Recombinant Human Bone Morphogenetic Protein 9 (rhBMP9) Induced Osteoblastic Behaviour on a Collagen Membrane Compared With rhBMP2

BACKGROUND Bone morphogenetic protein 9 (BMP9) has previously been characterized as one of the most osteogenic growth factors of the BMP-family, however, up until now, these experiments have only been demonstrated using adenovirus-transfection experiments (gene therapy). With the recent development of recombinant human (rh)BMP9, the aim of the present study was to investigate its osteopromotive potential versus rhBMP2 when loaded onto a collagen membrane. METHODS ST2 stromal bone marrow cells were seeded onto 1)control; 2)rhBMP2-low(10ng/ml); 3)rhBMP2-high(100ng/ml); 4)rhBMP9-low(10ng/ml); and 5)rhBMP9-high(100ng/ml) porcine collagen membranes. Groups were then compared for cell adhesion at 8 hours, cell proliferation at 1, 3 and 5 days real-time PCR at 3 and 14 days for genes encoding Runx2, alkaline phosphatase(ALP) and bone sialoprotein(BSP) at 3 and 14 days and alizarin red staining at 14 days. RESULTS While rhBMP2 and rhBMP9 demonstrated little effects on cell attachment and proliferation, pronounced increases were observed on osteoblast differentiation. It was found that all groups significantly induced ALP mRNA levels at 3 days and BSP levels at 14 days, however rhBMP9-high demonstrated significantly higher values when compared to all other groups for ALP levels (5-fold increase at 3 days and 2-fold increase at 14 days). Alizarin red staining further revealed that both concentrations of rhBMP9 induced up to 3-fold more staining when compared to rhBMP2. CONCLUSION These results indicate that the combination of collagen membranes with rhBMP9 significantly induced significantly higher ALP mRNA expression and alizarin red staining when compared to rhBMP2. These findings suggest that rhBMP9 may be a suitable growth factor for future regenerative procedures in bone biology.

Prognostic markers in lentigo maligna patients treated with imiquimod cream: A long-term follow-up study.

BACKGROUND More data are needed to define factors that predict long-term success after imiquimod therapy for lentigo maligna (LM). OBJECTIVE We sought to determine the demographic, clinical, and histologic prognostic markers of relapse-free survival in patients with LM who were treated with imiquimod. METHODS This was a single-arm, open-label, nonrandomized, prospective study. RESULTS Eighty-nine patients with histologically confirmed LM and a median follow-up time of 4.8 years after imiquimod treatment were included in our study. Sixteen patients (18%) relapsed. Statistically significant indicators of an increased risk of local recurrence included: the total number of melanocytes, the number of basal and suprabasal melanocytes and the number of pagetoid spreading melanocytes. LIMITATIONS Our study was a single-center, nonrandomized study. CONCLUSION An assessment of different melanocyte fractions in the diagnostic baseline biopsy specimen may help to predict the response of LM to imiquimod therapy.

A retrospective study of 1- versus 2-cm excision margins for cutaneous malignant melanomas thicker than 2 mm.

BACKGROUND Most guidelines recommend at least 2-cm excision margin for melanomas thicker than 2 mm. OBJECTIVE We evaluated whether 1- or 2-cm excision margins for melanoma (>2 mm) result in different outcomes. METHODS This is a retrospective cohort study on patients with melanomas (>2 mm) who underwent tumor excision with 1-cm (228 patients) or 2-cm (97 patients) margins to investigate presence of local recurrences, locoregional and distant metastases, and disease-free and overall survival. RESULTS In all, 325 patients with mean age of 61.84 years and Breslow thickness of 4.36 mm were considered for the study with a median follow-up of 1852 days (1995-2012). There was no significant difference in the frequency of locoregional and distant metastasis between the 2 groups (P = .311 and .571). The survival analysis showed no differences for disease-free (P = .800; hazard ratio 0.948; 95% confidence interval 0.627-1.433) and overall (P = .951; hazard ratio 1.018; 95% confidence interval 0.575-1.803) survival. LIMITATIONS The study was not prospectively randomized. CONCLUSIONS Our study did not show any significant differences in important outcome parameters such as local or distant metastases and overall survival. A prospective study testing 1- versus 2-cm excision margin is warranted.

Definitions and outcome measures for mucous membrane pemphigoid: recommendations of an international panel of experts

Mucous membrane pemphigoid encompasses a group of autoimmune bullous diseases with a similar phenotype characterized by subepithelial blisters, erosions, and scarring of mucous membranes, skin, or both. Although knowledge about autoimmune bullous disease is increasing, there is often a lack of clear definitions of disease, outcome measures, and therapeutic end points. With clearer definitions and outcome measures, it is possible to directly compare the results and data from various studies using meta-analyses. This consensus statement provides accurate and reproducible definitions for disease extent, activity, outcome measures, end points, and therapeutic response for mucous membrane pemphigoid and proposes a disease extent score, the Mucous Membrane Pemphigoid Disease Area Index.

Narcolepsy-Associated HLA Class I Alleles Implicate Cell-Mediated Cytotoxicity

OBJECTIVE Narcolepsy with cataplexy is tightly associated with the HLA class II allele DQB1*06:02. Evidence indicates a complex contribution of HLA class II genes to narcolepsy susceptibility with a recent independent association with HLA-DPB1. The cause of narcolepsy is supposed be an autoimmune attack against hypocretin-producing neurons. Despite the strong association with HLA class II, there is no evidence for CD4+ T-cell-mediated mechanism in narcolepsy. Since neurons express class I and not class II molecules, the final effector immune cells involved might include class I-restricted CD8+ T-cells. DESIGN HLA class I (A, B, and C) and II (DQB1) genotypes were analyzed in 944 European narcolepsy with cataplexy patients and in 4043 control subjects matched by country of origin. All patients and controls were DQB1*06:02 positive and class I associations were conditioned on DQB1 alleles. RESULTS HLA-A*11:01 (OR = 1.49 [1.18-1.87] P = 7.0*10-4), C*04:01 (OR = 1.34 [1.10-1.63] P = 3.23*10-3), and B*35:01 (OR=1.46 [1.13-1.89] P = 3.64*10-3) were associated with susceptibility to narcolepsy. Analysis of polymorphic class I amino-acids revealed even stronger associations with key antigen-binding residues HLA-A-Tyr9 (OR = 1.32 [1.15-1.52] P = 6.95*10-5) and HLA-C-Ser11 (OR=1.34 [1.15-1.57] P = 2.43*10-4). CONCLUSIONS Our findings provide a genetic basis for increased susceptibility to infectious factors or an immune cytotoxic mechanism in narcolepsy, potentially targeting hypocretin neurons.

Effect of Enamel Matrix Derivative Liquid on Osteoblast and Periodontal Ligament Cell Proliferation and Differentiation.

BACKGROUND Enamel matrix derivatives (EMDs) have been used clinically for more than a decade for the regeneration of periodontal tissues. The aim of the present study is to analyze the effect on cell growth of EMDs in a gel carrier in comparison to EMDs in a liquid carrier. EMDs in a liquid carrier have been shown to adsorb better to bone graft materials. METHODS Primary human osteoblasts and periodontal ligament (PDL) cells were exposed to EMDs in both gel and liquid carriers and compared for their ability to induce cell proliferation and differentiation. Alizarin red staining and real-time polymerase chain reaction for expression of genes encoding collagen 1, osteocalcin, and runt-related transcription factor 2, as well as bone morphogenetic protein 2 (BMP2), transforming growth factor (TGF)-β1, and interleukin (IL)-1β, were assessed. RESULTS EMDs in both carriers significantly increased cell proliferation of both osteoblasts and PDL cells in a similar manner. Both formulations also significantly upregulated the expression of genes encoding BMP2 and TGF-β1 as well as decreased the expression of IL-1β. EMDs in the liquid carrier further retained similar differentiation potential of both osteoblasts and PDL cells by demonstrating increased collagen and osteocalcin gene expression and significantly higher alizarin red staining. CONCLUSIONS The results from the present study indicate that the new formulation of EMDs in a liquid carrier is equally as potent as EMDs in a gel carrier in inducing osteoblast and PDL activity. Future study combining EMDs in a liquid carrier with bone grafting materials is required to further evaluate its potential for combination therapies.

Incidence and outcomes of symptomatic neonatal arterial ischemic stroke.

BACKGROUND AND OBJECTIVES Neonatal arterial ischemic stroke (NAIS) is associated with considerable lifetime burdens such as cerebral palsy, epilepsy, and cognitive impairment. Prospective epidemiologic studies that include outcome assessments are scarce. This study aimed to provide information on the epidemiology, clinical manifestations, infarct characteristics, associated clinical variables, treatment strategies, and outcomes of NAIS in a prospective, population-based cohort of Swiss children. METHODS This prospective study evaluated the epidemiology, clinical manifestations, vascular territories, associated clinical variables, and treatment of all full-term neonates diagnosed with NAIS and born in Switzerland between 2000 and 2010. Follow-up was performed 2 years (mean 23.3 months, SD 4.3 months) after birth. RESULTS One hundred neonates (67 boys) had a diagnosis of NAIS. The NAIS incidence in Switzerland during this time was 13 (95% confidence interval [CI], 11-17) per 100,000 live births. Seizures were the most common symptom (95%). Eighty-one percent had unilateral (80% left-sided) and 19% had bilateral lesions. Risk factors included maternal risk conditions (32%), birth complications (68%), and neonatal comorbidities (54%). Antithrombotic and antiplatelet therapy use was low (17%). No serious side effects were reported. Two years after birth, 39% were diagnosed with cerebral palsy and 31% had delayed mental performance. CONCLUSIONS NAIS in Switzerland shows a similar incidence as other population-based studies. About one-third of patients developed cerebral palsy or showed delayed mental performance 2 years after birth, and children with normal mental performance may still develop deficits later in life.

Na 1 Nachlass Max Horkheimer, 1 - Korrespondenzen u.a. mit Franz Alexander (p. I 1, 1-205)

1 Brief von Max Horkheimer an Abel, 16.03.1936; 3 Briefe zwischen Hubert Abrahamsohn und Max Horkheimer, 1935-1936, 21.12.1936; 2 Briefe zwischen Emanuel Adler und Max Horkheimer, 12.04.1946, 26.04.1946; 2 Briefe zwischen Max Adler und Max Horkheimer, 16.03.1935, 29.03.1935; 1 Brief von Eva Ahamson an Max Horkheimer, 01.11.1944; 2 Briefe der Aircraft Warning Service Brentwood an Max Horkheimer, Mai 1942; 6 Briefe zwischen Librairie Félix Alcan und Max Horkheimer, 1935, 18.12.1935; 11 Briefe zwischen Franz Alexander und Max Horkheimer, 1938-1940; 2 Briefe zwischen der American Historical Review New York und Max Horkheimer, 01.04.1941, 07.04.1941; 1 Brief von Paul Reiwald an Max Horkheimer, 18.10.1940; 2 Briefe zwischen Helen Manice Alexander und Max Horkheimer, 1936; 2 Briefe zwischen Bernardine Allen und Max Horkheimer, 17.06.1938, 24.06.1938; 1 Brief der Alumni Federation of Columbia University an Max Horkheimer, 21.07.1942; 1 Brief der American Friends Service Comittee an Max Horkheimer, 10.12.1940; 3 Briefe zwischen der American Academy of Political and Social Science Philadelphia und Max Horkheimer, 1939,1940, 16.01.1939; 1 Brief der American Automobile Association Washington an Max Horkheimer, 22.03.1938; 1 Brief der American Association for the Advancement of Science Washington an Max Horkheimer, 16.08.1937; 2 Briefe von Max Horkheimer an den American Consulate General Berlin, 1939; 1 Brief von Max Horkheimer an den American Consulate General Havana, 03.03.1941; 4 Briefe von Max Horkheimer an den American Consul London, 1939-1941; 2 Briefe von Max Horkheimer an den American Consulate General Stuttgart, 1939-1941; 1 Brief von Max Horkheimer an den American Consul Zürich, 1939; 1 Brief von Friedrich Pollock an den American Council of Learned Society, Washington, 27.06.1941; 2 Briefe von Max Horkheimer an die American Friends of German Freedom New York, 1941; 4 Briefe der American Historical Association Washington an Max Horkheimer, 1937-1938; 1 Brief von Max Horkheimer an den American Red Cross Westwood Office, 21.06.1943; 18 Briefe zwschen der American Society for the Prevention of Cruelty to Animals New York und Max Horkheimer, 1936-1941; 1 Brief von Max Horkheimer an die American Women's Volunteer Service Pacific Palisades, 27.07.1942; 23 Briefe zwischen Eugene Anderson und Max Horkheimer, 1937-1941; 2 Briefe zwischen Norah Andreae und Max Horkheimer, 27.10.1944, 09.09.1946; 1 Brief von Rosa Nebel-Schenk, 04.03.1946; 1 Brief von der National Catholic Welfare Conference, 14.08.1944; 12 Briefe zwischen Werner Andreae und Max Horkheimer, 1945-1954; 1 Brief von Julius Marx an Werner Andreae, 10.05.1946, 11.05.1950; 2 Briefe von Josef Messinger an Werner Andreae, 23.10.1946, ohne Datum; 3 Briefe zwischen dem Advokatenbüro Hodler und Max Horkheimer, 1946, 09.05.1946;

Na 1 Nachlass Max Horkheimer, 688 - "Fortune Polls on Antisemitism" (p. IX 153.1-18)

"Fortune Polls on Antisemitism" (1947) (veröffentlicht unter dem Titel "Fortune Survey Analyzed by AJC Consultant to Appraise Results", in: News Letter, American Jewish Committee, Dezember 1947, S. 4):; 1. Max Horkheimer: Über Fortune Polls, a) Typoskript, 3 Blatt, b) Typoskript, 3 Blatt, c) Typoskript mit eigenhändigen Korrekturen, 3 Blatt, d) Typoskript, 3 Blatt; 2. Max Horkheimer: Über Fortune Polls und die Gefahren eines neuen Antisemitismus (Vortragsskript?), Typoskript und Manuskript, 4 Blatt; 3. Theodor W. Adorno (?): "Some Results of Adult Project". Typoskript mit eigenhändigen Korrekturen, 2 Blatt; 4. "Education Counteracts Prejudice" Auszug aus "Antisemitism among American Labor". Typoskript, 1 Blatt; 5. "Discord versus Harmony", Excerpt from: The Annals of the American Academy of Political and Social Science, March 1946, Typoskript, 1 Blatt; 6. Theodor W. Adorno: "Memorandum, Subject: Poll Controversy", 24.4.1948; 7. Leo Löwenthal: "Memorandum on Fortune Poll" und "Supplementary Memorandum on Fortune Poll", 8.10.1947. Typoskripte mit eigenhändigen Ergänzungen, 4 Blatt; 8. "Massing's Comment" (8.10.1947). Typoskript, 2 Blatt; 9. "Excerpts from Fortune Magazine 'The Fortune Survey': Racial and Religious Intolerance". Typoskript, 3 Blatt, a) "Summary of 'Fortune Survey' on Antisemitism in U.S. (Fortune, April, 1939)", Typoskript, 2 Blatt; 10. Leo Löwenthal: 1 Brief mit Unterschrift an Max Horkheimer, New York, 4.10.1947, 1 Blatt; 11. Exzerpt der Umfrage-Materialien der Opinion Research Corporation, Typoskripte, 61 Blatt; 12. Zahlenmaterial zu den Umfragen, 16 Blatt; Office of War Information, Bureau of Intelligence: Berichte über Antisemitismus: 13. "Attitudes toward Jews in the United States", 27.10.1942, a) als Typoskript vervielfältigt, 22 Blatt, b) Typoskript, 35 Blatt; 14. "Political Anti-Semitism: A Study of Indoctrination" (27.10.1942), a) als Typoskript vervielfältigt, 18 Blatt, b) Typoskript, 26 Blatt; 15. "Anti-Semitism - a Symptom of Disaffection" (8.10.1942), a) als Typoskript vervielfältigt, 8 Blatt, b) Typoskript, 12 Blatt; 16. Samuel H. Flowerman und Marie Jahoda: "Polls on Anti-Semitism. How much do they tell us?", Sonderdruck, 4 Blatt; 17. Fragebogen, Drucksachen, 4 Blatt; 18. Zeitungausschnitte aus: The Fortune Survey, 9 Blatt;

If we call them, will they change? Feasibility of a telephone adaptation of motivational interviewing aimed at parents to reduce television time among 2nd and 4th grade children

Television viewing is a sedentary behavior that is modifiable. Reducing media-related behaviors via parent-focused interventions may hold promise for decreasing childhood obesity. This feasibility study examines a novel parent-centered brief telephone-delivered Motivational Enhancement Interview (MEI) to encourage parents of 2nd and 4th graders to set a rules limiting TV time or remove the TV from the child's bedroom. This quasi-experimental sub-study was part of the larger CATCH: En Vivo pilot study conducted in a Hispanic population in the Texas Rio Grande Valley. Parents in the MEI condition were contacted via telephone and encouraged to meet the American Academy of Pediatrics (AAP) recommended 2 hours per day or less of TV. Unconditional logistic regression was used to analyze the data. At post-test, 85% of parents of 4th graders in the MEI group (compared to 71% at pre-test) reported having a rule limiting TV time. The adjusted odds ratio for the MEI group compared to the control group was 3.88, 95% CI (0.72-20.99). At pre-test, 63.16% of 2nd graders had a television in their bedrooms. The 2nd grade MEI intervention reduced that number to 41.03% (OR=0.25, 95%CI (0.08-0.82)). This first look at using MEI to target parents of children to modify TV behavior presents evidence on a promising strategy for modifying children's home media environment and warrants further investigation. ^

Is family medicine meeting the HIV/AIDS challenge? A national survey of family physicians' beliefs, clinical competence, and experience regarding HIV disease

A national sample of family physicians was surveyed to (1) assess family physicians' beliefs about the human immunodeficiency virus (HIV) and individuals at risk for infection, their clinical competence regarding HIV-related issues, and their experiences with HIV disease; (2) present conclusions to the American Academy of Family Physicians (AAFP) to effect the development of an early clinical care protocol and a continuing medical education curriculum; and (3) collect base-line data for use in the evaluation of an early clinical care protocol and a continuing medical education curriculum, in the case that such programs are developed and disseminated. After considering retired or deceased respondents, of the 2,660 physicians surveyed, 1,678 (63.7%) responded. The resulting sample was representative of the active members of the AAFP. About 77% of the respondents were unable to accurately identify the universal precautions for blood and body fluids to prevent occupational transmission of HIV or hepatitis B virus (HBV). Residency trained and board certified physicians expressed fewer "external constraints," such as fear of losing patients, obviating them from providing treatment to individuals with HIV disease (p =.004 and p $<$.001, respectively). These physicians also manifested fewer "internal constraints" to the provision of HIV treatment, such as fear of becoming infected (p $<$.001 and p =.012, respectively). Residency trained physicians also expressed a greater comfort with discussing sexually-related topics with their patients than did non-residency trained physicians (p $<$.001). There were 67.1% of the physicians surveyed who reported never providing treatment to an individual with HIV disease. Residency trained and board certified physicians expressed a greater likelihood to provide treatment to HIV-infected patients (p $<$.001) than non-residency trained and non-board certified physicians.^ Among the various primary care specialties, family medicine is especially vulnerable to the current challenges of HIV/AIDS. These challenges are augmented by the epidemiologic pattern that characterizes AIDS. For the past several years, we have seen AIDS in this country assume a similar pattern to that seen in most other countries; HIV is becoming increasingly prevalent in the heterosexual population as well as in locations removed from metropolitan centers. This current phase of the epidemic generates greater pressures upon primary care physicians, particularly family physicians, to become better acquainted with the means to provide early care to HIV/AIDS patients and to prevent HIV/AIDS among their patients. Family medicine is especially appropriate for providing care to HIV patients because family medicine involves treatment to all age groups and conditions; other primary care specialties focus on limited patient populations or specific conditions. Family physicians should be armed with the expertise to confront HIV/AIDS. However, family physicians' clinical competence and experience with HIV is not known. The data collected in this survey describes their competencies, attitudes, and experiences. ^

Global practice experience: A useful lens for understanding patient and staff perceptions of successful integration of health information technology in primary care

Making healthcare comprehensive and more efficient remains a complex challenge. Health Information Technology (HIT) is recognized as an important component of this transformation but few studies describe HIT adoption and it's effect on the bedside experience by physicians, staff and patients. This study applied descriptive statistics and correlation analysis to data from the Patient-Centered Medical Home National Demonstration Project (NDP) of the American Academy of Family Physicians. Thirty-six clinics were followed for 26 months by clinician/staff questionnaires and patient surveys. This study characterizes those clinics as well as staff and patient perspectives on HIT usefulness, the doctor-patient relationship, electronic medical record (EMR) implementation, and computer connections in the practice throughout the study. The Global Practice Experience factor, a composite score related to key components of primary care, was then correlated to clinician and patient perspectives. This study found wide adoption of HIT among NDP practices. Patient perspectives on HIT helpfulness on the doctor-patient showed a suggestive trend that approached statistical significance (p = 0.172). Clinicians and staff noted successful integration of EMR into clinic workflow and their perception of helpfulness to the doctor-patient relationship show a suggestive increase also approaching statistical significance (p=0.06). GPE was correlated with clinician/staff assessment of a helpful doctor-patient relationship midway through the study (R 0.460, p = 0.021) with the remaining time points nearing statistical significance. GPE was also correlated to both patient perspectives of EMR helpfulness in the doctor-patient relationship (R 0.601, p = 0.001) and computer connections (R 0.618, p = 0.0001) at the start of the study. ^