Purpose: This study examined the effect of permissive underfeeding compared to target feeding and intensive insulin therapy (IIT) compared to conventional insulin therapy (CIT) on the inflammatory mediators monocyte chemoattractant protein 1 (MCP-1), soluble intercellular adhesion molecule 1 (sICAM-1), and tissue factor (TF) in critically ill patients. Methodology: This was a substudy of a 2 × 2 factorial design randomized controlled trial in which intensive care unit (ICU) patients were randomized into permissive underfeeding compared to target feeding groups and into IIT compared to CIT groups (ISRCTN96294863). In this substudy, we included 91 patients with almost equal numbers across randomization groups. Blood samples were collected at baseline and at days 3, 5, and 7 of an ICU stay. Linear mixed models were used to assess the differences in MCP-1, sICAM-1, and TF across randomization groups over time. Results: Baseline characteristics were balanced across randomization groups. Daily caloric intake was significantly higher in the target feeding than in the permissive underfeeding groups (P-value < 0.01), and the daily insulin dose was significantly higher in the IIT than in the CIT groups (P-value < 0.01). MCP-1, sICAM-1, and TF did not show any significant difference between the randomization groups, while there was a time effect for MCP-1. Baseline sequential organ failure assessment (SOFA) score and platelets had a significant effect on sICAM-1 (P-value < 0.01). For TF, there was a significant association with age (P-value < 0.01). Conclusions: Although it has been previously demonstrated that insulin inhibits MCP-1, sICAM-1 in critically ill patients, and TF in non-critically ill patients, our study demonstrated that IIT in critically ill patients did not affect these inflammatory mediators. Similarly, caloric intake had a negligible effect on the inflammatory mediators studied.
A catalog of common, intermediate and well‐documented (CIWD) HLA‐A, ‐B, ‐C, ‐DRB1, ‐DRB3, ‐DRB4, ‐DRB5, ‐DQB1 and ‐DPB1 alleles has been compiled from over 8 million individuals using data from 20 unrelated hematopoietic stem cell volunteer donor registries. Individuals are divided into seven geographic/ancestral/ethnic groups and data are summarized for each group and for the total population. P (two‐field) and G group assignments are divided into one of four frequency categories: common (≥1 in 10 000), intermediate (≥1 in 100 000), well‐documented (≥5 occurrences) or not‐CIWD. Overall 26% of alleles in IPD‐IMGT/HLA version 3.31.0 at P group resolution fall into the three CIWD categories. The two‐field catalog includes 18% (n = 545) common, 17% (n = 513) intermediate, and 65% (n = 1997) well‐documented alleles. Full‐field allele frequency data are provided but are limited in value by the variations in resolution used by the registries. A recommended CIWD list is based on the most frequent category in the total or any of the seven geographic/ancestral/ethnic groups. Data are also provided so users can compile a catalog specific to the population groups that they serve. Comparisons are made to three previous CWD reports representing more limited population groups. This catalog, CIWD version 3.0.0, is a step closer to the collection of global HLA frequencies and to a clearer view of HLA diversity in the human population as a whole.
In the last decade, cord blood (CB) has proven to be a valuable source of hematopoietic stem cells for transplantation to treat many hematological disorders. Since then, many CB banks have been established worldwide. Our aim was to estimate the level of public awareness of CB banking in Saudi Arabia.A self-administered questionnaire of 22 multiple choices was conveniently distributed, consisting of demographics, awareness measure, attitude toward banking preference, and donation for research data.A total of 1146 participants have completed the questionnaire. The majority were young female 19-25 years old (26%), who are college graduates (57%) with middle class socioeconomic status (82%). The subjective assessment of the overall knowledge was inadequate (66%). For the objective assessment, 12 questions were asked about CB source, collection, storage, and usage. Only half of the subjects (52%) knew that CB is a source of stem cells. More than half did not know the main use of CB. About half did not know about the method of collection nor the condition of storing.This study shows a high lack of knowledge about CB banking. More than half of the subjects were unaware of CB banking and its uses. However, most subjects are accepting CB storage, which anticipates great impact and efficacy on educational programs. Moreover, the data demonstrated that health professionals were not the source of knowledge. We recommend having comprehensive educational campaigns with clear information about CB banking to facilitate positive perspectives towards donation and scientific research.
Multiple sclerosis (MS) is a disease of the central nervous system (CNS) that is the result of the body's own immune cells being auto-reactive to the myelin regions of the body as if these regions were foreign antigens. This demyelination process is damaging to the electrical conductivity of neurons. The current medicines are only capable of fighting off the symptoms of the disease, but not the disease itself. Specialized stem cells, known as mesenchymal stem cells (MSCs), seem to be the candidate therapy to get rid of MS. MSCs can be isolated from multiple sources of the person's body, and even from the umbilical cord (UC) and placenta of a donor. These cells have anti-inflammatory effects so they can target the overactivity and self-antigen attacks by T cells and macrophages; this immune system overactivity is characteristic of MS. MSCs show the ability to locate into brain lesions when injected and thus can compensate for the loss of the brain function by differentiating into neuronal precursor cells and glial cells. The author has listed tables of clinical trials that have utilized MSCs from different sources, along with the years and the phase of study completed for each trial. The consensus is that these cells work on inhibiting CD4+ and CD8+ T cell activation, T regulatory cells (Tregs), and macrophage switch into the auto-immune phenotype. The best source of MSCs seems to be the UC due to the easiness of extraction, the noninvasive method of collection, their higher expansion ability and more powerful immune-modulating properties compared to other locations in the body. Studies showed there was a significant decline of mRNA expression of several cytokines after the administration of MSCs derived from the UC (UCMSCs). Other researchers were able to repair the defects of Tregs in MS patients by co-culturing Tregs from these patients with UCMSCs, which decreased the production of the pro-inflammatory cytokine IFN γ , and also suggested a strong link between Tregs lack of functionality in MS patients with the pathogenesis of the disease.
A comprehensive knowledge of human leukocyte antigen (HLA) molecular variation worldwide is essential in human population genetics research and disease association studies and is also indispensable for clinical applications such as allogeneic hematopoietic cell transplantation, where ensuring HLA compatibility between donors and recipients is paramount. Enormous progress has been made in this field thanks to several decades of HLA population studies allowing the development of helpful databases and bioinformatics tools. However, it is still difficult to appraise the global HLA population diversity in a synthetic way. We thus introduce here a novel approach, based on approximately 2000 data sets, to assess this complexity by providing a fundamental synopsis of the most frequent HLA alleles observed in different regions of the world. This new knowledge will be useful not only as a fundamental reference for basic research, but also as an efficient guide for clinicians working in the field of transplantation.
