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关键词： biological DMARD   Quality of life   Physical therapy   Physiotherapy   and Physical Activity   Pain   Fatigue  

摘要： Background: Anti-TNF-alpha and anti-IL-17 drugs are widely used in Psoriatic Arthritis (PsA) and have shown good results in terms of both efficacy and safety [1]. However, a subset of patients may still experience residual pain due to central sensitization mechanisms typical of Fibromyalgia (FM). This leads to more complex disease management and less satisfactory therapeutic outcomes. Objectives: The aim of our study is to evaluate the efficacy of anti-TNF-alpha and anti-IL-17 drugs in managing inflammatory and neuropathic pain, as well as fatigue, in patients diagnosed with PsA and concomitant FM. Methods: We enrolled 47 patients diagnosed with PsA (according to the CASPAR 2006 criteria) and FM (according to the ACR 2016 criteria) and treated with anti-TNF-alpha and anti-IL-17 drugs (Table 1). Disease activity was assessed using DAPSA, neuropathic pain using PDQ, subjective pain using VAS, and fatigue using FACIT. All data were collected at baseline and after 4 months of therapy. Statistical analysis was performed using the Wilcoxon test for paired samples and the Mann-Whitney U test for unpaired samples. Results: Comparing the two patient groups, we observed that patients treated with Anti-TNF-alpha showed an improved fatigue (p=0.0119) (Figure 1 A) and reduced PDQ by 28.5% (Figure1 B). Patients treated with Anti-IL-17 achieved greater DAPSA reduction (p=0.0094) (Figure1 C) but had limited impact on fatigue and neuropathic pain (Figure1 D, E). Conclusion: Residual pain in patients with psoriatic arthritis and concomitant fibromyalgia represents a challenging issue. Several studies have shown the role of anti-TNF-alpha and IL-17 in modulating neuropathic pain, suggesting a potential target for chronic pain [3, 4]. In our patients, there was also a reduction in fatigue and PDQ, demonstrating that these drugs have significant effects in improving chronic pain. Studies on a larger cohort of patients and long-term follow-up are needed to confirm the efficacy of these d

关键词： HLA class II   HLA-DQB1*02   novel alleles  

摘要： Sequencing of the novel alleles HLA-DQB1*02:02:32, DQB1*02:251N and DQB1*02:256.

关键词： Innate immunity   Cytokines and Chemokines   Targeted synthetic   drugs   Adaptive immunity  

关键词： Energy-efficient   SRAM cells   SPNM   WTP   tau(RA) and tau(WA)  

摘要： Portable biomedical devices aim to serve in human life at a reasonable cost. The portable devices having significant impact due to compact size and durable battery operation. The pixel information is storing in embedded memory for biomedical image processing equipment, where the pixel values hold vital information about the image. Static random-access memory (SRAM) is used in the majority of embedded memories for storing this vital information. To holds vital data, SRAM needs to be extremely reliable, stable and low in power consumption. The proposed research presents a revolutionary low-energy, silicon area efficient, robust FinFET based Intramural loop 7 T (IL 7 T) SRAM bit cell that achieves a large read static margin while operating in weak inversion region (lowering the supply voltage to lower power dissipation). It provides numerous of benefits in terms of area, power, latency over few current existing designs. In contrast to the traditional MOSFET based TG8T, 9 Transistors SRAM architectures, the proposed cell offers decrease in latency (Read delay / Access Time-tau(ra)) of 42.8%, 57.4%, a significant rise in 'static voltage noise margin' (SVNM) of 42.1% and 81.1%, and a limiting leakage power dissipation of 84.5% and 33.19%. Including the lower energy consumption and high reliability, the proposed work occupies in small silicon area. The 7 transistors are used in one memory cell, it requires 1.02X less area overhead than a conventional MOSFET based 6 T memory cell. This cell has the greatest performance metrics out of all the SRAM cells under consideration for compression. The used design functioned under weak inversion region and obtained the optimum performance metrics in memory design at a 300 mV supply voltage for biomedical applications.

关键词： Registries   Patient Reported Outcome Measures  

关键词： Atsttrin   Cell Culture   ErythrosineB   inflammation   intervertebral disc degeneration   Physcion-8-O-beta-D-monoglucoside   small molecules   tumor necrosis factor alpha  

摘要： BackgroundPainful intervertebral disc (IVD) degeneration (IVDD) involves chronic inflammation. Developing translational immunomodulatory strategies for IVDD is a priority with tumor necrosis factor alpha (TNF alpha) signaling an important target. TNF alpha binds to 2 receptors (TNFRs), with TNFR1 signaling promoting catabolism and apoptosis and TNFR2 signaling promoting anabolism and *** study developed translational strategies to evaluate and modulate TNFR1 and TNFR2 signaling in rat in vivo and in vitro IVDD models. We used blocking antibodies, the TNFR2-activator Atsttrin, and small molecule inhibitors of TNFR1 to discern distinct TNFR1 and TNFR2-effects on annulus fibrosus (AF) and nucleus pulposus (NP) cells and to identify effective strategies for modulating specific ***1 was significantly increased with IVDD in vivo in the NP while TNFR2 was unaffected with very faint staining. TNFR1-specific small molecule inhibitors were effective in reducing catabolic effects of TNF alpha, highlighting the efficacy of this small molecule strategy for TNFR1 signaling modulation. Meanwhile, TNFR1 and TNFR2 inhibition in vitro was not effective with blocking antibodies on NP or AF cells, likely due to species-specificity of available blocking antibodies. Further, TNFR2 activation with Atsttrin was similarly ineffective, likely due to extremely low TNFR2 levels in both AF and NP *** alpha receptor-specific signaling is important in rat IVDD in vivo and in vitro. TNFR1 inhibition was more effective with small molecules than using blocking antibodies. Low levels of TNFR2 in rat AF and NP cells and lack of efficacy of TNFR2-activator Atsttrin suggest native AF and NP cells have little capacity for TNFR2-dependent IVD repair.

关键词： IL36   acute generalized exanthematous pustulosis   AGEP   generalized pustular psoriasis   GPP   palmoplantar pustulo-sis   PPP   plaque psoriasis   cutaneous adverse drug reactions  

摘要： Background: Due to similarities, the distinction between generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis (AGEP) has been a matter of debate for a long time. Objectives: Our aim was to define the molecular features of GPP and AGEP. Methods: We analyzed skin biopsy samples and clinical data from 125 patients with AGEP, GPP, palmoplantar pustulosis (PPP), plaque psoriasis (PSO), and nonpustular cutaneous adverse drug reactions (ADRs), as well as from healthy skin controls using RNA-sequencing and blinded histopathologic analyses. Results: The transcriptome and histopathologic features of AGEP and GPP samples exhibited significant overlap (177 differentially expressed genes [DEGs] in GPP and AGEP compared to healthy skin, only 2 DEGs comparing AGEP and GPP). Yet, they displayed marked differences from those of PPP, PSO, and ADR samples, with a notable number of DEGs (131 DEGs comparing AGEP and PSO, 75 DEGs comparing AGEP and PPP, and 52 DEGs comparing AGEP and ADR). A transcriptome profile subgroup evaluation of >13,000 analyzed genes did not reveal any DEGs in drug-induced GPP and AGEP. Moreover, the immune response pattern and immune cell composition did not differ between drug-induced GPP and AGEP, whereas non-drug-induced GPP had higher expression of T(H)17-cell-related genes and a higher neutrophil count than AGEP. Conclusions: We propose that AGEP is a drug-induced variant of GPP and therefore part of IL-36-related pustulosis. A key signature overarching this spectrum was identified, thereby opening the therapeutic approach of IL-36 inhibition to all subtypes of the disease.

关键词： fibrosis   immunology and pathology   lymphocytes   peritoneal dialysis  

关键词： Inflammatory bowel disease   Dihydroartemisinin   Disease activity   Oxidative stress   Anti-inflammatory   Necroptosis   Apoptosis  

摘要： Background: Ulcerative colitis (UC) is an inflammatory bowel disease characterized by the overproduction of reactive oxygen species (ROS) and the release of inflammatory mediators. Dihydroartemisinin (DHA) is a semisynthetic active metabolite of artemisinin that has anti-inflammatory, antioxidant, and anti-fibrotic properties. Objective: This study aimed to assess the therapeutic benefits of DHA on acetic acid(AA) -induced UC in rats, with particular emphasis on its anti-inflammatory effects and its influence on NF kappa B/TNF-alpha/RIPK1 necroptotic pathways. Methods: Eighteen rats were allocated into control, acetic acid-induced colitis (AA), and DHA-treated (AA+DHA) groups. Colitis was caused by rectal instillation of 5 % acetic acid. DHA was supplied via intraperitoneal injection. Histological, biochemical studies of oxidative stress, inflammatory and anti-inflammatory mediators, Western blotting for TNF-alpha, RIPK1, and caspase 3, and immunohistochemical assessment of NF kappa B, TNF-alpha, and RIPK1, were conducted. Results: DHA treatment markedly diminished macroscopic damage, disease activity index, histopathology scores, and malondialdehyde (MDA) levels, enhancing glutathione (GSH) levels. Additionally, DHA decreased serum TNF-alpha and IL-6 and increased IL-10. Western blotting and immunohistochemistry investigations validated the reduced expression of TNF-alpha, RIPK1, and caspase 3 in DHA-treated rats. Conclusion: DHA demonstrates protective properties against acetic acid-induced UC by decreasing oxidative stress and inflammation, modifying TNF-alpha activity to regulate apoptotic and necroptotic pathways. So, DHA may be a favorable therapeutic alternative for the management of ulcerative colitis.