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The present study examines treatment length and timing of exposure from two child anxiety disorders clinics. Data regarding symptoms and treatment characteristics for 28 youth were prospectively obtained through self, parent, and therapist report at each session. Information regarding length of treatment, timing of exposure initiation, and drop-out rates were compared with those obtained through efficacy and effectiveness trials of manualized treatment for anxious youth. Findings from the authors’ clinical data revealed significantly shorter treatment duration with exposures implemented sooner than in the previous studies. Dropout rates were significantly higher than in the efficacy trial but comparable with the effectiveness trial. Outcome data from a subset of eight patients revealed large effect sizes. These findings suggest that effective treatment can be shorter and more focused on exposure than is often outlined in manuals and have important implications for outcome research and dissemination.

Exendin-(9,39) is a competitive antagonist of glucagon-like peptide-1 (GLP-1) at its receptor. However, it is unclear if it has direct and unique effects of its own. We tested the hypothesis that exendin-(9,39) and GLP-1-(9,36)amide have direct effects on hormone secretion and β-cell function as well as glucose metabolism in healthy subjects. Glucose containing [3-3H]glucose was infused to mimic the systemic appearance of glucose after a meal. Saline, GLP-1-(9,36)amide, or exendin-(9,39) at 30 pmol/kg/min (Ex 30) or 300 pmol/kg/min (Ex 300) were infused in random order on separate days. Integrated glucose concentrations were slightly but significantly increased by exendin-(9,39) (365 ± 43 vs. 383 ± 35 vs. 492 ± 49 vs. 337 ± 50 mmol per 6 h, saline, Ex 30, Ex 300, and GLP-1-[9,36]amide, respectively; P = 0.05). Insulin secretion did not differ among groups. However, insulin action was lowered by exendin-(9,39) (25 ± 4 vs. 20 ± 4 vs. 18 ± 3 vs. 21 ± 4 10−4 dL/kg[min per μU/mL]; P = 0.02), resulting in a lower disposition index (DI) during exendin-(9,39) infusion (1,118 ± 118 vs. 816 ± 83 vs. 725 ± 127 vs. 955 ± 166 10−14 dL/kg/min2 per pmol/L; P = 0.003). Endogenous glucose production and glucose disappearance did not differ significantly among groups. We conclude that exendin-(9,39), but not GLP-1-(9,36)amide, decreases insulin action and DI in healthy humans.

Purpose By using data from North Central Cancer Treatment Group Phase III Trial N0147, a randomized adjuvant trial of patients with stage III colon cancer, we assessed the relationship between smoking and cancer outcomes, disease-free survival (DFS), and time to recurrence (TTR), accounting for heterogeneity by patient and tumor characteristics. Patients and Methods Before random assignment to infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or FOLFOX plus cetuximab, 1,968 participants completed a questionnaire on smoking history and other risk factors. Cox models assessed the association between smoking history and the primary trial outcome of DFS (ie, time to recurrence or death), as well as TTR, adjusting for other clinical and patient factors. The median follow-up was 3.5 years among patients who did not experience events. Results Compared with never-smokers, ever smokers experienced significantly shorter DFS (3-year DFS proportion: 70% v 74%; hazard ratio [HR], 1.21; 95% CI, 1.02 to 1.42). This association persisted after multivariate adjustment (HR, 1.23; 95% CI, 1.02 to 1.49). There was significant interaction in this association by BRAF mutation status (P = .03): smoking was associated with shorter DFS in patients with BRAF wild-type (HR, 1.36; 95% CI, 1.11 to 1.66) but not BRAF mutated (HR, 0.80; 95% CI, 0.50 to 1.29) colon cancer. Smoking was more strongly associated with poorer DFS in those with KRAS mutated versus KRAS wild-type colon cancer (HR, 1.50 [95% CI, 1.12 to 2.00] v HR, 1.09 [95% CI, 0.85 to 1.39]), although interaction by KRAS mutation status was not statistically significant (P = .07). Associations were comparable in analyses of TTR. Conclusion Overall, smoking was significantly associated with shorter DFS and TTR in patients with colon cancer. These adverse relationships were most evident in patients with BRAF wild-type or KRAS mutated colon cancer.

Drug modulation of ion channels is a powerful means to alter physiological responses for therapeutic benefit, yet the structural bases of modulation remain poorly understood. Here we study potentiation of nicotinic α7 acetylcholine receptors, which are emerging drug targets in several neurological disorders. α7 receptors are ligand-gated ion channels composed of five identical subunits, each bearing a site for the potentiating drug PNU-120596 (PNU). How the individual subunits contribute to PNU potentiation is not known. Taking advantage of a PNU-resistant mutant, we generated receptors composed of normal and PNU-resistant subunits and tagged one of the subunits with conductance mutations to report subunit stoichiometry. We then used patch clamp recording to monitor PNU potentiation of single α7 receptors with defined stoichiometry in real time. We find that potentiation depends steeply on the number of PNU-resistant subunits and that four, and possibly five, subunits must be sensitive to PNU for potentiation to occur. Thus, by monitoring the activity of every possible subunit combination, our findings predict that at the macroscopic level, PNU potentiation is highly cooperative.

The objective of this study was to identify the relationship between lambda waves (LWs) and other occipital waveforms, in a retrospective analysis of electroencephalograms (EEGs) of clinic and hospitalized patients at a single center. The LWs were correlated with α rhythm, photic driving, and positive occipital sharp transients of sleep (POSTS). A computer-generated cursor quantified amplitude and duration of POSTS and LWs (3 waveforms and both hemispheres). Fisher exact test was used for significance ( P ≤ .05). A total of 116 patients were evaluated. Of 111 patients, with interpretable results, 74 (66.67%) had visual scanning during EEG, with 37 (50.0%) having LWs. The LWs (17.69 µV) were consistently smaller than POSTS (31.40 µV) despite similar morphology. Patients with an α rhythm of >8.5 Hz were strongly correlated with the presence of LWs ( P < .0001), and those with LWs were strongly predictive of normal EEG ( P = .001). Of the 37 patients, 27 (73.0%) with LWs had photic driving ( P = .0496). No correlation was found between LWs and POSTS ( P = .45). The presence of LWs and a low normal posterior dominant rhythm (PDR) suggests intact electrocerebral health. LWs and the photic driving response suggest similar generators but stimulus-specific networks. POSTS differ from LWs despite similar morphology, suggesting different network activation of occipital generators. LWs have clinical significance in excluding encephalopathy. Occipital generators are differentiated by state and stimulus-dependent network activation and not by location and morphology.

ObjectiveTo study left ventricular (LV) geometry in patients with rheumatoid arthritis (RA) and no history of heart failure compared with that in subjects with neither RA nor a history of heart failure, and to determine the impact of RA on LV remodeling.MethodsA cross‐sectional, community‐based study was conducted among adult (age ≥50 years) patients with RA and age‐ and sex‐matched subjects with neither RA nor a history of heart failure. All participants underwent standard 2‐dimensional Doppler echocardiography. LV geometry was classified into the following 4 categories based on relative wall thickness and sex‐specific cutoffs for the LV mass index: concentric remodeling, concentric hypertrophy, eccentric hypertrophy, or normal geometry.ResultsAmong 200 patients with RA and 600 age‐ and sex‐matched subjects without RA, the mean age was 65 years, and 74% of the individuals in both cohorts were female. Compared with subjects without RA, patients with RA were significantly more likely to have abnormal LV geometry (odds ratio [OR] 1.44, 95% confidence interval [95% CI] 1.03–2.00), even after adjusting for cardiovascular risk factors and comorbidities. Among subjects with abnormal LV geometry, the odds of concentric LV remodeling were significantly increased in patients with RA (OR 4.73, 95% CI 2.85–7.83). In linear regression analyses, the LV mass index appeared to be lower in patients with RA who were currently receiving corticosteroids (β ± SE −0.082 ± 0.027, P = 0.002), even after adjusting for cardiovascular risk factors and comorbidities.ConclusionRA was strongly associated with abnormal LV remodeling (particularly concentric LV remodeling) among RA patients without heart failure. This association remained significant after adjustment for cardiovascular risk factors and comorbidities. RA disease–related factors may promote changes in LV geometry. The biologic mechanisms underlying LV remodeling warrant further investigation.

ABSTRACT Introduction Inflatable penile prostheses (IPPs) are associated with excellent long-term outcomes and patient/partner satisfaction. A small percentage of patients remain dissatisfied, despite acceptable surgical results. Aims This study aims to evaluate factors associated with patient satisfaction and dissatisfaction, define patient characteristics, which may identify elevated risk of postoperative dissatisfaction, and describe management strategies to optimize functional and psychological patient outcomes. Methods A review of urologic and non-urologic cosmetic surgery literature was performed to identify factors associated with patient satisfaction/dissatisfaction. Emphasis was placed on articles defining “high risk” or psychologically challenging patients. Main Outcome Measures Preoperative factors associated with patient satisfaction/dissatisfaction and character traits, which may identify elevated risk of postoperative dissatisfaction or otherwise indicate a psychologically challenging patient. Results Contemporary patient and partner satisfaction rates following IPP are 92–100% and 91–95%, respectively. Factors associated with satisfaction include decreased preoperative expectations, favorable female partner sexual function, body mass index ≤30, and absence of Peyronie's disease or prior prostatectomy. Determinants of dissatisfaction include perceived/actual loss of penile length, decreased glanular engorgement, altered erectile/ejaculatory sensation, pain, diminished cosmetic outcome, difficulty with device function, partner dissatisfaction and perception of unnatural sensation, complications, and extent of alternative treatments offered. Personality characteristics which may indicate psychologically challenging IPP patients include obsessive/compulsive tendencies, unrealistic expectations, patients undergoing revision surgery, those seeking multiple surgical opinions, feeling of entitlement, patients in denial of their prior erectile/sexual function and current disease status, or those with other psychiatric disorders. The mnemonic CURSED Patient is presented: “Compulsive/obsessive, Unrealistic, Revision, Surgeon Shopping, Entitled, Denial, and Psychiatric.” Conclusions Although the majority of IPP patients experience excellent, durable satisfaction and outcomes, a challenging subset of patients may be at increased risk of postoperative dissatisfaction. Appropriate recognition/prevention and management of this cohort may help to establish and strengthen relationships, reduce physical, emotional, and legal risk, and ultimately enhance patient satisfaction.

Aneuploidy, an aberrant number of chromosomes, has been recognized as a feature of human malignancies for over a century, but compelling evidence for causality was largely lacking until mouse models for chromosome number instability were used. These in vivo studies have not only uncovered important new insights into the extremely complex aneuploidy–cancer relationship but also into the molecular mechanisms underlying proper and aberrant chromosome segregation. A series of diverse mouse models for the mitotic checkpoint protein BubR1 has provided evidence for a provocative novel link between aneuploidization and the development of age-related pathologies.