tbuckley/cabot-search huggingface dataset:
Neurotoxicity of the Parkinson Disease-Associated Pesticide Ziram Is Synuclein-Dependent in Zebrafish Embryos
Authors: Aaron Lulla, Lisa Barnhill, Gal Bitan, Magdalena I. Ivanova, Binh Nguyen, Kelley O’Donnell, Mark C. Stahl, Chase Yamashiro, Frank-Gerrit Klärner, Thomas Schrader, Alvaro Sagasti, Jeff M. Bronstein
Journal: Environmental Health Perspectives (2016)

Exposure to the commonly used dithiocarbamate (DTC) pesticides is associated with an increased risk of developing Parkinson disease (PD), although the mechanisms by which they exert their toxicity are not completely understood.We studied the mechanisms of ziram's (a DTC fungicide) neurotoxicity in vivo.Zebrafish (ZF) embryos were utilized to determine ziram's effects on behavior, neuronal toxicity, and the role of synuclein in its toxicity.Nanomolar-range concentrations of ziram caused selective loss of dopaminergic (DA) neurons and impaired swimming behavior. Because ziram increases α-synuclein (α-syn) concentrations in rat primary neuronal cultures, we investigated the effect of ziram on ZF γ-synuclein 1 (γ1). ZF express 3 synuclein isoforms, and ZF γ1 appears to be the closest functional homologue to α-syn. We found that recombinant ZF γ1 formed fibrils in vitro, and overexpression of ZF γ1 in ZF embryos led to the formation of neuronal aggregates and neurotoxicity in a manner similar to that of α-syn. Importantly, knockdown of ZF γ1 with morpholinos and disruption of oligomers with the molecular tweezer CLR01 prevented ziram's DA toxicity.These data show that ziram is selectively toxic to DA neurons in vivo, and this toxicity is synuclein-dependent. These findings have important implications for understanding the mechanisms by which pesticides may cause PD. Citation: Lulla A, Barnhill L, Bitan G, Ivanova MI, Nguyen B, O'Donnell K, Stahl MC, Yamashiro C, Klärner FG, Schrader T, Sagasti A, Bronstein JM. 2016. Neurotoxicity of the Parkinson disease-associated pesticide ziram is synuclein-dependent in zebrafish embryos. Environ Health Perspect 124:1766-1775; http://dx.doi.org/10.1289/EHP141.
EIO update
Authors: Thierry Ponchon
Journal: Endoscopy (2014)

TP: I found this to be a great opportunity to reinforce communication between clinical endoscopists, colleagues performing their endoscopy procedures on an everyday basis in their medical practices and the clinical researchers who often do their great job at “high end” endoscopy units with excellent technical equipment. For colleagues in hospitals for primary and secondary care, clinical research is one interest, but another is post graduate education and training.
Mechanism of Experimental Tumorigenesis. VI. Ultrastructural Alterations in Mouse Epidermis Caused by Locally Applied Carcinogen and Dipole-Type Tumor Promoter&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Kai Setälä, Lauri Merenmies, Eino Erkki Niskanen, Mauri Nyholm, Leo Stjernvall
Journal: JNCI Journal of the National Cancer Institute (1960)

An electron microscopic study of the effect of locally applied 7,12-dimethylbenz[a]anthracene (DMBA) and 3-methylcholanthrene (MCA) on the inter-follicular epidermis (IFE) of the back of the mouse was made. The pattern appeared to agree with that seen with the light microscope. Thus in light and electron microscopy, the hyperplastic response of the IFE that was caused by DMBA and MCA was totally different from and opposite to that of a locally applied dipole-type tumor promoter. Characteristic effects were: (a) abnormalities in cell surface-to-cell surface contact in which combined light and electron microscopy indicate disturbances in detachment of epidermal cells; (b) development of new patterns in the cytoplasm of nucleated cells; (c) accumulation of electron-dense inclusion bodies within mitochondria—the most characteristic and most regularly occurring change; (d) disturbances in keratinization; (e) an increase in nucleo/cytoplasmic ratio; and (f) variabilities in degree and quality of the changes in different places of the treatment area. When the skin was exposed to effective or prolonged doses of carcinogen, all these alterations were pronounced and the changes were easily reproducible. There was neither a reversion of the epidermal cells to normal basal cells nor to less-differentiated cell types; instead new cell types developed. Since related patterns were also evident in light microscopy on paraffin sections, the changes had arisen intra vitam. The nature and pattern of the alterations, by DMBA, by MCA, and by dipole-type tumor promoters, may clarify the regression mechanism of benign, regularly formed skin papillomas.
The human epididymis: its function in sperm maturation
Authors: Robert Sullivan, Roger Mieusset
Journal: Human Reproduction Update (2016)

Spermatozoa acquire their fertilizing ability and forward motility properties during epididymal transit. Our knowledge of gamete physiology is based on studies conducted in laboratory and domestic species; our knowledge of these processes in humans is limited. Medical indications for assisted reproductive technologies (ART) have progressed to include male infertility. Surgical procedures allow collection of spermatozoa from all along the human excurrent ducts, and the former have been used with some success in reproductive medicine. This has raised questions over the role of the epididymis in human sperm physiology.To reanalyze what we now know about epididymal physiology in humans and to assess the relevance of laboratory animal models for understanding human physiology and the pathophysiology of the epididymis.A systematic bibliographic search of PubMed for articles published in English before May 2015 was carried out using the search terms 'epididymis' and 'sperm maturation'. Literature on the consequences of vasectomy on the epididymis was also searched.Whereas the proximal epididymis is almost exclusively occupied by efferent ducts, the sperm reservoir capacity is poorly developed in humans. At the molecular level, the human transcriptome and proteome show some segment specificity; conflicting results persist with regard to secretome variation along the tubule. The number of genes regulated along the excurrent ducts in men is lower when compared to rodent species, but remains significant. It is challenging to reconcile biochemical and physiological studies with clinical data obtained from men undergoing reanastomosis of the vas deferens at different points along the excurrent duct. We propose that vasectomy/vasovasostomy is a model to understand the consequences of obstruction on epididymis function in humans.Despite the scarcity of biological material available, the interspecies variability of the male reproductive tract urges us to use modern molecular and cellular biology tools to better understand human epididymis physiology in order to apply ART in a more responsible manner.
Isolated Calcaneal Metastasis
Authors: Charanjeet Singh, Mamta Gupta, Jagadeesh Singh, Amjad Ali
Journal: Clinical Nuclear Medicine (2015)

A 63-year-old woman initially presented with progressive left foot pain for 3 months, not responding to conservative management. MRI of the left foot showed a suspicious lesion in calcaneus. An open biopsy was consistent with metastatic lung adenocarcinoma. Tc-MDP total-body bone scintigraphy was ordered for possible other bony lesions, and only left calcaneus lesion was identified on bone scan. CT scan of the chest revealed a soft tissue mass in the superior aspect of the right lower lobe. Staging FDG PET/CT showed hypermetabolic right lung mass and left calcaneus lesion. She received chemotherapy and local radiation to the left calcaneus metastatic lesion.
EPN-24EPIGENETIC SILENCING OF LDOC1 LEADS TO CHRONIC IL-6 SECRETION THROUGH UPREGULATION OF NF-kB PATHWAY IN GROUP A EPENDYMOMA: POTENTIAL FOR TAILORED THERAPIES
Authors: Andrea Griesinger, Randall Wong, Sydney Gosh, Sujatha Venkataraman, Ilango Balakrishnan, Andrew Donson, Jean Mulcahy Levy, Rajeev Vibhakar, Michael Handler, Nicholas Foreman
Journal: Neuro-Oncology (2016)
Methodological challenges when carrying out research on CKD and AKI using routine electronic health records
Authors: Helen I. McDonald, Catriona Shaw, Sara L. Thomas, Kathryn E. Mansfield, Laurie A. Tomlinson, Dorothea Nitsch
Journal: Kidney International (2016)

Research regarding chronic kidney disease (CKD) and acute kidney injury (AKI) using routinely collected data presents particular challenges. The availability, consistency, and quality of renal data in electronic health records has changed over time with developments in policy, practice incentives, clinical knowledge, and associated guideline changes. Epidemiologic research may be affected by patchy data resulting in an unrepresentative sample, selection bias, misclassification, and confounding by factors associated with testing for and recognition of reduced kidney function. We systematically explore the issues that may arise in study design and interpretation when using routine data sources for CKD and AKI research. First, we discuss how access to health care and management of patients with CKD may have an impact on defining the target population for epidemiologic study. We then consider how testing and recognition of CKD and AKI may lead to biases and how to potentially mitigate against these. Illustrative examples from our own research within the UK are used to clarify key points. Any research using routine renal data has to consider the local clinical context to achieve meaningful interpretation of the study findings.
Reply to F. Felix et al and M.F. Fay et al
Authors: Caroline Happold, Thierry Gorlia, Oliver Chinot, Mark R. Gilbert, L. Burt Nabors, Wolfgang Wick, Stephanie L. Pugh, Monika Hegi, Timothy Cloughesy, Patrick Roth, David A. Reardon, James R. Perry, Minesh P. Mehta, Roger Stupp, Michael Weller
Journal: Journal of Clinical Oncology (2016)
HG-43MOLECULAR DRUG IMAGING:<sup>89</sup>ZR-BEVACIZUMAB PET IN CHILDREN WITH DIFFUSE INTRINSIC PONTINE GLIOMA
Authors: Marc Jansen, Sophie Veldhuijzen van Zanten, Dannis van Vuurden, Marc Huisman, Danielle Vugts, Otto Hoekstra, Guus van Dongen, Gertjan Kaspers
Journal: Neuro-Oncology (2016)
GC-04INTENSITY-MODULATED RADIOTHERAPY (IMRT) FOR WHOLE VENTRICLES IN PATIENTS WITH INTRACRANIAL GERM CELL TUMOR
Authors: Etsuko Hattori, Yoshiki Arakawa, Takashi Mizowaki, Kengo Ogura, Yasuhiro Kawabata, Masahiro Tannji, Youhei Mineharu, Takeharu Kunieda, Masahiro Hiraoka, Susumu Miyamoto
Journal: Neuro-Oncology (2016)
Accuracy of DSM-III diagnoses following a training program
Authors: L J Webb, R S Gold, E E Johnstone, C C Diclemente
Journal: American Journal of Psychiatry (1981)

The authors describe a 2 1/2-day training program designed to teach mental health professionals how to use a new DSM-III classification scheme. The 251 participants had previous clinical training but no prior exposure to DSM-III. They were asked to diagnose three cases from a series of five videotapes case vignettes; the authors then compared the participants' diagnoses with the expert opinion of clinical faculty. The degree of agreement among the participants with the expert opinion varied across the five cases, but the overall level of agreement was high (74.2%). These results indicate that with adequate training the new DSM-III classification scheme can be accurately applied to diagnostic situations.
Keeping conceptual boundaries distinct between decision making and learning is necessary to understand social influence
Authors: Gaël Le Mens
Journal: Behavioral and Brain Sciences (2014)

Abstract Bentley et al. make the deliberate choice to blur the distinction between learning and decision making. This obscures the social influence mechanisms that operate in the various empirical settings that their map aims to categorize. Useful policy prescriptions, however, require an accurate understanding of the social influence mechanisms that underlie the dynamics of popularity.
FDG PET/CT Findings in Primary Diffuse Large B-cell Lymphoma, Leg Type
Authors: Chiayi Ni, Michael Lewis, Gholam Berenji
Journal: Clinical Nuclear Medicine (2015)

A 64-year-old man presented with complaints of worsening left foot pain and swelling. MRI showed a soft tissue mass overlying the dorsolateral aspect of the left foot. Following a 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), the left foot mass was biopsied and pathology indicated a diagnosis of primary diffuse large B-cell lymphoma, leg type (PDLBCL, LT). Review of the PET/CT images demonstrated hypermetabolic activity associated with the left foot mass, multiple subcutaneous nodules/nodes, sclerotic osseous lesions in the lower extremities, and left external iliac/left inguinal lymphadenopathy. At the moment, the patient is undergoing chemotherapy.
Reply
Authors: Wen‐Qing Li, Yikyung Park, Katherine A. McGlynn, Albert R. Hollenbeck, Philip R. Taylor, Alisa M. Goldstein, Neal D. Freedman
Journal: Hepatology (2014)

Potential conflict of interest: Nothing to report. We thank Dr. Vinciguerra for his interest in our article,1 which examined associations between two dietary indices, the Healthy Eating Index‐2010 (HEI‐2010) and the alternate Mediterranean Diet Score (aMED), with risk of chronic liver disease (CLD) mortality and hepatocellular carcinoma (HCC) incidence in the NIH‐AARP Diet and Health Study. He specifically asks about protein intake, pointing out a recently published study examining the association of protein intake with total mortality in NHANES III. In that study, the authors observed that high protein intake was associated with higher mortality among those 65 years or younger, but lower mortality among those aged 66 years or older.2 As discussed in our article, we examined overall dietary patterns because it is difficult to disentangle individual components of diet from each other. For example, individuals who like to eat red meat may be more likely to eat sweets and less likely to eat beans, fruits and vegetables, and whole grains. As we mentioned, both HEI‐2010 and aMED have been associated with a variety of disease outcomes.1 Nevertheless, it is also important to examine distinct aspects of diet as well, which is why we included these data. As there may be some confusion about the terms used for each dietary component in our article, we wish to clarify here. The total protein foods component in HEI‐2010 specifically refers to lean red meat and poultry, eggs, as well as beans and peas (which are included when the total protein foods standard is not met). It does not include dairy; or seafood and plant proteins (except beans and peas), which are separate components in HEI‐2010. We would also like to clarify that the red and processed meat of aMED was actually associated with CLD and HCC in the opposite direction, as mentioned by Vinciguerra, with participants eating more red and processed meat having nonsignificantly higher risk of HCC incidence and CLD mortality than participants eating less. Looking across the sources of protein, we see some evidence for increased risks, with eating more red and processed meat and decreased relative risks with eating more eggs, beans, and peas. Associations for dairy were mixed for each endpoint. As is always the case, and particularly with regard to observational studies, public health recommendations should only be made based on the totality of the evidence, not on the results of individual studies. Unfortunately, relatively few studies of diet in CLD and HCC are available. Future studies of dietary patterns and individual dietary components, such as protein, are needed.
LIMITATIONS OF CHEMOTHERAPY
Authors: H WEHRLIN
Journal: JAMA (1924)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
CKAP4 is identified as a receptor for Dickkopf in cancer cells
Authors: Dheeraj Bhavanasi, Kelsey F. Speer, Peter S. Klein
Journal: Journal of Clinical Investigation (2016)

The secretory protein Dickkopf-1 (DKK-1) is a known Wnt antagonist and has been shown to suppress tumorigenesis in some cancer cells; however, it is also upregulated in many types of cancer and associated with poor prognosis. Wnt-independent mechanisms by which DKK-1 promotes cancer cell proliferation are not well understood. In this issue of the JCI, Kimura and colleagues demonstrate that DKK-1 interacts with cytoskeleton-associated protein 4 (CKAP4) to promote activation of AKT. They show that both DKK-1 and CKAP4 are frequently upregulated in pancreatic and lung cancers. Importantly, targeting this interaction with an anti-CKAP4 antibody prevented tumor formation in murine xenograft models. These results identify a previously unrecognized DKK-1-mediated pathway and suggest CKAP4 as a potential therapeutic target for certain cancers.
Treatment of Compulsive Eating Disturbances with Anticonvulsant Medication
Authors: Richard S. Green, John H. Rau
Journal: American Journal of Psychiatry (1974)

Ten patients with symptoms of compulsive eating were treated pharmacologically with diphenylhydantoin. All but one had abnormal EEGs, indicating that neurological dysregulation may have been an etiological factor. Nine patients were treated successfully. The authors suggest that compulsive eating may be a function of neurological disturbance, with psychodynamic factors determining whether patients become anorectic or ohese or maintain their weight at normal levels.
Cutaneous Melanin Production in Mice Following Application of the Carcinogen 5, 9, 10-Trimethyl-1,2-Benzanthracene
Authors: F. H. Burgoyne, W. E. Heston, J. L. Hartwell, Harold L. Stewart
Journal: JNCI Journal of the National Cancer Institute (1949)

Cutaneous Melanin Production in Mice Following Application of the Carcinogen 5, 9, 10-Trimethyl-1,2-Benzanthracene Get access F. H. Burgoyne, F. H. Burgoyne Search for other works by this author on: Oxford Academic PubMed Google Scholar W. E. Heston, W. E. Heston Search for other works by this author on: Oxford Academic PubMed Google Scholar J. L. Hartwell, J. L. Hartwell Search for other works by this author on: Oxford Academic PubMed Google Scholar Harold L. Stewart Harold L. Stewart National Cancer Institute, National Institutes of Health, Public Health Service, Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 10, Issue 3, December 1949, Pages 665–687, https://doi.org/10.1093/jnci/10.3.665 Published: 01 December 1949 Article history Received: 11 October 1949 Published: 01 December 1949
Commentary: Decision aids in clinical practice
Authors: A Cranney
Journal: BMJ (2004)

Decision aids can be a useful format to communicate evidence based information on harms and benefits of therapies to individual patients. When used as an adjunct to the consultation, decision aids can change the format of the consultation process; decision aids are designed to enhance communication and interaction between patient and practitioner—not to replace it. Decision aids are not indicated for each clinical decision or scenario and they may not appeal to all physicians. But trials evaluating decision aids in the United Kingdom concluded that they helped patients use information to clarify their values and preferences.1-3

I have had the opportunity to use a decision aid in the clinical setting. This decision aid incorporates detailed information about self care and multiple therapies and has recently been adapted for use in a UK research project. I have found that exposing patients to the current evidence on efficacy, benefits, and harms enhances the consultation by focusing the discussion and ensures that consistent information is given to each patient.

Many respondents on bmj.com questioned the availability of such tools that include evidence based data and the plausibility of their use in everyday practice. New initiatives are making decision aids available on the web, which can be reviewed by patients in their own time or discussed with a nurse educator. If easily accessible and used correctly, decision aids can save time during the consultation. By helping determine the patient's preferred role for participating in the decision—for example, “doctor, what should I do?” or “I want to decide”—decision aids can help practitioners judge whether they can move quickly from facilitating the decision making process to planning treatment.

When introduced at the point of care, decision aids can be used to develop individual risk factor profiles. Treatment options can then be tailored according to the individual's risk. In this case, the physician knew that Mrs Patell had responded well to a non-steroidal anti-inflammatory drug; there was no question that Mrs Patell could be one of 94 who do not benefit. Incorporation of absolute numbers in a graphical format, in addition to an explanation of the risks and benefits, helps patients to understand the concept of number needed to treat. Use of absolute numbers can also result in a more realistic interpretation of the individual's risk profile and the potential harms and benefits of each treatment.

Decision aids enhance knowledge of available treatment and self care options and, by involving the patient, improve satisfaction with the decision making process. They have the potential to increase long term adherence with chosen treatments. Future priorities include the integration of decision aids at the point of care and exploring the role of other team members to prepare patients for discussion with their physician.
GC-03AREAS OF NON-CONSENSUS CHALLENGING THE MANAGEMENT OF INTRACRANIAL GERM CELL TUMOURS (ICGCT)
Authors: Matthew Murray, Masayuki Kanamori, Hirokazu Takami, Ute Bartels, Masao Matsutani, Jason Fangusaro, Keita Terashima, Ryo Nishikawa, James Nicholson
Journal: Neuro-Oncology (2016)