Receptor for advanced glycation endproduct modulators: a new therapeutic target in Alzheimer’s disease

Introduction: Reduction in the deposition of amyloid β (Aβ) has been the primary target for Alzheimer’s disease (AD) therapeutics recently, but in clinical trials this approach has generally been unsuccessful. A common feature of AD pathology is a complex inflammatory component that could be a target for treatment. One feature of this inflammation has been the involvement of the receptor for advanced glycation endproducts (RAGE), whose ligands include advanced glycation-endproduct-modified proteins as well as lipids and Aβ, which are found at elevated levels in AD brains.

Areas covered: In this article, the authors describe the key features of RAGE and how it could have a role in AD pathogenesis. They also summarize experimental animal and clinical data that demonstrate the therapeutic effect of RAGE inhibition and consider what these findings mean for human disease.

Expert opinion: RAGE has multiple ligands, including Aβ, that are increased in AD brains. Inhibiting RAGE-ligand interactions without activating receptor signaling can reduce multiple pathological pathways relevant for AD. Several RAGE inhibitors and modulators are now being tested as therapeutics for AD. Recent Phase II studies have established the good safety and tolerability of TTP448 with some evidence of positive benefit at lower dose. This suggests that further studies are required.     

Diagnosing Small Intestinal Bacterial Overgrowth: A Comparison of Lactulose Breath Tests to Small Bowel Aspirates

Background

Duodenal aspiration (DA) and lactulose breath tests (LBT) are commonly performed to diagnose small intestinal bacterial overgrowth (SIBO). There are no data directly comparing these tests.

Aims

To investigate the agreement between DA and LBT for the diagnosis of SIBO.

Methods

A retrospective cohort study of adult patients who underwent a LBT and a DA at a tertiary care center over 9 years was assembled. LBT was considered positive if the hydrogen baseline or peak change measurement was ≥?20 ppm, and/or if the methane baseline or peak change was ≥?10 ppm. DA was considered positive if >?100,000 cfu/mL of gram-negative flora was identified on culture, and contaminated if >?100,000 cfu/mL of gram-positive flora was identified.

Results

A total of 106 patients were evaluated; 81 (76.4%) were female; the mean age was 53.4?±?15.9 years. 21 patients (19.8%) had evidence of contamination on DA. 14 (16.5%) patients had a positive DA result. Patients with diabetes mellitus and those with PPI use were more likely to have a positive DA (94.4% vs. 71.4%, p?=?0.007; 62% vs. 28.6%, p?=?0.021, respectively). 33 (31.1%) patients had a positive LBT. Patients with a history of small bowel resection were more likely to have a positive LBT (12.1% vs. 1.4%, p?=?0.016). DA and LBT results agreed in 54 patients (63.5%; kappa?=???0.02), indicating poor agreement.

Conclusions

The agreement between LBT and DA in evaluation for SIBO was poor. LBT may be favorable to DA, as LBT is safer, cheaper, and less likely to yield a contaminant result.

     

Urinary Symptoms and Bladder Voiding Dysfunction Are Common in Young Men with Defecatory Disorders: A Retrospective Evaluation

Digestive Diseases and Sciences - Lower urinary tract symptoms (LUTS) are frequently reported by constipated patients. Prospective studies investigating the association between defecatory disorders...     

Sleep and moral awareness

The implications of sleep for morality are only starting to be explored. Extending the ethics literature, we contend that because bringing morality to conscious attention requires effort, a lack of sleep leads to low moral awareness. We test this prediction with three studies. A laboratory study with a manipulation of sleep across 90 participants judging a scenario for moral content indicates that a lack of sleep leads to low moral awareness. An archival study of Google Trends data across 6 years highlights a national dip in Web searches for moral topics (but not other topics) on the Monday after the Spring time change, which tends to deprive people of sleep. Finally, a diary study of 127 participants indicates that (within participants) nights with a lack of sleep are associated with low moral awareness the next day. Together, these three studies suggest that a lack of sleep leaves people less morally aware, with important implications for the recognition of morality in others.