Genetic resilience to amyloid related cognitive decline

Preclinical Alzheimer’s disease (AD) is characterized by amyloid deposition in the absence of overt clinical impairment. There is substantial heterogeneity in the long-term clinical outcomes among amyloid positive individuals, yet limited work has focused on identifying molecular factors driving resilience from amyloid-related cognitive impairment. We apply a recently developed predicted gene expression analysis (PrediXcan) to identify genes that modify the association between baseline amyloid deposition and longitudinal cognitive changes. Participants free of clinical AD (n = 631) were selected from the AD Neuroimaging Initiative (ADNI) who had a baseline positron emission tomography measure of amyloid deposition (quantified as a standard uptake value ratio), longitudinal neuropsychological data, and genetic data. PrediXcan was used to impute gene expression levels across 15 heart and brain tissues. Mixed effect regression models assessed the interaction between predicted gene expression levels and amyloid deposition on longitudinal cognitive outcomes. The predicted gene expression levels for two genes in the coronary artery (CNTLN, PROK1) and two genes in the atrial appendage (PRSS50, PROK1) interacted with amyloid deposition on episodic memory performance. The predicted gene expression levels for two additional genes (TMC4 in the basal ganglia and HMBS in the aorta) interacted with amyloid deposition on executive function performance. Post-hoc analyses provide additional validation of the HMBS and PROK1 effects across two independent subsets of ADNI using two additional metrics of amyloid deposition. These results highlight a subset of unique candidate genes of resilience and provide evidence that cell-cycle regulation, angiogenesis, and heme biosynthesis likely play a role in AD progression.     

Painful Diabetic Neuropathy Is Associated With Greater Autonomic Dysfunction Than Painless Diabetic Neuropathy

OBJECTIVE

Although a clear link between diabetic peripheral neuropathy (DPN) and autonomic neuropathy is recognized, the relationship of autonomic neuropathy with subtypes of DPN is less clear. This study aimed to investigate the relationship of autonomic neuropathy with painless and painful DPN.

RESEARCH DESIGN AND METHODS

Eighty subjects (20 healthy volunteers, 20 with no DPN, 20 with painful DPN, 20 with painless DPN) underwent detailed neurophysiological investigations (including conventional autonomic function tests [AFTs]) and spectral analysis of short-term heart rate variability (HRV), which assesses sympathovagal modulation of the heart rate. Various frequency-domain (including low frequency [LF], high frequency [HF], and total power [TP]) and time-domain (standard deviation of all normal-to-normal R-R intervals [SDNN] and root mean square of successive differences [RMSSD]) parameters were assessed.

RESULTS

HRV analysis revealed significant differences across the groups in LF, HF, TP, SDNN, and RMSSD (ANOVA P < 0.001). Subgroup analysis showed that compared with painless DPN, painful DPN had significantly lower HF (3.59 ± 1.08 [means ± SD] vs. 2.67 ± 1.56), TP (5.73 ± 1.28 vs. 4.79 ± 1.51), and SDNN (2.91 ± 0.65 vs. 1.62 ± 3.5), P < 0.05. No significant differences were seen between painless DPN and painful DPN using an AFT.

CONCLUSIONS

This study shows that painful DPN is associated with significantly greater autonomic dysfunction than painless DPN. These changes are only detected using spectral analysis of HRV (a simple test based on a 5-min electrocardiogram recording), suggesting that it is a more sensitive tool to detect autonomic dysfunction, which is still under-detected in people with diabetes. The greater autonomic dysfunction seen in painful DPN may reflect more predominant small fiber involvement and adds to the growing evidence of its role in the pathophysiology of painful DPN.Diabetic neuropathy is one of the most frequent complications of diabetes. The prevalence of some form of neuropathy has been reported to be as high as 66% in type 1 diabetes and 59% in type 2 diabetes (1). It is the source of great distress, disability, and premature death. It is the main initiating factor for foot ulceration and the most common cause of nontraumatic lower-limb amputation in the Western world (2). It is also one of the more poorly understood complications of diabetes.Although a clear relationship between diabetic peripheral neuropathy (DPN) and cardiac autonomic neuropathy (CAN) has been recognized, the nature of the relationship of CAN with painless or painful neuropathy was less clear. Recently, there has been some evidence that at the level of the peripheral nerve, local autonomic dysfunction has an important role to play in the generation of pain (3). However, clinical studies looking to see if this translates into more generalized autonomic neuropathy have shown mixed and often opposite results (4,5). Part of the reason for this may be that all of these studies used conventional autonomic function tests (AFTs), which tend to detect autonomic dysfunction only at more advanced stages (6).Over recent years, a number of different techniques have been developed that are more sensitive measures of autonomic function and are therefore able to detect subclinical abnormalities (7). One such technique is spectral analysis of heart rate variability (HRV). Short-term HRV analysis is relatively quick and simple to carry out because it is based on a 2- to 5-min resting electrocardiogram (ECG) recording. The recording is able to detect autonomic dysfunction in subjects in whom conventional AFTs are still normal (8).The aim of this study was to determine if there are differences in autonomic function between painful and painless DPN using spectral analysis of HRV.     

Correlates of Depressive Symptoms in Urban Youth at Risk for Type 2 Diabetes Mellitus

Background:  Rates of overweight in youth have increased at an alarming rate, particularly in minority youth, and depressive symptoms may affect the ability of youth to engage in healthy lifestyle behaviors to manage weight and reduce their risk for health problems. The purpose of this study was to examine the relationships between depressive symptoms, clinical risk factors, and health behaviors and attitudes in a sample of urban youth at risk for type 2 diabetes mellitus (T2DM).
Methods:  We obtained self-report questionnaire data on depressive symptoms and health attitudes and behaviors related to diet and exercise and clinical data on risk markers (eg, fasting insulin) from 198 youth from an urban setting. Seventh-grade students were eligible if they were at risk for developing T2DM because they had a body mass index (BMI) in the 85th percentile or higher and a family history of diabetes.
Results:  Clinically significant levels of depressive symptoms were evident in approximately 21% of the sample, and Hispanic youth reported higher levels of depressive symptoms than black youth. Higher levels of depression were associated with several health behaviors and attitudes, in particular less perceived support for physical activity and poorer self-efficacy for diet. Depressive symptoms were also related to some clinical risk markers, such as higher BMI and fasting insulin levels.
Conclusions:  Because depressive symptoms may affect ability to engage in healthy behavior changes, evaluation and treatment of depressive symptoms should be considered in preventive interventions for youth at risk for T2DM.     

Rosmarinus officinalis L. essential oil inhibits in vivo and in vitro leukocyte migration

Rosmarinus officinalis L. (Lamiaceae), popularly known as rosemary, is used for food flavoring and in folk medicine as an antispasmodic, analgesic, antirheumatic, diuretic, and antiepileptic agent. Few studies have shown the anti-inflammatory effects of rosemary essential oil (REO). This study evaluated the effects of REO on leukocyte migration through in vivo leukocyte migration and in vitro chemotaxis assay. REO was analyzed by using gas chromatography-mass spectometry, and the main components identified were camphor (27.59%), 1,8-cineole (15.74%), α-pinene (16.58%), and β-myrcene (10.02%). In rats, administration of REO reduced the number of leukocytes that rolled, adhered, and migrated to the scrotal chamber after carrageenan injection. All doses of REO tested significantly inhibited leukocyte chemotaxis induced by casein. The effects of REO on leukocyte migration highlight an important mechanism of the anti-inflammatory action of rosemary.     

Effects of anesthetic regimens and other confounding factors affecting the interpretation of motor evoked potentials during pediatric spine surgery

Children undergoing corrective spine surgery are at risk of serious neurologic injury. Monitoring transcranial electric motor evoked potentials (TCeMEPs) during these procedures may identify and help prevent injury to motor pathways. The difficulty in obtaining consistent motor evoked potential (MEP) responses during pediatric spine surgery can result in part to the suppression of evoked responses caused by volatile inhalational anesthetics, elevated levels of propofol, and/or physiologic variables. Data obtained from 140 pediatric patients who underwent spine surgery with MEP monitoring were retrospectively analyzed and evaluated for age and anesthetic effects on stimulation variables. MEPs acquired under inhalational anesthetic agents required greater stimulation compared to intravenous propofol anesthesia. Additionally, the responses were more variable when inhalational agents were used. These effects were more prominent in younger age patients. The number of alerts of MEP loss or reduction related to anesthetic levels or blood pressure changes was higher under inhalational agents.     

Pulmonary metastasectomy from soft tissue sarcomas

INTRODUCTION:

Isolated pulmonary metastases from soft tissue sarcomas occur in 20-50% of these (the issue is about metastases, not lung cancer) patients, and 70% of these patients will present disease limited only to the lungs. Surgical resection is well accepted as a standard approach to treat metastases from soft tissue sarcomas isolated in the lungs, and many studies investigating this technique have reported an overall 5-year survival ranging from 30-40%. The most consistent predictor of survival in these patients is complete resection. The aim of the present study was to determine the demographics and clinical treatment-related variables associated with long-term (90-month) overall survival in patients with lung metastases undergoing pulmonary metastasectomy from soft tissue sarcomas.

METHODS:

We performed a retrospective review of patients admitted in the Thoracic Surgery Department with lung metastases who underwent thoracotomy for resection following treatment of the primary tumor. Data regarding primary tumor features, demographics, treatment, and outcome were collected.

RESULTS:

One hundred twenty-two thoracotomies and 273 nodules were resected from 77 patients with previously treated soft tissue sarcomas. The median follow-up time of all patients was 36.7 months (range: 10-138 months). The postoperative complication rate was 9.1%, and the 30-day mortality rate was 0%. The 90-month overall survival rate for all patients was 34.7%. Multivariate analysis identified the following independent prognostic factors for overall survival: the number of metastases resected, the disease-free interval, and the number of complete resections.

CONCLUSION:

These results confirm that lung metastasectomy is a safe and potentially curative procedure for patients with treated primary tumors. A select group of patients can achieve long-term survival after lung resection.