Quantifying Cognitive Reserve in Older Adults by Decomposing Episodic Memory Variance: Replication and Extension

The theory of cognitive reserve attempts to explain why some individuals are more resilient to age-related brain pathology. Efforts to explore reserve have been hindered by measurement difficulties. Reed et al. (2010) proposed quantifying reserve as residual variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes). This residual variance represents the discrepancy between an individual's predicted and actual memory performance. The goals of the present study were to extend these methods to a larger, community-based sample and to investigate whether the residual reserve variable is explained by age, predicts longitudinal changes in language, and predicts dementia conversion independent of age. Results support this operational measure of reserve. The residual reserve variable was associated with higher reading ability, lower likelihood of meeting criteria for mild cognitive impairment, lower odds of dementia conversion in dependent of age, and less decline in language abilities over 3 years. Finally, the residual reserve variable moderated the negative impact of memory variance explained by brain pathology on language decline. This method has the potential to facilitate research on the mechanisms of cognitive reserve and the efficacy of interventions designed to impart reserve

Infectious Complications in Obese Patients Following Trauma

Background Obesity is a public health concern in the United States due to its increasing prevalence, especially in younger age groups. Trauma is the most common cause of death for people under aged 40 y. The purpose of this study is to determine the association between obesity and specific infectious complications after traumatic injury. Materials and methods A retrospective analysis was conducted using data from the 2012 National Trauma Data Bank. The National Trauma Data Bank defined obesity as having a body mass index of 30 or greater. Descriptive statistics were calculated and stratified by obesity status. A hierarchical regression model was used to determine the odds of experiencing an infectious complication in patients with obesity while controlling for age, gender, diabetes, number of comorbidities, injury severity, injury mechanism, head injury, and surgical procedure. Results Patients with a body mass index of 30 or greater compared with nonobese patients had increased odds of having an infectious complication (Odds Ratio, 1.59; 1.49-1.69). In addition to obesity, injury severity score greater than 29, age 40 y or older, diabetes, comorbid conditions, and having a surgical procedure were also predictive of an infectious complication. Conclusions Our results indicate that trauma patients with obesity are nearly 60% more likely to develop an infectious complication in the hospital. Infection prevention and control measures should be implemented soon after hospital arrival for patients with obesity, particularly those with operative trauma

Reduction of Endothelial Nitric Oxide Increases the Adhesiveness of Constitutive Endothelial Membrane ICAM-1 through Src-Mediated Phosphorylation

Nitric oxide (NO) is a known anti-adhesive molecule that prevents platelet aggregation and leukocyte adhesion to endothelial cells (ECs). The mechanism has been attributed to its role in the regulation of adhesion molecules on leukocytes and the adhesive properties of platelets. Our previous study conducted in rat venules found that reduction of EC basal NO synthesis caused EC ICAM-1-mediated firm adhesion of leukocytes within 10–30min. This quick response occurred in the absence of alterations of adhesion molecules on leukocytes and also opposes the classical pattern of ICAM-1-mediated leukocyte adhesion that requires protein synthesis and occurs hours after stimulation. The objective of this study is to investigate the underlying mechanisms of reduced basal NO-induced EC-mediated rapid leukocyte adhesion observed in intact microvessels. The relative levels of ICAM-1 at different cell regions and their activation status were determined with cellular fractionation and western blot using cultured human umbilical vein ECs. ICAM-1 adhesiveness was determined by immunoprecipitation in non-denatured proteins to assess the changes in ICAM-1 binding to its inhibitory antibody, mAb1A29, and antibody against total ICAM-1 with and without NO reduction. The adhesion strength of EC ICAM-1 was assessed by atomic force microscopy (AFM) on live cells. Results showed that reduction of EC basal NO caused by the application of caveolin-1 scaffolding domain (AP-CAV) or NOS inhibitor, L-NMMA, for 30 min significantly increased phosphorylated ICAM-1 and its binding to mAb1A29 in the absence of altered ICAM-1 expression and its distribution at subcellular regions. The Src inhibitor, PP1, inhibited NO reduction-induced increases in ICAM-1 phosphorylation and adhesive binding. AFM detected significant increases in the binding force between AP-CAV-treated ECs and mAb1A29-coated probes. These results demonstrated that reduced EC basal NO lead to a rapid increase in ICAM-1 adhesive binding via Src-mediated phosphorylation without de novo protein synthesis and translocation. This study suggests that a NO-dependent conformational change of constitutive EC membrane ICAM-1 might be the mechanism of rapid ICAM-1 dependent leukocyte adhesion observed in vivo. This new mechanistic insight provides a better understanding of EC/leukocyte interaction-mediated vascular inflammation under many disease conditions that encounter reduced basal NO in the circulation system

A Case of Kratom Induced Cholestasis

Learning Objective #1: Recognize that there are many uncommon and likely unrecognized drugs including prescription, over the counter and herbal remedies that can cause cholestasis CASE: The patient is a 42 year old female with a history of polio, with no residual deficits, who presented with generalized symptoms of subjective fever, fatigue, nausea and poor appetite. She was being worked up in an outpatient setting however when her urine turned dark orange, she decided to present to the hospital. When she initially presented, she had elevated transaminases; alanine aminotransferase (ALT) 371, aspartate aminotransfer-ase (AST) 171. Her ALT increased to 606 on recheck. Other labs included total bilirubin 3.3, alkaline phosphatase 298 and INR 0.97. Ultrasound of the abdomen showed a thickened gallbladder wall without murphy\u27s sign and a normal evaluation of the liver. On initial questioning, she denied a previous history of liver disease, alcohol use, or tylenol use. Autoimmune liver panel, hepatitis and HIV screen was negative. Epstein-Barr virus and cytomegalo-virus was negative. Alpha-1-antitrypsin, iron, ceruloplasmin were within normal limits. Upon further questioning of home medications, she reported kratom use for treatment of her chronic pain secondary to her past history of polio. Her duration of use of kratom was 4 months with her last use 4 weeks prior to presentation. She was diagnosed with herbal induced cholestasis by kratom. Her jaundice improved, liver enzymes trended down and she was discharged. Her one month outpatient follow up revealed normal liver enzymes with no further reported kratom use. IMPACT/DISCUSSION: The herbal remedy kratom has been long used in traditional medicine most commonly for depression, anxiety and pain since the nineteenth century, however its impact on the liver is not well known. The mechanism by which kratom induced liver injury in this patient is unknown. The pattern of liver injury was mixed between hepatocellular and cholestatic suggesting that there might be multiple mechanisms of injury. Injury can present with generalized symptoms which can often times be mistaken for other pathologies which is why a thorough history is required to further understand and discontinue offending agents such as kratom. Although kratom was helping to alleviate pain in this patient, discontinuation was necessary to allow complete resolution of liver injury. Conclusion: This case represented short term use of kratom which induced liver injury with subsequent resolution upon discontinuation. There are many oral agents that are still not fully understood or well known which cause liver injury. With this lack of knowledge, it remains important for internists to obtain thorough historys of everything that is ingested prior to presentation. With this information, better understanding and insight can be obtained to which agents should be avoided in the general population