Articles: function.
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Sensory systems in the peripheral and central nervous systems shape host response during infections.
The function of sensory cells has been largely investigated in the field of neuroscience for how they report the physical and chemical changes of the environment ("exteroception") and of internal physiology ("interoception"). Investigations over the last century have largely focused on the morphological, electrical and receptor properties of sensory cells in the nervous system focusing on conscious perception of external cues or homeostatic regulation upon detection of internal cues. ⋯ The corresponding neuronal activation associated with the presence of pathogens can impact their classical functions within the nervous system and trigger the release of compounds modulating the response to intruders, either triggering pain to raise awareness, enhancing host defense or sometimes, aggravating the infection. This perspective brings to light the need for interdisciplinary training in immunology, microbiology and neuroscience for the next generation of investigators in this field.
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Increasing evidence links genetic defects affecting actin-regulatory proteins to diseases with severe autoimmunity and autoinflammation, yet the underlying molecular mechanisms are poorly understood. Dedicator of cytokinesis 11 (DOCK11) activates the small Rho guanosine triphosphatase (GTPase) cell division cycle 42 (CDC42), a central regulator of actin cytoskeleton dynamics. The role of DOCK11 in human immune-cell function and disease remains unknown. ⋯ Germline hemizygous loss-of-function mutations affecting the actin regulator DOCK11 were shown to cause a previously unknown inborn error of hematopoiesis and immunity characterized by severe immune dysregulation and systemic inflammation, recurrent infections, and anemia. (Funded by the European Research Council and others.).
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Cochrane Db Syst Rev · Aug 2023
ReviewInterventions for chronic kidney disease in people with sickle cell disease.
Sickle cell disease (SCD), one of the commonest severe monogenic disorders, is caused by the inheritance of two abnormal haemoglobin (beta-globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Kidney disease is a frequent and potentially severe complication in people with SCD. Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function present for more than three months. Sickle cell nephropathy refers to the spectrum of kidney complications in SCD. Glomerular damage is a cause of microalbuminuria and can develop at an early age in children with SCD, with increased prevalence in adulthood. In people with sickle cell nephropathy, outcomes are poor as a result of the progression to proteinuria and chronic kidney insufficiency. Up to 12% of people who develop sickle cell nephropathy will develop end-stage renal disease. This is an update of a review first published in 2017. ⋯ We are unsure if hydroxyurea improves glomerular filtration rate or reduces hyperfiltration in children aged nine to 18 months, but it may improve their ability to concentrate urine and may make little or no difference to the incidence of acute chest syndrome, painful crises, and hospitalisations. We are unsure if ACEI compared to placebo has any effect on preventing or reducing kidney complications in adults with normal blood pressure and microalbuminuria. We are unsure if ACEI compared to vitamin C has any effect on preventing or reducing kidney complications in children with normal blood pressure and microalbuminuria. No RCTs assessed red blood cell transfusions or any combined interventions to prevent or reduce kidney complications. Due to lack of evidence, we cannot comment on the management of children aged over 18 months or adults with any known genotype of SCD. We have identified a lack of adequately designed and powered studies, although we found four ongoing trials since the last version of this review. Only one ongoing trial addresses renal function as a primary outcome in the short term, but such interventions have long-term effects. Trials of hydroxyurea, ACEIs or red blood cell transfusion in older children and adults are urgently needed to determine any effect on prevention or reduction of kidney complications in people with SCD.
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Prostaglandins are naturally occurring lipids that are synthesised from arachidonic acid. Multiple studies have evaluated the benefits of prostaglandins in reducing ischaemia reperfusion injury after liver transplantation. New studies have been published since the previous review, and hence it was important to update the evidence for this intervention. ⋯ Eleven trials evaluated prostaglandins in adult liver transplanted recipients. Based on low-certainty evidence, prostaglandins may reduce all-cause mortality up to one month; may cause little to no difference in serious adverse events, liver retransplantation, early allograft dysfunction, primary non-function of the allograft, and length of hospital stay; and may have a large reduction in the development of acute kidney injury requiring dialysis. We do not know the effect of prostaglandins on adverse events considered non-serious. We lack adequately powered, high-quality trials evaluating the effects of prostaglandins for people undergoing liver transplantation.
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Evidence-based treatments for chronic low back pain (cLBP) typically work well in only a fraction of patients, and at present there is little guidance regarding what treatment should be used in which patients. Our central hypothesis is that an interventional response phenotyping study can identify individuals with different underlying mechanisms for their pain who thus respond differentially to evidence-based treatments for cLBP. Thus, we will conduct a randomized controlled Sequential, Multiple Assessment, Randomized Trial (SMART) design study in cLBP with the following three aims. ⋯ In Aim 2, we will show that currently available, clinically derived measures, can predict differential responsiveness to the treatments. In Aim 3, a subset of participants will receive deeper phenotyping (n = 160), to identify new experimental measures that predict differential responsiveness to the treatments, as well as to infer mechanisms of action. Deep phenotyping will include functional neuroimaging, quantitative sensory testing, measures of inflammation, and measures of autonomic tone.