Search

Background and Aims: The COVID‐19 pandemic significantly disrupted lower limb diabetes care. We aimed to map trends in diabetes‐related lower limb amputation and hospitalisation rates through the COVID‐19 pandemic. Methods: We performed a retrospective cohort study of all individuals who underwent a lower limb amputation for a diabetes‐related foot complication from 2018 to 2021 at the Royal Melbourne Hospital, a quaternary hospital in Australia. Hospitalisation rates with a diabetes‐related foot complication were collected for comparison. The start of the COVID‐19 epoch was defined as 16 March 2020, when a state of emergency was declared in Melbourne. Results: During the study period, 360 lower limb amputations for diabetes‐related foot complications were performed in 247 individuals. The median monthly number of amputations remained stable prior to and during the COVID‐19 epoch; there was a median of 8.0 amputations per month (interquartile range (IQR) = 6.5–11) before COVID‐19, compared to 6.5 amputations (IQR = 5.0–8.3) during the COVID‐19 epoch (P = 0.23). Hospitalisation with a diabetes‐related foot complication significantly increased from a median monthly rate of 11 individuals (IQR = 9.0–14) before COVID‐19 to 19 individuals (IQR = 14–22) during the COVID‐19 epoch (p < 0.001). Conclusions: Despite increased hospitalisations for diabetes‐related foot complications during COVID‐19, there was not a corresponding increase in amputation rates. Face‐to‐face care of diabetes‐related foot complications was prioritised at this centre and may have contributed to stable amputation rates during the pandemic. [ABSTRACT FROM AUTHOR]

Introduction: In 2007 wildfires ravaged Southern California resulting in the largest evacuation due to a wildfire in American history. We report how these wildfires affected emergency department (ED) visits for respiratory illness.Methods: We extracted data from a Kaiser Permanente database for a single metropolitan community ED. We compared the number of visits due to respiratory illness at t ime intervals of 2 weeks before and during the time when the fires were burnin g. We counted the total number of patients with chief complaint of dyspnea, cough, and asthma and final international classification of disease 9 coding diagnosis of asthma, bronchitis, chronic obstructive pulmonary disease and respiratory syndrome, and analyzed data for both total number and proportion of ED visits. We evaluated the data using Early Aberration Reporting System software to determine significant single-visit increases compared to expected counts. We also analyzed the average length of ED stay. Data on air quality were extracted from the http:// www.airnow.gov site.Results: There were significant differences between pre-fire and fire period average visit counts for the chief complaints of dyspnea and asthma. Dypnea complaints increased by 3.2 visits per day. During the fire the diagnoses of asthma increased significantly by 2.6 patients per day. Air quality reached air quality index values of 300, indicating very unhealthy conditions. Average ED length of stay times remained unchanged during the fire period compared to the pre-fire period.Conclusion: The 2007 Southern California wildfires caused significant surges in the volume of ED patients seeking treatment for respiratory illness. Disaster plans should prepare for these surges when future wildfires occur. [West J Emerg Med 2013;14(2):79-84.]

Việc loại bỏ N và P ở nồng độ cao ra khỏi nguồn nước thải là một vấn đề quan trọng nhằm giảm thiểu ô nhiễm môi trường nước và cải thiện đáng kể chất lượng nguồn nước. Mục đích của nghiên cứu này là thu hồi N và P từ nước thải thực thông qua quá trình kết tinh ở các điều kiện công nghệ khác nhau. Struvite (Magie amoni photphat hydrat, MgNH4PO4.6H2O thu hồi từ nước thải thực có nồng độ N và P cao đã được nghiên cứu. Ảnh hưởng của pH, tỷ lệ mol Mg/P, nhiệt độ kết tủa và thời gian phản ứng đến hiệu suất thu hồi struvite đã được thảo luận. Kết quả cho thấy pH và tỷ lệ mol Mg/P là các thông số quan trọng ảnh hưởng đến hiệu suất thu hồi P thông qua struvite. Hiệu suất thu hồi struvite đạt 95,2±3,1 % ở pH 8,3, tỷ lệ mol Mg/P là 1:1, ở 30°C và thời gian phản ứng là 90 phút và thời gian làm già là 60 phút. Hơn nữa, nhiệt độ kết tinh trong khoảng 20-40°C ảnh hưởng không đáng kể đến hiệu suất kết tinh struvite. Nhiễu xạ tia X (XRD) xác nhận sự hình thành cấu trúc struvite được thu hồi từ nguồn nước thải thực. Struvite thu được từ nước thải có chứa hàm lượng dinh dưỡng (Mg, N và P) cao được đề xuất làm phân bón tan chậm cho các ứng dụng nông nghiệp.

Active magnetic bearings (AMBs) are electromagnetic mechanism systems in which non-contact bearings support a rotating shaft using attractive forces generated by electromagnets through closed-loop control. For complete support of a five degree of freedom (DOF) rotor system, most AMB structures include two radial actuators and one for the axial direction. Conical active magnetic bearings (CAMBs) is one of the development directions of conventional magnetic bearings in which the requirement of the axial bearing can be eliminated. In this paper, we propose a structure with a CAMB integrated into a canned motor pump to eliminate the need for mechanical bearings and shaft seals. However, this system necessitates a more complicated control strategy due to a significant coupling effect between rotor motion and hydrodynamic disturbances. This paper presents a fractional order active disturbance rejection control (FOADRC) including a fractional order extend state observer (FOESO) and a proportional derivative controller (PD) to track and reject lumped disturbances actively. The proposed controller achieves better performance than the integer-type ADRC and traditional PID controller. The control performance of the proposed FOADRC is illustrated in terms of very good disturbance rejection capability that is demonstrated through MATLAB/Simulink simulation results.

A series of TiO2/SiO2 photocatalysts were successfully synthesized by the sol-gel method. The TiO2/SiO2 monolith was also synthesized by dip-coating process. The crystalline structure of TiO2/SiO2 powders was identified as pure anatase. The photocatalytic activity of the TiO2/SiO2 powders was evaluated by photodegradation of 20 ppm methylene blue (MB) using a 26W lamp which has the wavelength in the visible light region under different Ti: Si molar ratios and calcination temperatures. The TiO2/SiO2 powders which have Ti: Si molar ratio of 85:15 (TS15) and calcined at 550tC showed the highest photodegradation yield of 84 % after 3h irradiation. Furthermore, the 550˚C calcined TS15 monolith performed the MB degradation yield of 88.9 % after 3h irradiation and its photoactivity still remained after 4 recycle times. The results of this study demonstrated that the TS15 monolith photocatalyst has a reasonable efficiency in the degradation of methylene blue, it could be a promising photocatalyst for removal and degradation of organic pollutants.

Cherubism is a rare autosomal dominant skeletal dysplasia, affecting the maxilla and/or mandible. The condition typically has childhood onset, followed by progression until puberty, with subsequent regression. Cherubism lesions share histological features with giant cell tumor of bone, where high-dose monthly denosumab is an effective medical treatment. Therefore, high-dose denosumab has also been trialed in children with cherubism with positive outcomes. However, the role of denosumab in adult cherubism, particularly a lower dose and frequency, has not been established. We present the case of a 60-year-old man with cherubism, reviewed for a new 39 × 21 mm left mandibular lesion. The patient had multiple surgeries up to the age of 30 for tumors in the right maxilla and mandible. Given the impact of further surgery on his appearance and quality of life, the patient was referred to Endocrinology for consideration of medical therapy. His bone turnover markers were slightly elevated with normal calcium, phosphate, 25-OH vitamin D, and parathyroid hormone levels. A bone density scan showed lumbar spine osteopenia. He was commenced on 60 mg denosumab 6-monthly with excellent clinical and radiological responses over the next 30 months. The most recent CT mandible showed a sustained reduction in the lesion size, measuring 36 × 18 mm, with osteoid formation and improvement in cortical thinning. Surgery is no longer indicated. No adverse effects from denosumab were reported in the patient. This is the first study to report the efficacy and safety of a low-dose denosumab regimen in the management of cherubism. This treatment approach was able to prevent major surgery and minimize denosumab-related adverse effects. While the optimal treatment duration remains unclear, the patient will continue with 60 mg denosumab 6-monthly in the short-term given the favorable response. In summary, a low-dose denosumab regimen should be considered for patients with cherubism, particularly those with contraindications or preferences to avoid surgery., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Summary: Diabetic ketoacidosis (DKA) is a complication of diabetes mellitus (DM) that can theoretically occur in people of any age. While DKA can typically be the first presentation of type 1 DM in younger people, a first presentation is rare in older adults. Pancreatic cancer often manifests with new DM or hyperglycaemia, but very rarely as DKA. We report a case of an 89-year-old woman who was incidentally diagnosed with DKA during workup for an unwitnessed fall. Her DKA was promptly managed, and she was subsequently diagnosed with metastatic pancreatic cancer. Given the advanced stage of her malignancy, the multidisciplinary team consensus was for a palliative approach. She passed away on day 10 of the admission. To our knowledge, this is the first report of a first DKA presentation as a manifestation of pancreatic cancer in an adult aged over 70 years. To date, there is no effective screening test for pancreatic cancer in the general population. However, new-onset DM in the appropriate context might indicate the need for further evaluation. While it is possible that unresectable tumours are identified, earlier diagnosis of DM with pancreatic cancer may facilitate more timely management, including earlier advanced care planning., Learning Points: A higher clinical suspicion for pancreatic cancer is required for older adults presenting with diabetic ketoacidosis without a previously diagnosed diabetes mellitus. A bi-directional relationship exists between diabetes and pancreatic cancer. Pancreatic cancer generally has a very poor prognosis due to its advanced stage at diagnosis and the lack of an effective screening test. New-onset diabetes in the appropriate context (such as weight loss) can indicate the need for further evaluation for underlying pancreatic cancer.

Aggregation has been widely described as a factor contributing to therapeutic antibody immunogenicity. Although production of high-affinity anti-drug antibodies depends on the activation of CD4 T lymphocytes, little is known about the T-cell response induced by antibody aggregates, especially for aggregates produced in mild conditions resulting from minor handling errors of vials. Large insoluble infliximab (IFX) aggregates produced in severe elevated temperature stress conditions have been previously shown to induce human monocyte-derived dendritic cell (moDC) maturation. We here showed that large IFX aggregates recruit in vitro a significantly higher number of CD4 T-cells compared to native IFX. Moreover, a larger array of T-cell epitopes encompassing the entire variable regions was evidenced compared to the native antibody. We then compared the responses of moDCs to different types of aggregates generated by submitting IFX to mild conditions of various times of incubation at an elevated temperature. Decreasing stress duration reduced aggregate size and quantity, and subsequently altered moDC activation. Of importance, IFX aggregates generated in mild conditions and not altering moDC phenotype generated an in vitro T-cell response with a higher frequency of CD4 T cells compared to native IFX. Moreover, cross-reactivity studies of aggregate-specific T cells showed that some T cells could recognize both native and aggregated IFX, while others responded only to IFX aggregates. Taken together, our results suggest that aggregation of antibodies in mild elevated temperature stress conditions is sufficient to alter moDC phenotype in a dose-dependent manner and to increase T-cell response., Competing Interests: Declaration of Competing Interest The authors state no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The use of magnetic beads bio-functionalized by antibodies (Ab) is constantly increasing with a wide range of biomedical applications. However, despite an urgent need for current methods to monitor Ab's grafting process and orientation, existing methods are still either cumbersome and/or limited. In this work, we propose a new simple and rapid analytical approach to evaluate antibody orientation and density on magnetic beads. This approach relies on the cleavage by IdeS, a highly specific protease for human immunoglobulin G (hIgG), of immobilized antibodies. The F(ab) 2 and Fc fragments could be then accurately quantified by size exclusion chromatography (SEC)-coupled to fluorescent detection (FLD), and the ratio of these fragments was used to give insight on the IgG orientation at the bead surface. Four different commercially available magnetic beads, bearing carboxyl groups, tosyl groups, streptavidin, or protein G on their surface have been used in this study. Results obtained showed that this approach ensures reliable information on hIgG orientation and bead surface coverage. Protein G magnetic beads demonstrated an optimal orientation of antibodies for antigen capture (75% of accessible F(ab) 2 fragment) compared to tosylactivated, carboxylated, and streptavidin ones. Capture efficiency of the different functionalized beads towards human TNF-α immunocapture, a biomarker of inflammation, has been also compared. Protein G beads provided a more efficient capture compared to other beads. In the future, this approach could be applied to any type of surface and beads to assess hIgG coverage and orientation after any type of immobilization. A rapid and simple approach to evaluate orientation and density of antibodies immobilized on magnetic beads., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

The development of anti-drug Abs in response to biological products (BP) is a major drawback in the treatment of patients. Factors related to the patient, the treatment, and the product can influence BP immunogenicity. Among these factors, BP aggregates have been suggested to promote immunogenicity by acting as danger signals recognized by dendritic cells (DC) facilitating the establishment of an anti-BP CD4 T cell-dependent adaptive immune response leading to anti-drug Abs production. To date, little is known on the mechanism supporting the effect of aggregates on DCs and consequently on the T cell response. The aim of this work was to identify key signaling pathways involved in BP aggregate DC activation and T cell response. We generated aggregates by submitting infliximab (IFX), an immunogenic anti-TNF-α chimeric Ab, to heat stress. Our results showed that IFX aggregates were able to induce human monocyte-derived DC (moDC) maturation in a concentration-dependent manner. Aggregate-treated moDCs enhanced allogeneic T cell proliferation and IL-5, IL-9, and IL-13 production compared with native Ab-treated moDCs. We then investigated the implication of FcγRIIa and spleen tyrosine kinase (Syk) in DC activation and showed that they were both strongly implicated in moDC maturation induced by IFX aggregates. Indeed, we found that neutralization of FcγRIIa inhibited DC activation, and consequently, Syk inhibition led to a decrease in T cell proliferation and cytokine production in response to IFX aggregates. Taken together, our results bring new insight, to our knowledge, on how protein aggregates could induce DC and T cell activation via the FcγRIIa-Syk signaling pathway., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Immunogenicity related to the degradation of therapeutic monoclonal antibodies (mAbs) remains a major concern for their therapeutic efficacy and safety. Therefore, an analytical method allowing characterization and detection of mAbs degradation is mandatory. In this study, a simultaneous coupling of size exclusion chromatography (SEC) to native mass spectrometry (MS) and fluorescence detection (FLD) is proposed to detect degraded therapeutic mAbs and biases of structural changes (e.g. dimerization, denaturation) that may occur during native MS. A comprehensive study on infliximab behaviors have been performed under different mobile phase conditions (e.g. composition, pH, organic solvent, etc.) and MS parameters (e.g. gas temperatures, CID energies, etc.). Experimental conditions avoiding artificial denaturation and/ or dimerization have been defined. We have also demonstrated that under the developed conditions infliximab affinity towards its biological target TNFα is preserved. In addition, using this method dimers, denatured monomers and fragments could be detected in trastuzmab samples stressed by a long-term storage. These results were confirmed by using SEC coupled to ion mobility mass spectrometry as an orthogonal method for the detection of denatured monomer., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Therapeutic monoclonal antibodies (mAbs) are complex glycoproteins and ensuring their safety, efficacy and quality is still challenging. Indeed, during their manufacturing process, they are exposed to several stresses that can lead to their denaturation, misfolding or dimerization. We report here a new method based on capillary electrophoresis coupled to native mass spectrometry (MS) with a sheath liquid interface to analyze an intact therapeutic mAb, Infliximab, under non-denaturing conditions that preserve its conformational heterogeneity as well as self-association without inducing further unfolding / denaturation. For capillary zone electrophoresis (CZE) separation, a triple layer coating using polybrene-dextran sulfate-polybrene was employed. A sheath liquid composed of isopropanol - water - acetic acid with a flow rate of 10 μL min -1 and mild MS conditions allowed optimal signal intensities. A specific mass spectrum was obtained for each Infliximab conformation in a "stressed" formulated preparation. This is the first time that within a single analysis different conformational states, i.e. native and unfolded monomers as well as dimers are simultaneously detected. The results and the lack of analytical bias arising from the CZE-MS conditions were confirmed by using atomic force microscopy (AFM) as an orthogonal technique. A middle-up approach combined to CZE-MS analysis of the stressed samples suggested that the dimer formation involved mostly Fab-Fab interactions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Acinetobacter baumannii has become one of the major infection threats in intensive care units (ICUs) globally. Since 2008, A. baumannii has been the leading cause of ventilator-associated pneumonia (VAP) in our ICU at an infectious disease hospital in southern Vietnam. The emergence of this pathogen in our setting is consistent with the persistence of a specific clone exhibiting resistance to carbapenems. Antimicrobial combinations may be a strategy to treat infections caused by these carbapenem-resistant A. baumannii. Therefore, we assessed potential antimicrobial combinations against local carbapenem-resistant A. baumannii by measuring in vitro interactions of colistin with four antimicrobials that are locally certified for treating VAP. We first performed antimicrobial susceptibility testing and multilocus variable number tandem repeat analysis (MLVA) genotyping on 74 A. baumannii isolated from quantitative tracheal aspirates from patients with VAP over an 18-month period. These 74 isolates could be subdivided into 21 main clusters by MLVA and >80 % were resistant to carbapenems. We selected 56 representative isolates for in vitro combination synergy testing. Synergy was observed in four (7 %), seven (13 %), 20 (36 %) and 38 (68 %) isolates with combinations of colistin with ceftazidime, ceftriaxone, imipenem and meropenem, respectively. Notably, more carbapenem-resistant A. baumannii isolates (36/43; 84 %) exhibited synergistic activity with a combination of colistin and meropenem than carbapenem-susceptible A. baumannii isolates (2/13; 15 %) (P = 0.023; Fisher's exact test). Our findings suggest that combinations of colistin and meropenem should be considered when treating carbapenem-resistant A. baumannii infections in Vietnam, and we advocate clinical trials investigating combination therapy for VAP.