Professional working at computer notebooks is associated with high requirements on the body posture in the seated position. By the high continuous static muscle stress resulting from this position at notebooks, professionals frequently working at notebooks for long hours are exposed to an increased risk of musculoskeletal complaints. Especially in subjects with back pain, new notebooks should be evaluated with a focus on rehabilitative issues.
In a field study a new notebook design with adjustable screen was analyzed and compared to standard notebook position.
There are highly significant differences in the visual axis of individuals who are seated in the novel notebook position in comparison to the standard position. Also, differences are present between further alternative notebook positions. Testing of gender and glasses did not reveal influences.
This study demonstrates that notebooks with adjustable screen may be used to improve the posture. Future studies may focus on patients with musculoskeletal diseases.
With massive amounts of data being generated in electronic format, there is a need in basic science laboratories to adopt new methods for tracking and analyzing data. An electronic laboratory notebook (ELN) is not just a replacement for a paper lab notebook, it is a new method of storing and organizing data while maintaining the data entry flexibility and legal recording functions of paper notebooks. Paper notebooks are regarded as highly flexible since the user can configure it to store almost anything that can be written or physically pasted onto the pages. However, data retrieval and data sharing from paper notebooks are labor intensive processes and notebooks can be misplaced, a single point of failure that loses all entries in the volume. Additional features provided by electronic notebooks include searchable indices, data sharing, automatic archiving for security against loss and ease of data duplication. Furthermore, ELNs can be tasked with additional functions not commonly found in paper notebooks such as inventory control. While ELNs have been on the market for some time now, adoption of an ELN in academic basic science laboratories has been lagging. Issues that have restrained development and adoption of ELN in research laboratories are the sheer variety and frequency of changes in protocols with a need for the user to control notebook configuration outside the framework of professional IT staff support. In this commentary, we will look at some of the issues and experiences in academic laboratories that have proved challenging in implementing an electronic lab notebook.
John Peters and his committee had a few basic goals. One was that local, state, and federal governments needed to provide money to construct facilities, support medical research and education, and care for the poor. And they wanted experts to call the shots. Over time, Peters and the committee got what they wanted for the most part: Hill-Burton money for building the hospitals, the rise of the National Institutes of Health, Medicare, Medicaid, a Veterans Administration system, and new and expanded medical schools. The experts calling the shots included David Kessler at the Food and Drug Administration and Surgeon General C. Everett Koop. In the halcyon days of American health system reform, back in 1993, Yale's Paul Beeson wrote about the Committee of 430 Physicians and its goals in the Pharos of Alpha Omega Alpha. Beeson was optimistic and he quoted from my 1991 JAMA health system reform editorial as a sharp contrast to what Fishbein had written - although coincidentally, we both quote Lincoln. My editorial began, "'with malice toward none, with charity for all...' so spoke Abraham Lincoln in his second inaugural address recognizing that he had no political consensus regarding either the constitutionality of states seceding or the morality of slavery being abolished. Nonetheless, he knew what was right and was able, through persuasive, often inspiring rhetoric, to conclude a bloody and decisive Civil War and constitute the foundation for this great republic.... Yet access to basic medical care for all of our inhabitants is still not a reality in this country. There are many reasons for this, not the least of which is a long-standing, systematic, institutionalized racial discrimination.... An aura of inevitablitiy is upon us. It is not acceptable morally, ethically, or economically for so many of our people to be medically uninsured or seriously underinsured. We can solve this problem. We have the knowledge and the resources, the skills, the time, and the moral prescience. We need only clear-cut objectives and proper organization of existing resources. Have we now the national will and leadership?" Beeson's answer to that question in 1993 was, "Yes, but not by one comprehensive act." He quoted Peters from his 1938 Annals of Internal Medicine article: "a sweeping program suddenly imposed in this country as a whole out of the head of any Jove would undoubtedly create confusion if not chaos. Thoughtful investigation and experiment promises more than grandiose projects born of emotional preconceptions. The programs must be built of an evolutionary manner, step by step." Very wise, very valid. But how long must our people wait?
This article presents a plethora of fragments from the medical notebooks found in the Cairo Genizah that comprise a unique source of historical data for scholarly study and for a better understanding of the ways in which medieval medical knowledge in Egypt was transferred from theory to practice and vice versa. These documents provide the most direct evidence we have for preferred practical medical recipes because they record the choices of medical practitioners in medieval Cairo. Since the language most commonly used in them was Judaeo-Arabic, they were evidently written by Jews. The medical genre in the notebooks was primarily pharmacopoeic, consisting of apparently original recipes for the treatment of various diseases. There are also a few notebooks on materia medica. The subject matter of the Genizah medical notebooks shows that they were mostly of an eclectic nature, i.e. the writers had probably learnt about these treatments and recipes from their teachers, applied them at the hospitals where they worked or copied them from the books they read. Foremost among the subjects dealt with were eye diseases, followed by skin diseases, coughs and colds, dentistry and oral hygiene, and gynaecological conditions. The writers of the Genizah notebooks apparently recorded the practical medical knowledge they wished to preserve for their future use as amateur physicians, students, traditional healers or professional practitioners.
Cairo Genizah; History of Medicine; Jewish; Medieval Middle East; Middle Ages; Notebook
John R. Paul, Professor of Preventive Medicine at the Yale University School of Medicine, wrote numerous monographs and papers defining and delimiting the field of preventive medicine and its fundamental science, clinical epidemiology. For Dr. Paul, preventive medicine was part of the continuum of clinical medicine; others believed that it was a separate entity deserving of departmental status. This paper discusses Dr. Paul's definition and philosophy of preventive medicine in contrast to other disciplines, such as social medicine and public health.
Part diary, part scientific record, biological field notebooks often contain details necessary to understanding the location and environmental conditions existent during collecting events. Despite their clear value for (and recent use in) global change studies, the text-mining outputs from field notebooks have been idiosyncratic to specific research projects, and impossible to discover or re-use. Best practices and workflows for digitization, transcription, extraction, and integration with other sources are nascent or non-existent. In this paper, we demonstrate a workflow to generate structured outputs while also maintaining links to the original texts. The first step in this workflow was to place already digitized and transcribed field notebooks from the University of Colorado Museum of Natural History founder, Junius Henderson, on Wikisource, an open text transcription platform. Next, we created Wikisource templates to document places, dates, and taxa to facilitate annotation and wiki-linking. We then requested help from the public, through social media tools, to take advantage of volunteer efforts and energy. After three notebooks were fully annotated, content was converted into XML and annotations were extracted and cross-walked into Darwin Core compliant record sets. Finally, these recordsets were vetted, to provide valid taxon names, via a process we call “taxonomic referencing.” The result is identification and mobilization of 1,068 observations from three of Henderson’s thirteen notebooks and a publishable Darwin Core record set for use in other analyses. Although challenges remain, this work demonstrates a feasible approach to unlock observations from field notebooks that enhances their discovery and interoperability without losing the narrative context from which those observations are drawn.
“Compose your notes as if you were writing a letter to someone a century in the future.”
Perrine and Patton (2011)
Field notes; notebooks; crowd sourcing; digitization; biodiversity; transcription; text-mining; Darwin Core; Junius Henderson; annotation; taxonomic referencing; natural history; Wikisource; Colorado; species occurrence records
Lancet is a new, simulator-independent Python utility for succinctly specifying, launching, and collating results from large batches of interrelated computationally demanding program runs. This paper demonstrates how to combine Lancet with IPython Notebook to provide a flexible, lightweight, and agile workflow for fully reproducible scientific research. This informal and pragmatic approach uses IPython Notebook to capture the steps in a scientific computation as it is gradually automated and made ready for publication, without mandating the use of any separate application that can constrain scientific exploration and innovation. The resulting notebook concisely records each step involved in even very complex computational processes that led to a particular figure or numerical result, allowing the complete chain of events to be replicated automatically. Lancet was originally designed to help solve problems in computational neuroscience, such as analyzing the sensitivity of a complex simulation to various parameters, or collecting the results from multiple runs with different random starting points. However, because it is never possible to know in advance what tools might be required in future tasks, Lancet has been designed to be completely general, supporting any type of program as long as it can be launched as a process and can return output in the form of files. For instance, Lancet is also heavily used by one of the authors in a separate research group for launching batches of microprocessor simulations. This general design will allow Lancet to continue supporting a given research project even as the underlying approaches and tools change.
IPython; pandas; reproducibility; workflow; simulation; batch computation; provenance; big data
John N. Brady, Chief of the Virus Tumor Biology Section of the Laboratory of Cellular Oncology, National Institutes of Health, died of cancer on 27 April 2009. John was a stellar member of the virology community. He was a longtime Journal of Virology reviewer and a member of the editorial board. He will be missed. Fatah Kashanchi of the George Washington University Medical Center has written John's memorial. Fatah worked with John at the NIH and published more than 30 papers with him. Fatah thanks all the people who contributed to John's obituary, including Kuan-Teh Jeang, Lou Laimins, Mary Loeken, Renaud Mehieux, Paul Lambert, Graziella Piras, Scott Gitlin, Paul Lindholm, Nadia Rosenthal, Sergi Nekhai, Brian Wigdahl, David Price, Susan J. Marriott, Cynthia Masison, Jurgen Dittmer, Eric Verdin, Bassel E. Sawaya, and John's longtime assistants Janet Duvall Grimm and Michael Radonovich, who gave immense support to all the individuals who went through John's lab.
eCAT is an electronic lab notebook (ELN) developed by Axiope Limited. It is the first online ELN, the first ELN to be developed in close collaboration with lab scientists, and the first ELN to be targeted at researchers in non-commercial institutions. eCAT was developed in response to feedback from users of a predecessor product. By late 2006 the basic concept had been clarified: a highly scalable web-based collaboration tool that possessed the basic capabilities of commercial ELNs, i.e. a permissions system, controlled sharing, an audit trail, electronic signature and search, and a front end that looked like the electronic counterpart to a paper notebook.
During the development of the beta version feedback was incorporated from many groups including the FDA's Center for Biologics Evaluation & Research, Uppsala University, Children's Hospital Boston, Alex Swarbrick's lab at the Garvan Institute in Sydney and Martin Spitaler at Imperial College. More than 100 individuals and groups worldwide then participated in the beta testing between September 2008 and June 2009. The generally positive response is reflected in the following quote about how one lab is making use of eCAT: "Everyone uses it as an electronic notebook, so they can compile the diverse collections of data that we generate as biologists, such as images and spreadsheets. We use to it to take minutes of meetings. We also use it to manage our common stocks of antibodies, plasmids and so on. Finally, perhaps the most important feature for us is the ability to link records, reagents and experiments."
By developing eCAT in close collaboration with lab scientists, Axiope has come up with a practical and easy-to-use product that meets the need of scientists to manage, store and share data online. eCAT is already being perceived as a product that labs can continue to use as their data management and sharing grows in scale and complexity.
During the past several years, Baylor College of Medicine has made a substantial commitment to the use of information technology in support of its corporate and academic programs. The concept of an Integrated Academic Information Management System (IAIMS) has proved central in our planning, and the IAIMS activities that we have undertaken with funding from the National Library of Medicine have proved to be important extensions of our technology development. Here we describe our Virtual Notebook system, a conceptual and technologic framework for task coordination and information management in biomedical work groups. When fully developed and deployed, the Virtual Notebook will improve the functioning of basic and clinical research groups in the college, and it currently serves as a model for the longer-term development of our entire information management environment.
Currently most biomedical labs in universities and government funded research institutions use paper lab notebooks for recording experimental data and spreadsheets for managing sample data. One consequence is that sample management and documenting experiments are viewed as separate and distinct activities, notwithstanding that samples and aliquots are an integral part of a majority of the experiments carried out by these labs.
Various drivers are pushing labs towards integrated management of sample data and experimental data. These include the ever increasing amounts of both kinds of data, the increasing adoption of online collaborative tools, changing expectations about online communication, and the increasing affordability of electronic lab notebooks and sample management software. There is now an opportunity for smaller labs, which have been slow to move from paper to electronic record keeping, to leapfrog better resourced commercial labs and lead the way in adopting the new generation of tools which permit integrated management of samples and experimental data and a range of tangible benefits to conducting research, including:
1. Fewer lost and mislabelled samples
2. Clearer visualization of relationships between samples and experiments
3. Reduction of experimental error
4. More effective search
5. Productivity gains
6. More efficient use of freezers, leading to cost reduction and enhanced sustainability
7. Improved archiving and enhanced memory at the lab and institutional levels
The objective of this study was to describe the distribution of Mycobacterium avium subsp. paratuberculosis (MAP) in the environment of infected dairy farms over time. Johne’s disease (JD) prevalence was monitored annually in 7 Michigan dairy herds. Environmental samples were collected bi-annually and cultured for MAP. Of 731 environmental samples that were cultured, 81 (11%) were positive. The lactating cow floor and manure storage areas were the areas most commonly contaminated, representing 30% and 33% of positive samples, respectively. When herd prevalence was > 2%, MAP was cultured from the lactating cow floor and/or manure storage area 75% of the time. When herd prevalence was ≤ 2%, MAP was never cultured from samples collected. For every 1 unit increase in number of positive environmental samples, within herd JD prevalence increased 1.62%. Environmental contamination with MAP is consistent over time on infected dairy farms, and management practices to reduce environmental contamination are warranted.
St. John's Wort is commonly known for its antiviral, antidepressant, and cytotoxic properties, but traditionally St. John's Wort has also been used to treat inflammation. In this study, we sought to characterize the mechanisms used by St. John's Wort to treat inflammation by examining the effect of the recently isolated protein from St. John's Wort, p27SJ on the expression of MCP-1. By employing an adenovirus expression vector, we demonstrate that a low concentration of p27SJ upregulates the MCP-1 promoter through the transcription factor C/EBPβ. In addition, we found that C/EBPβ-homologous protein (CHOP) or siRNA-C/EBPβ significantly reduced the ability of p27SJ to activate MCP-1 gene expression. Results from protein-protein interaction studies illustrate the existence of a physical interaction between p27SJ and C/EBPβ in microglial cells. The use of chromatin immunoprecipitation assay (ChIP) led to the identification of a new cis-element that is responsive to C/EBPβ within the MCP-1 promoter. Association of C/EBPβ with MCP-1 DNA was not affected by the presence of p27SJ. The biological activity of MCP-1 produced by cultures of adenovirus-p27SJ transduced cells was increased relative to controls as measured by the transmigration of human Jurkat cells. Thus, we conclude that at high concentration, p27SJ is a potential agent that may be developed as a modulator of MCP-1 leading to the inhibition of the cytokine-mediated inflammatory responses.
Adipocytes are insulin sensitive cells that play a major role in energy homeostasis. Obesity is the primary disease of fat cells and a major risk factor for the development of Type II diabetes, cardiovascular disease, and metabolic syndrome. Obesity and its related disorders result in dysregulation of the mechanisms that control adipocyte gene expression and function. To identify potential novel therapeutic modulators of adipocytes, we screened 425 botanical extracts for their ability to modulate adipogenesis and insulin sensitivity. We observed that less than 2% of the extracts had substantial effects on adipocyte differentiation of 3T3-L1 cells. Two of the botanical extracts that inhibited adipogenesis were extracts from St. John’s Wort (SJW). Our studies revealed that leaf and flower, but not root, extracts isolated from SJW inhibited adipogenesis as judged by examining PPARγ and adiponectin levels. We also examined the effects of these SJW extracts on insulin sensitivity in mature 3T3-L1 adipocytes. Both leaf and flower extracts isolated from SJW substantially inhibited insulin sensitive glucose uptake. The specificity of the observed effects was demonstrated by showing that treatment with SJW flower extract resulted in a time and dose dependent inhibition of insulin stimulated glucose uptake. SJW is commonly used in the treatment of depression. However, our studies have revealed that SJW may have a negative impact on adipocyte related diseases by limiting differentiation of preadipocytes and significantly inducing insulin resistance in mature fat cells.
Mycobacterium avium subspecies paratuberculosis (M. ap), the causative agent of Johne’s disease, infects many farmed ruminants, wild-life animals, and recently isolated from humans. To better understand the molecular pathogenesis of these infections, we analyzed the whole-genome sequences of several M. ap and M. avium subspecies avium (M. avium) isolates to gain insights into genomic diversity associated with variable hosts and environments. Using Next-generation sequencing technology, all six M. ap isolates showed a high percentage of similarity (98%) to the reference genome sequence of M. ap K-10 isolated from cattle. However, two M. avium isolates (DT 78 and Env 77) showed significant sequence diversity (only 87 and 40% similarity, respectively) compared to the reference strain M. avium 104, a reflection of the wide environmental niches of this group of mycobacteria. Within the M. ap isolates, genomic rearrangements (insertions/deletions) were not detected, and only unique single nucleotide polymorphisms (SNPs) were observed among M. ap isolates. While more of the SNPs (~100) in M. ap genomes were non-synonymous, a total of ~6,000 SNPs were detected among M. avium genomes, most of them were synonymous suggesting a differential selective pressure between M. ap and M. avium isolates. In addition, SNPs-based phylo-genomics had a enough discriminatory power to differentiate between isolates from different hosts but yet suggesting a bovine source of infection to other animals examined in this study. Interestingly, the human isolate (M. ap 4B) was closely related to a M. ap isolate from a dairy facility, suggesting a common source of infection. Overall, the identified phylo-genomes further supported the idea of a common ancestor to both M. ap and M. avium isolates. Genome-wide analysis described here could provide a strong foundation for a population genetic structure that could be useful for the analysis of mycobacterial evolution and for the tracking of Johne’s disease transmission among animals.
Mycobacteria; paratuberculosis; Johne’s disease; whole-genome sequencing; genomics; pathogenesis
This paper presents new data addressing two important controversies in psychiatry: the construct of Minor Depression (MinD) and the efficacy of St. John’s Wort for milder forms of depressive disorders. Data are from a three-arm, 12 week, randomized clinical trial of investigating the efficacy of St. John’s Wort (810 mg/day), citalopram (20 mg/day), or placebo for acute treatment of MinD. Due to a high placebo response on all outcome measures, neither St. John’s Wort nor citalopram separated from placebo on change in depressive symptom severity, quality of life, or well-being. However, systematic assessment of potential adverse effects (AEs) led to three important observations: (1) prior to the administration of study compound, 60% of subjects endorsed items that would be characterized as AEs once study compound was administered, (2) St. John’s Wort and citalopram were each associated with a significant number of new or worsening AEs during treatment, and (3) using a structured interview for identifying AEs at baseline and during treatment is informative. MinD was not responsive to either a conventional antidepressant or a nutraceutical, and both compounds were associated with a notable side effects burden. Other treatment approaches for MinD should be investigated.
While many factors contribute to resistance and susceptibility to infectious disease, a major component is the genotype of the host and the way in which it is expressed. Johne’s disease is a chronic inflammatory bowel disease affecting ruminants and is caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP). We have previously identified red deer breeds (Cervus elaphus) that are resistant; have a low rate of MAP infection and do not progress to develop Johne’s disease. In contrast, susceptible breeds have a high rate of MAP infection as seen by seroconversion and progress to develop clinical Johne’s disease. The aim of this study was to determine if immunological differences exist between animals of resistant or susceptible breeds. Macrophage cultures were derived from the monocytes of deer genotypically defined as resistant or susceptible to the development of Johne’s disease. Following in vitro infection of the cells with MAP, the expression of candidate genes was assessed by quantitative PCR as well as infection rate and cell death rate. The results indicate that macrophages from susceptible animals show a significantly higher upregulation of inflammatory genes (iNOS, IL-1α, TNF-α and IL-23p19) than the macrophages from resistant animals. Cells from resistant animals had a higher rate of apoptosis at 24 hours post infection (hpi) compared to macrophages from susceptible animals. The excessive expression of inflammatory mRNA transcripts in susceptible animals could cause inefficient clearing of the mycobacterial organism and the establishment of disease. Controlled upregulation of inflammatory pathways coupled with programmed cell death in the macrophages of resistant animals may predispose the host to a protective immune response against this mycobacterial pathogen.
St. John’s wort (Hypericum perforatum L.) is an herbaceous plant that is native to Europe, West Asia and North Africa and that is recognized and used worldwide for the treatment of mild and moderate depression. It also has been shown to be therapeutic for the treatment of burns, bruises and swelling and can be used for its wound healing, antiviral, antimicrobial, antioxidant, analgesic, hepato-protective and anxiolytic properties. The aim of this study was to evaluate the potential cytotoxic, mutagenic and antimutagenic action of H. Perforatum.
Meristematic cells were used as the test system for Allium cepa L., and bone marrow cells from Rattus norvegicus, ex vivo, were used to calculate the mitotic index and the percentage of chromosomal aberration. Statistical analysis was performed using the chi-square test.
This medicinal plant had no cytotoxic potential in the vegetal test system evaluated. In the animal test system, none of the acute treatments, including intraperitoneal gavage and subchronic gavage, were cytotoxic or mutagenic. Moreover, this plant presented antimutagenic activity against the clastogenic action of cyclophosphamide, as confirmed in pre-treatment (76% reduction in damage), simultaneous treatment (95%) and post-treatment (97%).
Thus, the results of this study suggest that the administration of H. perforatum, especially by gavage similar to oral consumption used by humans, is safe and with beneficial antimutagenic potential.
Chromosomal aberration; Pharmacological action; Wistar rats; Medicinal plant; Allium cepa L.; Mitotic index
St. John’s Wort (SJW), an over-the-counter antidepressant, contains hypericin, which absorbs light in the UV and visible ranges. In vivo studies have determined that hypericin is phototoxic to skin and our previous in vitro studies with lens tissues have determined that it is potentially phototoxic to the human lens. To determine if hypericin might also be phototoxic to the human retina, we exposed human retinal pigment epithelial cells to 10−7 to 10−5 M hypericin. Fluorescence emission detected from the cells (λexc = 488 nm; λem = 505 nm) confirmed hypericin uptake by human RPE. Neither hypericin exposure alone nor visible light exposure alone reduced cell viability. However when irradiated with 0.7 J/cm2 of visible light (λ> 400 nm) there was loss of cell viability as measured by MTS and LDH assays. The presence of hypericin in irradiated hRPE cells significantly changed the redox equilibrium of glutathione and a decrease in the activity of glutathione reductase. Increased lipid peroxidation as measured by the TBARS assay correlated to hypericin concentration in hRPE cells and visible light radiation. Thus, ingested SJW is potentially phototoxic to retina and could contribute to retinal or early macular degeneration.
The Hyp-1 protein suggested to be a phenolic oxidative-coupling enzyme involved in the biosynthesis of hypericin, a medicinally important natural compound found in St John’s wort (H. perforatum), has been expressed, purified and prepared in single-crystal form.
According to a debated hypothesis, the biosynthesis from emodin of the medicinally important natural compound hypericin is catalyzed in St John’s wort (Hypericum perforatum) by the phenolic oxidative-coupling protein Hyp-1. Recombinant St John’s wort Hyp-1 has been overexpressed in Escherichia coli and obtained in single-crystal form. The crystals belong to the orthorhombic system, space group P212121, with unit-cell parameters a = 37.5, b = 76.7, c = 119.8 Å, contain two protein molecules in the asymmetric unit and diffract X-rays to 1.73 Å resolution.
St John’s wort; hypericin; depression; PR-10 proteins
St John’s wort (SJW) extracts, prepared from the aerial parts of Hypericum perforatum, contain numerous pharmacologically active ingredients, including naphthodianthrones (e.g., hypericin and its derivatives), phloroglucinols derivatives (e.g., hyperforin, which inhibits the reuptake of a number of neurotransmitters, including serotonin), and flavonoids. Such extracts are widely used for the treatment of mild-to-moderate depression. As a monotherapy, SJW has an encouraging safety profile. However, relevant and, in some case, life-threatening interactions have been reported, particularly with drugs which are substrate of cytochrome P450 and/or P-glycoprotein. Well-documented SJW interactions include (1) reduced blood cyclosporin concentration, as suggested by multiple case reports as well as by clinical trials, (2) serotonin syndrome or lethargy when SJW was given with serotonin reuptake inhibitors, (3) unwanted pregnancies in women while using oral contraceptives and SJW, and (4) reduced plasma drug concentration of antiretroviral (e.g., indinavir, nevirapine) and anticancer (i.e., irinotecan, imatinib) drugs. Hyperforin, which is believed to contribute to the antidepressant action of St John’s wort, is also strongly suspected to be responsible of most of the described interactions.
cytochrome P450 enzymes; herb–drug interactions; herbal products; P-glycoprotein; St John’s wort