tbuckley/cabot-search huggingface dataset:
Modulation of the Relationship Between External Knee Adduction Moments and Medial Joint Contact Forces Across Subjects and Activities
Authors: Adam Trepczynski, Ines Kutzner, Georg Bergmann, William R. Taylor, Markus O. Heller
Journal: Arthritis & Rheumatology (2014)

The external knee adduction moment (EAM) is often considered a surrogate measure of the distribution of loads across the tibiofemoral joint during walking. This study was undertaken to quantify the relationship between the EAM and directly measured medial tibiofemoral contact forces (Fmed ) in a sample of subjects across a spectrum of activities.The EAM for 9 patients who underwent total knee replacement was calculated using inverse dynamics analysis, while telemetric implants provided Fmed for multiple repetitions of 10 activities, including walking, stair negotiation, sit-to-stand activities, and squatting. The effects of the factors "subject" and "activity" on the relationships between Fmed and EAM were quantified using mixed-effects regression analyses in terms of the root mean square error (RMSE) and the slope of the regression.Across subjects and activities a good correlation between peak EAM and Fmed values was observed, with an overall R(2) value of 0.88. However, the slope of the linear regressions varied between subjects by up to a factor of 2. At peak EAM and Fmed , the RMSE of the regression across all subjects was 35% body weight (%BW), while the maximum error was 127 %BW.The relationship between EAM and Fmed is generally good but varies considerably across subjects and activities. These findings emphasize the limitation of relying solely on the EAM to infer medial joint loading when excessive directed cocontraction of muscles exists and call for further investigations into the soft tissue-related mechanisms that modulate the internal forces at the knee.
Hepatic steatosis in HIV-HCV coinfected patients receiving antiretroviral therapy is associated with HCV-related factors but not antiretrovirals
Authors: Valérie Martinez, Thi Dieu Ngan TA, Zahra Mokhtari, Marguerite Guiguet, Patrick Miailhes, Marc-Antoine Valantin, Fréderic Charlotte, Philippe Bertheau, Jean-Michel Molina, Christine Katlama, Eric Caumes
Journal: Genome biology (2013)

In this paper we evaluate the economic gains of a joint deployment of femtocells and macrocells for the provision of Long Term Evolution (LTE) mobile broadband services in urban environments. Frequency bands of 2.6 GHz and 900 MHz are analyzed and different parameters related to the business model are considered for a 30% market share operator. Results show important benefits for the base case where the service is offered to fixed-broadband clients, up to 75%, for small bandwidths. It results feasible to attribute subscriber loop costs to the radio access network (RAN) costs, so that the service could be offered to non fixed-broadband clients, in both cases of closed access and open access femtocells. However, initial savings result notably reduced, up to 50% less than in the base case if closed access is adopted and up to 13% less for open access. Site reuse reduces the initial savings only in 3%.
Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-κb-inducing kinase
Authors: Reiko Shinkura, Kazuhiro Kitada, Fumihiko Matsuda, Kei Tashiro, Koichi Ikuta, Misao Suzuki, Katsumi Kogishi, Tadao Serikawa, Tasuku Honjo
Journal: Nature Genetics (1999)
Abstract 16899: Neutralization of Bleeding Induced by Direct Factor Xa and Thrombin Inhibitors by Prothrombin Complex Concentrates Alone and in Combination with Antifibrinolytic Agents
Authors: Walter Jeske, Vicki Escalante, Elizabeth McGeehan, Jeanine Walenga, Jawed Fareed, Mamdouh Bakhos
Journal: Circulation (2014)

Introduction: Concerns remain over bleeding with direct factor Xa and thrombin inhibitors in cases of overdose or medical emergency. This study tested the ability of PCCs to reverse bleeding induced by apixaban, rivaroxaban or dabigatran in a standardized rat tail resection model. Methods: Individual groups of anesthetized rats (8-10) were anticoagulated with apixaban, rivaroxaban or dabigatran and subsequently treated with vehicle, 3-factor (Profilnine), 4-factor (Beriplex) or activated 4-factor PCC (FEIBA). Five minutes post-PCC administration, a tail snip was performed and bleeding time was measured. Upon cessation of bleeding, a blood samples were collected for ex vivo analysis and the rat was humanely euthanized. Results: In comparison to saline control (6.8 + 1.1 sec) apixaban (300μg/kg) prolonged bleeding time (17.1±5.6; p=0.024). Beriplex at doses ≤10U/kg did not shorten bleeding time while 10U/kg Profilnine did. FEIBA prolonged bleeding beyond that seen with apixaban alone (22.6±11.4 and 37.5±5.2 min for 5 and 10U/kg doses; p&lt;0.001 apixaban + 10U/kg FEIBA vs. apixaban). 100 and 300μg/kg rivaroxaban prolonged bleeding time (20.8±2.5, p=0.002 vs. saline; 25.0±10.0 min, p&lt;0.001 vs. saline). Profilnine was more effective than Beriplex or FEIBA in reversing rivaroxaban-induced bleeding. Dabigatran-induced bleeding was prevented by Beriplex or Profilnine but enhanced by FEIBA (50.3±8.3 vs. 15.9±1.2 min; p&lt;0.001). Treatment of apixaban or rivaroxaban anticoagulated rats with FEIBA + 10mg/kg epsilon aminocaproic acid, produced bleeding times comparable to those of non-anticoagulated rats (apixaban: 6.7±5.0 min; rivaroxaban: 7.7±6.4 min). Ex vivo analysis of blood samples did not show any relevance with the observed bleeding or its modulation. Discussion: PCCs appear useful for neutralizing bleeding induced by direct factor Xa and thrombin inhibitors, but each PCC exhibits a distinct neutralization profile. Co-administration of a fibrinolytic inhibitor may enhance effectiveness of hemorrhage reversal by PCCs.
I Herbert Scheinberg
Authors: Geoff Watts
Journal: BMJ (2009)

Genetic disease expert who advanced the diagnosis and treatment of Wilson’s disease

That Dr I Herbert Scheinberg is the name most often associated with the diagnosis of Wilson’s disease is in part a product of the misfortune of the two scientists on whose previous work he was building. In 1948 the Swedish chemists C G Holmberg and C B Laurell had isolated ceruloplasmin, a copper carrying protein found in human serum. Because Wilson’s disease is caused by an accumulation of copper in the body, they suspected that this protein would be low in the serum of patients with the disorder. However, in samples from the one patient available to them, the prediction could not be confirmed. As it later turned out, this was hardly surprising; the patient in question was found to have been misdiagnosed.

With the discipline ripe for further study, Scheinberg and his colleague Dr David Gitlin, both of Harvard Medical School, published a paper in Science in 1952 …
59. Development of Conditionally Replicative Adenoviruses as Platforms for the Expression of shRNAs or Therapeutic Genes
Authors: Jan E. Carette, Frederik H. E. Schagen, Renée M. Overmeer, Jeroen D.C. Mastenbroek, Winald R. Gerritsen, Victor W. van Beusechem
Journal: Molecular Therapy (2004)

Conditionally replicative adenoviruses (CRAds) represent a novel class of anticancer agents, designed to selectively replicate in tumor cells and to destroy these cells by the induction of lysis. We aim to enhance CRAd oncolytic potency by suppressing apoptosis inhibitors or by expressing toxic proteins in CRAd-infected cancer cells. Towards the first goal, we explored the utility of RNA interference (RNAi) in the context of CRAd replication in cancer cells. RNAi is the sequence-specific gene-silencing induced by double-stranded RNA (dsRNA) and is now widely used to study the function of individual genes. By virtue of its excellent target specificity, RNAi also holds great promise as a new anticancer modality. The success of this approach largely depends on efficient delivery of dsRNA to tumor cells. As a proof of principle, we constructed CRAds encoding short hairpin RNAs (shRNAs) targeted against firefly luciferase and assessed their silencing efficiency. These replicating viruses silenced firefly luciferase expression relative to control virus in the four human cancer cell lines tested. In a time course experiment, the expression inhibition was especially evident during later stages of infection, reaching a maximum of approximately 70% silencing at the time when CPE became apparent. The CRAd-shRNA induced silencing was not observed in an experiment using a reporter plasmid with point mutations in the target site of the shRNA, confirming the sequence-specificity of the silencing effect. Thus, successful RNAi was accomplished.
THE RÔLE OF THE PERSONALITY IN PSYCHOTHERAPEUTICS
Authors: Austen Fox Riggs, Horace K. Richardson
Journal: Annals of Internal Medicine (1936)

Article1 July 1936THE RÔLE OF THE PERSONALITY IN PSYCHOTHERAPEUTICSAUSTEN FOX RIGGS, M.D., F.A.C.P., HORACE K. RICHARDSON, M.D., F.A.C.P.AUSTEN FOX RIGGS, M.D., F.A.C.P.Search for more papers by this author, HORACE K. RICHARDSON, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-10-1-13 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA psychoneurosis is an involuntary and automatic disorder of normal people, based on hypersensitiveness and the relative imbalance of instincts, causing inner conflict between instinctive forces and adult, intelligent strivings and ideals. Some outward maladaptation to life manifests itself by typical symptomatology in the vegetative, somatic, emotional or intellectual fields, thereby functioning as a compromise between the demands of the instinctive forces and the higher intellectual and ethical aims, and as a protective mechanism against whatever is painful and unacceptable emotionally and intellectually. The particular form of neurosis which develops is determined by the relative composition of individuality and environmental... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Stockbridge, Massachusetts*Presented at the Detroit meeting of the American College of Physicians, March 3, 1936. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1936Volume 10, Issue 1Page: 13-24KeywordsEmotionsInstinct ePublished: 1 December 2008 Issue Published: 1 July 1936 PDF downloadLoading ...
Lymphogranuloma venereum in Europe, 2003-2008
Authors: E  J Savage, M J van de Laar, A Gallay, M van der Sande, O Hamouda, A Sasse, S Hoffmann, M Diez, M J Borrego, C  M Lowndes, C Ison, None on behalf on the European Surveilla
Journal: Eurosurveillance (2009)

Lymphogranuloma venereum, caused by the L serovars of Chlamydia trachomatis, emerged in Europe in 2003 and a series of outbreaks were reported in different countries. The infection presents as a severe proctitis in men who have sex with men, many of whom are co-infected with HIV and other sexually transmitted infections. This paper reviews the number of cases reported over a five year period, from 2003 to 2008, from countries that were part of the European Surveillance of Sexually Transmitted Infections (ESSTI) network. Reports were received from Belgium, Denmark, France, Germany, the Netherlands, Portugal, Spain, Sweden, and the United Kingdom. It appears that after five years the characteristics of the patients infected has overall remained unchanged, although the total number of cases has increased and more countries in Europe have now identified cases of LGV.
JAK2 and JAK1 Constitutively Associate With an Interleukin-5 (IL-5) Receptor α and βc Subunit, Respectively, and Are Activated Upon IL-5 Stimulation
Authors: Norihisa Ogata, Taku Kouro, Atsuko Yamada, Masamichi Koike, Nobuo Hanai, Takeru Ishikawa, Kiyoshi Takatsu
Journal: Blood (1998)
Carbon Monoxide Poisoning
Authors: M C Dolan
Journal: BMJ (1945)

Carbon monoxide poisoning is a significant cause of illness and death. Its protean symptoms probably lead to a gross underestimation of its true incidence. Low levels of carbon monoxide aggravate chronic cardiopulmonary problems, and high levels are associated with cardiac arrhythmias and cerebral edema. Patients who survive acute poisoning are at risk of delayed neurologic sequelae. The measurement of carboxyhemoglobin levels does not reveal the tissue levels of carbon monoxide but is useful in determining therapy. Treatment includes the monitoring and management of cardiac arrhythmias and oxygenation. Hyperbaric oxygenation is beneficial, but there are currently no definite criteria for its use.
AIDS vaccines tested in Thailand and Uganda
Authors: Scott Gottlieb
Journal: BMJ (1999)

Researchers began the first African trial of an experimental AIDS vaccine and, separately, another group announced that it will soon begin a largescale efficacy test of a second vaccine in Thailand. Both trials are part of a worldwide effort to see if vaccines can prevent or reduce the rate of infection from HIV in the developing world.

Officials at Pasteur Merieux Connaught, the vaccine unit of French drug manufacturer Rhone-Polenc Group, said they had initiated a small test of the company's ALVAC vaccine …
Disordered Behavior. Basic Concepts in Clinical Psychiatry.
Authors: Eric Pfeiffer
Journal: Annals of Internal Medicine (1968)

a succinct summary of current knowledge on the Philadelphia chromosome. Despite good photomicrographs, the descriptions of morphologic de¬ tail in blood and marrow smears leave something to be desired. The problem is one of over-interpreta¬ tion without adequate clues as to what is really meant by the descrip¬ tive terms used. For example, on page 79 it is stated that, Myelonecrosis due to destruction of myeloid arteries has been blamed on corti¬
489. Comparison of AAV2 and AAV2/5 CFTR Vectors in the Lungs of Cynomolgus Macaques
Authors: Keith L. Munson, Laurie M. Tatalick, Carolina I. Smith, Anne C. Fischer, Pervin Anklesaria, Barrie J. Carter, William B. Guggino
Journal: Molecular Therapy (2004)

Cystic fibrosis is the most common autosomal recessive disorder in North America, leading to significant morbidity and early mortality. Cystic fibrosis is caused by a defect in the cystic fibrosis transmembrane regulator (CFTR) gene which encodes a chloride channel. The defect in chloride transport in epithelial cells affects a number of organs. The defect in airway epithelium in the lung leads to progressive loss of pulmonary function which is the primary cause of death. rAAV vectors have shown potential utility for treatment of cystic fibrosis. The primary objective of this study was to assess transduction efficiency of several full-length CFTR cDNA rAAV vectors. Two CFTR vectors, one with the AAV2 ITR as a promoter and the other with a small, synthetic 83 base promoter, were evaluated in either AAV type 2 or 5 capsids. Secondary objectives were to collect safety data and to assess the cell types transduced using GFP as a reporter gene. Safety parameters included clinical chemistry, hematology, gross necropsy, histopathology and AAV neutralizing antibody titers.
Brief Report: Stress‐Inducible Nuclear Protein 1 Regulates Matrix Metalloproteinase 13 Expression in Human Articular Chondrocytes
Authors: Raghunatha R. Yammani, Richard F. Loeser
Journal: Arthritis & Rheumatology (2014)

Nuclear protein 1 (Nupr1) is a stress-inducible protein that is involved in gene transcription. The present study was undertaken to determine whether chondrocytes express Nupr1 and whether Nupr1 regulates matrix metalloproteinase 13 (MMP-13) expression.Paraffin-embedded cartilage sections from normal human and osteoarthritic (OA) cartilage were immunostained using anti-Nupr1 antibody. To measure Nupr1 expression, total RNA was isolated from joint tissue obtained 8 weeks after surgery from young (12-week-old) and older (12-month-old) mice that underwent destabilization of the medial meniscus (DMM) to induce OA. Human chondrocytes were stimulated with 1-10 ng/ml interleukin-1β (IL-1β), 25 μM tert-butyl-hydroperoxide (tBHP), or 2 μM thapsigargin, and Nupr1 expression was analyzed by quantitative polymerase chain reaction. In addition, chondrocytes were transfected with small interfering RNA to knock down Nupr1 expression and then stimulated overnight with IL-1β. After incubation, the conditioned medium was collected and MMP levels measured.Increased Nupr1 immunostaining was noted in human OA cartilage compared to normal cartilage. Expression was also increased in joint tissue from 12-month-old mice that underwent DMM surgery compared to sham-operated controls. Stimulation of chondrocytes with IL-1β induced a 2-fold increase in Nupr1 messenger RNA (mRNA) within 1 hour, with the increase peaking to 4-fold at 6 hours. Treatment of chondrocytes with tBHP to induce oxidative stress increased Nupr1 mRNA expression by >2-fold; treatment with thapsigargin to induce endoplasmic reticulum stress did not produce a similar effect. Knockdown of Nupr1 inhibited IL-1β-mediated induction of MMP-13.Nupr1 is expressed in cartilage, and its levels are increased in OA. Nupr1 expression is required for IL-1β-mediated expression of MMP-13. These findings provide evidence of a novel pathway for regulation of IL-1β-mediated production of MMPs in chondrocytes.
Abstract #5544: The cytoprotective transcription factor Nrf2 mediates the antioxidant upregulation of human MGMT DNA repair protein
Authors: Nathan Bailey, Kalkunte Srivenugopal
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

MGMT (O6-Methylguanine-DNA methyltransferase) is a critical DNA repair protein that protects oncogenic genes and the global genome against mutations caused by endogenous and exogenous alkylating agents. Although human MGMT is not known to be inducible, we recently showed that the gene responds to a cysteine prodrug, dietary and natural antioxidants with a limited transcriptional enhancement in normal and tumor cells (Int J Oncol. 29, 1269-1278, 2006; Carcinogenesis 28, 378-389 2007). To assess the potential of MGMT-targeted chemoprevention, this study investigated the molecular mechanisms of antioxidant responsiveness of the MGMT gene. Inspection of the basal promoter of hMGMT showed the presence of two AREs (antioxidant response elements) which are typically recognized by NRF2. NRF2 (nuclear factor E2 related factor 2) is a basic leucine zipper transcription factor that rapidly turns over under homeostatic conditions, but is stabilized by redox imbalance and mediates the transcription of several phase 2 detoxifying enzymes that are inducible by antioxidants and xenobiotics. Consistent with our hypothesis, the activity of reporter genes (CAT or luciferase) linked to the 1 kb MGMT promoter were markedly upregulated (4-5 fold) by curcumin and silymarin, which also augmented MGMT expression in earlier studies. Further, the transient and stable tansfections of T47D breast cancer and HT29 colon cancer cells with an Nrf2 expression construct resulted in significant upregulation (3-5 fold) of MGMT gene transcripts, protein and activity. The transfected cells showed a similar increase in GSTP1, an established target of Nrf2. Electrophoretic mobility shift assays using the putative ARE sequences (22 bp ds-DNA) from the MGMT promoter showed only one of them bound the Nrf2 in nuclear extracts from curcumin and silymarin-treated tumor cells. Studies using siRNA and ChIP assays are underway to elucidate the role of Nrf2 in basal and chemopreventive-induced expression of MGMT. Because the ARE-Nrf2 interactions are hallmarks of oxidative stress/antioxidant- responsive genes, our findings suggest that human cells may enhance DNA repair via MGMT during redox stress. The results also suggest that dietary components can influence hMGMT expression and bear significance for chemopreventive augmentation of MGMT as a means to lower cancer risk (supported by NIH RO3CA125872 grant to KSS).

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5544.
Abstract 14843: Permanent Pacemaker Implant Improves Patient’s Sleep Habit
Authors: Sharma Kattel, Mohammed Zafar, Abdul J Samdani, Yuji Saito
Journal: Circulation (2014)

Background: Permanent pacemaker is indicated for patients with symptomatic bradycardia. It has been known that patients often report improved sleep habit after pacemaker implant. However, to date, there has been no study that investigated a possible effect of pacemaker implant on sleep habit. Methods: Total 97 patients who agreed to the study were included (82 pacemakers and 15 ICDs). Patients with biventricular pacemaker were excluded. Patients filled the questionnaires about sleep habit upon their routine device interrogation. Data were analyzed using paired T test and chi square test. Results: Indication of permanent pacemaker was sick sinus syndrome (71%), 2nd degree AV block (17%), 3rd degree AV block (10%), and syncope (2%). Indication of ICD was primary sudden cardiac death prevention without history of known symptomatic bradycardia (100%). The ICD group was used as the control group. Ventricular pacing was noted 47.6% of the time in the pacemaker group and 17.27 % in the ICD group (p=0.01). Genera...
Sir William Osler: Aphorisms from His Bedside Teachings and Writings.
Authors: Osler, William, Sir, Robert Bennett Bean
Journal: Annals of Internal Medicine (1950)

Aphorisms from His Bedside Teachings and Writings. Second Printing. Collected by Robert Bennett Bean, M.D. (1874-1944) ; edited by William Bennett Bean, M.D. Price, $4.00. Pp. 164, with no illustrations. Charles C Thomas, Publisher, 301-327 E. Lawrence Ave., Springfield, Ill., 1961. I had not heard of this book until I read of it recently in Dr. Noel Poynter's remarkable quarterly catalogue, Current Work in Medical History. To me it was all new, together with William Bean's 2 introductions (1951) and (1961) and that of the late John Fulton. In his postscriptive introduction William Bean treats of Osler's strange melancholy and wonders at its source. Did Osler really know more sorrow than others ? Did he feel the loss of his son more than other parents feel their bereavements? I do not think so ; the melancholy seems to have been acquired while he was young. Before I hazard my own guess at this, let me tell you how Osler appeared to me as a student and recent graduate. He was little
The relationship between airway bacterial load and airways inflammation in stable non-cystic fibrosis bronchiectasis
Authors: James D. Chalmers, Pallavi Mandal, Brian McHugh, Maeve Smith, Cathy Doherty, John R. Govan, Adam T. Hill
Journal: European Respiratory Journal (2011)

Objective:  To investigate the relationship between airway bacterial load and markers of airways inflammation in stable patients with bronchiectasis.   Methods:  302 patients with non-CF bronchiectasis confirmed by HRCT were enrolled. At 6 monthly review, spontaneous sputum samples were processed to determine bacterial load, expressed as log 10  colony forming units/ml (cfu/ml). Sputum sol was analysed for myeloperoxidase (MPO) and neutrophil elastase elastase activity. Interleukin-8 (IL-8), Interleukin 1-beta (IL-1β) and tumour necrosis factor alpha (TNF-α) were measured by ELISA.   Results:  67 patients (22.1%) of patients grew no pathogens. Pathogenic micro-organisms were obtained in 77.9% of patients, most frequently  Haemophilus influenzae  (37.4% of isolates),  Pseudomonas aeruginosa  (20.4%),  Staphylococcus aureus  (13.2%),  Streptococcus pneumoniae  (11.9%) and  Moraxella catarrhalis  (10.6%).  Airway inflammation increased progressively with increasing bacterial load. Statistically significant differences were observed, when compared to patients with no pathogens, at bacterial loads above 1×10 6 cfu/ml for MPO (p=0.01), neutrophil elastase activity (p=0.006) and IL-8 (p=0.02), and above 1×10 7  for TNF-α (p=0.04) and above 1×10 5  for IL-1β (p=0.003).   Conclusion:  There is a direct relationship between airway bacterial load and the degree of airway inflammation in stable bronchiectasis.