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  • Donna Berryman2017 Jul 24 1:48 p.m. (2 days ago) 2 of 2 people found this helpful

    While the authors do a pretty good job of pulling together the basic information about some popular readability formulas, they tend to support the idea that these formulas are somehow worthwhile. It is time to focus on the idea that grade level or readability formula results do not equate to reader understanding. As Leroy, Kauchak and Hogue (2016) write: "The lack of strong evidence for increased comprehension after using readability formulas may indicate that it is perceived difficulty that is being manipulated: The text looks easier but may not necessarily be easier to understand." (PMID 27043754) Wan et al (2013) do a good job of showing how different readability formulas vary in their calculations (see PMID 22835706). They conclude that "the SMOG formula appears to be more ideally suited for use in a health care context, as it has been validated against 100% comprehension..." But, beyond that, I would heartily encourage that we start thinking beyond written materials. I'd recommend the work of Donald L. Rubin on listenability (see PMID 23030569 for one example). Most health information is dispensed orally.

  • Effects of exercise and diet on chronic disease.

    Roberts CK.J Appl Physiol (1985). 2005.1 comment

    James M Heilman2017 Jul 25 2:25 p.m. (yesterday) 1 of 1 people found this helpful

    Have reviewed some of the claims in this paper and they are not supported by the associated references. For example figure 3: "Combined effect of Pritikin lifestyle intervention on blood glucose and need for oral hypoglycemic medication or insulin therapy. (Data from Refs. 38, 39, 40, 41, 43.)" 38, 40, 41, and 43 do not even mention the diet let alone support the conclusions?

  • Martine Crasnier-Mednansky2017 Jul 26 3:08 p.m. (9 hours ago)edited

    I do appreciate your answer to my comment, to which I gladly reply. First, there is prior work by Ghosh S, 2011 indicating colonization was attenuated in mutant strains that were incapable of utilizing GlcNAc, which included a nagE mutant strain. Second, Mondal M, 2014 analyzed the products of the ChiA2 reaction and found GlcNAc was the most abundant product. In fact, the amount of (GlcNAc)2 was found to be very low as compared to GlcNAc and (GlcNAc)3. Therefore, it is fully legitimate to conclude the PTS substrate GlcNAc is utilized in the host by V. cholerae for growth and survival.

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  • Ankur Dalia2017 Jul 26 12:55 p.m. (11 hours ago)

    Re: Martine Crasnier-Mednansky

    I appreciate your evaluation of the manuscript, however, I have to disagree with your comment. The study by Mondal et al. indicates that ChiA2 can liberate GlcNAc from mucin in vitro and that it is critical for bacterial growth in vivo, however, they did not test the role for GlcNAc uptake and/or catabolism in that study. In our manuscript, however, we demonstrate that loss of all PTS transporters (including the GlcNAc transporter) does not result in attenuation in the same infant mouse model, which is a more formal test for the role of GlcNAc transport during infection. It is formally possible that other carbohydrate moieties are liberated via the action of ChiA2 that are required for growth of V. cholerae in vivo, however, our results would indicate that these are not translocated by the PTS. Alternatively, the reduced virulence of the ChiA2 mutant observed in the Mondal et al study may indicate that ChiA2 has other effects in vivo (i.e. on immune evasion, resistance to antimicrobial peptides, etc.).

  • Martine Crasnier-Mednansky2017 Jul 24 09:46 a.m. (2 days ago)edited 2 of 2 people found this helpful

    The authors’ proposal 'the PTS has a limited role during infection' and concluding remark 'PTS carbohydrates are not available and/or not utilized in the host' are both questionable. Mondal M, 2014 established, when Vibrio cholerae colonizes the intestinal mucus, the PTS-substrate GlcNAc is utilized for growth and survival in the host intestine (upon mucin hydrolysis).

  • Sally Satel2017 Jul 26 11:46 a.m. (12 hours ago)edited

    Dartmouth demographer Samir Soneji and his co-authors find that the probability of cigarette smoking at follow-up is significantly higher among all e-cigarette users than among individuals who never used a nicotine product. Based on this finding, they conclude that “strong e-cigarette regulation” by the federal, state, and local governments are needed to minimize the potential “future population-level burden of tobacco.” This conclusion is unwarranted based on the nature of their results.

    The article compares the probability of smoking in the post-period conditional on e-cigarette use without smoking to the probability of smoking in the post-period conditional on neither e-cigarette use nor smoking. This is not the relevant comparison for the purpose of assessing public-health risk. The relevant comparison is between smoking behavior conditional on access to e-cigarettes and smoking behavior conditional on no access to e-cigarettes, as such a comparison incorporates both the potential gateway and deterrent/diversion effects of e-cigarette use.

    Such a comparison would take into account any beneficial effects of e-cigarettes on potential smokers who choose to reduce their cigarette smoking or to limit themselves to e-cigarette use altogether, as well as on smokers in the pre-period who switch to e-cigarettes partially or fully, or successfully use e-cigarettes as a cessation aid. It is on this comparison that regulatory choices should be based.

    The nascent market for e-cigarettes in the United States can make robust empirical research on the consequences of these products on tobacco use challenging. The importance of a proper analytical framework is illustrated in a recent National Bureau of Economic Research working paper by economists Mike Pesko of Weill Cornell Medical College and Janet Currie of Princeton. The economists identify an important unintended consequence of minimum legal sale age laws restricting access to e-cigarettes: smoking among underage pregnant teenagers increased by more than 2 percentage points.

    With teen smoking at a new low, policymakers should be celebrating a public health success instead of seeking a new regulatory expansion. Empirically, it is certainly not clear that more vaping has any causal effect on smoking among youth, as Soneji and his co-authors imply but do not demonstrate. Moreover, the type of analyses reported in JAMA Pediatrics fails to offer a reliable basis for developing an optimal regulatory framework for e-cigarettes and other modified risk tobacco products.

    -Alex Brill, Sally Satel, Stan Veuger

    NBER paper: http://www.nber.org/papers/w22792

  • Samir Soneji2017 Jul 20 9:08 p.m. (6 days ago) 2 of 2 people found this helpful

    We thank Joel Nitzkin for his interest in our article, which systematically reviewed 9 US-based longitudinal studies that assessed e-cigarette use and cigarette smoking among >17,000 adolescents and young adults. Our research concluded that e-cigarette use among adolescents who had never tried a cigarette was associated with subsequent cigarette smoking initiation and past 30-day cigarette smoking, with similar effect size across studies of adolescents and young adults. All of the studies used multivariable analysis to adjust for other factors that might make adolescent e-cigarette users at higher risk for use of multiple substances—risk factors such as friends who smoke, sensation seeking tendencies, and use of other substances like alcohol.

    Nitzkin asserted three claims about the research. First, Nitzkin claimed that the studies provided no evidence that e-cigarette use is related to consistent daily cigarette smoking. Second, he claimed that e-cigarette use was simply a marker for high-risk youth who were more likely to smoke anyway. Third, he claimed that the decline in youth cigarette smoking over time at the population level proves e-cigarette use does not increase the probability of cigarette smoking at the individual level. Empirical evidence contradicts these claims, as we describe below.

    Regarding Nitkin’s first claim that e-cigarette use is not related to consistent daily cigarette smoking, few adolescents smoke on a daily basis, which makes assessment of daily smoking impractical for most longitudinal studies that have a 1-2 year timeframe. Logically, smoking initiation is a necessary requisite to daily smoking. Moreover, recent longitudinal research found that smoking initiation identifies about two-thirds of adolescents who will be daily smokers two years later, with a false positive rate of 8 percent.1 In other words, smoking initiation is about as good at predicting eventual daily smoking as screening mammography is at predicting breast cancer.2 Although not perfect, smoking initiation presents a public health concern especially given the growing body of evidence that e-cigarettes are used by some youth unlikely to have ever smoked cigarettes.1,3,4 Furthermore, a recent longitudinal study by Leventhal et al. (2016) found that more frequent e-cigarette use at baseline was associated with more frequent and heavier patterns of cigarette smoking at follow-up using data from >3000 adolescents.5 Thus, smoking initiation, which the studies examined, is a sensible predictor of future daily smoking, and the pattern of e-cigarette use seems to predict the pattern of eventual cigarette smoking.

    Regarding Nitzkin’s second claim that e-cigarette users are just high-risk youth, the combined risk estimate represents a risk that adjusts for many risk factors, as we mentioned above, that would cause some adolescents to be at risk for using multiple substances. The fact that the adjusted estimate is very strong (odds ratio of almost 4) suggests to us that it is unlikely that one or more added covariables would completely confound the e-cigarette effect. Moreover, several studies concluded that adolescents who use e-cigarettes are medium-risk youth, not those who are necessarily destined to begin cigarette smoking anyway.6–10 Furthermore, several longitudinal studies have reported that the association between e-cigarette use and smoking initiation was strongest among the lowest risk youth (i.e., youth who stated that they were unlikely to try smoking in the future).9,11,12

    Regarding Nitzkin’s third claim that the recent decline in youth cigarette smoking proves e-cigarette use does not lead to cigarette use, youth cigarette smoking has been declining steadily in the US for the past 20 years and predates e-cigarettes.13,14 In other words, this steady decline in youth cigarette smoking began long before the introduction of e-cigarettes into the US in 2007 and before e-cigarette use became prevalent in youth around 2011. So the decline in youth cigarette smoking cannot be attributed to the advent of the e-cigarette.

    We believe our research underlines that the potential risks of e-cigarette use are significant and should not be discounted. Tobacco control efforts, including taxation, youth smoking prevention programs, and restrictions on tobacco advertising reduce youth smoking. The nearly twenty-year decline in youth smoking demonstrates the success of these tobacco control efforts despite youth e-cigarette use. We must acknowledge and address the public health harm posed by youth e-cigarette use to prevent a new generation of nicotine-addicted adult tobacco users.

    References

    1 Sargent JD, Gabrielli J, Budney A, Soneji S, Wills TA. Adolescent smoking experimentation as a predictor of daily cigarette smoking. Drug Alcohol Depend. 2017;175:55-59. doi:10.1016/j.drugalcdep.2017.01.038.

    2 Ferrini R, Mannino E, Ramsdell E, Hill L. Screening mammography for breast cancer: American College of Preventive Medicine practice policy statement. Am J Prev Med. 1996;12(5):340-341.

    3 Barrington-Trimis JL, Urman R, Leventhal AM, et al. E-cigarettes, Cigarettes, and the Prevalence of Adolescent Tobacco Use. Pediatrics. July 2016:e20153983. doi:10.1542/peds.2015-3983.

    4 Dutra LM, Glantz SA. E-cigarettes and National Adolescent Cigarette Use: 2004–2014. Pediatrics. January 2017:e20162450. doi:10.1542/peds.2016-2450.

    5 Leventhal AM, Stone MD, Andrabi N, et al. Association of e-Cigarette Vaping and Progression to Heavier Patterns of Cigarette Smoking. JAMA. 2016;316(18):1918-1920. doi:10.1001/jama.2016.14649.

    6 Wills TA, Knight R, Williams RJ, Pagano I, Sargent JD. Risk Factors for Exclusive E-Cigarette Use and Dual E-Cigarette Use and Tobacco Use in Adolescents. Pediatrics. 2015;135(1):e43-e51. doi:10.1542/peds.2014-0760.

    7 Kristjansson AL, Mann MJ, Sigfusdottir ID. Licit and Illicit Substance Use by Adolescent E-Cigarette Users Compared with Conventional Cigarette Smokers, Dual Users, and Nonusers. J Adolesc Health Off Publ Soc Adolesc Med. 2015;57(5):562-564. doi:10.1016/j.jadohealth.2015.07.014.

    8 Thrasher JF, Abad-Vivero EN, Barrientos-Gutíerrez I, et al. Prevalence and Correlates of E-Cigarette Perceptions and Trial Among Early Adolescents in Mexico. J Adolesc Health Off Publ Soc Adolesc Med. 2016;58(3):358-365. doi:10.1016/j.jadohealth.2015.11.008.

    9 Barrington-Trimis JL, Urman R, Berhane K, et al. E-Cigarettes and Future Cigarette Use. Pediatrics. June 2016:e20160379. doi:10.1542/peds.2016-0379.

    10 Leventhal AM, Strong DR, Sussman S, et al. Psychiatric comorbidity in adolescent electronic and conventional cigarette use. J Psychiatr Res. 2016;73:71-78. doi:10.1016/j.jpsychires.2015.11.008.

    11 Primack BA, Soneji S, Stoolmiller M, Fine MJ, Sargent JD. Progression to traditional cigarette smoking after electronic cigarette use among US adolescents and young adults. JAMA Pediatr. September 2015:1-7. doi:10.1001/jamapediatrics.2015.1742.

    12 Wills TA, Knight R, Sargent JD, Gibbons FX, Pagano I, Williams RJ. Longitudinal study of e-cigarette use and onset of cigarette smoking among high school students in Hawaii. Tob Control. January 2016:1-6. doi:10.1136/tobaccocontrol-2015-052705.

    13 Johnston L, O’Malley PM, Miech R, Emerson P, Bachman J, Schulenberg J. Monitoring the Future National Survey Results on Drug Use, 1975-2015: Overview, Key Findings on Adolescent Drug Use. Ann Arbor: Institute for Social Research, The University of Michigan; 2016.

    14 Office on Smoking and Health. Trends in Current Cigarette Smoking. Centers for Disease Control and Prevention http://www.cdc.gov/tobacco/data_statistics/tables/trends/cig_smoking/. Accessed July 13, 2017.

  • Alexander Kraev2017 Jul 20 12:57 p.m. (6 days ago)edited

    Note that this is likely one of about 150 publications affected by the MHC-driven MerCreMer transgene, notoriously prone to induction of dilated cardiomyopathy in the absence of any induced target gene expression, in this case calreticulin. See PMID:27165291 for details. Erratum for this article in PLoS One. 2013;8(11) was made for a different reason.

  • Donald Forsdyke2017 Jul 25 1:46 p.m. (yesterday)

    LECTIN PATHWAY STUDIES WITH PLANT MANNOSE-BINDING LECTINS

    Papers on the lectin pathway (LP) of complement activation in animal sera generally refer to animal mannose-binding lectins (MBLs), with little reference to work with plant MBLs. For example, citing May and Frank (1973), this fine paper states: "Reports of unconventional complement activation in the absence of C4 and/or C2 predate the discovery of LP." Actually, a case can be made that the discovery of the LP predates May-Frank.

    The MASP-binding motif on animal MBL, which is necessary for complement activation, includes the amino acid sequence GKXG (at positions 54-57), where X is often valine. The plant lectin concanavalin-A (Con-A) has this motif at approximately the same position in its sequence (the 237 amino acid subunit of Con-A had the sequence GKVG at positions 45-48). The probability of this being a chance event is very low. Indeed, prior to the discovery of MASP involvement, Milthorp & Forsdyke (1970) reported the dosage-dependent activation of complement by Con-A.

    As far as I am aware, it has not been formally shown that MASP is involved in the activation of the complement pathway by this plant MBL. Our studies in the 1970s demonstrated that Con-A activates complement through a cluster-based mechanism, which is consistent with molecular studies of animal MBL showing “juxtaposition- and concentration dependent activation” (Degn et al. 2014). References to our several papers on the topic may be found in a review of innate immunity (Forsdyke 2016).

    Degn SE et al. (2014) Complement activation by ligand-driven juxtaposition of discrete pattern recognition complexes. Proc Natl Acad Sci USA 111:13445-13450. Degn SE, 2014

    Forsdyke DR (2016) Almroth Wright, opsonins, innate immunity and the lectin pathway of complement activation: a historical perspective. Microb Infect 18: 450-459. Forsdyke DR, 2016

    May JE, Frank MM (1973) Hemolysis of sheep erythrocytes in guinea pig serum deficient in the fourth component of complement. I. antibody and serum requirements. J Immunol 111: 1671-1677. May JE, 1973

    Milthorp PM, Forsdyke DR (1970) Inhibition of lymphocyte activation at high ratios of concanavalin A to serum depends on complement. Nature 227:1351-1352 Milthorp P, 1970

    Yaseem et al. (2017) Lectin pathway effector enzyme mannan-binding lectin-associated serine protease-2 can activate native complement C3 in absence of C4 and/or C2. FASEBJ 31:2210-2219 Yaseen S, 2017

  • Richard Sauerheber2017 Jul 25 12:34 p.m. (yesterday)

    We now know that both calcium and magnesium ions at millimolar concentrations decrease the fluidity of biologic membranes. Inside cells, where calcium is at only micromolar concentrations and magnesium at millimolar concentrations, magnesium ion would be involved, particularly since the inner half bilayer phospholipids have negatively charged groups even at slightly acidic pH (6.9) inside cells. The outer half of the bilayer is also susceptible to effects of both calcium and magnesium at millimolar concentrations in extracellular fluid, where phosphate groups on phospholipids would be negatively charged at alkaline pH (7.3) of extracelluluar fluid. The detailed control of the lipid fluidity of membranes in vivo appears to be quite sophisticated.

  • Trevor Bell2017 Jul 25 05:18 a.m. (yesterday)

    Multiple sequence alignments containing only full-length sequences, for each genotype, are now also available for download from the alignments page. These sequences are a subset of the alignments already available.

  • In reply to a comment by Konstantinos Fountoulakis2017 Apr 12 12:28 p.m.

    Konstantinos Fountoulakis2017 Jul 24 8:01 p.m. (2 days ago)edited

    Nice way to reply without replying to exact and specific questions. You already know that the NEJM editor rejected a letter by me and as i can see here he has also rejected other similar letters which raised the same questions. These specific questions seem to burn and i again mention them here:

    1. Did you or you did not change the primary outcome after registering the trail and during the study, and after the results of some of the subjects were available? (not in my comments but it needs a definite answer which i did not see so far)
    2. Did you or you did not include in the paper a different primary outcome (3-5 years) from what you had eventually registered in the protocol (0-3 years) and specifically stated in the paper that this was the primary outcome of the study? Is 0-3 identical to 3-5?

    Well i have no way of publishing this as a letter to the editor, I have already tried. To make things worse, the reply letter says (verbatim) that 'As clearly stated in the article the primary outcome was extended to distinguish wheezing children from asthmatic children'. I hope you will respond to the above issues and clarify once and for all the problem.

  • In reply to a comment by Hilda Bastian2017 Jun 29 10:36 p.m.

    Frank M Sacks2017 Jul 24 4:52 p.m. (2 days ago)

    On behalf of the authors, I respond to comments by Hilda Bastian about the American Heart Association Presidential Advisory on Dietary Fats and Cardiovascular disease Sacks FM, 2017.

    The comprehensive advisory includes, (i) Clinical trials that tested the effects of dietary saturated fat compared to unsaturated fat or carbohydrate on cardiovascular disease (CVD) events, e.g. heart attack, (ii) Clinical trials that tested the effects of dietary fats on lipid risk factors, e.g. LDL-cholesterol, (iii) Prospective epidemiological studies on dietary fats and carbohydrates and CVD, and (iv) Animal models of diet and atherosclerosis. Thus, it reflects the “totality of evidence”. The confluence of findings provides a very strong scientific case for the recommendation that dietary saturated fat be replaced with unsaturated fat, especially polyunsaturated fat.

    Recent systematic reviews and meta-analyses Mozaffarian D, 2010, Chowdhury R, 2014, Hooper <PMID: 26068959 used well accepted methodologies, and included trials published up to 2009, 2013, and 2014. Only a small number of clinical trials evaluated direct effects of dietary fat on CVD. Most of these studies, and all that have an impact on the overall findings, were conducted years ago, and are well known. Contrary to the Bastian’s comments, there are no more recent trials on this topic. These 3 meta-analyses each confirm the beneficial effect of replacing saturated with polyunsaturated fat. The similarity of findings lends robustness to the overall conclusions of the report. The meta-analyses and all the individual trials are discussed critically in detail in the advisory.

    Because the topic of the advisory is the effect of dietary fats on CVD, coconut oil is well within its scope. Coconut oil is currently rated as a healthy oil by 72% of the American public, despite its composition derived from 98% saturated fats, which increase the blood level of LDL-cholesterol, a cause of atherosclerosis and CVD. The meta-analysis by Mensink reports the quantitative effects on LDL-cholesterol of the saturated fats that are in coconut oil, mainly lauric, myristic, and palmitic acids. Each of these increase LDL-cholesterol compared to carbohydrate and more so when compared to the unsaturated fats. This is sufficient to warn the public about anticipated adverse effects of coconut oil on CVD.

    Some studies tested coconut oil itself, and found that it increases LDL-cholesterol as would be predicted by its saturated fat content. These studies were identified and summarized in the systematic review by Eyres L, 2016 which used rigorous, well-accepted methodology. The criteria for inclusion of an article in the systematic review were well conceived. Eyres et al. concluded, “Overall, the weight of the evidence from intervention studies to date suggests that replacing coconut oil with cis unsaturated fats would alter blood lipid profiles in a manner consistent with a reduction in risk factors for cardiovascular disease.” Bastian implies that this systematic review is composed of weak studies and omitted several studies that would affect the conclusion of the advisory to avoid eating coconut oil. This is not true. Eyres et al. identified eight studies; all were controlled clinical trials that used valid nutritional protocols and statistical analyses. All reported higher LDL-C levels when coconut oil was consumed compared to unsaturated oils, including olive, corn and soybean oils, statistically significantly in 7 of them. Together, these trials included populations from the US, Sri Lanka, New Zealand, Pacific Islands, and Malaysia, demonstrating generalizability. There is no objective scientific reason to disparage them. The only substantive criticisms mentioned by Bastian are a short duration and small sample. These criticisms are unwarranted. Effects of diet on blood lipids, especially LDL-cholesterol, are established quickly, by 2 weeks. A small sample, with careful dietary control and execution, can yield a well-powered trial with valid results. In summary, the 8 trials in the Eyres et al. systematic review provide strong evidence that coconut oil increases LDL-C levels compared with unsaturated oils.

    What about the 7 studies named by Bastian that were not included in the systematic review? McKenney JM, 1995 reported that coconut oil increased LDL-cholesterol significantly by 12% compared with canola oil in 11 patients with hypercholesterolemia. In a second study in 17 patients treated with lovastatin, LDL-C increased nonsignificantly in the coconut oil period. Thus, the results of this small study would add to the overall effects of coconut oil shown in the other studies to increase LDL-cholesterol. Ganji V, 1996 reported that coconut oil increased LDL-cholesterol compared to soybean oil in 10 normal participants. Assunção ML, 2009 reported no difference in the effects of coconut and soybean oils on LDL-cholesterol levels. However, LDL-cholesterol levels increased during the soybean oil period, clearly an anomolous result. Cardoso DA, 2015 conducted a nonrandomized study comparing coconut oil, 13 mL per day, with no supplemental oil. Because there is no control for the coconut oil, it is unclear how to interpret the lack of difference in LDL-cholesterol between the groups. de Paula Franco E, 2015 conducted a sequential study of a calorie-reduced diet followed by coconut flour, 26 g per day. This study was not randomized and did not have a control group. Enns reported in her Ph.D. degree dissertation at the University of Manitoba the results of a randomized trial that compared a 2:1:1 mix of butter, coconut oil, and high-linoleic safflower oil, 25 g per day, with canola oil, 25 g per day. This trial did not claim to be a study on the effects of coconut oil. Finally, Shedden reported in her M.S. degree thesis at Arizona State University the results of a placebo-controlled randomized trial of coconut oil, 2 g per day. This miniscule amount of coconut oil did not affect LDL-cholesterol. In summary, among the 7 studies cited by Bastian not in the Eyers review, 4 would appropriately be excluded as result of being non-randomized, uncontrolled, using a very small amount, not including a control group or not even being a trial of coconut oil. Among the 3 randomized trials, McKenney et al., Ganji et al. and Assuncao et al., the first two found that coconut oil increased LDL-cholesterol levels. The trial of Assuncao et al. would likely fail an outlier test because it is the only one among 12 studies in which LDL-C levels is lower on coconut than soybean oil. Given the differences in study designs, populations, and localities, the results of coconut oil trials are remarkably uniform showing that it increases LDL-cholesterol levels, an established cause of cardiovascular disease.

    Bastian employs a tactic in common with some other critics of good nutritional science, namely, to a) disparage and misrepresent high quality studies that show harmful effects of saturated fat; b) promote and misrepresent seriously flawed and irrelevant studies that report the opposite; and c) cite meta-analyses with faulty designs often based on inclusion of flawed studies. We offer a challenge to those who assert health benefits to coconut oil, or saturated fat, in general. Produce well-designed and executed studies that show that there are beneficial effects on a bona fide health outcome or a recognized surrogate, e.g., LDL-cholesterol.

    Frank M. Sacks, for the authors.

  • Jakob Näslund2017 Jul 24 3:30 p.m. (2 days ago)

    For a discussion of this study regarding some outstanding issues relating to methodology, as well as the presence of a number of possible inaccuracies, see our commentary in Acta Neuropsychiatrica entitled "Multiple possible inaccuracies cast doubt on a recent report suggesting selective serotonin reuptake inhibitors to be toxic and ineffective", available at https://doi.org/10.1017/neu.2017.23

  • Richard E Goodman2017 Jul 24 1:34 p.m. (2 days ago)

    As one of the senior authors of the Siruguri et al., 2015 publication, with 20 years experience in evaluating the safety of Genetically Engineered (GE or GM) crops, I feel obligated to respond to the statements Dr. Sunil Verma is posting on PubMed COMMONS and now also in Science as an e-letter to the 2016 publication by Priyanka Pulls describing the development of this GE mustard. Dr. Verma's second comment posting here lists his letter in Science. Importantly, neither my comments, nor those of Verma are peer reviewed. We are giving our opinions (which differ markedly as does our experiences). I have written a response to Verma's e-letter in Science and it is available at http://science.sciencemag.org/content/352/6289/1043/tab-e-letters . It addresses the issues of the accepted hazard and risk evaluation of GE crops in India and internationally. Our 2015 publication here describes the assessment looking at the source of the genes, the sequences of proteins and the scientific rational is to evaluation potential risks for those who might be allergic to the protein (Barnase, Barstar or Bar), or to proteins that are highly identical, and could share IgE binding. Dr. Verma did not provide any data that demonstrates we are wrong, or that there are risks from this mustard. Instead in his supplemental information, he compared the sequence of Ani s 9, a minor allergen of a fish parasitic worm, to other sequences in the AllergenOnline.org database. And he implies that cross-reactivity might occur due to associated proteins like the SXP/RAL-2 proteins (Ani s 5 and Ani s 9). However, as noted by Garcia-Mayoral et al., 2014), similar proteins do not exist outside of worms (Nematodes). Ani s 9 has very little sequence similarity to Barnase, as described in our paper. Comparing Ani s 9 in AllergenOnline demonstrates that it is rather unique and unlikely to have cross-reactivity outside of the parasitic worm allergens. This mustard contains Barnase, not Ani s 9. Furthermore, he points to the six amino acid match of Barnase to Ani s 9. But as described in our paper and in my letter in Science, that six amino acid segment matches hundreds of proteins in the NCBI database, without any evidence of cross-reactivity or allergy. Furthermore, there is no evidence that a six amino acid match predicts cross-reactivity. The standard in CODEX is sequences matching >35% identity over 80 amino acids, and such matches are quite conservative (overpredict) both primary and confirmational epitopes (Goodman, 2006, Goodman et al., 2008). CODEX indicates you may do a short sequence match, but must justify the methods. If there are matches of >35% identity over 80, then serum IgE tests would be warranted using sera from at-risk (specifically allergic subjects (Goodman, 2008). In the future there will be improvements in the assessment (Goodman and Tetteh, 2011), however, Dr. Verma has not described any new method or any proof that he has an improvement. Instead, he has proposed hypothetical issues, a letter in Science and he has not posted the letter on facebook. If he thinks there can be improvements, he should do experiments and submit his results to a peer reviewed journal for scientific evaluation. The authors of the Siruguri et al 2015 paper stand by our results that this GM mustard is as safe as the non-GM mustards in use in India today.

    References: Garcia-Mayoral MF, Trevino MA et al., (2014). Relationships between IgE/IgG4 epitopes, structure and function in Anisakis simplex Ani s 5, a member of the SXP/RAL-2 protein family. PLOS, Negl Tropical Dis 8(3):e2735. Goodman RE. (2006) Practical and predictive bioinforamtics methods for the identiifcation of potentially cross-reactive protein matches. Mol Nutr Food Res 50:655-660. Goodman RE, Vieths S et al, (2008). Allergenicity assessment of genetically modified crops--what makes sense? Goodman RE. (2008) Performing IgE serum testing due to bioinformatics matches in the allergenicity assessment of GM crops. Food Chem Toxicol 46(Suppl 10):S24-S34. Goodman RE, Tetteh AO. (2011). Suggested improvements for the allergenicity assessment of genetically modified plants used in foods. Curr Allergy Asthma Rep 11(4):317-324.

  • In reply to a comment by Richard E Goodman2017 Jul 19 2:50 p.m. (7 days ago)

    Sunil Verma2017 Jul 21 4:35 p.m. (5 days ago)

    Reply to - Comment of Prof. Richard E. Goodman, and Vasanthi Siruguri 2017 Jul 19 2:50 p.m.

    Sunil Kumar Verma, Principal Scientist CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500 007, India.

    Dear Authors,

    I read your elaborated reply with great enthusiasm and with hope to find specific answers to my very specific queries on this specific paper (PMID: 26079618). Instead of replying to my scientific observations on the methodology used in this paper, your reply focus more on defending the release of GM mustard in India, which is not really the central theme of this specific paper in question. The scope of this specific paper was limited to assess the allergenic potential of the transgene Bar, Barnase, and Barstar expressed in Genetically Modified Indian Mustard for heterosis breeding, wherein, the technical methodology which was used in this paper was questionable as specifically explained in my previous comment (supported by 15 pages of supplementary information, please see attachment in previous comment) in detail.

    Of course, GM Mustard release could be a consequence of this publication, which could be discussed in detail at appropriate forum when safety data and complete dossier which you have cited in your reply above is made available for public review by the concerned authorities (see ref. 1). Until that complete dossier is available for review, your justifications on GM mustard release would be one sided. And for that reason, I would not like to even touch upon the matter beyond the scope of this specific paper and my technical comments which are still unaddressed.

    With reference to your first argument that I have misinterpreted recommendations of Indian Council of Medical Research (ICMR, 2008) guidelines on the safety of Genetically Engineered (GE) crops, I would like to highlight that even the ICMR guideline also emphasize on overall structural similarities to predict the allergenic potentials (see page 13-14 in ref. 2), however, in the light of my previous comment and provided data therein, we now know that primary amino acid sequence comparisons are not the best known indicators of structural similarities among proteins, therefore my technical objection remains valid.

    My second technical comment was on Barnase-barstar complex and its possible differential immune response compared to individual proteins in free form; this aspect you have left unaddressed in your reply above.

    In response to my third technical objection, you have written that AllergenOnline.org database is a peer reviewed database. I understand that it is a peer-reviewed database; however, it's peer-reviewed status does not change the newly revealed fact that this database fails to detect the known allergen 'Ani s 9' (GenBank: ABV55106.1) as allergen using the strategy as was followed to examine the GM Mustard transgenes; thus, the conclusions drawn in this analysis remain erroneous.

    My commentary on your paper and flawed conclusion therein has been published in Science (3). Authors are welcome to take this debate further so that a consensus could be reached beyond a reasonable doubt on the conclusion of this specific paper in question and a suitable action could be taken to correct the conclusions of this paper by the way of erratum if appropriate, as an outcome of this post publication review.

    References:

    (1) Priyanka Pulla, India nears putting GM mustard on the table. Science 27 May 2016: Vol. 352, Issue 6289, pp. 1043. DOI: 10.1126/science.352.6289.1043

    (2) Guidelines for the Safety Assessment of Foods Derived from Genetically Engineered Plants. Indian Council of Medical Research. New Delhi. 2008. https://goo.gl/HuAnGC Link accessed on 22/07/2017

    (3) Sunil Kumar Verma, RE: Letter on In Depth "New India nears putting GM mustard on the table" Science 10 July 2017. http://science.sciencemag.org/content/352/6289/1043/tab-e-letters Link Accessed on 22/07/2017

  • In reply to a comment by Irma Klerings2017 Jul 20 08:13 a.m. (6 days ago)

    Joseph J Drabick2017 Jul 24 10:39 a.m. (2 days ago) 1 of 1 people found this helpful

    Thank you for the comment for our article. We will clarify the literature searching strategy we used in the meta-analysis here. We used Pubmed, Cochrane Library, Ovid Medline and Ovid Healthstar databases, which are accessible from our medical center library. Other details for the search strategy, such as keywords, inclusion and exclusion criteria, are shown in our manuscript.

  • Giles Hardingham2017 Jul 23 10:39 a.m. (3 days ago)

    We would like to extend our sincere thanks to Michel Goedert for the use of his Thy1-P301S transgenic mouse (Allen et al. (2002), PMID: 12417659). Regrettably, this note was erroneously absent from the Acknowledgements section of the manuscript.

  • Randi Pechacek2017 Jul 22 8:11 p.m. (4 days ago) 2 of 2 people found this helpful

    Embriette Hyde made a blog post about this paper on microBEnet as part of a larger discussion on the microbiome of the built environment of our cars.

  • Randi Pechacek2017 Jul 21 6:16 p.m. (5 days ago)

    Embriette Hyde wrote a blog about this paper on microBEnet.

  • CO Stocco2017 Jul 21 2:23 p.m. (5 days ago)edited

    Thank you to the authors for such wonderful and detailed description of the extremely complex interaction between FSH and locally produced factors in the regulation of granulosa cells. This review will surely foster innovative ideas and projects to further explore the role of gonadotropins and growth factors in the regulation of female fertility.

  • Ten simple (empirical) rules for writing science.

    Weinberger CJ.PLoS Comput Biol. 2015.2 commentsAtanas G. Atanasov also commented

    Horacio Rivera2017 Jul 21 10:42 a.m. (5 days ago)

    Are citations related to a faulty writing style or simply to content? The results got by Weinberger et al. (2015) in their analysis of >1,000,000 abstracts may not be so surprising. Taking into account the pervasiveness of an improper writing style (Woodford FP, ed. Scientific Writing for Graduate Students, CBE 1986; Gopen&Swan, Am Sci 1990, 78: 550; Knight J, Nature 2003, 423: 376; Editorial, Nat Struct Mol Biol 2010, 17: 139), I guess that the decreased citation rate associated with half of 15 well-known stylistic features can equally be ascribed to the papers’ content. Actually, the opposite pattern found for the remaining features suggests that style alone is not a consistent predictor of citation rates. A more reliable study would compare a sample of "well written" vs "poorly written" abstracts, classified according to conventional wisdom by expert colleagues, instead of analyzing all available abstracts in a given period. I do two additional comments: 1. Rule 4 of the authors "Use the present tense" is unsuitable when dealing only with abstracts. At least in biomedicine, the general advice is to use the past tense in the "M&M" and "Results" sections that account for half or more of an abstract. Obviously, the results would have been the opposite ones if the rule "Use the past tense" had been applied. 2. The assertion that in "writing a paper, the limiting step is the ability to find the right article" appears nonsense inasmuch it disregards the crucial intellectual input required for successful writing. In other words, "to find the right article" is a preparatory rather than limiting step. To conclude, I praise the effort of Weinberger et al. (2015) in summarizing ten simple rules aimed to improve our writing style.

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Collaborating to bring journal clubs to PubMed Commons: A librarian’s perspective

July 5, 2017
Univ of Kansas Nursing-imgJournal clubs can be a great tool in graduate and medical education. They provide opportunities for students to practice important skills: literature searching, critical reading, scholarly debate, and in some cases, even writing. Julie Hartwell shares how a collaboration with faculty on PubMed Commons got started and its initial impact. See full blog post

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