tbuckley/cabot-search huggingface dataset:
Non-interventional management of acute coronary syndromes
Authors: A. Timmis
Journal: BMJ (2011)

OBJECTIVE: To ascertain the prevalence of HIV infection among people entering provincial adult prisons in British Columbia and to study associations between HIV infection and specific demographic and behavioural characteristics. DESIGN: Prospective, unlinked, voluntary survey involving HIV antibody testing of saliva specimens. SETTING: All adult provincial prisons in British Columbia through which inmates are admitted to the provincial correctional system. PARTICIPANTS: All adult inmates admitted to provincial prisons in British Columbia between Oct. 1 and Dec. 31, 1992. OUTCOME MEASURES: Rate of HIV positivity. Independent variables included sex, native status (native or non-native), self-reported HIV status, age group and history of injection drug use. RESULTS: A total of 2482 (91.3%) of 2719 eligible inmates volunteered for testing. Refusal was not associated with sex, native status, self-reported HIV status or age group; inmates who reported a history of injection drug use were more likely than the others to refuse HIV antibody testing (12.9% v. 6.8%; p &lt; 0.001). The 2482 inmates who were tested for HIV were similar to the general inmate population with regard to sex, native status and age group. A total of 28 inmates were confirmed to be HIV positive, for an overall prevalence rate in the study population of 1.1% (95% confidence interval 0.8% to 1.6%). The prevalence rates were higher among the women than among the men (3.3% v. 1.0%; p = 0.023, Fisher9s exact test) and among the inmates who reported a history of injection drug use than among those who did not report such a history (2.4% v. 0.6%; p &lt; 0.001). There was no association between HIV status and native status or age group. Logistic regression analysis revealed the higher prevalence rate among the women to be explained by more of the women than of the men reporting a history of injection drug use. Of the 30 people who stated that they were HIV positive and who were tested, 19 (63.3%) had a negative result; conversely, 17 who reported that they were HIV negative or had not been tested had a positive result. CONCLUSIONS: Unlinked, voluntary HIV antibody testing of inmates can achieve high participation rates. The overall prevalence rate of 1.1% and the rate among the female inmates of 3.3% confirm that HIV infection is a reality in prisons and that the virus has established a clear foothold in inmate populations. Harm-reduction interventions should include a comprehensive education program for inmates on infectious diseases, the availability of condoms throughout prisons and the distribution of bleach for sterilizing needles and syringes. From a public health perspective, these data suggest an urgent need for access to sterile injection equipment in addition to other preventive measures.
Schizophrenia: a genetic disorder of the synapse?
Authors: Michael J Owen, Michael C O'Donovan, Paul J Harrison
Journal: BMJ (2005)

relationships, or among individuals with HIV infectionrequires measured clinical judgment until further studies are available.Furthermore, the vexed question remains of whether the notable reduction in transmission provided by valaciclovir would be achieved by other antiviral drugs, such as aciclovir or famciclovir, and if so, at what dose?Without comparative data, individual prescribing decisions in specific healthcare settings will need to be made on the basis of factors including availability, potential adherence, and cost.That no evidence of viral resistance was detected in those individuals who became infected in this study is reassuring.That some susceptible individuals did become infected reinforces the message that valaciclovir reduced the frequency of HSV reactivation, subclinical shedding, and transmission of genital herpes, but it did not eliminate it.Antiviral treatment is thus not a substitute for other methods to control the spread of sexually transmitted infections but an additional tool.Patients should also be advised to continue using condoms, practise safer sex, and inform their partner about transmissible infections they have.The risk of transmitting genital herpes will not be removed, but patients can be assured that they are doing everything they can to reduce the risk of infecting a loved one.
Inhibition of leukocyte-endothelial cell interactions and inflammation by peptides from a bacterial adhesin which mimic coagulation factor X.
Authors: E Rozdzinski, J Sandros, M van der Flier, A Young, B Spellerberg, C Bhattacharyya, J Straub, G Musso, S Putney, R Starzyk
Journal: Journal of Clinical Investigation (1995)

Factor X (factor ten) of the coagulation cascade binds to the integrin CD11b/CD18 during inflammation, initiating procoagulant activity on the surface of leukocytes (Altieri, D.C., O.R. Etingin, D.S. Fair, T.K. Brunk, J.E. Geltosky, D.P. Hajjar, and T. S. Edgington. 1991. Science [Wash.DC]. 254:1200-1202). Filamentous hemagglutinin (FHA), an adhesin of Bordetella pertussis also binds to the CD11b/CD18 integrin (Relman D., E. Tuomanen, S. Falkow, D.T. Golenbock, K. Saukkonen, and S.D. Wright. 1990. Cell. 61:1375-1382). FHA and the CD11b/CD18 binding loops of Factor X share amino acid sequence similarity. FHA peptides similar to Factor X binding loops inhibited 125I-Factor X binding to human neutrophils and prolonged clotting time. In addition, ETKEVDG and its Factor X analogue prevented transendothelial migration of leukocytes in vitro and reduced leukocytosis and blood brain barrier disruption in vivo. Interference with leukocyte migration by a coagulation-based peptide suggests a novel strategy for antiinflammatory therapy.
Sex differences in aggression: Origins and implications for sexual integration of combat forces
Authors: Kingsley R. Browne
Journal: Behavioral and Brain Sciences (2009)

Abstract Sex differences in aggressive and risk-taking behaviors have practical implications for sexual integration of military combat units. The social-role theory implies that female soldiers will adapt to their role and display the same aggressive and risk-taking propensities as their male comrades. If sex differences reflect evolved propensities, however, adoption of the soldier's role is unlikely to eliminate those differences.
Deadly parasitic disease grips southern Sudan
Authors: A. Gulland
Journal: BMJ (2002)

Doctors are calling on drug companies and research institutes to develop a cheaper and more effective treatment for kala azar—a disease that is devastating the war torn population of southern Sudan.

The aid agency Medecins Sans Frontieres warned that kala azar, also known as visceral leishmaniasis, was nearing epidemic levels among the malnourished population of Sudan, which has seen two decades of civil war.

The agency, which has a clinic in Lankien in the Eastern Upper Nile state, has received more than 100 admissions …
Funding shortfalls jeopardise vital aid for Niger
Authors: P. Moszynski
Journal: BMJ (2010)

Funding shortfalls and logistical bottlenecks are still delaying the arrival of sufficient aid to prevent catastrophic levels of malnutrition caused by drought in Niger, aid agencies have said, despite calling for the international community to step up their response to the crisis back in June ( BMJ 2010;340:c3372, doi:10.1136/bmj.c3372). 

After a visit to Niger last month, the United Nations World Food Programme’s executive director, Josette Sheeran, described “an unfolding catastrophe for millions of people,” warning that the programme was “struggling against time to scale up quickly enough to reach the escalating number of hungry.” 

She said the programme would supply 7.9 million …
MicroRNAs and the Regulation of Vector Tropism
Authors: Elizabeth J Kelly, Stephen J Russell
Journal: Molecular Therapy (2008)

Despite being small (~22 nt) microRNAs (miRNAs) profoundly influence tissue-specific gene expression by interacting with complementary target sequences in cellular messenger RNAs, impairing their translation or marking them for early destruction. Recent work has shown that tissue-specific miRNAs offer a versatile target that can be exploited to control the tropisms of gene expression vectors and of replication-competent viruses. The principle of incorporating miRNA targets into vector genomes to control their tropisms was first demonstrated for nonreplicating lentiviral and adenoviral vectors, with subsequent extension of these studies to replication-competent (oncolytic) picornaviruses, rhabdoviruses, and adenoviruses. In contrast to previous targeting approaches, miRNA targeting looks set to be applicable across the entire spectrum of viruses and gene expression vectors. Here we provide a critique of the literature relevant to this new and rapidly developing field of endeavor. We also examine the possibility of engineering viruses for expression of tropism-regulating miRNAs. Despite being small (~22 nt) microRNAs (miRNAs) profoundly influence tissue-specific gene expression by interacting with complementary target sequences in cellular messenger RNAs, impairing their translation or marking them for early destruction. Recent work has shown that tissue-specific miRNAs offer a versatile target that can be exploited to control the tropisms of gene expression vectors and of replication-competent viruses. The principle of incorporating miRNA targets into vector genomes to control their tropisms was first demonstrated for nonreplicating lentiviral and adenoviral vectors, with subsequent extension of these studies to replication-competent (oncolytic) picornaviruses, rhabdoviruses, and adenoviruses. In contrast to previous targeting approaches, miRNA targeting looks set to be applicable across the entire spectrum of viruses and gene expression vectors. Here we provide a critique of the literature relevant to this new and rapidly developing field of endeavor. We also examine the possibility of engineering viruses for expression of tropism-regulating miRNAs.
Coordinated and unique functions of the E-selectin ligand ESL-1 during inflammatory and hematopoietic recruitment in mice
Authors: Vinatha Sreeramkumar, Magdalena Leiva, Anika Stadtmann, Christophe Pitaval, Inés Ortega-Rodríguez, Martin K. Wild, Brendan Lee, Alexander Zarbock, Andrés Hidalgo
Journal: Blood (2013)
Identification of Campath-1 (CD52) as Novel Drug Target in Neoplastic Stem Cells in 5q-Patients with MDS and AML
Authors: Katharina Blatt, Harald Herrmann, Gregor Hoermann, Michael Willmann, Sabine Cerny-Reiterer, Irina Sadovnik, Susanne Herndlhofer, Berthold Streubel, Werner Rabitsch, Wolfgang R. Sperr, Matthias Mayerhofer, Thomas Rülicke, Peter Valent
Journal: Clinical Cancer Research (2014)

The CD52-targeted antibody alemtuzumab induces major clinical responses in a group of patients with myelodysplastic syndromes (MDS). The mechanism underlying this drug effect remains unknown.We asked whether neoplastic stem cells (NSC) in patients with MDS (n = 29) or acute myelogenous leukemia (AML; n = 62) express CD52.As assessed by flow cytometry, CD52 was found to be expressed on NSC-enriched CD34(+)/CD38(-) cells in 8/11 patients with MDS and isolated del(5q). In most other patients with MDS, CD52 was weakly expressed or not detectable on NSC. In AML, CD34(+)/CD38(-) cells displayed CD52 in 23/62 patients, including four with complex karyotype and del(5q) and one with del(5q) and t(1;17;X). In quantitative PCR (qPCR) analyses, purified NSC obtained from del(5q) patients expressed CD52 mRNA. We were also able to show that CD52 mRNA levels correlate with EVI1 expression and that NRAS induces the expression of CD52 in AML cells. The CD52-targeting drug alemtuzumab, was found to induce complement-dependent lysis of CD34(+)/CD38(-)/CD52(+) NSC, but did not induce lysis in CD52(-) NSC. Alemtuzumab also suppressed engraftment of CD52(+) NSC in NSG mice. Finally, CD52 expression on NSC was found to correlate with a poor survival in patients with MDS and AML.The cell surface target Campath-1 (CD52) is expressed on NSC in a group of patients with MDS and AML. CD52 is a novel prognostic NSC marker and a potential NSC target in a subset of patients with MDS and AML, which may have clinical implications and may explain clinical effects produced by alemtuzumab in these patients.
Air Pollution and Symptoms of Depression in Elderly Adults
Authors: Youn-Hee Lim, Ho Kim, Jin Hee Kim, Sanghyuk Bae, Hye Yin Park, Yun-Chul Hong
Journal: Environmental Health Perspectives (2012)

Although the effect of air pollution on various diseases has been extensively investigated, few studies have examined its effect on depression.We investigated the effect of air pollution on symptoms of depression in an elderly population.We enrolled 537 participants in the study who regularly visited a community center for the elderly located in Seoul, Korea. The Korean version of the Geriatric Depression Scale-Short Form (SGDS-K) was used to evaluate depressive symptomatology during a 3-year follow-up study. We associated ambient air pollutants with SGDS-K results using generalized estimating equations (GEE). We also conducted a factor analysis with items on the SGDS-K to determine which symptoms were associated with air pollution.SGDS-K scores were positively associated with interquartile range (IQR) increases in the 3-day moving average concentration of particulate matter with an aerodynamic diameter ≤ 10 μm (PM10) [17.0% increase in SGDS-K score, 95% confidence interval (CI): 4.9%, 30.5%], the 0-7 day moving average of nitrogen dioxide [NO2; 32.8% (95% CI: 12.6%, 56.6%)], and the 3-day moving average of ozone [O3; 43.7% (95% CI: 11.5%, 85.2%)]. For these three pollutants, factor analysis showed that air pollution was more strongly associated with emotional symptoms such as feeling happy and satisfied than with somatic or affective symptoms.Our study suggests that increases in PM10, NO2, and O3 may increase depressive symptoms among the elderly. Of the symptoms evaluated, ambient air pollution was most strongly associated with emotional symptoms.
Massive Hematuria Due to Abnormal Uterovesical Venous Plexus
Authors: Nathan Chaset
Journal: New England Journal of Medicine (1962)

HEMATURIA is a common everyday occurrence in the practice of urology. In a great majority of cases it leads to an accurate diagnosis and to specific treatment. A recent case of massive hematuria without apparent cause proved to be a frustrating and frightening experience.Case ReportMrs. G.S. (P.L.I.H. 88977), a gravida 6, para 5, was admitted to the hospital on September 11, 1960, with hematuria. Her previous 5 pregnancies had all been terminated by low transverse cesarean sections. The last section, in 1958, was difficult because of adhesions, and the lower uterine segment was torn during attempts to separate . . .
Threatening or manifest reocclusion of the infarct artery in acute myocardial infarction treated with primary PTCA: Outcome after prolonged autoperfusionballoon catheter treatment ≥ 30 minutes
Authors: K. Emmerich, L. Ulbricht, I. Krakau, A. Bufe, H. Probst, H. Gülker
Journal: Journal of the American College of Cardiology (1996)
Partitional Respirometry in Cardio-pulmonary Disease
Authors: R. J. Shephard
Journal: Thorax (1959)

Respiratory disorders cannowbeclassified by theaveragelaboratory asprimary defects of respiratory mechanics orofgasuptake, andthe verdict isaccepted withreasonable confidence. However, further classification ofdisordered gas uptake isstill a tedious anduncertain business. Theaimofpartitional respirometry istomeet thischallenge, distinguishing threebasic components ofthegasuptake process (effective deadspace,diffusing capacity, andpulmonary perfusion). Inconvenience to thepatient is minimal, since allthatisrequired isthebreathing ofa composite gasmixture containing verylow concentrations (300p.p.m.) of ether, carbon monoxide, andacetylene. Theuptake ofeach gasisdetermined byinfra-red analysis. Ether uptake isdependent mainly on ventilation and slightly onperfusion, carbon monoxide uptake on ventilation anddiffusion, andacetylene uptake on perfusion andventilation. A series ofsimultaneousequations withtermsin ventilation, diffusion, andperfusion areobtained, anditis thena simple mattertopartition thegasuptake process intothese three independent components. Thetechnique was originally introduced by HatchandCook(1955), andsomedatarelating to mine-workers werebriefly reported atthattime. Morerecently, simultaneous analysis ofthethree gasesandotherrefinements haveconsiderably increased theprecision of themethod, and multiple regression analyses whichpermit the prediction ofnormalvalues havebeencompleted (Shephard, 1958). Themainobject ofthepresent paperistoevaluate theusefulness ofpartitional respirometry ina variety ofpatients studied in some detailby conventional clinical and physiological methods.
Mental health informatics and the rhythm of community care
Authors: G. Glover
Journal: BMJ (1995)

Information systems in psychiatry must be released from the asylums and updated

Clinical care in British psychiatry has been changing radically in the past two decades. Lifelong care for chronically disabled patients in institutions is giving way to networks of day hospitals, mental health centres, and small residential units. Care in hospital is now reserved largely for episodes of acute mental illness. But the information systems that record what patients, staff, and services are doing are still rooted in the asylum, and lack of appropriate data is impeding clinical work and the development of services. The Department of Health is reviewing the mental health minimum dataset (the information that NHS provider units must pass to purchasers and to the department). This offers an important chance to ensure that the right data are collected in the right way.

What information should be collected, and who needs to use it? At the point of care, staff need user friendly, accurate, and confidential information about patients' past and current problems and care, particularly when emergencies arise outside normal working hours. Electronically held current clinical summaries can also ensure that staff know their responsibilities in each patient's care.1 The Clinical Standards Advisory Group has recently emphasised the value of maintaining a register of patients' care plans.2 Providers managing clinical teams need to …
Abstract 96: Conformational and thermodynamics analyses of the regulation of trifluoperazine on camodulin binding to Fas: Implications for cancer chemotherapy
Authors: Di Pan, Qi Yan, Yabing Chen, Jay M. McDonald, Yuhua Song
Journal: Cancer Research (2010)

Abstract Fas-mediated signaling pathway is an important mechanism for apoptosis in a variety of cells, including cholangiocarcinoma and other cancer cells. The formation of death inducing signaling complex (DISC) is a critical step for Fas-mediated signaling. Recent experimental studies showed that calmodulin (CaM) binds to Fas and regulates Fas-mediated DISC formation and the binding of CaM to Fas is inhibited by the CaM antagonist, trifluoperazine (TFP) (J Cell Biochem, 103:788, 2008). The present study sought to determine the structural basis and molecular mechanisms of TFP regulation of Fas-mediated DISC formation. We used a combination of molecular dynamics simulations and binding free energy analyses to investigate the effect of TFP on CaM-Fas binding. We studied the interactions of different number(s) of TFP(s) with CaM and the effect of the resulting conformational changes of CaM on CaM/Fas binding. We found that the binding affinity of one TFP with CaM was affected by the sequential binding of other TFP(s) to CaM, which was consistent with near-UC circular dichroism data (Biochemistry 37:15300, 1998). The number of TFP(s) bound to CaM was shown to affect the conformational and motion changes of CaM, and thus directly affect CaM binding to Fas. Consistent with previous experimental observations that CaM-Fas binding was affected by TFP concentrations (J Biol Chem, 280:29964, 2005), we demonstrated that one TFP bound to CaM inhibited CaM-Fas binding while the subsequent two TFPs or four TFPs bound to CaM resulted in the recovery of CaM-Fas binding (Table 1). Results also showed that conformational and motional changes of Fas by binding to CaM were directly related to the number of TFPs bound to CaM, which could further affect Fas recruitment of FADD to the DISC. This study provides structural and thermodynamics evidence elucidating the role of the CaM antagonist, TFP, in regulating CaM-Fas binding and Fas-mediated DISC formation and apoptosis.Table 1.The change of CaM-Fas binding affinity by the CaM antagonist, TFP. CaM_Fas_WTCaM_1TFP_FasCaM_2TFPs_FasCaM_4TFPs_FasΔG−7.11±4.67−1.32±0.99−6.96±3.47−6.42±1.06ΔΔG 5.79*0.150.69All values in this table were expressed in terms of kcal/mol. ΔG is the binding free energy for the complex, and ΔΔG is the relative binding free energies with respect to the CaM-Fas complex without CaM antagonist TFP(s). * Differences are statistically significant (Student's t-test, p&amp;lt;0.05) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 96.
Abstract 5615: Effects of corticosteroids on tumor immunity induced by anti-CTLA-4 mAb therapy in a mouse model
Authors: Yuka Maeda, Takuma Kato, Linan Wang, Daisuke Muraoka, Eiichi Sato, Jedd D. Wolchok, Lloyd J. Old, Hiroshi Shiku, Hiroyoshi Nishikawa
Journal: Cancer Research (2010)

Abstract Blockade of CTLA-4 activates/augments CD4+ and CD8+ tumor-specific T cell responses and results in tumor rejection. However, concomitant immune related adverse events (irAEs) in some anti-CTLA-4 mAb treated patients, such as skin rash and gastrointestinal inflammation, suggest that the breaking of tolerance to some normal self-antigens may accompany anti-tumor responses. As a consequence, patients are treated with immunosuppressive drugs, such as corticosteroids. Surprisingly, corticosteroids have not been reported to affect the anti-tumor responses induced by anti-CTLA-4 mAb; indeed, complete and enduring tumor regression has been seen in patients treated for irAEs with various immunosuppressive medications. In this study, we investigated the impact of corticosteroids on anti-tumor immune responses elicited by anti-CTLA-4 mAb in BALB/c mice bearing CMS5a-NY-ESO-1, a transplantable fibrosarcoma expressing NY-ESO-1 (an extensively studied human cancer/testis antigen). After CMS5a-NY-ESO-1 tumor inoculation, graded doses of methylprednisolone injection were initiated. Low doses of corticosteroids, similar to those used to treat patients with irAEs, did not suppress anti-tumor effects of anti-CTLA-4 mAb. However, high doses of corticosteroids, exceeding those used to treat patients with irAEs, impaired tumor growth inhibition by anti-CTLA-4 mAb. Furthermore, when high doses of corticosteroids were injected after the complete regression of tumors, approximately 30% of mice exhibited recurrence of CMS5a-NY-ESO-1 tumors at the initial tumor inoculation sites. This was associated with suppression of CD4+ and CD8+ T cell responses, indicating that anti-CTLA-4 mAb treatment induced an equilibrium-state of anti-tumor immunity, but not tumor eradication in these mice. Analyses of NY-ESO-1-specific CD4+ and CD8+ T cell responses in these mice showed that corticosteroids decreased the number of NY-ESO-1 specific T cells. We propose that dose and timing are important considerations for use of immunosuppression to treat irAEs of CTLA-4 blockade. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5615.