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Juhl Philipsen posted an update 2 weeks, 6 days ago
Taken together, these findings suggested that miR-155-5p aggravated the inflammatory response of AR dominated by ILC2s via targeting TP53INP1, which may aid in the development of novel therapeutic agents for AR.
To systematically evaluate the diagnostic performance of procalcitonin (PCT) and C-reactive protein (CRP) for distinguishing bacterial infections from lupus flares in systemic lupus erythematosus (SLE) via meta-analysis.
Electronic databases were comprehensively searched. The pooled standard mean difference (SMD) and 95% confidence interval (CI) were calculated to estimate the differences of serum PCT and CRP levels between bacterial infections and flares in SLE. Sensitivity, specificity and summary receiver operating characteristics (SROC) curve were used to assess the diagnostic values of PCT and CRP. The use of fixed or random effects model depended on heterogeneity.
Fifteen studies were included in the analysis. Serum PCT and CRP levels were significantly higher in SLE patients with bacterial infections compared to SLE patients with flares (PCT SMD=1.035, 95%CI=0.708 to 1.362; CRP SMD=1.000, 95%CI=0.758 to 1.242). The overall sensitivity, specificity, area under the SROC curve, positive likelihood ratios (PLR) and negative likelihood ratios (NLR) of PCT were 0.62, 0.88, 0.862, 6.63 and 0.36, respectively, while the same indicators for CRP were 0.72, 0.70, 0.784, 2.45 and 0.38, respectively.
Serum PCT and CRP levels were significantly increased in SLE with bacterial infections. PCT had a better diagnostic performance than CRP. PCT had a high value of PLR and could serve as a rule-in marker, while CRP testing may result in a high false-positive rate due to low PLR; both markers had a suboptimal value of NLR and are not appropriate for ruling out bacterial infections.
Serum PCT and CRP levels were significantly increased in SLE with bacterial infections. PCT had a better diagnostic performance than CRP. PCT had a high value of PLR and could serve as a rule-in marker, while CRP testing may result in a high false-positive rate due to low PLR; both markers had a suboptimal value of NLR and are not appropriate for ruling out bacterial infections.
Pressure ulcers are a common issue for people who have limited mobility. This study tested the impact of liquiritin on human keratinocyte HaCaT cell inflammatory damage aroused by lipopolysaccharide (LPS).
HaCaT cells were underwent LPS and/or liquiritin incubation. Cell viability, apoptosis and inflammatory molecules interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and cyclooxygenase-2 (Cox-2) expressions, along with nuclear factor kappa B (NF-κB) and c-Jun N-terminal kinase (JNK) pathways activities were tested by MTT assay, Guava Nexin assay, ELISA and western blotting, respectively. qRT-PCR was done for measuring microRNA-31 (miR-31) expression. miR-31 inhibitor was transfected to silence miR-31. Animal pressure ulcers was established on the dorsal skin of adult rats. The effects of liquiritin on wound healing were analyzed by measuring wound closure rates.
LPS aroused HaCaT cell inflammatory damage, as evidenced by the decrease of cell viability, increase of cell apoptosis and enhanced expressght be implemented via raising miR-31 expression, lowering MyD88 expression, and repressing NF-κB and JNK pathways.Auranofin (AF), a gold compound, has been used to treat rheumatoid arthritis (RA) for more than 40 years; however, its mechanism of action remains unknown. We revealed that AF inhibited the induction of proinflammatory proteins and their mRNAs by the inflammatory stimulants, cyclooxygenase-2 and inducible nitric oxide synthase, and their upstream regulator, NF-κB. AF also activated the proteins peroxyredoxin-1, Kelch-like ECH-associated protein 1, and NF-E2-related factor 2, and inhibited thioredoxin reductase, all of which are involved in oxidative or electrophilic stress under physiological conditions. Although the cell membrane was previously considered to be permeable to AF because of its hydrophobicity, the mechanisms responsible for transporting AF into and out of cells as well as its effects on the uptake and excretion of other drugs have not yet been elucidated. Antibodies for cytokines have recently been employed in the treatment of RA, which has had an impact on the use of AF. Trials to repurpose AF as a risk-controlled agent to treat cancers or infectious diseases, including severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019, are ongoing. Novel gold compounds are also under development as anti-cancer and anti-infection agents.
During the ongoing COVID-19 pandemic, immunocompromised patients are at a higher risk of severe infection, since the immune system has an important role in defeating this disease. This study compares the severity of COVID-19 in patients taking methotrexate with the severity of their family members’ illness as patients with normal immune system function.
A total of 35 participants, including 14 patients taking methotrexate and 21 patients with normal immune function, entered this study, and the indicators of COVID-19 severity were compared between these two groups.
The case group, who were on methotrexate therapy, had significantly less severe COVID-19 based on their symptoms, including fever (p=0.000) and cough and dyspnea (p=0.01) as well as in terms of COVID-19 severity indicators such as pulmonary involvement (p=0.001), ferritin level (p=0.001), white blood cell count (p=0.008) and CRP level (p=0.006), compared to the control group. There was a significant correlation between taking methotrexate and lower severity in COVID-19 disease.
The present findings demonstrated that methotrexate does not predispose patients to severe COVID-19; on the contrary, patients taking methotrexate may experience a milder disease, possibly due to their reduced severe inflammatory reactions as a result of inhibited TNFα, lowered IL6, and increased T regulatory cells. According to these findings, methotrexate appears to be a suitable treatment option for patients who need immunosuppressive medications during the COVID-19 pandemic.
The present findings demonstrated that methotrexate does not predispose patients to severe COVID-19; on the contrary, patients taking methotrexate may experience a milder disease, possibly due to their reduced severe inflammatory reactions as a result of inhibited TNFα, lowered IL6, and increased T regulatory cells. According to these findings, methotrexate appears to be a suitable treatment option for patients who need immunosuppressive medications during the COVID-19 pandemic.
Erectile dysfunction (ED) and ejaculatory dysfunction (EjD) are known outcomes of traditional surgery and some pharmacotherapies for treatment of benign prostatic hyperplasia (BPH). Minimally invasive treatment options, including water vapor thermal therapy (WVTT), are now available to treat lower urinary tract symptoms (LUTS) due to BPH.
The objective of this analysis was to evaluate long-term impact of a single water vapor thermal therapy procedure on erectile and ejaculatory function in subjects enrolled in the Rezum II prospective, multicenter, randomized, blinded controlled trial.
Fifteen centers enrolled 197 subjects with International Prostate Symptom Score (IPSS) ≥ 13, maximum flow rate (Qmax) ≤ 15 mL/s, and prostate volume 30-80 cc. Subjects were randomized (21) to (WVTT) or sham procedure (control) and followed for 5 years. Erectile and ejaculatory functions were quantitatively assessed at baseline and yearly thereafter. After 3 months, control subjects could opt to requalify for cross-over tong-term evidence of durable outcomes after treatment with Rezum without impact on sexual function scores. McVary KT, El-Arabi A, Roehrborn C. Preservation of Sexual Function 5 Years After Water Vapor Thermal Therapy for Benign Prostatic Hyperplasia. Sex Med 2021;9100454.
The age at which transgender women (TW) and men (TM) first experience gender dysphoria (GD) has not been reported in a U.S. population of adults seeking genital gender-affirming surgery (gGAS). Because gender is an innate part of identity, we hypothesized that untreated GD would be a part of individuals’ earliest memories. Understanding GD onset can help guide providers with when and how to focus care to patients not yet identified as “transgender AIM (i) Determine the age at which transgender adults seeking gGAS first experience GD (ii) Determine the number of life-years that transgender adults spend living with untreated GD METHODS During initial consultation for gGAS, we asked patients the earliest age at which they experienced GD and the age at which they had their earliest episodic memory. We also queried history of anxiety, depression, and suicide attempt.
Patients self-reported their earliest recollections of experiencing GD, earliest memories in general, and history of anxiety, depression, and suim. Sex Med 2021;XXXXXXXX.
Our findings suggest that GD typically manifests in early childhood and persists untreated for many years before individuals commence gender transition. Diagnosis and early management during childhood and adolescence can improve quality of life and survival. Zaliznyak M, Yuan N, Bresee C, et al. How Early in Life do Transgender Adults Begin to Experience Gender Dysphoria? Why This Matters for Patients, Providers, and for Our Healthcare System. Sex Med 2021;XXXXXXXX.Supervised deep learning models have proven to be highly effective in classification of dermatological conditions. These models rely on the availability of abundant labeled training examples. However, in the real-world, many dermatological conditions are individually too infrequent for per-condition classification with supervised learning. Although individually infrequent, these conditions may collectively be common and therefore are clinically significant in aggregate. To prevent models from generating erroneous outputs on such examples, there remains a considerable unmet need for deep learning systems that can better detect such infrequent conditions. These infrequent ‘outlier’ conditions are seen very rarely (or not at all) during training. In this paper, we frame this task as an out-of-distribution (OOD) detection problem. We set up a benchmark ensuring that outlier conditions are disjoint between the model training, validation, and test sets. ESI-09 datasheet Unlike traditional OOD detection benchmarks where the task is comparison to baseline. Furthermore, we go beyond traditional performance metrics and introduce a cost matrix for model trust analysis to approximate downstream clinical impact. We use this cost matrix to compare the proposed method against the baseline, thereby making a stronger case for its effectiveness in real-world scenarios.Brain functional connectivity (FC) derived from resting-state functional magnetic resonance imaging (rs-fMRI) has been widely employed to study neuropsychiatric disorders such as autism spectrum disorder (ASD). Existing studies usually suffer from (1) significant data heterogeneity caused by different scanners or studied populations in multiple sites, (2) curse of dimensionality caused by millions of voxels in each fMRI scan and a very limited number (tens or hundreds) of training samples, and (3) poor interpretability, which hinders the identification of reproducible disease biomarkers. To this end, we propose a Multi-site Clustering and Nested Feature Extraction (MC-NFE) method for fMRI-based ASD detection. Specifically, we first divide multi-site training data into ASD and healthy control (HC) groups. To model inter-site heterogeneity within each category, we use a similarity-driven multiview linear reconstruction model to learn latent representations and perform subject clustering within each group. We then design a nested singular value decomposition (SVD) method to mitigate inter-site heterogeneity and extract FC features by learning both local cluster-shared features across sites within each category and global category-shared features across ASD and HC groups, followed by a linear support vector machine (SVM) for ASD detection.