TIP47 is not a component of lipid droplets

TIP47 functions in the delivery of mannose 6-phosphate receptors from endosomes to the trans-Golgi network both in vitro and in vivo. It binds directly and very specifically to the cytoplasmic domains of both the cation-independent and cation-dependent mannose 6-phosphate receptors. TIP47 is 43% identical to a lipid droplet-associated protein named adipophilin; much of the identity resides near the N termini of these proteins. It was recently reported in this journal, in a study using antiserum from this laboratory, that TIP47 is a constituent of lipid droplets (Wolins, N. E., Rubin, B., and Brasaemle, D. L. (2001) J. Biol. Chem. 276, 5101-5108). We show here that the findings of Wolins et al. were likely due to either a cross-reactive, unidentified protein in HeLa cells that is recognized by our antiserum and/or the fact that our serum also cross-reacts with the adipophilin protein itself, shown directly by expression of adipophilin in Escherichia coli. Using antibodies specific for residues 152-434 of TIP47, we show that TIP47 is not a constituent of lipid droplets

Observation Versus Intervention for Low-Grade Intracranial Dural Arteriovenous Fistulas

BACKGROUND: Low-grade intracranial dural arteriovenous fistulas (dAVF) have a benign natural history in the majority of cases. The benefit from treatment of these lesions is controversial. OBJECTIVE: To compare the outcomes of observation versus intervention for low-grade dAVFs. METHODS: We retrospectively reviewed dAVF patients from institutions participating in the CONsortium for Dural arteriovenous fistula Outcomes Research (CONDOR). Patients with low-grade (Borden type I) dAVFs were included and categorized into intervention or observation cohorts. The intervention and observation cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was modified Rankin Scale (mRS) at final follow-up. Secondary outcomes were excellent (mRS 0-1) and good (mRS 0-2) outcomes, symptomatic improvement, mortality, and obliteration at final follow-up. RESULTS: The intervention and observation cohorts comprised 230 and 125 patients, respectively. We found no differences in primary or secondary outcomes between the 2 unmatched cohorts at last follow-up (mean duration 36 mo), except obliteration rate was higher in the intervention cohort (78.5% vs 24.1%, P < .001). The matched intervention and observation cohorts each comprised 78 patients. We also found no differences in primary or secondary outcomes between the matched cohorts except obliteration was also more likely in the matched intervention cohort (P < .001). Procedural complication rates in the unmatched and matched intervention cohorts were 15.4% and 19.2%, respectively. CONCLUSION: Intervention for low-grade intracranial dAVFs achieves superior obliteration rates compared to conservative management, but it fails to improve neurological or functional outcomes. Our findings do not support the routine treatment of low-grade dAVFs

Onyx embolization for dural arteriovenous fistulas:a multi-institutional study

BACKGROUND: Although the liquid embolic agent, Onyx, is often the preferred embolic treatment for cerebral dural arteriovenous fistulas (DAVFs), there have only been a limited number of single-center studies to evaluate its performance. OBJECTIVE: To carry out a multicenter study to determine the predictors of complications, obliteration, and functional outcomes associated with primary Onyx embolization of DAVFs. METHODS: From the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database, we identified patients who were treated for DAVF with Onyx-only embolization as the primary treatment between 2000 and 2013. Obliteration rate after initial embolization was determined based on the final angiographic run. Factors predictive of complete obliteration, complications, and functional independence were evaluated with multivariate logistic regression models. RESULTS: A total 146 patients with DAVFs were primarily embolized with Onyx. Mean follow-up was 29 months (range 0-129 months). Complete obliteration was achieved in 80 (55%) patients after initial embolization. Major cerebral complications occurred in six patients (4.1%). At last follow-up, 84% patients were functionally independent. Presence of flow symptoms, age over 65, presence of an occipital artery feeder, and preprocedural home anticoagulation use were predictive of non-obliteration. The transverse-sigmoid sinus junction location was associated with fewer complications, whereas the tentorial location was predictive of poor functional outcomes. CONCLUSIONS: In this multicenter study, we report satisfactory performance of Onyx as a primary DAVF embolic agent. The tentorium remains a more challenging location for DAVF embolization, whereas DAVFs located at the transverse-sigmoid sinus junction are associated with fewer complications

Living with colorectal cancer : naturalistic assessment of daily life

textEcological momentary assessment provides a unique way of studying quality of life factors of colorectal cancer patients. It has yet to be used to study the behavioral expression of distress or depression by colorectal cancer patients. The current study utilized the Electronically Activated Recorder (EAR) technology to capture the daily activities and conversations of forty-eight adults with colorectal cancer. The study had two purposes: 1) to test the feasibility of the EAR with colorectal cancer patients; 2) to examine separate (self-report and behavioral) indicators of physical functioning, coping, and social support for their relationship to depression. Study participants wore the EAR, a portable digital recorder, for two consecutive days as the EAR recorded 30 seconds every 12.5 minutes. The EAR digital data were transcribed and analyzed for behavioral and linguistic indicators of physical functioning, coping, and social support. The acoustic data were analyzed using the standardized coding system Social Environment Coding of Sound Inventory (SECSI) and the Linguistic Inquiry and Word Count (LIWC2007) computer program. The results provided preliminary evidence that the EAR operated as a feasible and non-disruptive tool for gathering naturalistic data about colorectal patients’ lives. The EAR data revealed information about both the colorectal patients’ internal emotional world as well as their external world which was characterized by solitary acts of daily living. Study subjects were more likely to accept and receive tangible support from others than directly discuss their cancer with others. Analysis of language found that personal disclosure to others was associated with coping through emotional support while causation words (e.g., because, effect, hence) were significantly related with self-report cognitive scales. Furthermore, the study found that first-person singular pronouns were associated not only with depression, but with appraisal of social support. Lastly, a predictive model was tested to see whether self-reported tangible and emotional support and behavioral coding of emotional support each contributed uniquely to the prediction of depression. Only self-reported tangible support was found to significantly predict depression.Educational Psycholog

Patient-Centered Communication: Do Patients Really Prefer It?

OBJECTIVE To investigate patient preferences for a patient-centered or a biomedical communication style. DESIGN Randomized study. SETTING Urgent care and ambulatory medicine clinics in an academic medical center. PARTICIPANTS We recruited 250 English-speaking adult patients, excluding patients whose medical illnesses prevented evaluation of the study intervention. INTERVENTION Participants watched one of three videotaped scenarios of simulated patient-physician discussions of complementary and alternative medicine (CAM). Each participant watched two versions of the scenario (biomedical vs. patient-centered communication style) and completed written and oral questionnaires to assess outcome measurements. MEASUREMENTS AND MAIN RESULTS Main outcome measures were 1) preferences for a patient-centered versus a biomedical communication style; and 2) predictors of communication style preference. Participants who preferred the patient-centered style (69%; 95% confidence interval [CI], 63 to 75) tended to be younger (82%[51/62] for age \u3c 30; 68%[100/148] for ages 30–59; 55%[21/38] for age \u3e 59; P \u3c .03), more educated (76%[54/71] for postcollege education; 73%[94/128] for some college; 49%[23/47] for high school only; P = .003), use CAM (75%[140/188] vs. 55%[33/60] for nonusers; P = .006), and have a patient-centered physician (88%[74/84] vs. 30%[16/54] for those with a biomedical physician; P \u3c .0001). On multivariate analysis, factors independently associated with preferring the patient-centered style included younger age, use of herbal CAM, having a patient-centered physician, and rating a “doctor\u27s interest in you as a person” as “very important.” CONCLUSIONS Given that a significant proportion of patients prefer a biomedical communication style, practicing physicians and medical educators should strive for flexible approaches to physician-patient communication

Amyloid formation and depolymerization of tumor suppressor p16INK4a are regulated by a thiol-dependent redox mechanism

The conversion of a soluble protein into polymeric amyloid structures is a process that is poorly understood. Here, we describe a fully redox-regulated amyloid system in which cysteine oxidation of the tumor suppressor protein p16INK4a leads to rapid amyloid formation. We identify a partially-structured disulfide-bonded dimeric intermediate species that subsequently assembles into fibrils. The stable amyloid structures disassemble when the disulfide bond is reduced. p16INK4a is frequently mutated in cancers and is considered highly vulnerable to single-point mutations. We find that multiple cancer-related mutations show increased amyloid formation propensity whereas mutations stabilizing the fold prevent transition into amyloid. The complex transition into amyloids and their structural stability is therefore strictly governed by redox reactions and a single regulatory disulfide bond

Identification of Individuals With Patellofemoral Pain Whose Symptoms Improved After a Combined Program of Foot Orthosis Use and Modified Activity: A Preliminary Investigation

Background and Purpose. In patients with patellofemoral pain syn-drome (PFPS), the authors determined which aspects of the examina-tion could be used to identify those patients most likely to respond to off-the-shelf foot orthoses and instruction in activity modification. Participants and Methods. Fifty participants were enrolled in the study, and data for 5 individuals were excluded from analysis. Thirty-four men and 11 women completed the study. Participants were given foot orthoses and instructed in activity modification for 3 weeks. A 50% reduction in pain was considered a success. Likelihood ratios (LRs) were computed to determine which examination findings were most predictive of success. Results. The best predictors of improvement were forefoot valgus alignment of 2 degrees (LR4.0, 95 % confidence interval [CI]0.7–21.9), great toe extension of 78 degrees (LR4.0, 95 % CI0.7–21.9), and navicular drop of 3 mm (LR2.4, 95 % CI1.3–4.3). Discussion and Conclusion. The results suggest that patients with PFPS who have forefoot valgus alignment of 2 degrees, passive great toe extension of 78 degrees, or navicular drop of 3 mm are most likely to respond favorably to initial intervention with an off-the-shelf foot orthosis and instruction in activity modification. [Sutlive TG, Mitchell SD, Maxfield SN, et al. Identification of individuals with patellofemoral pain whose symptoms improved after a combined program of foot orthosis use and modified activity: a preliminary investigation. Phys Ther. 2004;84:49–61.