What do academic primary care physicians want in an electronic journal?

To determine the interest of academic general internists and family physicians in specific features of electronic journal publications, we surveyed 350 physicians, 175 randomly selected from each of 2 medical societies: the Society of General Internal Medicine, and the Society of Teachers of Family Medicine. The response rate was 70%. Most general internists and family physicians used online journals sometimes or often. Most general internists and family physicians reported moderate to high interest in having links from original articles, reviews, or editorials to listed references (77% to 89% of internists and 65% to 81% of family physicians) and electronic medical reference texts (73% to 78% of internists and 65% to 83% of family physicians). Less than 25% of both groups reported moderate to high interest in having links to initiate dialog with other readers or to communicate comments to the author or editor. General internists were more likely than were family physicians to have moderate to high interest in having links to appendices and supportive material (e.g., 66% of general internists versus 46% of family physicians for original articles; P < .05) and less likely to have moderate to high interest in links to health-related web sites (44% of general internists versus 69% of family physicians for original articles; P < .05). We conclude that academic general internists and family physicians have strong but not identical interests in specific features of electronic publication that primary care-oriented journals should consider.     

Solitary vulvar metastasis from early-stage endometrial cancer: Case report and literature review

Rationale:Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. It is usually diagnosed at early-stage and presents a favorable prognosis. Conversely, advanced or recurrent disease shows poor outcome. Most recurrences occur within 2 years postoperatively, typically in pelvic and para-aortic lymph nodes, vagina, peritoneum, and lungs. Vulvar metastasis (VM) is indeed anecdotal probably because of the different regional lymphatic drainage from corpus uteri.Patient concerns:A 3 cm, reddish, bleeding lesion of the posterior commissura/right labia was found in a 74-year-old woman treated with radical hysterectomy, surgical staging, and adjuvant radiotherapy 1 year before for a grade 2 endometrioid type, International Federation of Gynecology and Obstetrics Stage IB. Vulvar biopsy confirmed the EC recurrence. Pelvic magnetic resonance imaging and positron emission tomography excluded other metastases so VM was radically resected.Diagnosis:Postoperative histopathology confirmed the diagnosis of grade 2 EC VM.Interventions:A radical excision of VM was performed.Outcomes:Patient died from a severe sepsis 27 months after first surgery.Lessons:Vulvar metastases can show different appearance, occurring as single or diffuse lesions on healthy or injured skin. The surgical approach seems not to influence the metastatic risk, but tumor seeding and vaginal injuries should be avoided. Whether isolated or associated with recurrence in other locations, vulvar metastases imply poor prognosis despite radical treatment. Therefore, any suspected vulvar lesion arisen during EC follow-up should be biopsied and monitored closely, despite that the vulva represents an unusual metastatic site.     

Is Ustekinumab Effective in Refractory Crohn’s Disease of the Pouch and Chronic Pouchitis? A Systematic Review

Digestive Diseases and Sciences - Crohn’s disease (CD) of the pouch and chronic pouchitis represent the most common long-term complications of total proctocolectomy and ileal pouch anal...     

Characteristics of oleate binding to liver plasma membranes and its uptake by isolated hepatocytes

To clarify mechanisms of hepatic free fatty acid uptake, [3H]oleate uptake by isolated rat hepatocytes was studied, using solutions of 150 microM bovine serum albumin at oleate:albumin molar ratios of 0.033-6.7:1. Oleate partitioning between liver plasma membranes and albumin was also studied, and used to ascertain the membrane binding function for oleate. The experimental uptake curve was complex, but could be resolved by computer fitting into a sum of two components, one a saturable and the second a linear function of the unbound oleate concentration. The saturable component comprises > 90% of total oleate uptake when the oleate:albumin molar ratio is < 2.5, but < 50% when this ratio is > 5. Membrane binding also consisted of a sum of a saturable and a linear component. By comparison of the computer-fitted uptake and binding functions, separate rate constants for the transfer into the cell of the saturably and non-saturably bound oleate were estimated to be 0.7 s-1 and 0.05 s-1, respectively. The former is compatible with a specific, protein-mediated process. It is 15-times greater than the corresponding rate constant for transfer of non-saturably bound oleate into the cell, which in turn is similar to reported rates of non-specific 'flip-flop' of fatty acids across lipid bilayers. The observed kinetics are not consistent with models in which uptake occurs principally from the albumin-bound pool of oleate, or solely from the oleate which has partitioned passively into the lipid bilayer of the plasma membrane.     

Selective targeted delivery of TNFalpha to tumor blood vessels

We sought to enhance the selective toxicity of tumor necrosis factor alpha (TNFalpha) to permit its systemic use in cancer therapy. Because ligand-targeted therapeutics have proven successful in improving the selective toxicity of drugs, we prepared a fusion protein (L19mTNFalpha) composed of mouse TNFalpha and a high-affinity antibody fragment (L19 scFv) to the extradomain B (ED-B) domain of fibronectin, a marker of angiogenesis. L19mTNFalpha was expressed in mammalian cells, purified, and characterized. L19mTNFalpha was an immunoreactive and biologically active homotrimer. Radiolabeled L19mTNFalpha selectively targeted tumor neovasculature in tumor-bearing mice, where it accumulated selectively and persistently (tumor-to-blood ratio of the percentage of injected dose per gram [%ID/g] of 700, 48 hours from injection). L19mTNFalpha showed a greater anticancer therapeutic activity than both mTNFalpha and TN11mTNFalpha, a control fusion protein in which an antibody fragment, irrelevant in the tumor model used, substituted for L19. This activity was further dramatically enhanced by its combination with melphalan or the recently reported fusion protein L19-IL2. In conclusion, L19mTNFalpha allows concentrating therapeutically active doses of TNFalpha at the tumor level, thus opening new possibilities for the systemic use of TNFalpha in cancer therapy.     

Complete 15N and 1H NMR assignments for the amino-terminal domain of the phage 434 repressor in the urea-unfolded form

The amino-terminal domain of the phage 434 repressor consisting of residues 1-69 forms a globular structure of five tightly packed helices, with nearly identical molecular architectures in crystals and in solution. Upon addition of urea to an aqueous solution of this protein, the NMR spectrum of a second form of the protein appears in addition to the native form, and at a urea concentration of 7 M, this urea-unfolded form is the only species observed. At intermediate urea concentrations, the two forms of the protein inter-convert at a rate that allows the observation of the exchange process by NMR. Starting from the previous assignments for the native protein, we obtained nearly complete sequence-specific (1)H and (15)N NMR assignments for the unfolded form of the protein. For most amino acid residues, the (1)H chemical shifts of the urea-unfolded protein are very similar to the random coil values, but some discrete regions of the polypeptide chain were identified that are likely to retain residual nonrandom spatial structure as evidenced by deviations of (1)H chemical shifts and amide proton exchange rates from the expected random coil values.     

A 2-year pilot trial of continuous subcutaneous insulin infusion versus intensive insulin therapy in patients with newly diagnosed type 1 diabetes (IMDIAB 8)

In a pilot study, the metabolic effects of continuous subcutaneous insulin infusion (CSII) versus intensive subcutaneous insulin therapy (ISIT) started at diagnosis in patients with Type 1 diabetes and continued for a 2-year period were evaluated and compared. Twenty-three patients (between 12 and 35 years old, mean +/- SD 18.4 +/- 9 years) were randomized into two treatment groups (CSII vs. ISIT), and both received supplemental nicotinamide (NA), 25 mg/kg of body weight. CSII was started immediately after admission to the hospital. Parameters of metabolic control [insulin dose, hemoglobin A1c (HbA1c), and C-peptide] were evaluated for a 2-year follow-up period. Data are presented for a total of 19 patients who remained in the study for its duration. Two years after diagnosis, mean +/- SD HbA1c was 6.3 +/- 0.5% and 6.2 +/- 0.3% for the CSII and ISIT groups, respectively (p=not significant). Compared with baseline values, an increase of baseline C-peptide of 38% for the CSII group and 27% for the ISIT group was observed; however, the difference between the groups was not significant. The insulin requirement for the entire duration of the study, but not at entry and 3 months, was significantly higher in CSII compared with ISIT patients (0.62 +/- 0.4 IU/kg/day vs. 0.3 +/- 0.4 IU/kg/day, respectively; p<0.01). After trial completion patients on CSII continued with this mode of therapy. Implementation of CSII as well as ISIT at diagnosis of Type 1 diabetes and continuation for 2 years thereafter achieved similar and optimal metabolic control, but more insulin was required with the CSII group. Both types of intensive insulin therapy combined with NA are able to preserve C-peptide secretion or even increase baseline levels for up to 2 years after diagnosis.     

Assessment programs to enhance learning

Background: Assessment is an essential part of the educational system. Usually, assessment is used to measure students’ knowledge, but it can also be used to drive students’ learning and behaviors. Assessment programs should be constructed in a well-balanced way allowing not only measuring students’ knowledge but also changing students’ behavior.

Objectives: In this paper, we will discuss different strategies that can be used to change students’ behaviors which may improve their learning.

Main findings: Assessment as well as the learning material should be congruent with the objectives. Based on the literature, we summarize findings that would address key points to allow assessment for learning instead of learning.

Conclusions: When constructing an assessment program, choices have to be made that depend on aspects like logistics, financial, organizational, managerial, educational culture, and cooperation of individual and key faculty members. It is important to realize that whatever decisions you make, students will always adapt their behavior to the way you construct your assessment program.