Miracle-dz/UniFAR-FTUs huggingface dataset:
Attachment and growth behaviour of human gingival fibroblasts on titanium and zirconia ceramic surfaces

The attachment, growth behaviour and the genetic effect of human gingival fibroblasts (HGF) cultured on titanium and different zirconia surfaces were investigated. HGF cells were cultured on (1) titanium discs with a machined surface, (2) yttrium-stabilized tetragonal zirconia polycrystals (Y-TZP) with a smooth surface and (3) Y-TZP with 100 µm grooves. The cell proliferation activity was evaluated through a MTT assay at 24 h and 48 h, and the cell morphology was examined by SEM. The mRNA expression of integrin-β1, type I and III collagen, laminin and fibronectin in HGF were evaluated by RT-PCR after 24 h. From the MTT assay, the mean optical density values for the titanium and grooved zirconia surfaces after 48 h of HGF adhesion were greater than the values obtained for the smooth zirconia surfaces. SEM images showed that more cells were attached to the grooves, and the cells appeared to follow the direction of the grooves. The results of RT-PCR suggest that all groups showed comparable fibroblast-specific gene expression. A zirconia ceramic surface with grooves showed biological responses that were comparable to those obtained with HGF on a titanium surface.
Morbidity and quality of life during thermotherapy using magnetic nanoparticles in locally recurrent prostate cancer: Results of a prospective phase I trial

Purpose: To investigate the treatment-related morbidity and quality of life (QoL) during thermotherapy using superparamagnetic nanoparticles in patients with locally recurrent prostate cancer. Materials and Methods: Ten patients with biopsy-proven locally recurrent prostate cancer following primary therapy with curative intent and no detectable metastases were entered on a prospective phase I trial. Endpoints were feasibility, toxicity and QoL. Following intraprostatic injection of a nanoparticle dispersion, six thermal therapy sessions of 60 min duration were delivered at weekly intervals using an alternating magnetic field. National Cancer Institute (NCI) common toxicity criteria (CTC) and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-PR25 questionnaires were used to evaluate toxicity and QoL, respectively. In addition, prostate specific antigen (PSA) measurements were carried out. Results: Maximum temperatures up to 55°C were achieved in the prostates at 25–30% of the available magnetic field strength. Nanoparticle deposits were detectable in the prostates one year after thermal therapy. At a median follow-up of 17.5 months (3–24), no systemic toxicity was observed. Acute urinary retention occurred in four patients with previous history of urethral stricture. Treatment-related morbidity was moderate and QoL was only temporarily impaired. Prostate-specific antigen (PSA) declines were observed in eight patients. Conclusions: Interstitial heating using magnetic nanoparticles was feasible and well tolerated in patients with locally recurrent prostate cancer. Deposition of nanoparticles in the prostate was highly durable. Further refinement of the technique is necessary to allow application of higher magnetic field strengths.
Matrix metalloproteinases in human choroidal neovascular membranes excised following verteporfin photodynamic therapy

Aim: To evaluate expression of proangiogenic matrix metalloproteinases (MMP) 2 and 9 at distinct intervals after verteporfin photodynamic therapy (PDT) in human choroidal neovascular membranes (CNV) secondary to age-related macular degeneration (AMD). Methods: Retrospective review of an interventional case series of 49 patients who underwent removal of CNV. Twenty-six patients were treated with PDT 3 to 383 days prior to surgery. Twenty-three CNV without previous treatment were used as controls. CNV were stained for CD34, cytokeratin 18, endostatin, MMP-2 and MMP-9 by immunohistochemistry. Results: CNV without previous therapy disclosed MMP-2, MMP-9 in RPE–Bruch’s membrane, vessels and stroma in different intensities. Three days after PDT, MMP-9 expression was significantly weaker in stroma (p = 0.0019). Endostatin was significantly reduced in vessels (p<0.001). At longer post-PDT intervals, a significant increase of MMP-9 in stroma (p = 0.037) and of endostatin in RPE–Bruch’s membrane (p = 0.02), vessels (p = 0.005) and stroma (p<0.001) were disclosed. No significant changes in MMP-2 expression were detected. Conclusions: PDT induced an early, temporary decrease in MMP-9 and endostatin expression. At longer intervals, MMP-9 increase is possibly associated with the angiogenic process responsible for recurrence after PDT. MMP-9, however, acts as a double-edged sword by concomitant induction of endostatin, an endogenous inhibitor of angiogenesis.
Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study.

PURPOSE For several decades, the treatment of elderly patients with multiple myeloma (MM) has consisted of melphalan and prednisone (MP). The Dutch-Belgium Hemato-Oncology Cooperative Group (HOVON) investigated the efficacy of thalidomide added to MP (MP-T) in a randomized phase III trial. The objective of this study was to investigate the efficacy, toxicity, and effects on quality of life of MP-T. PATIENTS AND METHODS A randomized phase III trial compared standard MP with MP-T (thalidomide 200 mg/d) in newly diagnosed patients with multiple myeloma older than age 65 years. Maintenance therapy with thalidomide 50 mg/d was administered to patients after MP-T until relapse. The primary end point was event-free survival (EFS); response rate, overall survival (OS), and progression-free survival (PFS) were secondary end points. RESULTS An intent-to-treat analysis of 333 evaluable patients showed significantly higher response rates in MP-T-treated patients compared with MP-treated patients a response (> or = partial response: 66% v 45%, respectively; P < .001; and > or = very good partial response [VGPR]: 27% v 10%, respectively; P < .001). EFS was 13 months with MP-T versus 9 months with MP (P < .001). OS was 40 months with MP-T versus 31 months with MP (P = .05). CONCLUSION This study demonstrates that thalidomide improves the response rate and VGPR in elderly patients with newly diagnosed MM. MP-T also results in a better EFS, PFS, and OS.
Interrater agreement on the Benton visual retention test.

To address overlapping needs in clinical neuropsychology and epidemiology of the elderly, we report an in-depth analysis of interrater scoring for a test commonly used to assess visual memory in older persons. Benton Visual Retention Test protocols (Form C, Administration A) from 277 community-dwelling male participants (M = 65.2 years) in two ongoing cardiovascular epidemiologic studies were scored independently by two trained raters. Interrater reliabilities, calculated as intraclass correlations, were . 963 and . 974 for total number of correct reproductions and total number of errors, respectively. Interrater agreements on categorical determinations of the presence or absence of 6 error codes on 10 separate designs were evaluated using kappa measures of agreement. Kappa values for each of the 10 designs ranged between . 780 and . 930. Kappa values for each of the error codes ranged from a high of . 976 for omissions to a moderate . 737 for size errors. Kappa values by error code type within each of the 10 designs revealed particular problem areas for misplacements on design 9 and size errors on design 10 (kappa being as low as .440 and .480 respectively). Suggestions for improving the accuracy of scoring are presented.
Differential trends in the intestinal and diffuse types of gastric carcinoma in the United States, 1973-2000: increase in the signet ring cell type.

CONTEXT During the last 50 years, the incidence and mortality of gastric cancer has declined in many countries. This decline has primarily included the intestinal type (Lauren classification). However, there is an impression among pathologists that the diffuse type, especially the signet ring cell subtype, has become more prevalent. OBJECTIVES Using data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, we analyzed the trends of the 2 primary types (intestinal and diffuse) of gastric carcinomas from 1973 through 2000. DESIGN Trends in age-adjusted rates were determined for gastric carcinomas through the SEER statistical program (SEER*Stat), which is available on the Internet to the public. RESULTS During the period studied, the intestinal type continued to decline in males, females, African Americans, and whites. The intestinal type was more common in males than in females and more common in African Americans than in whites. In contrast, a consistent increase in the rate of the diffuse type of gastric carcinoma was seen during this period. The rate increased from 0.3 cases per 100 000 persons in 1973 to 1.8 cases per 100 000 persons in 2000. This increase was seen in males, females, African Americans, and whites. The predominant increase occurred in the signet ring type. CONCLUSIONS The results indicate a progressive decrease in the incidence of the intestinal type of gastric cancer and an increase in the diffuse type of gastric carcinoma, especially the signet ring cell type. The clinical implications of the increase are considered.
Integrin‐mediated inhibition of interleukin‐8 secretion from human neutrophils by collagen type I

The function of neutrophils in the inflammatory response is modulated by contact with ECM proteins. We have now investigated the effect of collagen type I on secretion of the cytokine IL‐8 by human neutrophils in vitro. Collagen type I inhibited the secretion of IL‐8 from neutrophils maintained under basal conditions or stimulated with fMLF. This effect was accompanied by down‐regulation of IL‐8 mRNA, and it appeared to be specific to collagen type I among ECM proteins, in that it was not observed with fibronectin or laminin. The inhibitory effect of collagen type I on IL‐8 secretion was dependent on collagen concentration and cell density. It was also abolished in the presence of antibodies to integrin α2β1 but was not affected by antibodies to integrin α5β1 or β4. Our results thus suggest that collagen type I inhibits the secretion of IL‐8 by human neutrophils in a selective manner and that this effect is mediated by the interaction of collagen with integrin α2β1.
Induction of a major histocompatibility complex class I-restricted cytotoxic T-lymphocyte response to a highly conserved region of human immunodeficiency virus type 1 (HIV-1) gp120 in seronegative humans immunized with a candidate HIV-1 vaccine

Efforts to induce broadly reactive immunity against human immunodeficiency virus type 1 (HIV-1) have been impaired by the extent of sequence variation exhibited by this lentivirus. Cytotoxic T lymphocytes (CTL) specific for other viruses such as influenza virus have been shown to mediate immunity against divergent viral strains, a property that is related to the ability of CTL to recognize processed antigen derived from conserved viral proteins. A recent candidate HIV-1 vaccine regimen has been described in which subjects receive a primary immunization with a recombinant vaccinia virus expressing gp160 and then a booster immunization with recombinant gp160. Volunteers immunized with this regimen have exhibited augmented humoral responses and have also developed CD4+ and CD8+ CTL specific for gp160. In this report, we have identified the epitopes recognized by CD4+ and CD8+ CTL obtained from two vaccines. An immunodominant CD8+ CTL response was HLA-A3.1 restricted and recognized a 10-amino-acid epitope (gp120/38-47) in a highly conserved region of gp120. CTL specific for the epitope gp120/38-47 were able to lyse targets sensitized with peptides corresponding to all known natural sequence variants in this region. In addition, other HLA class I-restricted CTL epitopes were identified in relatively conserved regions of gp120 and gp41, and CD4+ CTL were shown to recognize two different regions of gp120. Thus, in these two volunteers, immunization with a single strain of HIV-1 induced CD4+ and CD8+ CTL that are specific for multiple conserved regions of HIV-1 and would be expected to recognize a broad range of viral isolates.
Unadjusted Plasma Renin Activity as a “First‐Look” Test to Decide Upon Further Investigations for Primary Aldosteronism

The authors sought to define the 95th percentile of plasma renin activity (PRA) in a sample of patients with confirmed primary aldosteronism (PA) prior to adjustment of medications as a practical “first‐look” test to identify those with very low ultimate likelihood of having PA. The aldosterone to renin ratio (ARR) was measured without adjustment of antihypertensive medications, with further workup as appropriate. Two groups were defined: patients with surgically “confirmed PA” (n=58) and patients with “high‐probability PA” (n=59), defined as having any of the following: computed tomography–confirmed adrenal adenoma plus lateralizing adrenal vein sampling (AVS) without surgery, high ARR and hypokalemia but nonlateralizing AVS, or ARR more than four times the upper limit of normal. The PRA 95th percentile was 1.0 ng/mL/h. All outliers had hypokalemia and two had adrenal adenomas. There was no difference between the confirmed and high probability groups. In the absence of highly suspicious clinical features, patients with unadjusted PRA >1.0 ng/mL/h do not warrant further investigation for PA.
Emil Kraepelin's habilitation and his thesis: A pioneer work for modern systematic reviews, psychoimmunological research and categories of psychiatric diseases

Abstract Objectives. Although Kraepelin and his oeuvre have been in scientific focus over the past decades, main aspects have still been neglected. Thus the exact circumstances under which and on what topic Kraepelin wrote his habilitation thesis and qualified as university lecturer (in Germany the prerequisite to be appointed as professor) are still widely unknown. Methods. This study reconstructs his habilitation at the Medical Faculty of Leipzig University in 1882. Results. The study reveals the difficulties he had to habilitate on a topic from Wilhelm Wundt's experimental psychology and the opposition he faced from Paul Flechsig. Yet Kraepelin succeeded, mainly due to a positive review by neurologist Wilhelm Erb on his study “On the Influence of Acute Diseases on the Development of Mental Illnesses” (1881/82). Conclusions. This work must be regarded as his actual habilitation thesis. It provides an update of organic psychiatric disorders following acute inflammatory diseases and a meta-analysis on the basis of raw data. In addition it discusses possibilities to categorize and understand the pathophysiological mechanism of these disorders and to classify them into those appearing when the fever rises and those occurring when it falls, which has a high impact from a very modern psychoimmunological viewpoint.
La inversión directa en China: implicaciones derivadas de su entrada en la OMC

En este articulo se estudian las profundas consecuencias que la entrada de China en la OMC tiene para las inversiones extranjeras. Su adhesion al Acuerdo General sobre Comercio de Servicios (GATS) implica la liberalizacion de la participacion de empresas extranjeras en sectores, anteriormente cerrados, tan importantes como las telecomunicaciones, los seguros, la banca, la distribucion comercial, el turismo y los servicios profesionales, con los limites establecidos en el Protocolo de Adhesion. Por otra parte, la adhesion al Acuerdo sobre Inversiones relacionadas con el Comercio (TRIMS) supone cambios fundamentales en la normativa, tales como la eliminacion de algunos de los actuales requisitos de exportacion o el mantenimiento de balances en moneda extranjera, aplicables hasta la fecha a las filiales en China de las empresas extranjeras.
Révision de la méthode proposée par Schmitt (2005) pour estimer l'âge au décès des adultes à partir de la surface sacro-pelvienne iliaque

La surface auriculaire de l'ilium a fait l'objet de nombreuses methodes pour estimer l'âge au deces des adultes. En 2005, Schmitt proposait un systeme de cotation simple (4 criteres morphologiques avec 2 a 4 modalites), l'utilisation de probabilites, l'aggregation de plusieurs series europeennes d'âge connu et un intervalle chronologique plutot qu'un âge precis, pour une estimation sur les echantillons archeologiques. Cette methode permet d'identifier les individus decedes apres 60 ans, ce qui n'est pas le cas des methodes classiques, et privilegie la fiabilite a la precision. Toutefois, la limite majeure est l'impossibilite d'estimer l'âge de certains sujets. Les donnees ont ete traitees par une autre approche statistique basee sur l'estimateur du noyau de la densite (" kernel density procedure "), tenant compte des observations au voisinage de chaque point. Ce nouveau systeme permet une approximation de l'âge de tous les individus et des intervalles chronologiques moins larges que ceux proposes dans la methode initiale. Martins, R. ,
Modified Two‐Layer Preservation Method (M‐Kyoto/PFC) Improves Islet Yields in Islet Isolation

Islet allotransplantation can achieve insulin independence in patients with type I diabetes. Recent reports show that the two‐layer method (TLM), which employs oxygenated perfluorochemical (PFC) and UW solution, is superior to simple cold storage in UW for pancreas preservation in islet transplantation. However, UW solution has several disadvantages, including the inhibition of Liberase activity. In this study, we investigated the features of a new solution, designated M‐Kyoto solution. M‐Kyoto solution contains trehalose and ulinastatin as distinct components. Trehalose has a cytoprotective effect against stress, and ulinastatin inhibits trypsin. In porcine islet isolation, islet yield was significantly higher in the M‐Kyoto/PFC group compared with the UW/PFC group. There was no significant difference in ATP content in the pancreas between the two groups, suggesting that different islet yields are not due to their differences as energy sources. Compared with UW solution, M‐Kyoto solution significantly inhibited trypsin activity in the digestion step; moreover, M‐Kyoto solution inhibited collagenase digestion less than UW solution. In conclusion, the advantages of M‐Kyoto solution are trypsin inhibition and less collagenase inhibition. Based on these data, we now use M‐Kyoto solution for clinical islet transplantation from nonheart‐beating donor pancreata.
Efforts to change transfusion practice and reduce transfusion rates are effective in coronary artery bypass surgery.

OBJECTIVES Efforts to decrease allogeneic blood transfusion and avoid unnecessary transfusions in cardiac surgery are important because transfusions are associated with increased postoperative morbidity and mortality. The purpose of the present study was to evaluate the long-term effects of multidisciplinary efforts to reduce allogeneic blood transfusion rates and avoid unnecessary red blood cell (RBC) transfusions in primary elective coronary artery bypass graft (CABG) surgery. DESIGN A retrospective observational study. SETTING A single center study in a university-affiliated hospital. PARTICIPANTS A total of 450 patients undergoing primary elective CABG surgery during 2004, 2008, or 2010. INTERVENTIONS The application of systematic multimodal perioperative blood-sparing techniques and interventions directed to change transfusion behaviors. MEASUREMENTS AND MAIN RESULTS The results from an audit on transfusion practices in 2004 were compared with similar audits performed in 2008 and 2010 using a before-and-after study design. The patient populations were comparable throughout the years. The median postoperative chest tube bleeding was decreased from 950 mL in 2004 to 750 mL in 2010. The proportion of patients transfused with allogeneic blood products was decreased from 64% to 47%. Overtransfusion with allogeneic RBCs defined as the proportion of patients transfused with RBCs discharged with hemoglobin >7 mmol/L (11.3 g/dL) was reduced from 36% to 16%. CONCLUSIONS Multimodal efforts to change transfusion behaviors and decrease transfusion rates in CABG surgery have persistent effects for several years.
Adhesion of human breast cancer cell line MCF‐7 to human vascular endothelial cells in culture. enhancement by activated platelets

The interactions of MCF‐7 tumor cells with human vascular endothelial cells (EC) and subendothelial extracellular matrices (ECM) were morphologically observed by electron microscopy and quantitatively evaluated by labelling tumor cells with 111Indium‐oxine. MCF‐7 tumor cells adhered more rapidly to ECM than to the apical surface of a confluent monolayer of EC. The affinity of MCF‐7 cells for type‐IV collagen was greater than for fibronectin, suggesting that type‐IV collagen contributes to the higher rate of adhesion of MCF‐7 cells to the subendothelial ECM. Otherwise, the attachment of tumor cells to EC was increased in the presence of both washed platelets and 0.1% citrated platelet‐poor plasma (cPPP), a condition accelerating platelet aggregation by tumor cells. The enhancement of MCF‐7 adhesion to EC in the presence of platelets and cPPP was completely blocked by the addition of prostacyclin, or hirudin, a specific thrombin inhibitor. In ultrastructural studies, MCF‐7 initiated EC retraction, and firm attachment and flattening occurred on exposed ECM. When MCF‐7 cells were incubated with platelets and cPPP, most of the tumor cells adhering to the EC and inducing disruption of endothelial monolayer were closely packed and associated with platelet aggregates. MCF‐7 cells appeared to adhere more efficiently to exposed subendothelial ECM when they were associated into multicellular aggregates containing platelets and trapped in a fibrin thrombus. Thus, this homologous human system of cultured vascular EC and breast carcinoma line MCF‐7 cells may be used to assess anti‐aggregant compounds for their ability to alter tumor‐cell implantation on EC‐lined surfaces.
Current pharmacotherapy for obesity: extrapolation of clinical trials data to practice

Introduction: When used prudently and in combination with lifestyle modification, pharmacotherapy has an important role in the management of obesity. Areas covered: This review covers targets for antiobesity drugs, challenges and limitations, failed translation of basic science to clinical practice, methodological and regulatory issues in clinical trials of pharmacotherapy, efficacy and risks of drugs currently approved for obesity, and clinical practice issues when using antiobesity drugs with emphasis on recently approved drugs. Expert opinion: Drugs currently approved for long-term therapy of obesity offer modest benefits for most patients, substantial benefits for some and no benefits for others. Numerous methodological problems including exclusion of the type of patients who are most often seen in clinical practices, inadequate enrollment of men and minorities, exclusion of patients taking antidepressants, high dropout rates, lack of follow-up after treatment discontinuation, and less than ideal imputation methods in data analysis limit the interpretation of clinical trials data and generalizability. Single-drug therapies offer small to moderate weight-loss benefits, but are generally better tolerated. Efficacy is enhanced with combination drug therapies, but so are the hazards. Clinicians should base their decisions on the expected and observed benefit-to-risk balance.