Sunday, June 30, 2013

Does life have a purpose?

Does life have a purpose?

Nobody expects atoms and molecules to have purposes, so why do we still think of living things in this way?
"So what of now? Today’s scientists are pretty certain that the problem of teleology at the individual organism level has been licked. Darwin really was right. Natural selection explains the design-like nature of organisms and their characteristics, without any need to talk about final causes. On the other hand, no natural selection lies behind mountains and rivers and whole planets. They are not design-like. That is why teleological talk is inappropriate, and why the Gaia hypothesis is so criticised. And overall that is why biology is just as good a science as physics and chemistry. It is dealing with different kinds of phenomena and so different kinds of explanation are appropriate. There was a Newton of the blade of grass and his name was Charles Darwin.
But historical teleology — the question of whether evolution itself takes a direction, in particular a progressive one, is a trickier problem, and I cannot say that there is yet, nor the prospect of there ever being, a satisfactory answer. One popular way to explain the apparent progress in evolution is as a biological arms race (a metaphor coined by Julian Huxley, incidentally). Through natural selection, prey animals get faster and so in tandem do predators. Perhaps, as in military arms races, eventually electronics and computers get ever more important, and the winners are those who do best in this respect. The British evolutionary biologist Richard Dawkins has argued that humans have the biggest on-board computers and that is what we expect natural selection to produce. But it is not obvious that arms races would result in humans — those physically feeble and mentally able omnivorous primates. Nor that lines of prey and predator evolve in tandem more generally."

Current Landscape and New Paradigms of Proficiency Testing and External Quality Assessment for Molecular Genetics

Current Landscape and New Paradigms of Proficiency Testing and External Quality Assessment for Molecular Genetics

Lisa V. Kalman PhDIra M. Lubin PhDShannon Barker PhDDesiree du Sart PhDRob Elles PhDWayne W. Grody MD, PhDMario Pazzagli PhDSue Richards PhDIris Schrijver MDBarbara Zehnbauer PhD
From the Laboratory Research and Evaluation Branch, Division of Laboratory Science and Standards, Office of Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention, Atlanta, Georgia (Drs Kalman, Lubin, Barker, and Zehnbauer); the Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia (Dr Barker); the Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, Victoria Australia (Dr du Sart); the Manchester Academic Health Science Centre, Genetic Medicine, St Mary's Hospital, Manchester, Greater Manchester, United Kingdom (Dr Elles); the Departments of Pathology & Laboratory Medicine, Pediatrics, and Human Genetics, University of California, Los Angeles School of Medicine, Los Angeles, California (Dr Grody); the Department of Clinical Physiopathology, University of Florence, Florence, Italy (Dr Pazzagli); the Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon (Dr Richards); and the Departments of Pathology and Pediatrics, Stanford University School of Medicine, Stanford, California (Dr Schrijver).
Context.—Participation in proficiency testing (PT) or external quality assessment (EQA) programs allows the assessment and comparison of test performance among different clinical laboratories and technologies. In addition to the approximately 2300 tests for individual genetic disorders, recent advances in technology have enabled the development of clinical tests that quickly and economically analyze the entire human genome. New PT/EQA approaches are needed to ensure the continued quality of these complex tests.
Objectives.—To review the availability and scope of PT/EQA for molecular genetic testing for inherited conditions in Europe, Australasia, and the United States; to evaluate the successes and demonstrated value of available PT/EQA programs; and to examine the challenges to the provision of comprehensive PT/EQA posed by new laboratory practices and methodologies.
Data Sources.—The available literature on this topic was reviewed and supplemented with personal experiences of several PT/EQA providers.
Conclusions.—Proficiency testing/EQA schemes are available for common genetic disorders tested in many clinical laboratories but are not available for most genetic tests offered by only one or a few laboratories. Provision of broad, method-based PT schemes, such as DNA sequencing, would allow assessment of many tests for which formal PT is not currently available. Participation in PT/EQA improves the quality of testing by identifying inaccuracies that laboratories can trace to errors in their testing processes. Areas of research and development to ensure that PT/EQA programs can meet the needs of new and evolving genetic tests and technologies are identified and discussed.

Almost 1/5 of pathology residency applications contain publication misrepresentations (but most appear minor)

Prevalence and Types of Misrepresentation of Publication Record by Pathology Residency Applicants

Jennifer Raible Kaley MDJoshua Bornhorst PhDMichael Wiggins MDMarwan Yared MD
From the Departments of Pathology (Drs Kaley, Bornhorst, and Yared) and Ophthalmology (Dr Wiggins), and Chemistry, Immunology, Point of Care Testing and Pediatric Laboratory (Dr Bornhorst), University of Arkansas for Medical Sciences, Little Rock.
Context.—Publication misrepresentation among residency applicants has been demonstrated in various specialties. This study examines the prevalence of publication misrepresentation among US-trained and non–US-trained pathology residency applicants.
Objective.—To determine the prevalence of publication misrepresentation in the pathology applicant pool at our institution, to compare the rates of misrepresentation among US-trained and non–US-trained applicants, and to compare results to published results from other medical specialties.
Design.—All peer-reviewed journal articles reported on applications to our program in 2010 and 2011 were examined for veracity. Applications from current or past trainees and applications with unverifiable manuscripts were excluded. The type of misrepresentation and the country in which the applicant trained were recorded.
Results.—Seven hundred applications were reviewed. Of 319 (46%) reported publications, 25 were from US graduates (8%) and 294 (92%) were from non-US graduates. Eighty-six applications were excluded owing to unverifiable manuscripts. Publication misrepresentations were found in 42 (18%) of the remaining 233 applications. The most common misrepresentations were omission of authors (69%), nonauthorship (14%), and self-promotion on the author list (12%). A significantly higher percentage of foreign medical graduates listed publications (P < .001). The misrepresentation rate by foreign graduates (19%) did not differ significantly from that of US-trained graduates (13%) (P = .45).
Conclusions.—Publication misrepresentation was present among pathology residency applicants. Similar rates were seen among US and non-US applicants. Percentages of misrepresentation among applicants to our pathology program and applicants to other medical specialties (18% and 17%, respectively) were comparable.

Diagnostic Medical Home: A Model for Health and Well-Being

Diagnostic Medical Home: A Model for Health and Well-Being

Bennett W. Pafford MD, MPHCathy A. Petti MD
From HealthSpring Global, Inc, Albuquerque, New Mexico.

From lay press to scientific journals, changes in medical diagnostic technology have been described as revolutionary, disruptive, and transformative. And, without doubt, the era of “omics” (ie, genomic, exomic, proteomic) has forged exciting discoveries about disease, ourselves, and the world in which we live. In the near future, home- or office-based diagnostic devices will provide real-time information on disease indicators, such as cardiac status and blood glucose levels, and perform preventive screening. However, our health care system appears to be in a state of uncertainty on how to manage the data from these advanced technologies, and currently, no systematic approach has emerged. With experts claiming (with limited supporting data) that approximately 70% of medical decisions are based on diagnostic tests,1 we need to critically examine the architecture of our health care model to ensure that we are poised to optimize the data from our diagnostic transformation.

A Multiplex Technology Platform for the Rapid Analysis of Clinically Actionable Genetic Alterations and Validation for BRAF p.V600E Detection in 1549 Cytologic and Histologic Specimens

A Multiplex Technology Platform for the Rapid Analysis of Clinically Actionable Genetic Alterations and Validation for BRAF p.V600E Detection in 1549 Cytologic and Histologic Specimens

David L. Smith PhDAude Lamy PhDSylvie Beaudenon-Huibregtse PhDRichard Sesboüé MDWalairat Laosinchai-Wolf ,PhDJean-Christophe Sabourin PhD, MDEmmanuel Labourier PhD
From Asuragen Inc, Austin, Texas, (Drs Smith, Beaudenon-Huibregtse, Laosinchai-Wolf, and Labourier); the Department of Pathology, Rouen University Hospital, Rouen, France (Drs Lamy and Sabourin); and INSERM U1079, Faculty of Medicine, Rouen University, Rouen, France (Dr Sesboüé).
Context.—Current clinicopathologic assessment of malignant neoplastic diseases entails the analysis of specific genetic alterations that provide diagnostic, prognostic, or therapy-determining information.
Objective.—To develop and validate a robust molecular method to detect clinically relevant mutations in various tissue types and anatomic pathology specimens.
Design.—Genes of interest were amplified by multiplex polymerase chain reaction and sequence variants identified by liquid bead array cytometry. The BRAF assay was fully characterized by using plasmids and genomic DNA extracted from cell lines, metastatic colorectal cancer formalin-fixed, paraffin-embedded (FFPE) tissues, and thyroid nodule fine-needle aspirates.
Results.—Qualitative multiplex assays for 22 different mutations in the BRAFHRASKRASNRAS, or EGFR genes were established. The high signal-to-noise ratio of the technology enabled reproducible detection of BRAF c.1799T>A (p.V600E) at 0.5% mutant allele in 20 ng of genomic DNA. Precision studies with multiple operators and instruments showed very high repeatability and reproducibility with 100% (98.7%–100%) qualitative agreement among 292 individual measures in 38 runs. Evaluation of 1549 representative pathologic specimens in 2 laboratories relative to independent reference methods resulted in 99.0% (97.6%–99.6%) agreement for colorectal FFPE tissues (n = 416) and 98.9% (98.2%–99.4%) for thyroid fine-needle aspiration specimens (n = 1133) with an overall diagnostic odds ratio of 10 856 (2451–48 078).
Conclusions.—The multiplex assay system is a sensitive and reliable method to detect BRAF c.1799T>A mutation in colorectal and thyroid lesions. This optimized technology platform is suitable for the rapid analysis of clinically actionable genetic alterations in cytologic and histologic specimens.

Now online in the Archives: CAP's New Cancer Biomarker Reporting Templates for Lung Cancer and Colorectal Cancer

CAP Cancer Biomarker Reporting Templates:

Introducing New College of American Pathologists Reporting Templates for Cancer Biomarkers

Patrick L. Fitzgibbons MDAlexander J. Lazar MD, PhDSamantha Spencer MD
From the Department of Pathology, St Jude Medical Center, Fullerton, California (Dr Fitzgibbons);
the Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston (Dr Lazar);
and the College of American Pathologists, Northfield, Illinois (Dr Spencer).

Lung Cancer:

Template for Reporting Results of Biomarker Testing of Specimens From Patients With Non–Small Cell Carcinoma of the Lung

Philip T. Cagle MDLynette M. Sholl MDNeal I. Lindeman MDRanda Alsabeh MDDimitrios X. G. Divaris MB, ChBPhilipFoulis MD, MPHGemma Lee BSc, PMPJoel W. Neal MD, PhDJan A. Nowak PhD, MDPeter P. Yu MDfor the Members of the Cancer Biomarker Reporting Workgroup, College of American Pathologists
From the Department of Pathology and Genomic Medicine, the Methodist Hospital, Houston, Texas (Dr Cagle);
the Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (Drs Sholl and Lindeman);
the Department of Laboratory Medicine, Grand River Hospital, Kitchener, Ontario, Canada (Dr Divaris);
the Department of Pathology, James A. Haley Veterans' Hospital, Tampa, Florida (Dr Foulis);
the Cancer Information Program, Cancer Care Ontario, Ontario, Canada (Ms Lee);
the Department of Medicine, Division of Oncology, Stanford Cancer Center, Stanford, California (Dr Neal);
the Department of Pathology and Laboratory Medicine, NorthShore University HealthSystem, Evanston, Illinois (Dr Nowak);
and the Department of Hematology-Oncology, Palo Alto Medical Foundation, Mountain View, California (Dr Yu).
Dr Alsabeh is in private practice, Beverly Hills, California.

Colorectal Cancer:

Template for Reporting Results of Biomarker Testing of Specimens From Patients With Carcinoma of the Colon and Rectum

Angela N. Bartley MDStanley R. Hamilton MDRanda Alsabeh MDEdward P. Ambinder MDMichael Berman MDElaineCollins MA, RHIA, CTRPatrick L. Fitzgibbons MDDonna M. Gress RHIT, CTRJan A. Nowak PhD, MDWade S. Samowitz ,MDS. Yousuf Zafar MD, MHSfor the Members of the Cancer Biomarker Reporting Workgroup, College of American Pathologists
From the Department of Pathology, St. Joseph Mercy Hospital, Ann Arbor, Michigan (Dr Bartley); the Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston (Dr Hamilton); the Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York (Dr Ambinder); the Department of Pathology, Jefferson Regional Medical Center, Jefferson Hills, Pennsylvania (Dr Berman); St Paul, Minnesota (Ms Collins); the Department of Pathology, St. Jude Medical Center, Fullerton, California (Dr Fitzgibbons); the American Joint Committee on Cancer, Chicago, Illinois (Ms Gress); the Department of Pathology and Laboratory Medicine, NorthShore University HealthSystem, Evanston, Illinois (Dr Nowak); the Department of Pathology, University of Utah, Salt Lake City (Dr Samowitz); and the Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina (Dr Zafar). Dr Alsabeh is in private practice, Beverly Hills, California.

U Mass's Armando Fraire debutes his "Five Top Stories" series in the July Archives: First up-Cytopathology

U Mass's Armando Fraire debutes his "Five Top Stories" series in the July Archives:

Five Top Stories in Anatomic Pathology: Stories From the Faculty at UMass Medical School and UMass Memorial Medical Center, Worcester, Massachusetts

Armando E. Fraire MD
From the Department of Pathology, University of Massachusetts Medical School, Worcester.

First up-Cytopathology:

Clinical Implications of Current Developments in Genitourinary Pathology

Amy G. Zhou MDChristopher L. Owens MDEdiz F. Cosar MDZhong Jiang MD
From the Department of Pathology, University of Massachusetts Medical School, Worcester.
Context.—Several developments in genitourinary pathology are likely to change our understanding and management of some genitourinary cancers considerably.
Objective.—To review 5 stories in genitourinary pathology: (1) fusion in the ETS (E26) gene family in prostatic adenocarcinoma; (2) insulin-like growth factor II messenger RNA-binding protein 3 (IMP3), an important prognostic biomarker for kidney and bladder cancers; (3) translocation renal cell carcinoma; (4) UroVysion fluorescence in situ hybridization test in urine cytology for detection of bladder cancer; and (5) the use of triple immunostaining for diagnosis of prostate cancer.
Data Sources.—Literature review and authors' personal experiences.
Conclusions.—Many scientific findings have contributed recently to the understanding of the natural pathogenesis and progression of genitourinary cancers. This translational research helps in diagnosing, predicting, and potentially, treating genitourinary cancers.

Five Top Stories in Cytopathology

Andrew H. Fischer MDCynthia C. Benedict MDMojgan Amrikachi MD
From the Department of Pathology, University of Massachusetts Medical Center, Worcester, Massachusetts (Dr Fischer); the Department of Cytopathology, DCL Medical Laboratories, Inc, Indianapolis, Indiana (Dr Benedict); and the Department of Pathology and Genomic Medicine, The Methodist Hospital, Houston, Texas (Dr Amrikachi).
Context.—Cytology relies heavily on morphology to make diagnoses, and morphologic criteria have not changed much in recent years. The field is being shaped predominantly by new techniques for imaging and for acquiring and processing samples, advances in molecular diagnosis and therapeutics, and regulatory issues.
Objective.—To review the importance of classical morphology in the future of cytopathology, to identify areas in which cytology is expanding or contracting in its scope, and to identify factors that are shaping the field.
Data Sources.—Literature review.
Conclusions.—Five stories paint a picture in which classical cytomorphology will continue to have essential importance, both for diagnosis and for improving our understanding of cancer biology. New endoscopy and imaging techniques are replacing surgical biopsies with cytology samples. New molecularly targeted therapies offer a chance for cytology to play a major role, but they pose new challenges. New molecular tests have the potential to synergize with, but not replace, morphologic interpretation of thyroid fine-needle aspirations. Ultrasound-guided fine-needle aspiration performed by cytopathologists is opening a new field of “interventional cytopathology” with unique value. For the productive evolution of the field, it will be important for cytopathologists to play an active role in clinical trials that document the ability of cytology to achieve cost-effective health care outcomes.

From 'beastly philosophy' to medical genetics: eugenics in Russia and the Soviet Union

 2011 Jan;68(1):61-92.

From 'beastly philosophy' to medical genetics: eugenics in Russia and the Soviet Union.


University of Toronto, Toronto, Canada.


This essay offers an overview of the three distinct periods in the development of Russian eugenics: Imperial (1900-1917), Bolshevik (1917-1929), and Stalinist (1930-1939). Began during the Imperial era as a particular discourse on the issues of human heredity, diversity, and evolution, in the early years of the Bolshevik rule eugenics was quickly institutionalized as a scientific discipline--complete with societies, research establishments, and periodicals--that aspired an extensive grassroots following, generated lively public debates, and exerted considerable influence on a range of medical, public health, and social policies. In the late 1920s, in the wake of Joseph Stalin's 'Great Break', eugenics came under intense critique as a 'bourgeois' science and its proponents quickly reconstituted their enterprise as 'medical genetics'. Yet, after a brief period of rapid growth during the early 1930s, medical genetics was dismantled as a 'fascist science' towards the end of the decade. Based on published and original research, this essay examines the factors that account for such an unusual--as compared to the development of eugenics in other locales during the same period--historical trajectory of Russian eugenics.

Saturday, June 29, 2013

Beyond Workers' Compensation: Men's Mental Health In and Out of Work

 2013 May 30. [Epub ahead of print]

Beyond Workers' Compensation: Men's Mental Health In and Out of Work.


1University of British Columbia, Vancouver, British Columbia, Canada.


The mental health of men is an important issue with significant direct and indirect costs emerging from work-related depression and suicide. Although the merits of men's community-based and workplace mental health promotion initiatives have been endorsed, few programs are mandated or formally evaluated and reported on. Conspicuously absent also are gender analyses detailing connections between masculinities and men's work-related depression and suicide on which to build men-centered mental health promotion programs. This article provides an overview of four interconnected issues, (a) masculinities and men's health, (b) men and work, (c) men's work-related depression and suicide, and (d) men's mental health promotion, in the context of men's diverse relationships to work (including job insecurity and unemployment). Based on the review, recommendations are made for advancing the well-being of men who are in as well as of those out of work.

From Ohio State U: What is Patient-Centered Care?

 2013 Jun 27. [Epub ahead of print]

What is Patient-Centered Care? A Typology of Models and Missions.


Division of Health Services Management and Policy, College of Public Health, The Ohio State University, 200B Cunz Hall, 1841 Neil Ave., Columbus, OH, 43201, USA,


Recently adopted health care practices and policies describe themselves as "patient-centered care." The meaning of the term, however, remains contested and obscure. This paper offers a typology of "patient-centered care" models that aims to contribute to greater clarity about, continuing discussion of, and further advances in patient-centered care. The paper imposes an original analytic framework on extensive material covering mostly US health care and health policy topics over several decades. It finds that four models of patient-centered care emphasize: patients versus their parts; patients versus providers; patients/providers/states versus "the system"; and patients and providers as persons. Each type is distinguishable along three dimensions: epistemological orientations, practical accommodations, and policy tools. Based on this analysis, the paper recommends that four questions be asked of any proposal that claims to provide patient-centered care: Is this care a means to an end or an end in itself? Are patients here subjects or objects? Are patients here individuals or aggregates? How do we know what patients want and need? The typology reveals that models are neither entirely compatible nor entirely incompatible and may be usefully combined in certain practices and policies. In other instances, internal contradictions may jeopardize the realization of coherent patient-centered care.

Acquired resistance to targeted therapies in advanced non-small cell lung cancer

 2013;2013:272-8. doi: E10.1200/EdBook_AM.2013.33.e272.

Acquired resistance to targeted therapies in advanced non-small cell lung cancer.


From the Swedish Cancer Institute, Seattle, WA; Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO.


Although the transition to molecularly defined patient subgroups in advanced non-small cell lung cancer (NSCLC) often leads to dramatic and prolonged responses to an inhibitor of an identified oncogenic mutation, acquired resistance eventually ensues. The optimal approach to management in that setting remains the subject of ongoing research, although it is possible to identify several points that distinguish it from traditional tenets based on conventional chemotherapy. Such patients are not equivalent to those who have progressed on first-line chemotherapy, and consideration of initiation of chemotherapy-based regimens as if the patient were being treated first line in the absence of an oncogenic mutation is a reasonable consideration. Acquired resistance is often partial; therefore, continued treatment with the same targeted therapy or another agent against the same target is a strategy favored by many experts, in part to minimize the risk of "rebound progression" that may occur when the targeted therapy is withdrawn. Progression within the central nervous system (CNS) may occur because of poor penetration of the systemic targeted therapy into the CNS, rather than true cellular resistance to the therapy itself; accordingly, local therapy for "brain only" progression with sustained targeted therapy for extracranial disease can be associated with prolonged disease control. Finally, patients with acquired resistance to a targeted therapy are ideal candidates for clinical trials when available, particularly when repeat biopsies of progressing lesions can help elucidate mechanisms of resistance and thereby lead to histologically and molecularly informed treatment decisions.

From Uppsala U-Sweden: Possibilities and limits of mind-reading: A neurophilosophical perspective

 2013 Jun 24;22(3):887-897. doi: 10.1016/j.concog.2013.05.011. [Epub ahead of print]

Possibilities and limits of mind-reading: A neurophilosophical perspective.


Centre for Research Ethics and Bioethics (CRB), Uppsala University, Sweden. Electronic address:


Access to other minds once presupposed other individuals' expressions and narrations. Today, several methods have been developed which can measure brain states relevant for assessments of mental states without 1st person overt external behavior or speech. Functional magnetic resonance imaging and trace conditioning are used clinically to identify patterns of activity in the brain that suggest the presence of consciousness in people suffering from severe consciousness disorders and methods to communicate cerebrally with patients who are motorically unable to communicate. The techniques are also used non-clinically to access subjective awareness in adults and infants. In this article we inspect technical and theoretical limits on brain-machine interface access to other minds. We argue that these techniques hold promises of important medical breakthroughs, open up new vistas of communication, and of understanding the infant mind. Yet they also give rise to ethical concerns, notably misuse as a consequence of hypes and misinterpretations.

Friday, June 28, 2013

From Shanghai Jiao Tong U: Snail, slug, and colorectal cancer


Epithelial-mesenchymal Transition and Its Role in the Pathogenesis of Colorectal Cancer.


Department of Surgery, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China E-mail :


Epithelial-to-mesenchymal transition (EMT) is a collection of events that allows the conversion of adherent epithelial cells, tightly bound to each other within an organized tissue, into independent fibroblastic cells possessing migratory properties and the ability to invade the extracellular matrix. EMT contributes to the complex architecture of the embryo by permitting the progression of embryogenesis from a simple single-cell layer epithelium to a complex three-dimensional organism composed of both epithelial and mesenchymal cells. However, in most tissues EMT is a developmentally restricted process and fully differentiated epithelia typically maintain their epithelial phenotype. Recently, elements of EMT, specially the loss of epithelial markers and the gain of mesenchymal markers, have been observed in pathological states, including epithelial cancers. Increasing evidence has confirmed its presence in human colon during colorectal carcinogenesis. In general, chronic inflammation is considered to be one of the causes of many human cancers including colorectal cancer(CRC). Accordingly, epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel disease, have an increased risk of developing CRC. A large body of evidence supports roles for the SMAD/STAT3 signaling pathway, the NF-kB pathway, the Ras-mitogen- activated protein kinase/Snail/Slug and microRNAs in the development of colorectal cancers via epithelial-to- mesenchymal transition. Thus, EMT appears to be closely involved in the pathogenesis of colorectal cancer, and analysis refered to it can yield novel targets for therapy.

Dracula's children: Molecular evolution of vampire bat venom

 2013 Jun 5. pii: S1874-3919(13)00310-2. doi: 10.1016/j.jprot.2013.05.034. [Epub ahead of print]

Dracula's children: Molecular evolution of vampire bat venom.


Venom Evolution Lab, School of Biological Sciences, University of Queensland, St. Lucia, Queensland 4072, Australia.


While vampire bat oral secretions have been the subject of intense research, efforts have concentrated only on two components: DSPA (Desmodus rotundus salivary plasminogen activator) and Draculin. The molecular evolutionary history of DSPA has been elucidated, while conversely draculin has long been known from only a very small fragment and thus even the basic protein class was not even established. Despite the fact that vampire bat venom has a multitude of effects unaccounted by the documented bioactivities of DSPA and draculin, efforts have not been made to establish what other bioactive proteins are secreted by their submaxillary gland. In addition, it has remained unclear whether the anatomically distinct anterior and posterior lobes of the submaxillary gland are evolving on separate gene expression trajectories or if they remain under the shared genetic control. Using a combined proteomic and transcriptomic approach, we show that identical proteins are simultaneously expressed in both lobes. In addition to recovering the known structural classes of DSPA, we recovered a novel DSPA isoform as well as obtained a very large sequence stretch of draculin and thus established that it is a mutated version of the lactotransferrin scaffold. This study reveals a much more complex secretion profile than previously recognised. In addition to obtaining novel versions of scaffolds convergently recruited into other venoms (allergen-like, CRiSP, kallikrein, Kunitz, lysozyme), we also documented novel expression of small peptides related to calcitonin, PACAP, and statherin. Other overexpressed protein types included BPI-fold, lacritin, and secretoglobin. Further, we investigate the molecular evolution of various vampire bat venom-components and highlight the dominant role of positive selection in the evolution of these proteins. Conspicuously many of the proteins identified in the proteome were found to be homologous to proteins with known activities affecting vasodilation and platelet aggregation. We show that vampire bat venom proteins possibly evade host immune response by the mutation of the surface chemistry through focal mutagenesis under the guidance of positive Darwinian selection. These results not only contribute to the body of knowledge regarding haematophagous venoms but also provide a rich resource for novel lead compounds for use in drug design and development. 
BIOLOGICAL SIGNIFICANCE: These results have direct implications in understanding the molecular evolutionary history of vampire bat venom. The unusual peptides discovered reinforce the value of studying such neglected taxon for biodiscovery.

Zombie allusions: They just keep on coming-Mixing metaphors

Are Gold and Silver Now Zombie Metals?

Jun 29, 2013 - 01:37 AM GMT

Analysts who once talked up the metals are now saying gold will slump to $900 an ounce… or lower. Investors who once loved mining stocks now loathe them. And on the other side, you have respectable people, furious over gold’s decline, talking about the metal going to “infinity.”

You know who you are, and if the shoe fits, start upping your meds.

It’s easy to see that the short-term forces have turned against precious metals. However, those who say gold and silver are “zombie” investments – slowly shuffling their way into the financial graveyard – don’t have a leg to stand on.

The second "time-out": a surgical safety checklist for lengthy robotic surgeries

 2013 Jun 3;7(1):19. doi: 10.1186/1754-9493-7-19.

The second "time-out": a surgical safety checklist for lengthy robotic surgeries.


Washington University in St, Louis School of Medicine, 4960 Children's Place, Campus Box 8242, St, Louis, MO 63110, USA.


Robotic surgeries of long duration are associated with both increased risks to patients as well as distinct challenges for care providers. We propose a surgical checklist, to be completed during a second "time-out", aimed at reducing peri-operative complications and addressing obstacles presented by lengthy robotic surgeries. A review of the literature was performed to identify the most common complications of robotic surgeries with extended operative times. A surgical checklist was developed with the goal of addressing these issues and maximizing patient safety. Extended operative times during robotic surgery increase patient risk for position-related complications and other adverse events. These cases also raise concerns for surgical, anesthesia, and nursing staff which are less common in shorter, non-robotic operations. Key elements of the checklist were designed to coordinate operative staff in verifying patient safety while addressing the unique concerns within each specialty. As robotic surgery is increasingly utilized, operations with long surgical times may become more common due to increased case complexity and surgeons overcoming the learning curve. A standardized surgical checklist, conducted three to four hours after the start of surgery, may enhance perioperative patient safety and quality of care.

"When public health and primary care work well, virtually nobody notices."

 2011 Jan 1;2(1):65-68. Epub 2010 Oct 27.

Public Health and Primary Care: Struggling to "Win Friends and Influence People"


University of Richmond, Richmond, VA, USA.


Why are the goals of public health and primary care less politically popular and financially supported than those of curative medicine? A major part of the answer to this question lies in the fact that humans often worry wrongly by assessing risk poorly. This reality is a significant obstacle to the adequate promotion of and investment in public health, primary care, and prevention. Also, public health's tendency to infringe on personal privacy-as well as to call for difficult behavioral change-often sparks intense controversy and interest group opposition that discourage broader political support. Finally, in contrast to curative medicine, both the cost-benefit structure of public health (costs now, benefits later) and the way in which the profession operates make it largely invisible to and, thus, underappreciated by the general public. When curative medicine works well, most everybody notices. When public health and primary care work well, virtually nobody notices.