RESUMO
This review examines the role of impaired amyloid-β clearance in the accumulation of amyloid-β in the brain and the periphery, which is closely associated with Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). The molecular mechanism underlying amyloid-β accumulation is largely unknown, but recent evidence suggests that impaired amyloid-β clearance plays a critical role in its accumulation. The review provides an overview of recent research and proposes strategies for efficient amyloid-β clearance in both the brain and periphery. The clearance of amyloid-β can occur through enzymatic or non-enzymatic pathways in the brain, including neuronal and glial cells, blood-brain barrier, interstitial fluid bulk flow, perivascular drainage, and cerebrospinal fluid absorption-mediated pathways. In the periphery, various mechanisms, including peripheral organs, immunomodulation/immune cells, enzymes, amyloid-β-binding proteins, and amyloid-β-binding cells, are involved in amyloid-β clearance. Although recent findings have shed light on amyloid-β clearance in both regions, opportunities remain in areas where limited data is available. Therefore, future strategies that enhance amyloid-β clearance in the brain and/or periphery, either through central or peripheral clearance approaches or in combination, are highly encouraged. These strategies will provide new insight into the disease pathogenesis at the molecular level and explore new targets for inhibiting amyloid-β deposition, which is central to the pathogenesis of sporadic AD (amyloid-β in parenchyma) and CAA (amyloid-β in blood vessels).
RESUMO
Objective: The current study aims to explore the factors associated with outcome among patients with severe sepsis and septic shock admitted to the intensive care unit, Northwest General Hospital and Research Centre, Peshawar, Pakistan
Methods: A prospective observational study was carried out at intensive care unit of our hospital from February 2014 to October 2015. Data was collected using a structured format and statistical analysis was done using SPSS version 20®. Regression model was applied to identify the factors contributing to the outcome of severe sepsis and septic shock. P-value less than 0.05 was considered statistically significant
Results: Majority of the patients meeting the criteria of this study were male 147 [54.9%] with a mean age of 54.8. The most common source of sepsis was lung infections [42.2%] followed by urinary tract infections [18.7%], soft tissue infections [6.3%] abdominal infections [6%] and in 6.3% patients the source remained unknown. Further analysis has revealed that increase in number of days of hospitalization was observed to be slightly associated with the outcome of the treatment [1.086 [1.002 - 1.178], 0.046]. Moreover, the risk of mortality was the higher among the patients with septic shock 22.161[10.055 - 48.840], and having respiratory, kidney and central nervous system complications. Overall it is seen that septic shock alone was found responsible to cause death among 32.0% of the patients [Model 1: R2 0.32, p=0.000], and upon involvement of the organ complications the risk of mortality was observed to 42.0%
Conclusion: Chances of recovery were poor among the patients with septic shock. Moreover, those patients having respiratory and urinary tract infection are least likely to survive