied by lung infiltration of both Th1 and Th17 cells. EV 50–200 nm in diameter were present (102.5 μg protein concentration/g dust) in indoor dust. These vesicles were internalized by airway epithelial cells and alveolar macrophages, and this process was blocked by treatment of polymyxin B (an antagonist of lipopolysaccharide, an outer‐membrane component of Gram‐negative bacteria). Intranasal application of 0.1 or 1 μg of these vesicles for 4 weeks elicited neutrophilic pulmonary inflammation. This phenotype was accompanied by lung infiltration of both Th1 and Th17 cells, which were reversed by treatment of polymyxin B. Serum dust EV‐reactive IgG1 levels were significantly higher in atopic children with asthma than in atopic healthy children and those with rhinitis or dermatitis.
Conclusion & Clinical Relevance
Indoor dust EV, especially derived from Gram‐negative bacteria, is a possible causative agent of neutrophilic airway diseases.
Summary
Atopic dermatitis (AD) is chronic, pruritic, inflammatory skin disease that affects a significant portion of the population in industrialized nations. For nonresponders to conventional ...therapies, AD can significantly reduce sleep quality and quality of life. AD pathogenesis is multifactorial and involves multiple immune pathways, with recent evidence of T helper (Th)2, Th17 and Th22 axis attenuation in various AD endotypes and racial subtypes. Inhibition of the conserved Janus kinase (JAK) signalling pathway represents a promising therapeutic avenue to reduce the activation of multiple proinflammatory mediators involved in AD pathogenesis. JAK inhibitors exist in both oral and topical forms with variable specificity for the receptor tyrosine kinases JAK1, JAK2, JAK3 and tyrosine kinase 2. Oral formulations include abrocitinib, upadacitinib, baricitinib and gusacitinib, and are most appropriate for patients with moderate to severe AD. Emerging topical formulation in development include ruxolitinib and deglocitinib, which may be used in patients with localized AD and also adjunctively with systemic therapy in patients with more severe disease. With observed rapidity in itch relief and accompanying dramatic reduction in inflammatory lesion count, JAK inhibitors represent a promising new treatment to revolutionize the management of AD.
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The symptoms of Ischiogluteal Bursitis (IGB) are often nonspecific and atypical, and its diagnosis is more challenging. Moreover, it is difficult to predict cases of chronic progression or poor ...treatment response. Therefore, the aim of this study was to investigate the clinical course of IGB patients and identify factors that are predictive of failure of conservative treatment.
Our study consisted of IGB patients diagnosed between 2010 March and 2016 December who had been followed-up for at least one year. Structured questionnaires and medical records were reviewed to analyse demographic characteristics, lifestyle patterns, blood tests, and imaging studies. We categorized the cases into two groups based on the response to conservative treatment and the need for surgical intervention.
The most common initial chief symptoms were buttock pains in 24 patients (37.5%). Physical examinations showed the tenderness of ischial tuberosity area in 59 (92.2%) patients, but no specific findings were confirmed in 5 patients (7.8%). 51 patients (79.7%) responded well to the conservative management, 11 patients (17.2%) needed injection, and 2 patients (3.1%) had surgical treatment performed due to continuous recurrence. There was no difference in demographic and blood lab data between the two groups. However, the incidence of inflammatory diseases (response group: 10.3% vs non-response group: 66.7%, p=0.004) was significantly different between the two groups.
The diagnosis of IGB can be missed due to variations in clinical symptoms, and cautions should be exercised in patients with inflammatory diseases as conservative treatment is less effective in them, leading to chronic progression of IGB.
Summary
Background
Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intense pruritus, but information on patient experience and impact on quality of life (QoL) remains ...understudied.
Aim
To characterize disease characteristics and QoL in a global sample of patients with PN.
Methods
An anonymous survey was distributed via patient support groups for PN.
Results
In total, 231 members responded to the survey. The majority of respondents reported itch localized both to nodules and to intervening skin (67.0%). Associated symptoms included prickling, pain, stinging and burning. The extensor lower legs (69% right, 67.3% left) and flexor forearms (66.1% right, 62% left) were the most common sites of itch. Participants reported frequent healthcare utilization, with 36.3% visiting a doctor ≥ 10 times in the past year. Physician‐diagnosed anxiety (45.4%), depression (16.4%) and the atopic triad (18.7%) were commonly reported. Patients with PN had mean scores of 16.4, 11.6 and 16.8 on the Dermatology Life Quality Index, Pittsburgh Sleep Quality Index and 5‐Dimensions Itch, respectively.
Conclusions
Severe pruritus with accompanying pain, stinging and burning is characteristic of PN, with the majority of patients experiencing itch in both nodular and interlesional skin. Patients further report decreased QoL scores and impaired sleep. Patient experiences should guide future management of PN.
Summary
Individuals with poor knowledge of osteoporosis and lower socioeconomic status, including being single and having a lower level of annual income, are less likely to be assessed or treated for ...osteoporosis. Individuals with particular osteoporosis risk factors such as smokers and heavy drinkers are overlooked for diagnosis. Further study is needed to identify and address the existing barriers and to promote osteoporosis management for women with these risk factors.
Introduction
Despite the negative health consequences of osteoporosis and the availability of effective treatment, a pervasive and persistent prevention care gap for osteoporosis remains present throughout the world. We attempted to identify the factors affecting the willingness of patients to either undergo or avoid assessment and treatment for osteoporosis.
Methods
A nationwide online survey was conducted in 926 Korean women over age 50. The survey included questions addressing three domains: (1) clinical and socio-demographic characteristics, (2) questions concerning the reasons for undergoing or avoiding osteoporosis assessment or treatment, and (3) knowledge of osteoporosis as measured using the modified Korean version of Facts on Osteoporosis Quiz. The assessed and non-assessed participants were compared in terms of their clinical and socioeconomic statuses, reasons for undergoing or avoiding osteoporosis management, and levels of knowledge of osteoporosis.
Results
The highest-ranked reason for undergoing osteoporosis assessment was fear of osteoporotic fracture, while the highest-ranked reason for avoiding osteoporosis assessment was not feeling a need to get tested for osteoporosis. Participants who sought assessment for osteoporosis were older and more likely to be married, and had greater knowledge of osteoporosis than those who did not seek assessment. The two groups were found to be similar in terms of tobacco use and daily alcohol use. Patients who had been diagnosed with osteoporosis but either did not initiate or discontinued osteoporosis treatment within 1 year were younger and had lower levels of annual income than those who began and continued treatment.
Conclusion
Individuals with poor knowledge of osteoporosis and those of lower socioeconomic status, including those who were single and had a lower level of annual income, were less likely to be assessed and treated for osteoporosis. Individuals with particular osteoporosis risk factors such as smokers and heavy drinkers are overlooked for diagnosis. Further study is needed to identify and address the existing barriers and to promote osteoporosis management for women with these risk factors.
A power-efficient complementary voltage-to-time converter (CVTC) is proposed for a flash ADCs. The alternating reset direction according to the signal development direction reduces the power consumed ...by the reset operation and the operational frequency of the CVTC is effectively reduced by half. Accordingly, the logic circuits following the CVTC work in a time-interleaved manner, resulting in significant power saving. A 5-bit 2.5 GS/s flash ADC designed for a 40 nm CMOS process shows a 27% power reduction over the conventional voltage-to-time conversion-based flash ADC.
Accurate diagnosis of undisplaced periprosthetic femoral fracture (PFF) after hip arthroplasty is crucial, as overlooked PFF may affect its treatment and prognosis. The undisplaced PFF is often ...difficult to distinguish from radiolucent lines of nutrient artery canal (NAC) of the femur present on post-operative radiographs. We aimed to identify the radiographic features of NAC to distinguish them from PFFs.
In this retrospective radiological study, a total of 242 cases in 215 patients with hip arthroplasty were analysed using pre-operative and post-operative anteroposterior (AP) and translateral (TL) radiographs. Interobserver agreement of the measurements was assessed by two independent experienced orthopaedic surgeons. The kappa value ranged from 0.83 to 0.87, indicating strong agreement according to the Landis and Koch criteria.
The NACs were found pre-operatively in 94 (39.8%) cases on AP views and in 122 cases (50.4%) on TL views. The radiolucent lines were observed post-operatively in 42 (17.4%) on AP views and 122 (50.4%) on the TL views. three cases (1.2%) had a fracture around the stem that were detected on radiographs. One case with PFF presented simultaneously with NAC on the immediate post-operative radiographs. All patients were treated by conservative measures, and the radiolucent lines did not appear on follow-up radiographs.
It is not easy to differentiate undisplaced PFFs that can occur after hip arthroplasty operation from NACs. However, accurate diagnosis is possible through careful observation and comparison of pre-operative and post-operative radiologic images.
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