Twenty-seven of the 4202 identified studies were included. The quality of 15 of 27 studies was fair, and most studies were of β-lactams (12/27). Best evidence was available for meropenem four studies were included, of which two studies were of good quality. Drug exposure for meropenem is 158% to 286% higher in patients with impaired renal function receiving reduced doses compared to patients with adequate renal function receiving regular doses. For all other antibiotics, a maximum of one good-quality study could be identified.

No good-quality evidence on the recommended dose reduction of renally cleared antibiotics in patients with impaired renal function is present, with the exception of meropenem.

No good-quality evidence on the recommended dose reduction of renally cleared antibiotics in patients with impaired renal function is present, with the exception of meropenem.Gait adaptation is crucial for adults at risk for mobility disability, and executive function and physical function may be important for adaptation performance. Gait adaptation can be measured using a treadmill with two belts, known as a split-belt treadmill. Increasing evidence supports that gait adaptability, executive function, and physical function are interrelated in older adults. The purpose of this study was to determine if a) executive function and measures of relative effort of the ankle and knee relate to split-belt treadmill adaptation; b) older adults classified as fast adapters display differences in relative effort, executive function, and propulsive impulse (push-off) compared to slow adapters; and c) spatial and temporal control differ between individuals with faster rate of adaptation compared to those with slower rates of adaptation. Greater effort of the knee on the slow belt was related to faster early adaptation (r = 0.650, p = 0.005) indicating its importance for adapting quickly to the perturbation. We did not observe a relationship between cognitive tests and adaptation performance. We did not detect any statistical differences in cognitive tests performance, push-off, spatial or temporal control between fast adapters compared to slow adapters. Our results suggest that in older adults at risk for mobility disability, higher effort at the knee is important for early split-belt adaptation.Normal brain aging is accompanied by intensification of free radical processes and compromised bioenergetics. Caloric restriction is expected to counteract these changes but the underlying protective mechanisms remain poorly understood. The present work aimed to investigate the intensity of oxidative stress and energy metabolism in the cerebral cortex comparing mice of different ages as well as comparing mice given one of two regimens of food availability ad libitum versus every-other-day fasting (EODF). Levels of oxidative stress markers, ketone bodies, glycolytic intermediates, mitochondrial respiration, and activities of antioxidant and glycolytic enzymes were assessed in cortex from 6-, 12- and 18-month old C57BL/6J mice. The greatest increase in oxidative stress markers and the sharpest decline in key glycolytic enzyme activities was observed in mice upon the transition from young (6 months) to middle (12 months) age, with smaller changes occurring upon transition to old-age (18 months). Brain mitochondrial respiration showed no significant changes with age. A decrease in the activities of key glycolytic enzymes was accompanied by an increase in the activity of glucose-6-phosphate dehydrogenase suggesting that during normal brain aging glucose metabolism is altered to lower glycolytic activity and increase dependence on the pentose-phosphate pathway. Interestingly, levels of ketone bodies and antioxidant capacity showed a greater decrease in the brain cortex of females as compared with males. The EODF regimen further suppressed glycolytic enzyme activities in the cortex of old mice, and partially enhanced oxygen consumption and respiratory control in the cortex of middle aged and old males. Thus, in the mammalian cortex the major aging-induced metabolic changes are already seen in middle age and are slightly alleviated by an intermittent fasting mode of feeding.Endoplasmic reticulum (ER) stress has been linked to various metabolic pathologies, neurodegeneration and aging. Although various mechanistic aspects of the resulting unfolded protein response (UPR) have been elucidated, its regulation in genetically diverse populations remains elusive. In the present study we evaluated the expression of chaperones BiP/GRP78, GRP94 and calnexin (CANX) in the lungs, liver and brain of 7 months old and 2-3 years old outbred deer mice P. maniculatus and P. leucopus. Chaperones’ expression was highly variable between species, tissues and ages suggesting that levels of expression of individual chaperones do not change consistently during aging. Despite this variation, a high degree of coordination was maintained between chaperones’ expression indicating the tight regulation of the UPR which is consistent with its adaptive activity to maintain homeostasis. In the brain though of older P. maniculatus, at which neurodegenerative changes were detected, loss of coordination was revealed, especially between BiP and either of GRP94 or calnexin which indicates that de-coordination rather than aberrant expression is linked to deregulation of the UPR in aging. These findings underscore the involvement of UPR in the onset of aging-related pathologies and suggest that beyond levels of expression, concerted activation may be of significance to attain homeostasis. These findings emphasize the value of genetically diverse models and suggest that beyond levels of expression of individual targets the coordination of transcriptional networks should be considered when links to pathology are explored.Even though Alzheimer’s disease (AD) is the most common cause of dementia, the mechanisms governing the establishment and progression of the disease remain largely unknown. Here, we investigated the implication of the neuroprotective protein BMI1 (B lymphoma Mo-MLV insertion region 1 homolog) in AD and the possibility to reverse the onset of the disease through the administration of extra virgin olive oil (EVOO) in Mild Cognitive Impairment (MCI) patients. For this purpose, we utilized a wide bank of MCI patient samples to examine the potential effects of EVOO. We found that while EVOO treatment increases BMI1 levels, p53 levels drop in MCI patient serum after EVOO treatment for 12 months. Additionally, AD-related biomarkers (p-tau, Aβ1-42 and Aβ1-42/Aβ-40 ratio) return to normal levels after administration of EVOO in MCI patients for 12 months. BIIB129 inhibitor Moreover, we show that upon EVOO administration, BMI1-upregulation correlates with reduction of oxidative stress and inflammatory responses. In conclusion, we provide clinical trial evidence to confirm that restoration of BMI1 activity through EVOO administration in MCI patients constitutes a potential therapeutic approach against neurodegeneration leading to AD.