Factors associated with early return visits to the emergency department in patients with vaso-occlusive crisis.

Background And Aim: One of the most common presentations of sickle cell disease (SCD) in the emergency department (ED) is acute severe pain episodes due to a vaso-occlusive crisis (VOC). Management of these episodes is primarily through intravenous pain control, but patients often return to the ED with the same complaint a few days after discharge. While some global studies have explored the risk factors for ED revisits due to VOC, the literature is lacking in the adult population, specifically in Saudi Arabia where SCD prevalence is high.

Vaccinations for Hajj: Enhancing health and global health security.

The Hajj pilgrimage, one of the world's largest and most diverse mass gatherings, poses unique challenges for preventing infectious disease outbreaks. Vaccinations are vital in reducing the risk and spread of diseases during this event. This narrative review examines the impact of vaccination programs on infectious disease mitigation during the Hajj and their broader implications for global health security (GHS).

The Prevalence of Simultaneously Ordering Amylase and Lipase for Diagnosing Pancreatitis.

Background: The simultaneous measurement of serum amylase and lipase levels in the diagnosis of pancreatitis was deemed unnecessary in several studies. We aim at evaluating the prevalence of the simultaneous co-ordering of serum amylase and lipase.

Methods: This retrospective chart review was conducted at King Saud University Medical City in Riyadh, Saudi Arabia, between January 2021 and January 2022.

Autophagy preserves hematopoietic stem cells by restraining MTORC1-mediated cellular anabolism.

Adult stem cells are long-lived and quiescent with unique metabolic requirements. Macroautophagy/autophagy is a fundamental survival mechanism that allows cells to adapt to metabolic changes by degrading and recycling intracellular components. Here we address why autophagy depletion leads to a drastic loss of the stem cell compartment.

Autophagy orchestrates the crosstalk between cells and organs.

Over the recent years, it has become apparent that a deeper understanding of cell-to-cell and organ-to-organ communication is necessary to fully comprehend both homeostatic and pathological states. Autophagy is indispensable for cellular development, function, and homeostasis. A crucial aspect is that autophagy can also mediate these processes through its secretory role.

The central role of DNA damage in immunosenescence.

Ageing is the biggest risk factor for the development of multiple chronic diseases as well as increased infection susceptibility and severity of diseases such as influenza and COVID-19. This increased disease risk is linked to changes in immune function during ageing termed immunosenescence. Age-related loss of immune function, particularly in adaptive responses against pathogens and immunosurveillance against cancer, is accompanied by a paradoxical gain of function of some aspects of immunity such as elevated inflammation and increased incidence of autoimmunity.

Differential effect of lactate on synovial fibroblast and macrophage effector functions.

Introduction: The synovial membrane is the main site of inflammation in rheumatoid arthritis (RA). Here several subsets of fibroblasts and macrophages, with distinct effector functions, have been recently identified. The RA synovium is hypoxic and acidic, with increased levels of lactate as a result of inflammation.

Fibroblast heterogeneity: Keystone of tissue homeostasis and pathology in inflammation and ageing.

Fibroblasts, derived from the embryonic mesenchyme, are a diverse array of cells with roles in development, homeostasis, repair, and disease across tissues. In doing so, fibroblasts maintain micro-environmental homeostasis and create tissue niches by producing a complex extracellular matrix (ECM) including various structural proteins. Although long considered phenotypically homogenous and functionally identical, the emergence of novel technologies such as single cell transcriptomics has allowed the identification of different phenotypic and cellular states to be attributed to fibroblasts, highlighting their role in tissue regulation and inflammation.

Adipocyte autophagy limits gut inflammation by controlling oxylipin and IL-10.

Lipids play a major role in inflammatory diseases by altering inflammatory cell functions, either through their function as energy substrates or as lipid mediators such as oxylipins. Autophagy, a lysosomal degradation pathway that limits inflammation, is known to impact on lipid availability, however, whether this controls inflammation remains unexplored. We found that upon intestinal inflammation visceral adipocytes upregulate autophagy and that adipocyte-specific loss of the autophagy gene Atg7 exacerbates inflammation.

Age-related mechanisms in the context of rheumatic disease.

Ageing is characterized by a progressive loss of cellular function that leads to a decline in tissue homeostasis, increased vulnerability and adverse health outcomes. Important advances in ageing research have now identified a set of nine candidate hallmarks that are generally considered to contribute to the ageing process and that together determine the ageing phenotype, which is the clinical manifestation of age-related dysfunction in chronic diseases. Although most rheumatic diseases are not yet considered to be age related, available evidence increasingly emphasizes the prevalence of ageing hallmarks in these chronic diseases.

Mapping autophagosome contents identifies interleukin-7 receptor-α as a key cargo modulating CD4+ T cell proliferation.

CD4+ T cells are pivotal cells playing roles in the orchestration of humoral and cytotoxic immune responses. It is known that CD4+ T cell proliferation relies on autophagy, but identification of the autophagosomal cargo involved is missing. Here we create a transgenic mouse model, to enable direct mapping of the proteinaceous content of autophagosomes in primary cells by LC3 proximity labelling.

Polyamines Control eIF5A Hypusination, TFEB Translation, and Autophagy to Reverse B Cell Senescence.

Failure to make adaptive immune responses is a hallmark of aging. Reduced B cell function leads to poor vaccination efficacy and a high prevalence of infections in the elderly. Here we show that reduced autophagy is a central molecular mechanism underlying immune senescence.

Multi-OMICS analyses unveil as a potential modifier gene in mevalonate kinase deficiency.

Objectives: The objective of the present study was to explain why two siblings carrying both the same homozygous pathogenic mutation for the autoinflammatory disease hyper IgD syndrome, show opposite phenotypes, that is, the first being asymptomatic, the second presenting all classical characteristics of the disease.

Methods: Where single omics (mainly exome) analysis fails to identify culprit genes/mutations in human complex diseases, multiomics analyses may provide solutions, although this has been seldom used in a clinical setting. Here we combine exome, transcriptome and proteome analyses to decipher at a molecular level, the phenotypic differences between the two siblings.

Management of traumatic corneal abrasion by a sample of practicing ophthalmologists in Saudi Arabia.

Purpose: Corneal epithelial defect (CED) is a common medical emergency condition involving loss of surface epithelial layer of the cornea. The aim of the study is to explore the practice patterns of ophthalmologists in management of traumatic CED in Saudi Arabia and to assess the variance in clinical practice from the established clinical practice guidelines.

Methods: A Survey based study at King Abdulaziz University Hospital between March 2015 and January 2016.

Mitochondria: An Organelle of Bacterial Origin Controlling Inflammation.

Inflammation is a cellular and molecular response to infection and/or tissues injury. While a suited inflammatory response in intensity and time allows for killing pathogens, clearing necrotic tissue, and healing injury; an excessive inflammatory response drives various diseases in which inflammation and tissues damages/stress self-sustain each other. Microbes have been poorly implied in non-resolving inflammation, emphasizing the importance of endogenous regulation of inflammation.

Experience of parents of children with autism on YouTube: are there educationally useful videos?

The aims of this study were to determine the following: first, are there educationally useful videos of parents of children with autism sharing their experiences? Second, do any of the data related to videos help in identifying useful videos? And third, what do posted comments tell us? YouTube was searched for videos of parents sharing their experiences. The following parameters were collected: title, creator, URL, duration, number of viewers, likes, dislikes, comments, days on YouTube, and country. Based on agreed-upon criteria, videos were divided independently into educationally useful and non-useful categories.

Long-term efficacy and safety of antitumour necrosis factor alpha treatment in rhupus: an open-label study of 15 patients.

Background: The efficacy of antitumour necrosis factor alpha (anti-TNF-α) treatment is well recognised in rheumatoid arthritis (RA) but remains controversial in systemic lupus erythematosus (SLE). Therefore, the role of anti-TNF-α treatment in 'Rhupus', a disease sharing features of RA and SLE, is still debated.

Objective: To evaluate the efficacy and tolerance of anti-TNF-α in patients with rhupus.

Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond-like features.

Shwachman-Diamond syndrome (SDS) (OMIM #260400) is a rare inherited bone marrow failure syndrome (IBMFS) that is primarily characterized by neutropenia and exocrine pancreatic insufficiency. Seventy-five to ninety percent of patients have compound heterozygous loss-of-function mutations in the Shwachman-Bodian-Diamond syndrome (sbds) gene. Using trio whole-exome sequencing (WES) in an sbds-negative SDS family and candidate gene sequencing in additional SBDS-negative SDS cases or molecularly undiagnosed IBMFS cases, we identified 3 independent patients, each of whom carried a de novo missense variant in srp54 (encoding signal recognition particle 54 kDa).

Therapeutic Modulation of Plasmacytoid Dendritic Cells in Experimental Arthritis.

Objective: The role of plasmacytoid dendritic cells (PDCs) and type I interferons (IFNs) in rheumatoid arthritis (RA) remains a subject of controversy. This study was undertaken to explore the contribution of PDCs and type I IFNs to RA pathogenesis using various animal models of PDC depletion and to monitor the effect of localized PDC recruitment and activation on joint inflammation and bone damage.

Methods: Mice with K/BxN serum-induced arthritis, collagen-induced arthritis, and human tumor necrosis factor transgene insertion were studied.

IFN-β-induced reactive oxygen species and mitochondrial damage contribute to muscle impairment and inflammation maintenance in dermatomyositis.

Dermatomyositis (DM) is an autoimmune disease associated with enhanced type I interferon (IFN) signalling in skeletal muscle, but the mechanisms underlying muscle dysfunction and inflammation perpetuation remain unknown. Transcriptomic analysis of early untreated DM muscles revealed that the main cluster of down-regulated genes was mitochondria-related. Histochemical, electron microscopy, and in situ oxygraphy analysis showed mitochondrial abnormalities, including increased reactive oxygen species (ROS) production and decreased respiration, which was correlated with low exercise capacities and a type I IFN signature.

Homozygosity for the V377I mutation in mevalonate kinase causes distinct clinical phenotypes in two sibs with hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS).

Objective: Mevalonate kinase (MVK) deficiency is a rare autosomal recessive auto-inflammatory disorder characterised by recurring episodes of fever associated with multiple non-specific inflammatory symptoms and caused by mutations in the MVK gene. The phenotypic spectrum is wide and depends mostly on the nature of the mutations. Hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) is a relatively mild presentation and predominantly associated with a c.