Cell-free fat extract regulates oxidative stress and alleviates Th2-mediated inflammation in atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disease that significantly affects patients' quality of life. This study aimed to evaluate the therapeutic potential of cell-free fat extract (FE) in AD. In this study, the therapeutic effect of DNCB-induced AD mouse models was investigated. Dermatitis scores and transepidermal water loss (TEWL) were recorded to evaluate the severity of dermatitis. Histological analysis and cytokines measurement were conducted to assess the therapeutic effect. Additionally, the ability of FE to protect cells from ROS-induced damage and its ROS scavenging capacity both in vitro and in vivo were investigated. Furthermore, we performed Th1/2 cell differentiation with and without FE to elucidate the underlying therapeutic mechanism. FE reduced apoptosis and cell death of HaCat cells exposed to oxidative stress. Moreover, FE exhibited concentration-dependent antioxidant activity and scavenged ROS both in vitro and vivo. Treatment with FE alleviated AD symptoms in mice, as evidenced by improved TEWL, restored epidermis thickness, reduced mast cell infiltration, decreased DNA oxidative damage and lower inflammatory cytokines like IFN-γ, IL-4, and IL-13. FE also inhibited the differentiation of Th2 cells in vitro. Our findings indicate that FE regulates oxidative stress and mitigates Th2-mediated inflammation in atopic dermatitis by inhibiting Th2 cell differentiation, suggesting that FE has the potential as a future treatment option for AD.

Correlation of drug exposure and bacterial susceptibility with treatment response for Mycobacterium avium complex lung disease: protocol for a prospective observational cohort study.

INTRODUCTION: The burden of Mycobacterium avium complex (MAC) lung disease is increasing globally and treatment outcome is in general poor. Therapeutic drug monitoring has the potential to improve treatment outcome by ensuring adequate drug exposure. However, very limited population-based studies exist for MAC lung disease. This study aims to describe the distribution of drug exposure for key antimycobacterial drugs at population level, and to analyse them in relationship to treatment outcome in patients with MAC lung disease. METHODS AND ANALYSIS: A prospective cohort aiming to include 100 adult patients diagnosed with and treated for MAC lung disease will be conducted in Shanghai Pulmonary Hospital, China. Blood samples will be collected after 1 month MAC treatment for measurement of macrolides, rifamycin, ethambutol, amikacin and/or fluoroquinolones, using a validated liquid-chromatography tandem mass spectrometry method. Respiratory samples will be collected at inclusion and once every 3 months for mycobacterial culture until treatment completion. Minimum inhibitory concentration (MIC) determination will be performed using a commercial broth microdilution plate. In addition to mycobacterial culture, disease severity and clinical improvement will be assessed from the perspective of lung function, radiological presentation and self-reported quality of life. Whole genome sequencing will be performed for any longitudinal isolates with significant change of MIC to explore the emergence of drug resistance-conferring mutations. The relationship between drug exposure and treatment outcome will be analysed and potential confounders will be considered for adjustment in multivariable models. Meanwhile, the associations between drug exposure in relation to MIC and markers of treatment response will be explored using Cox proportional hazards or binary logistic regression models, as appropriate. ETHICS AND DISSEMINATION: This study has been approved by the ethics committee of Shanghai Pulmonary Hospital (No. K22-149Z). Written and oral informed consent will be obtained from all participants. The study results will be submitted to a peer-reviewed journal. TRIAL REGISTERATION NUMBER: NCT05824988.

Risk factors for microbiological persistence after 6 months of treatment for Mycobacterium intracellulare and its impact on the drug-resistance profile.

Patients with Mycobacterium intracellulare pulmonary disease are more likely to experience poor treatment outcomes if they have been observed with microbiological persistence after 6 months of treatment. This study aims to identify the risk factors for microbiological persistence and describe the changes in the minimum inhibitory concentration (MIC) during antimycobacterial treatment. This retrospective case-control study enrolled patients diagnosed with M. intracellulare pulmonary disease between April 2017 and September 2021 at Shanghai Pulmonary Hospital. Patients with positive cultures after 6 months of treatment (positive group) were matched by age and sex in a 1:1 ratio to patients with negative conversion (negative group). Totally, 46 pairs of patients were analyzed. Risk factors for microbiological persistence at month 6 were smoking, previous tuberculosis treatment, chronic lung diseases, a positive baseline acid-fast bacilli smear, and adverse drug reactions; the risk was reduced by a regimen containing ethambutol, ≥3 effective drugs, and a higher pre-treatment absolute lymphocyte count. Regarding the drug-resistance profile, the negative group had a higher proportion of susceptibility to clarithromycin (100.0% vs 84.8%, P = 0.012). Most isolates were susceptible or intermediate to amikacin in both groups (93.5% and 84.8%, respectively). Nine patients (16.4%, 9/55) had a change in the drug-resistance profile, including four who changed from clarithromycin susceptible to clarithromycin resistant, and the other three reversed. Two pairs of isolates had a change in resistance to amikacin. In conclusion, risk factors for microbiological persistence were identified, and the change in MIC values during antimycobacterial treatment indicated the need for monitoring to enable timely adjustment of the regimen.IMPORTANCENontuberculous mycobacteria pulmonary disease (NTM-PD) has been recognized as an important public health issue because of its increasing incidence globally, low cure rate, and high recurrence rate. NTM-PD has innate resistance to many first-line anti-tuberculous drugs, which limits the treatment options. Mycobacterium intracellulare is reportedly the most important pathogenic NTM and accounts for the highest proportion of NTM-PD in China. A previous study suggested that poor microbiological response after 6 months of treatment is predictive of treatment failure. The present study investigated the risk factors associated with persistent positive sputum cultures by treatment month 6 in patients with M. intracellulare pulmonary disease and the variation in minimum inhibitory concentration patterns in clinical settings. This information might help to identify patients at higher risk of treatment failure and enable the timely provision of necessary interventions.

Performance of Interferon-Gamma Release Assays in the Diagnosis of Nontuberculous Mycobacterial Diseases-A Retrospective Survey From 2011 to 2019.

There is an urgent need for precise diagnosis to distinguish nontuberculous mycobacterial (NTM) diseases from pulmonary tuberculosis (PTB) and other respiratory diseases. The aim of this study is to evaluate the diagnostic performance of Interferon-gamma (IFN-γ) release assays (IGRAs), including antigen-specific peripheral blood-based quantitative T cell assay (T-SPOT.TB) and QuantiFERON-TB-Gold-Test (QFT-G), in differentiating NTM infections (N = 1,407) from culture-confirmed PTB (N = 1,828) and other respiratory diseases (N = 2,652). At specie level, 2.56%, 10.73%, and 16.49% of NTM-infected patients were infected by Mycobacterium kansasii, M. abscessus, and with M. avmm-intracellulare complex (MAC), respectively. Valid analyses of T-SPOT.TB (ESAT-6, CFP-10) and QFT-G were available for 37.03% and 85.79% in NTM-infected patients, including zero and 100% (36/36) of M. kansasii infection, 21.85% (33/151) and 92.05% (139/151) of M. abscessus infection, and 17.67% (41/232) and 91.24% (211/232) of MAC infection. Based on means comparisons and further ROC analysis, T-SPOT.TB and QFT-G performed moderate accuracy when discriminating NTM from PTB at modified cut-off values (ESAT-6 < 4 SFCs, CFP-10 < 3 SFCs, and QFT-G < 0.667 IU/ml), with corresponding AUC values of 0.7560, 0.7699, and 0.856. At species level of NTM, QFT-G effectively distinguished between MAC (AUC=0.8778), M. kansasii (AUC=0.8834) or M. abscessus (AUC=0.8783) than T-SPOT.TB. No significant differences in discriminatory power of these three IGRA tools were observed when differentiating NTM and Controls. Our results demonstrated that T-SPOT.TB and QFT-G were both efficient methods for differentiating NTM disease from PTB, and QFT-G possessed sufficient discriminatory power to distinguish infections by different NTM species.

Controllable Motion-Blur Effects in Still Images.

Motion blur in a photo is the consequence of object motion during the image acquisition. It results in a visible trail along the motion of a recorded object and can be used by photographers to convey a sense of motion. Nevertheless, it is very challenging to acquire this effect as intended and requires much experience from the photographer. To achieve actual control over the motion blur, one could be added in a post process but current solutions require complex manual intervention and can lead to artifacts that mix moving and static objects incorrectly. In this paper, we propose a novel method to add motion blur to a single image that generates the illusion of a photographed motion. Relying on a minimal user input, a filtering process is employed to produce a virtual motion effect. It carefully handles object boundaries to avoid artifacts produced by standard filtering methods. We illustrate the effectiveness of our solution with various complex examples, including multi-directional blur, reflections, multiple objects, and illustrate how several motion-related artistic effects can be achieved. Our post-processing solution is an alternative to capturing the intended real-world motion blur directly and enables fine-grained control of the motion-blur effect.

Immunological recovery in patients with pulmonary tuberculosis after intensive phase treatment.

Objectives This study aimed to examine the change and significance of immune parameters in patients with sputum smear-positive pulmonary tuberculosis (TB) after 2 months of intensive phase anti-TB treatment. Methods The immune parameters of 232 cases of sputum smear-positive pulmonary TB were detected before and after 2 months of intensive phase anti-TB treatment and compared with 50 cases from healthy volunteers (controls). The T lymphocyte cell population in peripheral blood was detected using flow cytometry. Serum levels of interleukin (IL)-1ß, soluble interleukin-2 receptor, IL-6, and tumour necrosis factor-α were measured by ELISA. Results After 2 months of intensive phase anti-TB treatment, a reduction in the percentage of CD4+ T cells showed a significant restoration similar to that of controls. Moreover, after intensive anti-TB treatment, serum levels of IL-1ß, soluble interleukin-2 receptor, IL-6, and tumour necrosis factor-α were significantly decreased compared with before treatment. Additionally, serum levels of IL-1ß and IL-6 showed a diminished recovery compared with controls. Conclusions Our findings suggest immunological recovery in patients with pulmonary TB after intensive phase treatment. Therefore, serum cytokine levels are considered potential host biomarkers for monitoring the response of treatment for pulmonary TB.

Evaluation of a MEMS-based dual metal-layer thin-film microelectrode array for suprachoroidal electrical stimulation.

A double metal-layer thin-film platinum microelectrode array was fabricated for implantation between sclera and choroid based on MEMS processing techniques and photosensitive polyimide material. The array was composed of 60 stimulating sites (6 × 10) and four selectable returning electrodes. The diameter of each stimulating electrode was 350 µ m with a center-to-center spacing of 750 µm. The transient voltage responses of the electrode to current pulse stimulation indicated a charge-injection capacity greater than 52.1 µ C/cm (2) . Acute in vivo animal experiments showed that the implicit time of electrically evoked potentials (EEPs) was 17.09±1.45 ms at a threshold current of 25.55 ±5.43 µA for a full-row of simultaneously stimulated electrodes (i.e., current applied simultaneously to each of the 10 electrodes). Individual electrode stimulation threshold was 48.57 ±6.90 µA. The corresponding threshold charge densities were 13.28 ±2.82 µC/cm (2) and 25.24 ±3.59 µC/cm (2) , respectively. The spatial spread of the maximally recorded P1 response in the EEPs indicated a correspondence between the retinal stimulation site and the focal response location in the cortex. This method of array fabrication is suitable for acute suprachoroidal stimulation, and has a potential use for the fabrication of a visual prosthesis.

Novel GATA6 mutations associated with congenital ventricular septal defect or tetralogy of fallot.

Congenital heart disease (CHD) is the most common form of developmental malformation and is the leading noninfectious cause of infant mortality. Emerging evidence indicates that genetic defects are involved in the pathogenesis of CHD. Nevertheless, CHD is genetically heterogeneous, and the molecular basis for CHD in a majority of patients remains unknown. In this study, the whole coding region of GATA6, a gene encoding a zinc-finger transcription factor crucial for normal cardiogenesis, was sequenced in 380 unrelated patients with CHD. The relatives of the index patients harboring the identified mutations and 200 unrelated control individuals were subsequently genotyped. The functional effect of the mutations was characterized using a luciferase reporter assay system. As a result, two novel heterozygous GATA6 mutations, p.D404Y and p.E460X, were identified in two families with ventricular septal defect and tetralogy of Fallot, respectively. The mutations co-segregated with CHD in the families with complete penetrance, and were absent in 400 control chromosomes. Functional analysis demonstrated that the mutated GATA6 proteins were associated with significantly decreased transactivational activity in comparison with their wild-type counterpart. These findings provide novel insight into the molecular mechanism implicated in CHD, suggesting potential implications for the early prophylaxis and personalized treatment of CHD.