Citations

Linking data from a case–control study of Alzheimer’s disease with data from a Minnesota Multiphasic Personality Inventory (MMPI) outpatient study, we identified 13 Alzheimer's disease cases and 16 controls for case–control comparison. The mean time between personality testing and onset of Alzheimer's disease (or corresponding age for controls) was 13 years in cases and 14 years in controls. Alzheimer's disease cases, but not the controls, had scores significantly greater than the normative reference on MMPI scales measuring Social Introversion (p = 0.05), and Pessimism (p = 0.01). When compared to controls, Alzheimer's disease cases had significantly greater scores on the Social Introversion scale (p = 0.03). Despite the small sample size and some design limitations of this exploratory study, our findings may suggest that subjects who score higher on these personality scales have a greater risk of Alzheimer's disease.

Objective IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies. Design We conducted a GWA study (GWAS) of IBS in a general population sample of 11 326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls. Results One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein), showed consistent IBS risk effects in the index GWAS and all replication cohorts and reached p=9.31×10 −6 in a meta-analysis of all datasets. Several SNPs in this region are associated with cis effects on KDELR2 expression, and a trend for increased mucosal KDLER2 mRNA expression was observed in IBS cases compared with controls. Conclusions Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations.

Abstract Tumor metastasis refers to spread of a tumor from site of its origin to distant organs and causes majority of cancer deaths. Although >30 metastasis suppressor genes (MSGs) that negatively regulate metastasis have been identified so far, two issues are poorly understood: first, which MSGs oppose metastasis in a tumor type, and second, which molecular function of MSG controls metastasis. Herein, integrative analyses of tumor-transcriptomes (n = 382), survival data (n = 530) and lymph node metastases (n = 100) in lung cancer patients identified non-metastatic 2 (NME2) as a key MSG from a pool of >30 metastasis suppressors. Subsequently, we generated a promoter-wide binding map for NME2 using chromatin immunoprecipitation with promoter microarrays (ChIP-chip), and transcriptome profiling. We discovered novel targets of NME2 which are involved in focal adhesion signaling. Importantly, we detected binding of NME2 in promoter of focal adhesion factor, vinculin. Reduced expression of NME2 led to enhanced transcription of vinculin. In comparison, NME1, a close homolog of NME2, did not bind to vinculin promoter nor regulate its expression. In line, enhanced metastasis of NME2-depleted lung cancer cells was found in zebrafish and nude mice tumor models. The metastatic potential of NME2-depleted cells was remarkably diminished upon selective RNA-i-mediated silencing of vinculin. Together, we demonstrate that reduced NME2 levels lead to transcriptional de-repression of vinculin and regulate lung cancer metastasis.

Background: Ankle arthrodesis is considered to be a well-accepted technique for end-stage ankle arthritis. Our purpose was to evaluate outcomes of patients with bilateral ankle arthrodeses with attention to radiographic and functional outcomes. Methods: Medical records of 31 patients were reviewed from 1977 through 2007. All patients had 1 year of clinical follow-up after their contralateral ankle arthrodesis, with an average follow-up of 11.2 years following the initial arthrodesis. Pertinent patient demographics and information pertaining to the operative procedure, complications, and subsequent adjacent joint fusions was collected. Radiographs were reviewed for time to fusion and adjacent joint arthritis. Functional outcomes were measured using the Foot and Ankle Ability Measure (FAAM) and the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle and Hindfoot scale. Results: Ten females and 21 males underwent bilateral ankle fusions at an average age of 57 years at the time of the initial fusion. The contralateral fusion occurred on average 3.1 years following the initial fusion. Radiographic fusion occurred 12 weeks following the initial fusion and 14 weeks following the contralateral fusion. There was a significant increase ( P = .0001) in the average AOFAS score postoperatively in both ankles. The average FAAM score at last follow-up was 70. Adjacent joint arthritis developed in the majority of patients; however, most of the patients were free from adjacent fusions and reported their function as “normal” or “nearly normal” at last follow-up. Conclusion: Bilateral ankle arthrodesis was an acceptable treatment option for patients with bilateral, end-stage ankle arthritis. Level of Evidence: Level IV, retrospective case series.

Mini‐AbstractNoncompaction cardiomyopathy is characterized by prominent ventricular trabeculations and deep intertrabecular recesses with high risk of mortality and morbidity secondary to heart failure, thromboembolic events, and malignant arrhythmias. We herein report a 19‐year‐old man with isolated noncompaction cardiomyopathy in which the echocardiography and cardiac magnetic resonance were very useful in decision making regarding his optimal management.

Purpose The role of adjuvant radiotherapy (aRT) in treating patients with pN1 prostate cancer is controversial. We tested the hypothesis that the impact of aRT on cancer-specific mortality (CSM) in these individuals is related to tumor characteristics. Methods We evaluated 1,107 patients with pN1 prostate cancer treated with radical prostatectomy and anatomically extended pelvic lymph node dissection between 1988 and 2010 at two tertiary care centers. All patients received adjuvant hormonal therapy with or without aRT. Regression tree analysis stratified patients into risk groups on the basis of their tumor characteristics and the corresponding CSM rate. Cox regression analysis tested the relationship between aRT and CSM rate, as well as overall mortality (OM) rate in each risk group separately. Results Overall, 35% of patients received aRT. At multivariable analysis, aRT was associated with more favorable CSM rate (hazard ratio [HR], 0.37; P < .001). However, when patients were stratified into risk groups, only two groups of men benefited from aRT: (1) patients with positive lymph node (PLN) count ≤ 2, Gleason score 7 to 10, pT3b/pT4 stage, or positive surgical margins (HR, 0.30; P = .002); and (2) patients with PLN count of 3 to 4 (HR, 0.21; P = .02), regardless of other tumor characteristics. These results were confirmed when OM was examined as an end point. Conclusion The beneficial impact of aRT on survival in patients with pN1 prostate cancer is highly influenced by tumor characteristics. Men with low-volume nodal disease (≤ two PLNs) in the presence of intermediate- to high-grade, non–specimen-confined disease and those with intermediate-volume nodal disease (three to four PLNs) represent the ideal candidates for aRT after surgery.

Background/Objective Between attacks, migraine is associated with hypersensitivities to sensory stimuli. The objective of this study was to investigate hypersensitivity to pain in migraineurs between attacks. Methods Cutaneous heat pain thresholds were measured in 112 migraineurs, migraine free for ≥48 hours, and 75 healthy controls. Pain thresholds at the head and at the arm were compared between migraineurs and controls using two-tailed t-tests. Among migraineurs, correlations between heat pain thresholds and headache frequency, allodynia symptom severity, and time interval until next headache were calculated. Results Migraineurs had lower pain thresholds than controls at the head (43.9℃ ± 3.2℃ vs. 45.1℃ ± 3.0℃, p = 0.015) and arm (43.2℃ ± 3.4℃ vs. 44.8℃ ± 3.3℃, p < 0.001). There were not significant correlations between pain thresholds and headache frequency or allodynia symptom severity. For the 41 migraineurs for whom time to next headache was known, there were positive correlations between time to next headache and pain thresholds at the head ( r = 0.352, p = 0.024) and arm ( r = 0.312, p = 0.047). Conclusions This study provides evidence that migraineurs have low heat pain thresholds between migraine attacks. Mechanisms underlying these lower pain thresholds could also predispose migraineurs to their next migraine attack, a hypothesis supported by finding positive correlations between pain thresholds and time to next migraine attack.