Microglia, the resident macrophages of the central nervous system, rapidly activate in nearly all kinds of neurological diseases. These activated microglia become highly motile, secreting inflammatory cytokines, migrating to the lesion area, and phagocytosing cell debris or damaged neurons. During the past decades, the secretory property and chemotaxis of microglia have been well-studied, while relatively less attention has been paid to microglial phagocytosis. So far there is no obvious concordance with whether it is beneficial or detrimental in tissue repair. This review focuses on phagocytic phenotype of microglia in neurological diseases such as Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, traumatic brain injury, ischemic and other brain diseases. Microglial morphological characteristics, involved receptors and signaling pathways, distribution variation along with time and space changes, and environmental factors that affecting phagocytic function in each disease are reviewed. Moreover, a comparison of contributions between macrophages from peripheral circulation and the resident microglia to these pathogenic processes will also be discussed.

We have examined the trafficking and metabolism of the beta-amyloid precursor protein (APP), an APP homolog (APLP1), and TrkB in neurons that lack PS1. We report that PS1-deficient neurons fail to secrete Abeta, and that the rate of appearance of soluble APP derivatives in the conditioned medium is increased. Remarkably, carboxyl-terminal fragments (CTFs) derived from APP and APLP1 accumulate in PS1-deficient neurons. Hence, PS1 plays a role in promoting intramembrane cleavage and/or degradation of membrane-bound CTFs. Moreover, the maturation of TrkB and BDNF-inducible TrkB autophosphorylation is severely compromised in neurons lacking PS1. We conclude that PS1 plays an essential role in modulating trafficking and metabolism of a selected set of membrane and secretory proteins in neurons.

Uric acid is the product of purine metabolism. It is known that hyperuricemia, defined as high levels of blood uric acid, is the major etiological factor of gout. A number of epidemiological reports have increasingly linked hyperuricemia with cardiovascular and neurological diseases. Studies highlighting the pathogenic mechanisms of uric acid point to an inflammatory response as the primary mechanism for inducing gout and possibly contributing to uric acid's vascular effects. Monosodium urate (MSU) crystals induce an inflammatory reaction, which are recognized by Toll-like receptors (TLRs). These TLRs then activate NALP3 inflammasome. MSU also triggers neutrophil activation and further produces immune mediators, which lead to a proinflammatory response. In addition, soluble uric acid can also mediate the generation of free radicals and function as a pro-oxidant. This review summarizes the epidemiological studies of hyperuricemia and cardiovascular disease, takes a brief look at hyperuricemia and its role in neurological diseases, and highlights the studies of the advanced pathological mechanisms of uric acid and inflammation.

Survivors of severe acute kidney injury remain at high risk of death well after apparent recovery from the initial insult. Here we determine whether early nephrology follow-up after a hospitalization complicated by severe acute kidney injury associates with patient survival. This consisted of a cohort study of all hospitalized adults in Ontario from 1996 to 2008 with acute kidney injury who received temporary inpatient dialysis and survived for 90 days following discharge independent from dialysis. Propensity scores were used to match individuals with early nephrology follow-up, defined as a visit with a nephrologist within 90 days of discharge, to those without. The outcome was time to all-cause mortality of 3877 patients who met the eligibility criteria within a maximum follow-up of 2 years. A total of 1583 patients had early nephrology follow-up of whom 1184 were successfully matched 1:1 to those not receiving early follow-up. The incidence of all-cause mortality was lower in those patients with early nephrology follow-up compared with those without (8.4 compared with 10.6 per 100-patient years, hazard ratio 0.76 (95% CI: 0.62-0.93)). Thus, early nephrology follow-up after hospitalization with acute kidney injury and temporary dialysis was associated with improved survival. This finding requires definitive testing in a randomized controlled trial.

Irisin is a recently identified myokine secreted from the muscle in response to exercise. In the rats and mice, immunohistochemical studies with an antiserum against irisin peptide fragment (42–112), revealed that irisin-immunoreactivity (irIRN) was detected in three types of cells; namely, skeletal muscle cells, cardiomyocytes, and Purkinje cells of the cerebellum. Tissue sections processed with irisin antiserum pre-absorbed with the irisin peptide(42–112) (1 μg/ml) showed no immunoreactivity. Cerebellar Purkinje cells were also immunolabeled with an antiserum against fibronectin type II domain containing 5 (FNDC5), the precursor protein of irisin. Double-labeling of cerebellar sections with irisin antiserum and glutamate decarboxylase (GAD) antibody showed that nearly all irIRN Purkinje cells were GAD-positive. Injection of the fluorescence tracer Fluorogold into the vestibular nucleus of the rat medulla retrogradely labeled a population of Purkinje cells, some of which were also irIRN. Our results provide the first evidence of expression of irIRN in the rodent skeletal and cardiac muscle, and in the brain where it is present in GAD-positive Purkinje cells of the cerebellum. Our findings together with reports by others led us to hypothesize a novel neural pathway, which originates from cerebellum Purkinje cells, via several intermediary synapses in the medulla and spinal cord, and regulates adipocyte metabolism.

Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. It has a physiologic role in DNA metabolism via methylation, a process governed by the presentation of folate, and vitamins B6 and B12. Physiologic Hcy levels are determined primarily by dietary intake and vitamin status. Elevated plasma levels of Hcy (eHcy) can be caused by deficiency of either vitamin B12 or folate, or a combination thereof. Certain genetic factors also cause eHcy, such as C667T substitution of the gene encoding methylenetetrahydrofolate reductase. eHcy has been observed in several medical conditions, such as cardiovascular disorders, atherosclerosis, myocardial infarction, stroke, minimal cognitive impairment, dementia, Parkinson's disease, multiple sclerosis, epilepsy, and eclampsia. There is evidence from laboratory and clinical studies that Hcy, and especially eHcy, exerts direct toxic effects on both the vascular and nervous systems. This article provides a review of the current literature on the possible roles of eHcy relevant to various neurologic disorders.

Research CMAJBackground: Acute kidney injury is a serious complication of elective major surgery. Acute dialysis is used to support life in the most severe cases. We examined whether rates and outcomes of acute dialysis after elective major surgery have changed over time. Methods:We used data from Ontario's universal health care databases to study all consecutive patients who had elective major surgery at 118 hospitals between 1995 and 2009. Our primary outcomes were acute dialysis within 14 days of surgery, death within 90 days of surgery and chronic dialysis for patients who did not recover kidney function.Results: A total of 552 672 patients underwent elective major surgery during the study period, 2231 of whom received acute dialysis. The incidence of acute dialysis increased steadily from 0.2% in 1995 (95% confidence interval [CI] 0.15-0.2) to 0.6% in 2009 (95% CI 0.6-0.7). This increase was primarily in cardiac and vascular surgeries. Among patients who received acute dialysis, 937 died within 90 days of surgery (42.0%, 95% CI 40.0-44.1), with no change in 90-day survival over time. Among the 1294 patients who received acute dialysis and survived beyond 90 days, 352 required chronic dialysis (27.2%, 95% CI 24.8-29.7), with no change over time.Interpretation: The use of acute dialysis after cardiac and vascular surgery has increased substantially since 1995. Studies focusing on interventions to better prevent and treat perioperative acute kidney injury are needed. Abstract

The anterolateral thigh flap based on the descending branch of the lateral circumflex femoral vessel is one of the musculocutaneous or septocutaneous flaps in the thigh. The descending branch of the lateral circumflex femoral vessel has either perforating branches or direct cutaneous branches from the intermuscular space to the anterolateral femoral skin. Since 1983, we have transferred 168 anterolateral thigh flaps for reconstruction of old burn scars, infected wounds, carcinoma excisions, for coverage of open bone fracture of the lower leg, and for congenital diseases. One hundred fifty-two cases were free flaps. The other 16 cases were pedicled flaps. The skin branches were divided into four types in our clinical series: musculocutaneous perforators (135/168 [80.4%]); intermuscular cutaneous perforators (16/168 [9.5%]); direct cutaneous branches (14/168 [8.3%]); and tiny cutaneous perforators (3/168 [1.8%]). The results were satisfactory. Only one case resulted in a failure due to tiny cutaneous branches.