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\"Discusses blood and its role in functioning and protecting the body\"--Provided by publisher.

William Harvey is the riveting story of a seventeenth-century man of medicine and the scientific revolution he sparked with his amazing discoveries about blood circulation within the body. A revealing look at the changing social, religious, and political beliefs of the time, William Harvey documents how one man's originality helped introduce a new way of conducting scientific experiments that we still use today.

\"Provides comprehensive information on the role the heart plays in the body science of humans and animals\"--Provided by publisher.

Background Genome-wide association studies (GWAS) have pinpointed a multitude of risk loci associated with Juvenile Idiopathic Arthritis (JIA), but it is challenging to decipher novel plasma proteins. To address this, we applied an integrative omics pipeline to uncover novel proteins associated with JIA risk. Methods In this research, we utilized an integrative omics method to identify new plasma proteins associated with JIA. Complementary results from an independent cohort were analyzed through Whole Genome Sequencing (WGS), single-cell RNA sequencing (scRNA-seq), and bulk RNA sequencing (bulk RNA-seq) at the Children's Hospital of Chongqing Medical University to validate the reliability of the identified novel proteins. Additionally, to assess the therapeutic potential of novel proteins, we performed Phe-WAS and conducted an extensive review of existing literature using PubMed and Web of Science. Results An integrative omics pipeline analysis identified ERAP2 as having putatively causal effects on JIA. In the fourth step of Summary-data-based Mendelian randomization analysis, we discovered that the SNP rs2927608 and rs2910686 can regulate the expression of the ERAP2 gene, thereby regulating the protein content of both ERAP2 and ERAP1. WGS analysis also detected two potentially pathogenic mutations on ERAP2 in sJIA patients. ScRNA-seq reveals that ERAP2 expression is significantly elevated in patients with sJIA compared to normal and other subtypes, particularly in monocytes. Bulk RNA-seq with ROC analysis demonstrating significant diagnostic power (AUC = 0.86, 95%CI: 0.71–1.00) in discriminating sJIA from healthy controls. Literature and Phe-WAS search revealed that ERAP2 is primarily studied in the context of genetic predisposition to disease and is closely related to autoimmune disorders. Conclusions ERAP2 was identified as a candidate associated with JIA, especially sJIA, through integrative omics analysis, indicating its potential role in protein-mediated disease mechanisms and therapeutic targeting.

Your hardworking heart started beating eight months before you were born and continues to beat about one hundred thousand times a day. \"By the time you're seventy years old, it will have beaten about 2.5 billion times.\" Find out the story behind each beat on a journey through the body's circulatory system.

In this systematic review we analyzed the published articles related to the predictive value for flare of subclinical synovitis assessed by ultrasound (US) in juvenile idiopathic arthritis (JIA). Medline, Embase and Cochrane databases were searched from 1990 to 2020 by two authors, using PICO methodology. The study is built and reported according to PRISMA guidelines. Searches identified four articles comprising a total of 187 JIA patients in clinical remission from at least 3 months. Two of the articles found US subclinical signs of synovitis to be predictive for flare, with a five times higher risk (with Power Doppler signal as an important feature), while in the other two baseline US abnormalities did not predict a clinical flare. The articles differed for protocols, definitions, and length of follow-up. US has an expanding role in pediatric rheumatology, with interest-ing applications especially during the follow-up, potentially identifying subclinical inflammatory signs predictive of flare. However, the few studies available do not allow definite conclusions at this time.

TTC7A deficiencyUltra-rare autosomal-recessive variants in tetratricopeptide repeat domain 7A gene (TTC7A) have been discovered in patients presenting with severe intestinal disease. Mutations in the TTC7A gene cause intestinal epithelial and immune defects resulting in apoptotic enterocolitis, multiple intestinal atresia, and recurrent intestinal stenosis. Patients face high mortality rates with palliation as the current standard of care.1 LeflunomideIn 2020 a high throughput screen identified drugs that increased cell viability in patients with TTC7A; leflunomide reduced caspase 3 and 7 (responsible for cell death) activity in cells by 96%. In zebrafish with disruption of TTC7A, leflunomide restored gut motility, reduced intestinal tract narrowing, and increased intestinal cell survival.1 From a literature review, only 3 patients in the world have been prescribed leflunomide for TTC7A deficiency with ‘encouraging results’.2 however no case reports have been completed on treatment safety or effectiveness.A common adverse effect of leflunomide is liver toxicity due to production of a toxic intermediate; however, the reaction appears to be idiosyncratic and unpredictable.3 Full blood count and liver function tests must be checked before initiation of leflunomide, every two weeks during the first six months of treatment, and every 8 weeks thereafter.4 The patientA 7-year-old male on home parenteral nutrition with TTC7A deficiency was admitted to hospital with high ileostomy output and persistent vomiting with a background of mucosal gastrointestinal inflammation and pyloric stenosis. On behalf of the gastroenterology team, the paediatric gastroenterology pharmacist applied for urgent internal funding and clinical governance approval for leflunomide treatment with the aim to ameliorate intestinal disease. Leflunomide 10 mg daily costs £3.11/month. Treatment was approved, the patient and his family were counselled by the pharmacist and the patient began treatment of leflunomide 10 mg via PEG tube daily.Adverse eventAfter two weeks of treatment the patient’s alkaline phosphate (ALP) and Gamma GT (GGT) had doubled and their alanine transaminase (ALT) had increased 10-fold. Advice from the pharmacist was sought. On review of the leflunomide summary of product characteristics4: ‘Rare cases of severe liver injury, including cases with fatal outcome, have been reported during treatment with leflunomide//If ALT elevations of more than 3-fold the upper limit of normal are present, leflunomide must be discontinued and wash-out procedures initiated.’ A decision was made to stop treatment, however a washout procedure with cholestyramine or activated charcoal was not possible as the patient had minimal oral intake due to vomiting. The pharmacist filed a yellow card report.Follow upThe patient’s ALT normalised after 3 weeks and GGT after 2 months of treatment cessation. It took 8 months for the patient’s ALP to normalise.Lessons learntUnfortunately, it was impossible to assess the potential gastrointestinal benefits of leflunomide in this patient due to the rapid onset of significant liver toxicity. Liver toxicity may have been identified sooner if a blood test was taken 1 week after treatment initiation. Monitoring liver function earlier following initiation of leflunomide treatment may be helpful to minimise liver toxicity in patients with TTC7A deficiency.ReferencesJardine S, Anderson S, Babcock S, et al. Drug screen identifies leflunomide for treatment of inflammatory bowel disease caused by TTC7A deficiency. Gastroenterology 2020;158:1000–1015.Cerretani J. Going ‘all in’ for Khori: new hope for congenital enteropathy [Internet]. Boston Children’s Hospital, 2020. [accessed May 2022]. Available from: https://answers.childrenshospital.org/khori-congenital-enteropathy/Nuray Aktay A, Gul Karadag S, Cakmak F, et al. Leflunomide in juvenile rheumatoid arthritis. Future Rheumatol 2006;1(6):673–682.Electronic Medicines Compendium [Internet]. Leflunomide 10 mg film-coated tablets, 2017 [cited May 2022]. Available from: https://www.medicines.org.uk/emc/product/5395/smpc

Introduces the workings of the heart and circulatory system in the human body.

Background Some juvenile idiopathic arthritis (JIA) patients have a familial aggregation of the disease, and a few have been found to have a juvenile arthritis (JA) phenotype caused by a genetic mutation. JA due to LACC1 defects is a rare condition and it was never reported in China. Methods The clinical and molecular characteristics of a child with LACC1 gene mutation‐related juvenile arthritis, diagnosed by high‐throughput sequencing in Wuhan children's Hospital in 2021 were analyzed retrospectively; The literature and database were reviewed to summarize the clinical data and genotype characteristics of patients with JA caused by LACC1 gene mutation. Results Here, we report a 19‐month‐old Chinese male patient who presented with bilateral limb edema without a history of fever. Laboratory tests showed had moderate anemia and signs of inflammation: hemoglobin of 76 g/L, white blood cell count of 20.53 × 109, and platelet count of 1194 × 109; MRI showed the patient had synovitis and tenosynovitis in bilateral hands and wrists. Whole‐exome sequencing (WES) detected compound heterozygous variants, novel c.446_449dupTAAA and c.889T>C, in the LACC1 gene. Of the 52 patients reported in the literature (including this case), 38.9% had clinical symptoms of systemic juvenile idiopathic arthritis (sJIA), which tended to be caused by loss‐of‐function (LOF) mutation. Findings in this study expanded the spectrum of pathogenic variants and reveal the phenotypic heterogeneity of LACC1‐JA. Conclusions Our study reported a rare case of juvenile arthritis, which is due to the compound heterozygous mutation of LACC1, including a new novel frameshift mutation c.446_449dupTAAA, and LACC1 C297R variant causes disease by potentially modifying the local conformation of proteins. The clinical and genetic findings in our study show that LACC1‐JA is highly heterogeneous, and gene testing is required for juvenile arthritis patients with a high inflammatory response at a young onset age. Our study reported a rare case of juvenile arthritis, which is due to the compound heterozygous mutation of LACC1, including a new novel frameshift mutation c.446_449dupTAAA, and LACC1 C297R variant causes disease by potentially modifying the local conformation of proteins.