Lifetime and baseline alcohol intake and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition (EPIC)

Alcohol consumption may be associated with risk of colorectal cancer (CRC), but the epidemiological evidence for an association with specific anatomical subsites, types of alcoholic beverages and current vs. lifetime alcohol intake is inconsistent. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 478,732 study subjects free of cancer at enrolment between 1992 and 2000 were followed up for an average of 6.2 years, during which 1,833 CRC cases were observed. Detailed information on consumption of alcoholic beverages at baseline (all cases) and during lifetime (1,447 CRC cases, 69% of the cohort) was collected from questionnaires. Cox proportional hazard models were used to examine the alcohol-CRC association. After adjustment for potential confounding factors, lifetime alcohol intake was significantly positively associated to CRC risk (hazard ratio, HR=1.08, 95%CI=1.04-1.12 for 15 g/day increase), with higher cancer risks observed in the rectum (HR=1.12, 95%CI=1.06-1.18) than distal colon (HR=1.08, 95%CI=1.01-1.16), and proximal colon (HR=1.02, 95%CI=0.92-1.12). Similar results were observed for baseline alcohol intake. When assessed by alcoholic beverages at baseline, the CRC risk for beer (HR=1.38, 95%CI=1.08-1.77 for 20-39.9 vs. 0.1-2.9 g/day) was higher than wine (HR=1.21, 95%CI=1.02-1.44), although the two risk estimates were not significantly different from each other. Higher HRs for baseline alcohol were observed for low levels of folate intake (1.13, 95%CI=1.06-1.20 for 15 g/day increase) compared to high folate intake (1.03, 95%CI=0.98-1.09). In this large European cohort, both lifetime and baseline alcohol consumption increase colon and rectum cancer risk, with more apparent risk increases for alcohol intakes greater than 30 g/day.     

Imaging of amyloid beta in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism

BACKGROUND: Amyloid-beta (Abeta) plaque formation is a hallmark of Alzheimer's disease (AD) and precedes the onset of dementia. Abeta imaging should allow earlier diagnosis, but clinical application is hindered by the short decay half-life of current Abeta-specific ligands. (18)F-BAY94-9172 is an Abeta ligand that, due to the half-life of (18)F, is suitable for clinical use. We thus studied the effectiveness of this ligand in identifying patients with AD. METHODS: 15 patients with mild AD, 15 healthy elderly controls, and five individuals with frontotemporal lobar degeneration (FTLD) were studied. (18)F-BAY94-9172 binding was quantified by use of the standardised uptake value ratio (SUVR), which was calculated for the neocortex by use of the cerebellum as reference region. SUVR images were visually rated as normal or AD. FINDINGS: (18)F-BAY94-9172 binding matched the reported post-mortem distribution of Abeta plaques. All AD patients showed widespread neocortical binding, which was greater in the precuneus/posterior cingulate and frontal cortex than in the lateral temporal and parietal cortex. There was relative sparing of sensorimotor, occipital, and medial temporal cortex. Healthy controls and FTLD patients showed only white-matter binding, although three controls and one FTLD patient had mild uptake in frontal and precuneus cortex. At 90-120 min after injection, higher neocortical SUVR was observed in AD patients (2.0 [SD 0.3]) than in healthy controls (1.3 [SD 0.2]; p<0.0001) or FTLD patients (1.2 [SD 0.2]; p=0.009). Visual interpretation was 100% sensitive and 90% specific for detection of AD. INTERPRETATION: (18)F-BAY94-9172 PET discriminates between AD and FTLD or healthy controls and might facilitate integration of Abeta imaging into clinical practice.     

Further studies on the interaction of the 5-hydroxytryptamine3 (5-HT3) receptor with arylpiperazine ligands. development of a new 5-HT3 receptor ligand showing potent acetylcholinesterase inhibitory properties

Novel arylpiperazine derivatives bearing lipophilic probes were designed, synthesized, and evaluated for their potential ability to interact with the 5-hydroxytryptamine(3) (5-HT(3)) receptor. Most of the new compounds show subnanomolar 5-HT(3) receptor affinity. Ester 6bc showing a picomolar K(i) value is one of the most potent 5-HT(3) receptor ligands so far synthesized. The structure-affinity relationship study suggests the existence of a certain degree of conformational freedom of the amino acid residues interacting with the substituents in positions 3 and 4 of the quipazine quinoline nucleus. Thus, the tacrine-related heterobivalent ligand 6o was designed in an attempt to capitalize on the evidence of such a steric tolerance. Compound 6o shows a nanomolar potency for both the 5-HT(3) receptor and the human AChE and represents the first example of a rationally designed high-affinity 5-HT(3) receptor ligand showing nanomolar AChE inhibitory activity. Finally, the computational analysis performed on compound 6o allowed the rationalization of the structure-energy determinants for AChE versus BuChE selectivity and revealed the existence of a subsite at the boundary of the 5-HT(3) receptor extracellular domain, which could represent a "peripheral" site similar to that evidenced in the AChE gorge.     

Anatomy of hierarchy: Feedforward and feedback pathways in macaque visual cortex

The laminar location of the cell bodies and terminals of interareal connections determines the hierarchical structural organization of the cortex and has been intensively studied. However, we still have only a rudimentary understanding of the connectional principles of feedforward (FF) and feedback (FB) pathways. Quantitative analysis of retrograde tracers was used to extend the notion that the laminar distribution of neurons interconnecting visual areas provides an index of hierarchical distance (percentage of supragranular labeled neurons [SLN]). We show that: 1) SLN values constrain models of cortical hierarchy, revealing previously unsuspected areal relations; 2) SLN reflects the operation of a combinatorial distance rule acting differentially on sets of connections between areas; 3) Supragranular layers contain highly segregated bottom‐up and top‐down streams, both of which exhibit point‐to‐point connectivity. This contrasts with the infragranular layers, which contain diffuse bottom‐up and top‐down streams; 4) Cell filling of the parent neurons of FF and FB pathways provides further evidence of compartmentalization; 5) FF pathways have higher weights, cross fewer hierarchical levels, and are less numerous than FB pathways. Taken together, the present results suggest that cortical hierarchies are built from supra‐ and infragranular counterstreams. This compartmentalized dual counterstream organization allows point‐to‐point connectivity in both bottom‐up and top‐down directions. J. Comp. Neurol. 522:225–259, 2014. © 2013 Wiley Periodicals, Inc.     

The history of pituitary dysfunction after traumatic brain injury

Pituitary - To estimate the total number of articles on traumatic brain injury (TBI)-related hypopituitarism and patients (including children and adolescents) with such disorder that were published...     

Cardiac damage due to nonpenetrating trauma. Report of four cases

Four examples of cardiac damage secondary to nonpenetrating trauma in road accidents are described. Two patients had interventricular septal defect and other two had tricuspid insufficiency. In all four cases the lesion was not recognized at the time of the accident but became clinically important later. The time interval between trauma and surgery was one month to thirteen years. After surgical treatment, all four patients have continued to be asymptomatic.     

Quantitative comparison of technetium-99m tetrofosmin and thallium-201 images of the thyroid and abnormal parathyroid glands

The aim of the study was to quantitatively compare the scintigraphic images of the thyroid and abnormal parathyroid glands obtained with technetium-99m tetrofosmin and thallium-201 in patients with hyperparathyroidism. Forty-six patients with hyperparathyroidism underwent ²⁰¹Tl (74 MBq), ^99mTc-pertechnetate (74 MBq) and ^99mTc-tetrofosmin (555–740 MBq) scintigraphy in a single session. Image analysis included the computation of the thyroid/background ratio in the whole study population and the parathyroid/background ratio, parathyroid/thyroid ratio and diagnostic sensitivity in 17 patients who underwent parathyroid surgery. The pertechnetate subtraction technique was used. ²⁰¹Tl and ^99mTc-tetrofosmin showed a similar thyroid/background ratio (1.79±0.41 and 1.81±0.47, respectively, P=NS); however, ^99mTc-tetrofosmin showed a higher parathyroid/background ratio than ²⁰¹Tl (2.06±0.54 vs 1.79± 0.50, P=0.007). Despite the superior quality of ^99mTc-tetrofosmin images, both tracers showed identical sensitivity in detecting enlarged parathyroid glands in patients with primary hyperparathyroidism (89%) and in those with secondary hyperparathyroidism (50%).     

Intra-articular fate of degradable poly(ethyleneglycol)-hydrogel microspheres as carriers for sustained drug delivery

A novel degradable microsphere (MS) for intra-articular drug delivery, composed of a polyethylene glycol (PEG) core containing degradable regions made of short poly-(lactic-co-glycolic acid) (PLGA) sequences – named PEG-hydrogel MS – was injected into the cavity of sheep shoulder joint, and compared to non-degradable MS devoid of hydrolysable crosslinker in terms of location, degradation and inflammation. One week after intra-articular injection both groups of MS were localized beneath the synovial lining of the synovial fringes located at bottom of the shoulder joint, while a fraction of particles remained in synovial fluid. Histological analyses made one and 4 weeks after intra-articular injection showed cell proliferation around the non-degradable MS entrapped within the synovium. By contrast, degradable PEG-hydrogel MS were surrounded by few cells. The degradation of degradable PEG-hydrogel MS within the synovium was slow and was not fully complete after four weeks. Our findings indicate that the tissue entrapment of MS below the synovial lining was independent of the material degradability, while degradable PEG-hydrogel MS are less inflammatory than the non-degradable one. Degradable PEG-hydrogel MS offer several advantages over the non-degradable MS as carriers for a sustained drug delivery in synovial tissue according to the low intensity of inflammatory reaction triggered in synovium.     

The role of attitudes in understanding disparities in adult influenza vaccination

BACKGROUND: Racial/ethnic disparities in influenza vaccine coverage of adults aged 65 years and older persist even after controlling for access, healthcare utilization, and socioeconomic status. Differences in attitudes toward vaccination may help explain these disparities. The purpose of this study was to describe patient characteristics and attitudes toward influenza vaccination among whites and African Americans aged 65 years and older, and to examine their effect on racial disparities in vaccination coverage. METHODS: A cross-sectional telephone survey of Medicare beneficiaries in five U.S. sites, sampled on race/ethnicity and ZIP code. Multivariate analysis controlling for demographics, healthcare utilization, and attitudes toward influenza vaccination was conducted in 2005 to assess racial disparities in vaccine coverage during the 2003-2004 season. RESULTS: The analysis included 1859 white and 1685 African-American respondents; 79% of whites versus 50% of African Americans reported influenza vaccination in the past year (p < 0.00001). Both vaccinated and unvaccinated African Americans were significantly less likely than whites to report positive attitudes toward influenza vaccination. Even among respondents with provider recommendations, respondents with positive attitudes were more likely to be vaccinated than those with negative attitudes. After multivariate adjustment, African Americans had significantly lower odds of influenza vaccination than whites (odds ratio = 0.55, 95% confidence interval = 0.42-0.72). CONCLUSIONS: A significant gap in vaccination coverage between African Americans and whites persisted even after controlling for specific respondent attitudes. Future research should focus on other factors such as vaccine-seeking behavior.     

Laparoscopic, minilaparoscopic and single-port hysterectomy: perioperative outcomes

Objective

This study was designed to compare perioperative outcomes and postoperative pain of standard laparoscopic (S-LPS), minilaparoscopic (M-LPS), and laparoendoscopic single-site (LESS) hysterectomy.

Methods

A single-institutional, matched, retrospective, cohort study was performed. Between May 2010 and March 2011, 85 consecutive women were submitted to a total laparoscopic hysterectomy by S-LPS, M-LPS, and single-port LESS. Perioperative outcomes of these three techniques were analyzed and compared.

Results

Demographics and baseline characteristics of each group were absolutely comparable. The median operative time was longer [105 (range, 75?C125) min] in the LESS group compared with the M-LPS group [90 (range, 60?C120) min; p?<?0.011] and S-LPS [80 (range, 50?C110) min; p?<?0.001]. No statistically significant differences have been reported for estimated blood loss or intra- and early postoperative complications. Postoperative pain control was better for LESS and M-LPS than S-LPS.

Conclusions

M-LPS and LESS hysterectomy can be performed safely, and both seem to be associated with a halving of early postoperative pain with a lower request of analgesics.