Effectiveness of nutritional countermeasures in microgravity and its ground-based analogues to ameliorate musculoskeletal and cardiopulmonary deconditioning–A Systematic Review

Peter H. Sandal; David Kim; Leonie Fiebig; Andrew Winnard; Nick Caplan; David A. Green; Tobias Weber

doi:10.1371/journal.pone.0234412

Peer Review History

Original SubmissionApril 7, 2020
15 May 2020 Decision Letter - Sakamuri V. Reddy, Editor PONE-D-20-10013 Effectiveness of nutritional countermeasures in microgravity and its ground-based analogues to ameliorate musculoskeletal and cardiopulmonary deconditioning – A Systematic Review PLOS ONE Dear Dr Weber, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised by the reviewer and editorial comments during the review process. Though the authors have conducted an extensive survey of nutritional countermeasures to musculoskeletal and cardiopulmonary challenges in microgravity conditions, I suggest improving the quality of all figures, details in all legends including the supplemental information provided. We would appreciate receiving your revised manuscript by Jun 29 2020 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. We look forward to receiving your revised manuscript. Kind regards, Dr. Sakamuri V. Reddy Academic Editor PLOS ONE Additional Editor Comments: In this manuscript, Dr. Weber and colleagues performed a systematic review to evaluate the effectiveness of nutritional countermeasure to ameliorate the physiological challenges of the musculoskeletal and cardiopulmonary systems in microgravity conditions necessary to maintain human health during space flight missions. The survey concluded that nutrition alone cannot be expected to be an effective countermeasure in maintaining musculoskeletal and cardiopulmonary integrity during space flight and bed rest. The authors have performed systematic review with a thorough background literature. Specific comments to further improve the manuscript are as follow. Title- The authors may consider rephrasing the title for a review article- “Nutritional countermeasures to musculoskeletal and cardiopulmonary challenges in microgravity conditions”. They have conducted a Systematic Review and Meta-Analyses of data. They have used PRISMA 2009 flow diagram. I suggest the authors to verify the journal policy and using statistical methods appropriately. Also, improve the quality of all figures provided. Fig.1 legend, please provide ref#35 for Fiebig et al 2018 noted. References: Please remove the repeated information for references provided ex., Ref#21: “Available from:----------” verify complete details for Ref#37 “AMSRG Data extraction form v2. 2017” following a journal article for citations listed. Although the Methods section include Data analysis, I suggest providing details in legends with for Figures 1-4 with statistical methods and significance data (p.15); also, details in legends for “Supporting information” data provided. Journal requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. Please provide the date range for when the literature was searched. 3. Thank you for stating the following in the Financial Disclosure section: 'The author(s) received no specific funding for this work.' We note that one or more of the authors are employed by a commercial company: KBR GmbH a. Please provide an amended Funding Statement declaring this commercial affiliation, as well as a statement regarding the Role of Funders in your study. If the funding organization did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors' salaries and/or research materials, please review your statements relating to the author contributions, and ensure you have specifically and accurately indicated the role(s) that these authors had in your study. You can update author roles in the Author Contributions section of the online submission form. Please also include the following statement within your amended Funding Statement. “The funder provided support in the form of salaries for authors [insert relevant initials], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.” If your commercial affiliation did play a role in your study, please state and explain this role within your updated Funding Statement. b. Please also provide an updated Competing Interests Statement declaring this commercial affiliation along with any other relevant declarations relating to employment, consultancy, patents, products in development, or marketed products, etc. Within your Competing Interests Statement, please confirm that this commercial affiliation does not alter your adherence to all PLOS ONE policies on sharing data and materials by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests) . If this adherence statement is not accurate and there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared. c. Please include both an updated Funding Statement and Competing Interests Statement in your cover letter. We will change the online submission form on your behalf. Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: This is a very elaborate and detailed review regarding the effect of microgravity on the health of Astronauts during prolonged space flight. The authors have analyzed with effective statistical tools published data from several papers related to this field and have reported the results of their analysis on bone density, cardiovascular health, renal, vitamins, minerals, orthostatic hypotension,immune system and other relevant physiological changes pertaining to disturbance of normal homeostasis during prolonged space flight.This is a very well researched manuscript and could be a great source for information for biologist and physiologists doing microgravity research. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Hirendra Nath Banerjee [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0234412.r001
Revision 1
22 May 2020 Author Response Comments from Dr Sakamuri V. Reddy: Though the authors have conducted an extensive survey of nutritional countermeasures to musculoskeletal and cardiopulmonary challenges in microgravity conditions, I suggest improving the quality of all figures, details in all legends including the supplemental information provided. Thank you. We have done as suggested. Comments from Dr Prof Banerjee: Dear Professor Banerjee, Thank you for your helpful suggestions and comments. Please find your comments highlighted in red color, followed by our answers in black color below. All changes in the revised manuscript have been highlighted using the track changes function in word. In this manuscript, Dr Weber and colleagues performed a systematic review to evaluate the effectiveness of nutritional countermeasure to ameliorate the physiological challenges of the musculoskeletal and cardiopulmonary systems in microgravity conditions necessary to maintain human health during space flight missions. The survey concluded that nutrition alone cannot be expected to be an effective countermeasure in maintaining musculoskeletal and cardiopulmonary integrity during space flight and bed rest. The authors have performed systematic review with a thorough background literature. Specific comments to further improve the manuscript are as follow. � Thank you for your thorough review! Title- The authors may consider rephrasing the title for a review article- “Nutritional countermeasures to musculoskeletal and cardiopulmonary challenges in microgravity conditions”. � Thanks for proposing a new title. However, the authors of the present manuscript feel that the original title better reflects study design and purpose of the study, so we decided to keep the title as it is. They have conducted a Systematic Review and Meta-Analyses of data. They have used PRISMA 2009 flow diagram. I suggest the authors to verify the journal policy and using statistical methods appropriately. � Thank you for highlighting this, and apologies if this was not clear. We have not done a full meta-analysis due to the high heterogeneity of study designs and outcomes. More precisely, we did not do a meta-analysis, as either the RCT/CT data was too heterogeneous, or there were only within participant designs which would break the meta analysis statistical assumptions. However, to still provide an overall summary, we converted all included data to effect sizes in standardised units to give an overall comparable summary of the evidence base as it stands today. In conclusion, we have used statistical methods appropriately and the present methodology is in line with the highest standards available for systematic literature reviews (Cochrane guidelines). We have added a sentence to the data analysis section to make this clear. Also, improve the quality of all figures provided. Fig.1 legend, please provide ref#35 for Fiebig et al 2018 noted. � Thank you. We have done as suggested. References: Please remove the repeated information for references provided ex., Ref#21: “Available from:----------” � Thank you. We have done as suggested. Verify complete details for Ref#37 “AMSRG Data extraction form v2. 2017” following a journal article for citations listed. � Thank you. We have verified this and revised the references in the bibliography. Although the Methods section include Data analysis, I suggest providing details in legends with for Figures 1-4 with statistical methods and significance data (p.15); also, details in legends for supporting information data provided. � Thank you. We have done as suggested This is a very elaborate and detailed review regarding the effect of microgravity on the health of Astronauts during prolonged space flight. The authors have analyzed with effective statistical tools published data from several papers related to this field and have reported the results of their analysis on bone density, cardiovascular health, renal, vitamins, minerals, orthostatic hypotension,immune system and other relevant physiological changes pertaining to disturbance of normal homeostasis during prolonged space flight. This is a very well researched manuscript and could be a great source for information for biologist and physiologists doing microgravity research. � Once again, thank you for your thorough review! Journal requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf � Thank you. We verified this and can confirm that the PLOSONE requirements are met. 2. Please provide the date range for when the literature was searched. � Thank you. We have done as suggested and added this information to the methods section. 3. Thank you for stating the following in the Financial Disclosure section: 'The author(s) received no specific funding for this work.' We note that one or more of the authors are employed by a commercial company: KBR GmbH a. Please provide an amended Funding Statement declaring this commercial affiliation, as well as a statement regarding the Role of Funders in your study. If the funding organization did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors' salaries and/or research materials, please review your statements relating to the author contributions, and ensure you have specifically and accurately indicated the role(s) that these authors had in your study. You can update author roles in the Author Contributions section of the online submission form. Please also include the following statement within your amended Funding Statement. “The funder provided support in the form of salaries for authors [insert relevant initials], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.” � Thank you. We have done as suggested and added this information to the author contribution section. If your commercial affiliation did play a role in your study, please state and explain this role within your updated Funding Statement. � Not applicable. b. Please also provide an updated Competing Interests Statement declaring this commercial affiliation along with any other relevant declarations relating to employment, consultancy, patents, products in development, or marketed products, etc. � Not applicable. Within your Competing Interests Statement, please confirm that this commercial affiliation does not alter your adherence to all PLOS ONE policies on sharing data and materials by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests) . If this adherence statement is not accurate and there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared. � We have done as suggested and added this information to the author contribution section. c. Please include both an updated Funding Statement and Competing Interests Statement in your cover letter. We will change the online submission form on your behalf. � We have done as suggested. Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests � This has been noted, and the PLOS ONE information on competing interests has been reviewed, and the corresponding author has declared all potential conflicts of interest on behalf of all contributing authors. While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step. � We have done as suggested. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0234412.r002
27 May 2020 Decision Letter - Sakamuri V. Reddy, Editor Effectiveness of nutritional countermeasures in microgravity and its ground-based analogues to ameliorate musculoskeletal and cardiopulmonary deconditioning – A Systematic Review PONE-D-20-10013R1 Dear Dr. Weber, We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements. Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication. Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. With kind regards, Dr. Sakamuri V. Reddy Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0234412.r003
Formally Accepted
29 May 2020 Acceptance Letter - Sakamuri V. Reddy, Editor PONE-D-20-10013R1 Effectiveness of nutritional countermeasures in microgravity and its ground-based analogues to ameliorate musculoskeletal and cardiopulmonary deconditioning – A Systematic Review Dear Dr. Weber: I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. For any other questions or concerns, please email plosone@plos.org. Thank you for submitting your work to PLOS ONE. With kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Sakamuri V. Reddy Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0234412.r004

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