Crystal Deposition Research Articles

Calcium pyrophosphate crystal arthritis associated with immune checkpoint inhibitor successfully treated with intra-articular glucocorticoid: A case report.

Immune checkpoint inhibitors (ICIs) sometimes induce immune-related adverse events (irAEs), and arthritis is one of the irAE symptoms. Recently, crystal-induced arthritis, such as calcium pyrophosphate (CPP) crystal deposition disease and gout, has been reported to occur after ICI administration. However, the distinction between ICI-associated crystal arthritis and ICI-induced non-crystal arthritis is difficult because their symptoms are similar. Besides, optimal treatment for ICI-associated crystal arthritis has not been established. Here, we report a patient who developed CPP crystal arthritis twice after pembrolizumab (ICI) administration and was successfully treated with intra-articular glucocorticoid injection. He suffered arthritis and acute interstitial nephritis simultaneously after ICI administration. Musculoskeletal ultrasound of his affected joint suggests that his arthritis was crystal-induced arthritis, and arthrocentesis detected CPP crystal in synovial fluid. Thus, we diagnosed his arthritis as ICI-associated cystal arthritis. Therefore, our case encourages the use of musculoskeletal ultrasound in patients with arthritis after treatment with ICI because it may distinguish between ICI-associated crystal arthritis and ICI-induced non-crystal arthritis. Besides, ICI-associated crystal arthritis could be treatable by intra-articular glucocorticoid injection.

Sterol O-acyltransferase (SOAT/ACAT) activity is required to form cholesterol crystals in hepatocyte lipid droplets

ObjectiveExcess cholesterol storage can induce the formation of cholesterol crystals in hepatocyte lipid droplets. Such crystals distinguish metabolic dysfunction associated steatohepatitis (MASH) from simple steatosis and may underlie its pathogenesis by causing cell damage that triggers liver inflammation. The mechanism linking cholesterol excess to its crystallization in lipid droplets is unclear. As cholesteryl esters localize to and accumulate in lipid droplets more readily than unesterified free cholesterol, we investigated whether cholesterol esterification by sterol O-acyltransferase (SOAT), also known as acyl co-A cholesterol acyltransferase (ACAT), is required for hepatocyte lipid droplet crystal formation. MethodCholesterol crystals were measured in cholesterol loaded Hep3B hepatocytes, RAW264.7 macrophages, and mouse liver using polarizing light microscopy. We examined the effect of blocking SOAT activity on crystal formation and compared these results to features of cholesterol metabolism and the progression to intracellular crystal deposits. ResultsCholesterol loading of Hep3B cells caused robust levels of lipid droplet localized crystal formation in a dose- and time-dependent manner. Co-treatment with SOAT inhibitors and genetic ablation of SOAT1 blocked crystal formation. SOAT inhibitor also blocked crystal formation in low density lipoprotein (LDL) treated Hep3B cells, acetylated LDL treated RAW 264.7 macrophages, and in the liver of mice genetically predisposed to hepatic cholesterol overload and in mice with cholesterol enriched diet-induced MASH. ConclusionSOAT1-mediated esterification may underlie cholesterol crystals associated with MASH by concentrating it in lipid droplets. These findings imply that inhibiting hepatocyte SOAT1 may be able to alleviate cholesterol associated MASH. Moreover, that either a lipid droplet localized cholesteryl ester hydrolase is required for cholesterol crystal formation, or the crystals are composed of cholesteryl ester.

Simultaneous measurements for fast neutron flux and tritium production rate using pulse shape discrimination and single crystal CVD diamond detector

This paper presents the development of a simultaneous measurement method for fast neutron energy spectra and tritium production rates within mixed radiation fields using a single crystal chemical vapour deposition diamond detector combined with a lithium fluoride (LiF) foil. The method involves the separation of pulses with rectangular shapes and the determination of the depth position within the single crystal diamond (SCD) struck by fast neutrons or nuclear reaction products including recoil tritons from the LiF foil based on pulse width, extracting pulse events occurred at the specific bulk region and the surface region of the SCD. Subsequently, unfolding techniques were employed to analyse the energy deposition spectrum of pulses at the specific bulk region which are induced only by fast neutrons, allowing the deduction of the fast neutron energy spectrum. To evaluate the tritium production rate, the energy deposition spectrum of pulses from events occurring at the SCD surface facing the LiF foil was analysed. By estimating the energy deposition spectrum solely induced by fast neutrons striking the SCD surface and subtracting it from the energy deposition spectrum of events at the SCD surface, the contribution of energetic ions, such as recoil tritons generated by the 6Li(n,α)3H reaction in the LiF foil, was determined. The fast neutron flux and tritium production rate obtained through this study were consistent with particle transport calculations, demonstrating the successful development of a method suitable for performance testing of fusion reactor blankets.

Deficiency of histone deacetylases 3 in macrophage alleviates monosodium urate crystals-induced gouty inflammation in mice

BackgroundGout is caused by monosodium urate (MSU) crystals deposition to trigger immune response. A recent study suggested that inhibition of Class I Histone deacetylases (HDACs) can significantly reduce MSU crystals-induced inflammation. However, which one of HDACs members in response to MSU crystals was still unknown. Here, we investigated the roles of HDAC3 in MSU crystals-induced gouty inflammation.MethodsMacrophage specific HDAC3 knockout (KO) mice were used to investigate inflammatory profiles of gout in mouse models in vivo, including ankle arthritis, foot pad arthritis and subcutaneous air pouch model. In the in vitro experiments, bone marrow-derived macrophages (BMDMs) from mice were treated with MSU crystals to assess cytokines, potential target gene and protein.ResultsDeficiency of HDAC3 in macrophage not only reduced MSU-induced foot pad and ankle joint swelling but also decreased neutrophils trafficking and IL-1β release in air pouch models. In addition, the levels of inflammatory genes related to TLR2/4/NF-κB/IL-6/STAT3 signaling pathway were significantly decreased in BMDMs from HDAC3 KO mice after MSU treatment. Moreover, RGFP966, selective inhibitor of HDAC3, inhibited IL-6 and TNF-α production in BMDMs treated with MSU crystals. Besides, HDAC3 deficiency shifted gene expression from pro-inflammatory macrophage (M1) to anti-inflammatory macrophage (M2) in BMDMs after MSU challenge.ConclusionsDeficiency of HDAC3 in macrophage alleviates MSU crystals-induced gouty inflammation through inhibition of TLR2/4 driven IL-6/STAT3 signaling pathway, suggesting that HDAC3 could contribute to a potential therapeutic target of gout.

Abstract PO2-12-11: Ocular Toxicity of Tamoxifen in Patients with Breast Cancer

Abstract Background: The latest recommendations in breast cancer treatment protocols with tamoxifen indicate that it should be used from five to 10 years. It depends mainly on the cumulative dose of the drug in the body. Despite its multiplicity, the various studies conducted on this subject did not reach conclusive results. Objectives: This research aims to study retinopathy associated with hormonal treatment of breast cancer using tamoxifen. Methods: A cross-sectional study was conducted at Al-Mouwasat University Hospital on a sample of 130 eyes according to (G-Power) with a statistical power of 95%. The participants were briefed on the research and consented on the ethical considerations. Then, the patients who entered the study were interrogated, clinically examined, and were asked about their medical history, the time of breast cancer diagnosis along with the details about the treatment protocols they underwent or currently undergoing. The refractive errors were measured with an automatic refractive device, then they were examined on the slit lamp to investigate the refractory media, then the corrected and uncorrected visual acuity were taken. Finally, after ensuring that the inclusion criteria were met and excluding those who fulfil one or more of the exclusion criteria, optical coherence tomography was performed using SD-OCT technique to measure and review the retinal thickness map in circles of 1-3-6 mm, respectively, to notice possible changes on it. Results: We found that the use of tamoxifen irrespective to cumulative dose leads to increase in the macula thickness values in the upper and lower sectors within the 3 mm circle, and to significant decrease in the macula thickness values in the upper and lower sectors within the 6 mm circle, in addition to decrease in nasal sector thickness within the circles of 3 and 6 mm. Conclusion: We conclude that the difference between people treated with tamoxifen and those not treated with it is not limited to the occurrence of crystals deposition in the macular area or the presence of a cavity in the central macula (with or without typical cystic macular edema), but rather to existence of macula thickness differences unrelated to the cumulative dose of the drug, whether by increase or decrease in thickness of the upper, lower and nasal segments. Citation Format: Husain Alhouz, Arwa Azmeh, Maher Saifo. Ocular Toxicity of Tamoxifen in Patients with Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-11.

Imaging Assessment of Nontraumatic Pathologic Conditions at the Craniovertebral Junction: A Comprehensive Review.

Nontraumatic pathologic conditions of the craniovertebral junction encompass a range of conditions affecting the complex anatomy of this region without direct physical injury. These conditions include congenital syndromes that predispose individuals to ligamentous laxity, potentially leading to instability. Additionally, rare but noteworthy cases such as Grisel syndrome, a cause of pediatric torticollis, may arise without a traumatic trigger. Inflammatory diseases, including rheumatoid arthritis, ankylosing spondylitis, and crystal deposition, can lead to cervical instability and spinal cord compression. Infections at the upper cervical spine are dominated by tuberculosis, typically transmitted through hematologic or lymphatic routes with characteristic imaging findings. On the other hand, purulent bacterial infections in this area are rare. Furthermore, although tumors involving the structures of the craniovertebral junction are infrequent, they can lead to significant complications, albeit less frequently through cord compression and more commonly via pathologic fractures or subluxation. The craniocervical junction is a complex anatomic region comprising ligaments, bones, joints, and muscles that support the head's weight and enable its wide range of motion. Accurate recognition and understanding of the complex anatomy and the various nontraumatic pathologic conditions at the craniovertebral junction are pivotal for initiating timely and appropriate treatment strategies. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Chronic multiarticular tophaceous gout with abnormally large tophi, case of surgical intervention: a case report from Nepal

Introduction and importance: Gout is an inflammatory disease caused by the deposition of monosodium urate monohydrate crystals around the synovial joints, affecting the first metatarsophalangeal joints followed by ankle and knees. It is found to be more prevalent among men and older women. Tophi tends to develop if the acute phase of the disease is not controlled. In contrast, our patient had an unusual presentation of multiple tophi affecting several joints accompanied by deformities. Case presentation: Here, the authors present a case of a 63 years old male with chronic multiarticular tophaceous gout with a history of more than 30 years. He presented with multiple joint deformities and prior surgical history of excision of tophi. Laboratory reports revealed elevated serum uric acid, and X-ray showed joint deformities with tophi. However, the parameters of renal function test were normal. Surgical excision of the tophi was done. Clinical discussion: Gout is one of the most common inflammatory arthritis, which if untreated can progress to tophi formation. The diagnosis can be made clinically and by several investigations including serum uric acid estimation and aspiration of the joint to reveal monosodium urate monohydrate crystals. A long standing case of multiarticular tophi causing joint deformities does require surgical intervention. Conclusion: Early treatment and diagnosis of hyperuricemia prevent the progression to gouty arthritis and tophi formation. Long history of multiple tophaceous gout is an unusual presentation, which we intend to present here as a novel case report. Nevertheless, such cases require surgical interventions.

DESCRIBING THE LOCATION AND MORPHOLOGY OF THE DOTS IN WHITE DOT FOVEA USING ADAPTIVE OPTICS.

To characterize the white dots in white dot fovea, an entity chiefly described in Japan, using adaptive optics imaging and propose a hypothesis regarding their origin. The patient underwent comprehensive ophthalmic examination, including color and green monochromatic fundus photography, fluorescein angiography, spectral-domain optical coherence tomography, and adaptive optics imaging. An asymptomatic 66-year-old Korean woman presented with bilateral white, glistening deposits in a ring pattern around the fovea of both eyes. The dots were highly reflective on green monochromatic images, were not visible on fluorescein angiography, and appeared hyperreflective in the inner retina using spectral-domain optical coherence tomography. Adaptive optics showed polygonal granules ranging from 1 to 10 μ m in size. The patient denied any systemic disorder or the use of any medications related to crystalline retinopathy. The patient had lived in Japan for 35 years before just moving to the United States. The location, small size, and polygonal shape of the dots in white dot fovea are suggestive of intraretinal deposition of crystals, and not cells on the surface of the fovea as has been previously proposed. Carotenoid deposition related to dietary habits is a plausible cause because of the similarity to other retinopathies associated to these compounds.

Porous Se@SiO2 nanocomposites play a potential inhibition role in hyperoxaluria associated kidney stone by exerting antioxidant effects.

Nephrolithiasis seriously affects people's health with increasing prevalence and high recurrence rates. However, there is still a lack of effective interventions for the clinical prevention of kidney stones. Hyperoxaluria-induced renal tubular epithelial cell (TEC) injury is a known key factor in kidney stone formation. Thus, developing new drugs to inhibit the hyperoxaluria-induced TEC injury may be the best way. We synthesized the Se@SiO2 nanocomposites as described in Zhu's study. The size and morphology of the Se@SiO2 nanocomposites were captured by transmission electron microscopy. Cell viability was measured by a Cell Counting Kit-8 (CCK-8) assay. The mice were randomly divided into the following four groups: (I) the control group (n=6); (II) the Se@SiO2 group (n=6); (III) the glyoxylic acid monohydrate (GAM) group; and (IV) the GAM + Se@SiO2 group (n=6). The concentration of Se in the mice was quantified using inductively coupled plasma atomic emission spectroscopy. The CCK-8 assays showed that Se@SiO2 nanocomposites had almost no obvious cytotoxicity on the Transformed C3H Mouse Kidney-1 (TCMK-1) cell. The mice kidney Se concentration levels in the Se@SiO2 groups (Se@SiO2 6.905±0.074 mg/kg; GAM + Se@SiO2 7.673±2.85 mg/kg) (n=6) were significantly higher than those in the control group (Control 0.727±0.072 mg/kg; GAM 0.747±0.074 mg/kg) (n=6). The Se@SiO2 nanocomposites reduced kidney injury, calcium oxalate crystal deposition, and the osteoblastic-associated proteins in the hyperoxaluria mice models. Se@SiO2 nanocomposites appear to protect renal TECs from hyperoxaluria by reducing reactive oxygen species production, suggesting the potential role of preventing kidney stone formation and recurrence.

E048 Spinal gout: an unusual cause of paraplegia

Abstract Background/Aims Gout is a common inflammatory arthritis caused by the deposition of monosodium urate crystals. Gout usually causes peripheral joint arthritis. Axial involvement is likely under-recognised, affecting an estimated 10-20% of gout patients. Spinal gout is an established phenomenon in patients with chronic tophaceous gout and sustained hyperuricaemia. Gout can affect any segment of the spine. Clinical presentation of spinal gout is variable including back pain, radiculopathy and cord compression. Due to its nonspecific presentation, it can be confused for other spinal pathologies such as epidural abscess, malignancy, spondylodiscitis and vertebral osteomyelitis. Methods We present a case report of a young male with tophaceous gout of the thoracic spine. Results A 37 year old man presented with 4 day history of acute thoracic back pain followed by flaccid lower limb paralysis. He was morbidly obese (BMI 60) and had a 13-year history of poorly controlled gout with most recent uric acid being 627. He had previously declined urate lowering therapy but commenced allopurinol treatment one month prior to admission. On examination power was 0/5 in both lower limbs with absent reflexes and a T12 sensory level. MRI showed multi-level facet joint arthropathy. An epidural collection was present at T8-10, causing complete occlusion of the vertebral artery. He underwent an urgent posterior thoracic decompression. ‘White cheese like epidural pus’ was removed and he was initially treated as facet joint infection. He had ongoing fevers [>38.5C], despite empirical antibiotics, and C-reactive-protein was persistently elevated [highest at 360mg/L]. Uric acid was 423. Enrichment culture of the epidural collection and serial blood cultures were negative. Repeat MRI of spine did not demonstrate any reoccurrence of collection. Subsequently the histology of the epidural collection was reported as characteristic of gout with ‘amorphous material and giant cells’. No urate crystals were identified as the sample was prepared with formalin, which would have dissolved any crystals present. He was referred to rheumatology who identified synovitis in his hands, wrist and elbows, consistent with active polyarticular gout. There were small tophi present on his heels and pinna. The patient was commenced on oral prednisolone and allopurinol was rapidly up-titrated. Unfortunately, the patient did not recover neurological function. Conclusion We present a unique case of acutely presenting tophaceous thoracic spinal gout causing irreversible paraplegia in a young patient, mimicking an epidural abscess. Our patient had hyperuricaemia for over 10 years without treatment, raising his risk of axial complications. A high index of suspicion for spinal gout is needed for patients presenting with acute back pain and neurological symptoms with a history of chronic gout. This case highlights diagnostic challenges in identifying spinal gout and the importance of treating tophaceous gout early to prevent devastating long-term complications. Disclosure C.A. Zollinger-Read: None. M. Cox: None. R. Kumari: None.

E046 Lytic lesions; metastatic disease or gout?

Abstract Background/Aims Uric acid crystal deposition in the spine is uncommonly diagnosed, although the frequency of axial involvement is thought to be as high as 14-35%. Studies have shown that spinal gout is more common in men aged 35-75 years, with a history of chronic polyarticular tophaceous gout which is not optimally controlled being a key risk factor. Recent studies have shown that spinal gout is under and misdiagnosed due to its non-specific presentation of back pain or absence of symptoms. Our case report exemplifies this diagnostic challenge. Methods In this report we describe a case of a 79-year-old male with a history of polyarticular tophaceous gout, chronic kidney disease and previous renal carcinoma treated with curative radiotherapy. He presented with a 4-week history of progressive exertional dyspnoea and orthopnoea. He was commenced on intravenous diuretics which lead to an acute kidney injury, with his eGFR dropping to 14mL/min. His preadmission allopurinol and colchicine were held and clinically he developed a flare of gout affecting his right wrist and right second and third MCP joints. A CT scan of his abdomen and pelvis, carried out to investigate potential bowel obstruction, showed no evidence of obstruction but it did reveal multiple lytic lesions in the spine with potential extension into the spinal canal at T9 and L5. He did not have any back pain and his neurological examination was normal. Results A working diagnosis of spinal metastasis with potential cord compression was made and the patient was commenced on high dose steroids. He subsequently underwent an MRI whole spine which showed marrow abnormalities and destructive soft tissues changes affecting various facet joints in the thoracic and lumbar spine. The primary differential remained metastases but due to the unusual distribution of the marrow changes in which the vertebral bodies were completely spared, the initial CT images were reviewed on spectral scanning which demonstrated uric acid deposition in the affected facet joints. The diagnosis was confirmed as gout in the spine when a PET-CT scan revealed no potential primary source of malignancy. The gout flare in his hand settled with the steroids prescribed to treat the potential cord compression and he continued to deny suffering from back pain. Conclusion A literature search demonstrates that reports of spinal gout being described as lytic lesions on CT are rare. Spinal gout should be considered as a differential in a patient with facet joint lytic lesions on imaging, without involvement of the vertebral body and where no primary malignancy is found. Our case demonstrates how dual energy CT scanning can prevent the need for invasive biopsy in cases of diagnostic uncertainty in patients with a history of poorly controlled chronic tophaceous gout. Disclosure S.K. Stewart: None. D.J. Coulter: None. C. Masih: None.

Identification of SOCS3 and PTGS2 as new biomarkers for the diagnosis of gout by cross-species comprehensive analysis

BackgroundGout is the most common inflammatory arthritis in adults. Gout is an arthritic disease caused by the deposition of monosodium urate crystal (MSU) in the joints, which can lead to acute inflammation and damage adjacent tissue. Hyperuricemia is the main risk factor for MSU crystal deposition and gout. With the increasing burden of gout disease, the identification of potential biomarkers and novel targets for diagnosis is urgently needed. MethodsFor the analysis of this subject paper, we downloaded the human gout data set GSE160170 and the gout mouse model data set GSE190138 from the GEO database. To obtain the differentially expressed genes (DEGs), we intersected the two data sets. Using the cytohubba algorithm, we identified the key genes and enriched them through GO and KEGG. The gene expression trends of three subgroups (normal control group, intermittent gout group and acute gout attack group) were analyzed by Series Test of Cluster (STC) analysis, and the key genes were screened out, and the diagnostic effect was verified by ROC curve. The expression of key genes in dorsal root nerve and spinal cord of gout mice was analyzed. Finally, the clinical samples of normal control group, hyperuricemia group, intermittent gout group and acute gout attack group were collected, and the expression of key genes at protein level was verified by ELISA. ResultWe obtained 59 co-upregulated and 28 co-downregulated genes by comparing the DEGs between gout mouse model data set and human gout data set. 7 hub DEGs(IL1B, IL10, NLRP3, SOCS3, PTGS2) were screened out via Cytohubba algorithm. The results of both GO and KEGG enrichment analyses indicate that 7 hub genes play a significant role in regulating the inflammatory response, cytokine production in immune response, and the TNF signaling pathway. The most representative hub genes SOCS3 and PTGS2 were screened out by Series Test of Cluster, and ROC analysis results showed the AUC values were both up to 1.000. In addition, we found that PTGS2 expression was significantly elevated in the dorsal root ganglia and spinal cord in monosodium urate(MSU)-induced gout mouse model. The ELISA results revealed that the expression of SOCS3 and PTGS2 was notably higher in the acute gout attack and intermittent gout groups compared to the normal control group. This difference was statistically significant, indicating a clear distinction between the groups. ConclusionThrough cross-species comprehensive analysis and experimental verification, SOCS3 and PTGS2 were proved to be new biomarkers for diagnosing gout and predicting disease progression.

Gout and its management.

Gout is a common and treatable chronic disease of monosodium urate crystal deposition. It is experienced as extremely painful episodes of joint inflammation that impact all aspects of the person's life. This Clinical Perspectives article provides an update on gout diagnosis, medications and strategies to improve the quality of gout care.

β,γ-Methylene-ATP and its metabolite medronic acid affect both arterial media calcification and bone mineralization in non-CKD and CKD rats.

Arterial media calcification or pathological deposition of calcium-phosphate crystals in the vessel wall contributes significantly to the high mortality rate observed in patients with CKD. Extracellular nucleotides (ie, ATP or UTP) regulate the arterial calcification process by interacting with (1) purinergic receptors and (2) breakdown via ecto-nucleotidases, such as ectonucleotide pyrophosphatase/phosphodiesterase NPP1 or NPP3, affecting the local levels of calcification inhibitor, pyrophosphate, and stimulator inorganic phosphate (PPi/Pi ratio). Also, it has been shown that ATP analogs (ie, β,γ-methylene-ATP [β,γ-meATP]) inhibit vascular smooth muscle cell calcification in vitro. In the first experiment, daily dosing of β,γ-meATP (2mg/kg) was investigated in rats fed a warfarin diet to trigger the development of non-CKD-related arterial medial calcifications. This study showed that β,γ-meATP significantly lowered the calcium scores in the aorta and peripheral vessels in warfarin-exposed rats. In a second experiment, daily dosing of 4mg/kg β,γ-meATP and its metabolite medronic acid (MDP) was analyzed in rats fed an adenine diet to promote the development of CKD-related arterial medial calcification. Administration of β,γ-meATP and MDP did not significantly decrease aortic calcification scores in this model. Moreover, both compounds induced deleterious effects on physiological bone mineralization, causing an imminent risk for worsening the already compromised bone status in CKD. Due to this, it was not possible to raise the dosage of both compounds to tackle CKD-related arterial calcification. Again, this points out the difficult task of targeting solely ectopic calcifications without negatively affecting physiological bone mineralization. On the other hand, aortic mRNA expression of Enpp1 and Enpp3 was significantly and positively associated with aortic calcification scores, suggesting that normalizing the aortic NPP1/3 activity to control values might be a possible target to treat (CKD-induced) arterial media calcifications.

Kegiatan Penapisan Pemeriksaan Kadar Asam Urat terhadap Hiperurisemia pada Populasi Lanjut Usia

Hyperuricemia, characterized by increased serum uric acid levels, occurs due to an imbalance between uric acid production and excretion. The prevalence in adults and the elderly in China is 12.69% and is higher in men (17.7%) than women (8.5%). Contributing factors such as genetics, diet, and lifestyle changes, lead to an increased risk of gout, kidney stones, and cardiovascular disease. Chronic hyperuricemia can cause joint damage and deformity due to the deposition of urate crystals. This activity uses the PDCA (Plan-Do-Check-Action) methodology to screen for hyperuricemia in the elderly at St. Mary's Church. Francis of Assisi. The screening results showed that 12 people (33.33%) of the 36 participants had hyperuricemia. Early detection of hyperuricemia is very important in preventing complications such as gout and cardiovascular disease. Regular check-ups and lifestyle changes can significantly improve health outcomes and quality of life for seniors.

The Clinical Significance of Serum Interleukin-36α Levels in Patients with Gout

ABSTRACT Background Gout is a chronic inflammatory diseases caused by monosodium urate crystal deposition. However, the role of interleukin (IL)-36 in gout has not dbeen elucidated. Methods We enrolled 75 subjects, including 20 healthy controls (HC), 30 patients with acute gout attack and 25 patients in remission. Baseline data were obtained through clinical interrogation and laboratory data were obtained through tests of blood samples. Serum levels of IL-36α were detected using enzyme-linked immunosorbent assay. Spearman correlation analysis was used to investigate the correlation of IL-36α with other parameters. The diagnostic value of IL-36α was demonstrated using a receiver operating characteristic curve. Results The serum IL-36α level of gout patients in acute attack and remission stage was significantly higher than that of HC. Serum IL-36α was positively correlated with alanine transaminase (ALT) and aspartate transaminase (AST). Serum amyloid A (SAA) levels positively correlated with C-reactive protein levels and erythrocyte sedimentation rates. Glutamyl transpeptidase levels positively correlated with AST and ALT levels. Conclusion In conclusion, serum IL-36α levels were elevated in patients with gout and correlated with the clinical markers of inflammation. Our findings suggest that IL-36α may be a novel inflammatory indicator for gout.

Comparison of Scheimpflug Corneal Tomography and Anterior Segment Optical Coherence Tomography Measurements in Corneal Cystinosis: A Case Series.

To report the clinical course and compare the utility of Scheimpflug tomography (ST) and anterior segment optical coherence tomography (AS-OCT) for central corneal thickness (CCT) and corneal densitometry (CD) assessment in patients with corneal crystals owing to nephropathic cystinosis. A retrospective chart analysis of three patients with nephropathic cystinosis and the presence of corneal cystine crystals in both eyes was performed. All patients underwent clinical examination and anterior segment photography, ST, and AS-OCT scans. Corneal densitometry was exported from built-in proprietary software for ST and from custom-made validated software for AS-OCT. Anterior segment optical coherence tomography images were rescaled to grayscale units from 0 (maximum transparency) to 100 (minimum transparency) to match built-in ST densitometry readings. Furthermore, the mean pixel intensity, representative of CD, was calculated from the pixels corresponding to the segmented cornea. All three patients had pathognomonic cystine crystals deposits in the cornea and were treated with cysteamine medications that resulted in clinical improvement. The CCT measured using ST exhibited a range from 560 to 958 μm. Conversely, when assessed with AS-OCT, the CCT varied within the range of 548 to 610 μm. Both examinations could be performed, but in the more severe cases, AS-OCT showed far greater utility to estimate CD. In four of six eyes examined, ST showed disproportionate CCT values, compared with the AS-OCT, whereas reliable CD measurements were only available in AS-OCT. The AS-OCT could be considered a baseline ocular measurement in cystinosis and in the evaluation of disease progression and treatment efficacy.

CD8 T cell-derived perforin regulates macrophage-mediated inflammation in a murine model of gout.

Gout is characterized by hyperuricemia and recurrent inflammatory episodes caused by intra-articular crystal deposition of monosodium urate (MSU). There is a clear relationship between gout and metabolic syndrome. Recent evidence indicates that perforin plays a role in regulating glucose homeostasis and provides protection in diet-induced non-alcoholic steatohepatitis models. However, the impact of perforin on immune inflammation in gout remains unclear. We induced acute gout models in both wild-type (WT) mice and Prf1null mice by administering intra-articular injections of MSU crystals. We compared the ankle joint swelling and the histological score between the two groups. Furthermore, we investigated underlying mechanisms through in vitro co-culture experiments involving CD8 T cells and macrophages. In this study, Prf1null mice showed significantly more pronounced ankle swelling with increased inflammatory cell infiltrations compared with WT mice 24h after local MSU injection. Moreover, MSU-induced Prf1null mice exhibited increased accumulation of CD8 T cells but not NK cells. Perforin-deficient CD8 T cells displayed reduced cytotoxicity towards bone marrow-derived M0 and M1 macrophages and promoted TNF-α secretion from macrophage. Perforin from CD8 T cells limits joint inflammation in mice with acute gout by downregulating macrophage-mediated inflammation. Key Points • Perforin deficiency increased swelling in the ankle joints of mice upon MSU injection. • Perforin deficiency is associated with increased immune cell recruitment and severe joint damage in gout. • Perforin regulated CD8 T cell accumulation in gout and promoted CD8 T cell cytotoxicity towards M0 and M1 macrophages. • CD8 T cell-derived perforin regulated pro-inflammatory cytokine secretion of macrophage.

Adsorption of phosphate over a novel magnesium-loaded sludge-based biochar.

The production of sludge-based biochar to recover phosphorus (P) from wastewater and reuse the recovered phosphorus as agricultural fertilizer is a preferred process. This article mainly studied the removal of phosphate (PO4-P) from aqueous solution by synthesizing sludge-based biochar (MgSBC-0.1) from anaerobic fermentation sludge treated with magnesium (Mg)-loading-modification, and compared it with unmodified sludge-based biochar (SBC). The physicochemical properties, adsorption efficiency, and adsorption mechanism of MgSBC-0.1 were studied. The results showed that the surface area of MgSBC-0.1 synthesized increased by 5.57 times. The material surface contained MgO, Mg(OH)2, and CaO nanoparticles. MgSBC-0.1 can effectively remove phosphate in the initial solution pH range of 3.00-7.00, with a fitted maximum phosphorus adsorption capacity of 379.52 mg·g-1. The adsorption conforms to the pseudo second-order kinetics model and Langmuir isotherm adsorption curve. The characterization of the adsorbed composite material revealed the contribution of phosphorus crystal deposition and electrostatic attraction to phosphorus absorption.

Spatiotemporal Observation of Monosodium Urate Crystals Deposition in Synovial Organoids Using Label-Free Stimulated Raman Scattering.

Gout, a common form of arthritis, is characterized by the deposition of monosodium urate (MSU) crystals in joints. MSU deposition in synovial tissues would initiate arthritis flares and recurrence, causing irreversible joint damage. However, the dynamic deposition of MSU crystals in tissues lacks experimental observation. In this study, we used chemical-specific, label-free stimulated Raman scattering (SRS) microscopy to investigate the spatiotemporal deposition and morphological characteristics of MSU crystals in human synovial organoids. Our findings revealed a critical 12-h window for MSU deposition in the lining layer of gouty synovium. Moreover, distinctive inflammatory reactions of the lining and sublining synovial layers in gout using SRS microscopy were further verified by immunofluorescence. Importantly, we identified a crucial proinflammatory role of sublining fibroblast-like synoviocytes, indicating a need for targeted medication treatment on these cells. Our work contributes to the fundamental understanding of MSU-based diseases and offers valuable insights for the future development of targeted gout therapies.