Increased Inflammatory Markers at AMPH-Addicts Are Related to Neurodegenerative Conditions: Alzheimer’s Disease

Round 1

Reviewer 1 Report

Major changes

• The title does not reach the central objective of the study.  I recommend that both title and introduction should be restructured considering the connection between inflammatory markers observed in AMPH-addict people with the Alzheimer disease or neurodegenerative diseases in general, as described in the manuscript.

 

• As suggestion, three titles could be used to better illustrate the manuscript:

- Increased inflammatory markers at AMPH-addicts are related to neurodegenerative conditions: Alzheimer 's disease

- Relationship between  amphetamine-addicts inflammatory markers and neurodegenerative disease.

- Amphetamine addiction increases inflammatory markers that are modified in neurodegenerative disease.

 

• I would like to understand why the collected data occurred only in persons of  male gender. Why did the study not use women?

 

• The number of participants described in the text is different from what is described in the abstract. Please describe this data clearly in the methods section.

 

• Many sentences throughout the discussion are not referenced, please pay attention to that.

 

• The final conclusion is not clear, considering the hypothesis

  of the authors. The initial hypothesis should be resumed at the end of the discussion, emphasizing the importance of the study.

 

• The conclusion should be short and to the point

 

Minor points

• In the methods section, what was analyzed was not described, only how it was analyzed. I suggest indicating the markers that were made in this section.
• The acronyms CNS / CSF / REGB / FTD are not described previously. In addition, when making an abbreviation, I suggest putting its description at the beginning of each new section.
• I believe that there was a deformity in the Greek letters, because sometimes it appears * in the middle of the sentence.

Example: 329-330 “Reactivated microglia might en gulf the debris of injured tissue and the deposition of A* as phagocytes in the CNS”

 

• The “Oxygen free radicals” description, it is a exclusive description; I strongly suggest the term  FREE RADICALS (FR), since this term is referred to both oxygen and nitrogen derivatives, in a general way.

 

• On the line 325: I don't understand what  mean by the word milieu... “... to the AD brain's inflammatory milieu [31].”

 

• The format of the Table 1 is not suitable for a scientific publication. It should have only horizontal lines, comparable to the one in table 2. Standardize this issue.

 

• Figures: amphetamine addicted could be described in a short form We suggest to use acronyms (AMPH-add, for example) through the manuscript and in the figures, in order to reduce writing;

 

• It's more suitable to write in full or not put numbers: “serum of 8 alcoholic drinkers”

 

Author Response

Thank you for giving me the opportunity to submit a revised draft of my manuscript titled

 [Amphetamine addiction increases inflammatory markers that are modified in neurodegenerative disease.] to [Applied Sciences]. I appreciate the time and effort that you have dedicated to providing your valuable feedback on my manuscript. I am grateful to the reviewers for their insightful comments on my paper. I have been able to incorporate changes to reflect most of the suggestions provided by the reviewers. I have highlighted the changes within the manuscript.

Here is a point-by-point response to the reviewers’ comments.

A native English speaker revised and edited the whole work.

Author Response File: Author Response.docx

Reviewer 2 Report

The paper entitled "Alteration of some neurodegeneration inflammatory 2 biomarkers at an amphetamine-addicts young age" is very interesting and actual. A wide problem is amphetamine addiction and the correlation with physical and mental problems, including neurodegeneration. The paper needs to improve the material methods, in particular, are not described the control cases, I think is better to insert the data about the healthy patients, like the cases. The results and statistical analysis are clear. The study is about male patients, which is good, but a very important follow of this study could be to compare the data with female patients. I suggest talking about the difference between female and male gender and inserting the topic in the discussion.

 

Author Response

Thank you for giving me the opportunity to submit a revised draft of my manuscript titled

 [Amphetamine addiction increases inflammatory markers that are modified in neurodegenerative disease.] to [Applied Sciences]. I appreciate the time and effort that you have dedicated to providing your valuable feedback on my manuscript. I am grateful to the reviewers for their insightful comments on my paper. I have been able to incorporate changes to reflect most of the suggestions provided by the reviewers. I have highlighted the changes within the manuscript.

Here is a point-by-point response to the reviewers’ comments.

A native English speaker revised and edited the whole work.

Author Response File: Author Response.docx

Reviewer 3 Report

(37) "HD" is better to replace with "ND"
Throughout the text: it is better to use "neurodegenerative disease" instead of "neurodegenerative illnesses"
2.1 (81) the number of patients is not stated
(105) "...10 minutes at 1000 x g to separate the serum from the plasma...". I am not sure it is possible to separate serum from the plasma only by 1000g centrifugation.
(113) The assay buffer composition is not specified.
What exactly was tested? What were the values? Section 2.3 is very poorly written.
2.5 Which criterion was used to test the hypothesis about the type of distribution? What is the magnitude of the observed effect?
(170) Table 1. The description in the text does not match the data presented in the table.
(190) What is the accuracy of the measurement? On what basis are two decimal places indicated?
Table 2 shows patient counts that do not match the text, methods, and data presented in Table 1.
The figures duplicate the tables, something needs to be removed.
(260) There is no basis for this conclusion!
(280) There is no data on IL-1 in the text.

Author Response

Thank you for giving me the opportunity to submit a revised draft of my manuscript titled

 [Amphetamine addiction increases inflammatory markers that are modified in neurodegenerative disease.] to [Applied Sciences]. I appreciate the time and effort that you have dedicated to providing your valuable feedback on my manuscript. I am grateful to the reviewers for their insightful comments on my paper. I have been able to incorporate changes to reflect most of the suggestions provided by the reviewers. I have highlighted the changes within the manuscript.

Here is a point-by-point response to the reviewers’ comments.

A native English speaker revised and edited the whole work.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Major changes

• The title does not reach the central objective of the study.  I recommend that both title and introduction should be restructured considering the connection between inflammatory markers observed in AMPH-addict people with the Alzheimer disease or neurodegenerative diseases in general, as described in the manuscript.

            The title was changed as requested, but the necessary changes throughout the   text, mainly in the introduction section, were not modified.

 

• As suggestion, three titles could be used to better illustrate the manuscript:

- Increased inflammatory markers at AMPH-addicts are related to neurodegenerative conditions: Alzheimer 's disease

- Relationship between amphetamine-addicts inflammatory markers and neurodegenerative disease.

- Amphetamine addiction increases inflammatory markers that are modified in neurodegenerative disease.

• I would like to understand why the collected data occurred only in persons of  male gender. Why did the study not use women?

            There was no answer for this question.

 

• The number of participants described in the text is different from what is described in the abstract. Please describe this data clearly in the methods section.

            The requested request has been fulfilled.

• Many sentences throughout the discussion are not referenced, please pay attention to that.

            No new references added.

• The final conclusion is not clear, considering the hypothesis

  of the authors. The initial hypothesis should be resumed at the end of the discussion, emphasizing the importance of the study.

            The authors managed to end the discussion in a much better way according to   the request that was answered.

• The conclusion should be short and to the point

            The modification was made, but the authors still do not show clarity in what they             themselves did. The body and purpose of the text is one while the ending is       another.

 

Minor points

• In the methods section, what was analyzed was not described, only how it was analyzed. I suggest indicating the markers that were made in this section.

      The request made has been modified

• The acronyms CNS / CSF / REGB / FTD are not described previously. In addition, when making an abbreviation, I suggest putting its description at the beginning of each new section.

      The request made has been modified

 

• I believe that there was a deformity in the Greek letters, because sometimes it appears * in the middle of the sentence.

Example: 329-330 “Reactivated microglia might en gulf the debris of injured tissue and the deposition of A* as phagocytes in the CNS”

 

 

• The “Oxygen free radicals” description, it is a exclusive description; I strongly suggest the term  FREE RADICALS (FR), since this term is referred to both oxygen and nitrogen derivatives, in a general way.

      The request made has been modified.

 

• On the line 325: I don't understand what  mean by the word milieu... “... to the AD brain's inflammatory milieu [31].”

      The request made has been modified.

 

• The format of the Table 1 is not suitable for a scientific publication. It should have only horizontal lines, comparable to the one in table 2. Standardize this issue.

No changes to the Table 1 have been made.

• Figures: amphetamine addicted could be described in a short form We suggest to use acronyms (AMPH-add, for example) through the manuscript and in the figures, in order to reduce writing;

            The request made has been modified.

 

• It's more suitable to write in full or not put numbers: “serum of 8 alcoholic drinkers”

            The request made has been modified.

 

• All abbreviations throughout the Methods section where temperature is described must be modified (an acronym for °C is being used, which is not universal) - modify the symbol universally assigned to °

 

• Change the shape of the scale of the figures. Numerical scale can be reduced in graphics to make it more acceptable.

            No changes to the graphics have been made.

• In the table 4, only the top and side bold must be maintained (the middle context does not need to be bold) / put the r only once (not 6x).

            No changes to the graphics have been made.

• All the figures must be standardized. The scientific format shoul be used with lighter strokes. Use abbreviations on the abscissa line.

            No changes to the graphics have been made.

 

• All the three figures showing ALT and AST can be merged into one figure (A, B and C) to reduce the space used.

            No changes to the graphics have been made.

 

 

Author Response

Dear reviewer

 

Thank you for allowing us to submit a revised draft of our manuscript originally titled “Amphetamine addiction increases inflammatory markers that are modified in neurodegenerative disease” (Manuscript ID: applsci-1716615).

First, we are pleased to have received a positive evaluation. We would like to express our appreciation for the time and effort you have dedicated to providing your valuable feedback on our manuscript.

We fundamentally agree with all the comments made by the reviewers and have incorporated corresponding revisions into the manuscript.

Our responses to the comments made by each reviewer are provided below, and the changes are highlighted in yellow in the revised manuscript.

We believe that our manuscript has considerably improved because of these revisions. Therefore, we hope that our manuscript, “Amphetamine addiction increases inflammatory markers that are modified in neurodegenerative disease” is now acceptable for publication in Applied Sciences

We would like to thank you once again for your consideration of our work and for inviting us to submit the revised manuscript. We look forward to hearing from you.

Author Response File: Author Response.docx

Reviewer 2 Report

I understand the problem with female patients, and I respect the cultural difference between various countries. 

Author Response

Dear reviewer

 

Thank you for allowing us to submit a revised draft of our manuscript originally titled “Amphetamine addiction increases inflammatory markers that are modified in neurodegenerative disease” (Manuscript ID: applsci-1716615).

First, we are pleased to have received a positive evaluation. We would like to express our appreciation for the time and effort you have dedicated to providing your valuable feedback on our manuscript.

We fundamentally agree with all the comments made by the reviewers and have incorporated corresponding revisions into the manuscript.

Our responses to the comments made by each reviewer are provided below, and the changes are highlighted in yellow in the revised manuscript.

We believe that our manuscript has considerably improved because of these revisions. Therefore, we hope that our manuscript, “Amphetamine addiction increases inflammatory markers that are modified in neurodegenerative disease” is now acceptable for publication in Applied Sciences

We would like to thank you once again for your consideration of our work and for inviting us to submit the revised manuscript. We look forward to hearing from you.

Author Response File: Author Response.docx

Reviewer 3 Report

 

The conclusion contains a description of the limitations of the study. The limitations should be replaced to another paragraph. The conclusion needs to be revised. What is the merit of the researchers? What is the evidence base for your conclusion?

Author Response

Dear reviewer

 

Thank you for allowing us to submit a revised draft of our manuscript originally titled “Amphetamine addiction increases inflammatory markers that are modified in neurodegenerative disease” (Manuscript ID: applsci-1716615).

First, we are pleased to have received a positive evaluation. We would like to express our appreciation for the time and effort you have dedicated to providing your valuable feedback on our manuscript.

We fundamentally agree with all the comments made by the reviewers and have incorporated corresponding revisions into the manuscript.

Our responses to the comments made by each reviewer are provided below, and the changes are highlighted in yellow in the revised manuscript.

We believe that our manuscript has considerably improved because of these revisions. Therefore, we hope that our manuscript, “Amphetamine addiction increases inflammatory markers that are modified in neurodegenerative disease” is now acceptable for publication in Applied Sciences

We would like to thank you once again for your consideration of our work and for inviting us to submit the revised manuscript. We look forward to hearing from you.

Author Response File: Author Response.docx

Round 3

Reviewer 1 Report

In both Introduction and Discussion sections, authors present Alzheimer disease and its inflammatory markers in confusion with drug addiction data. Only in the results section, the approach is related to AMPH addiction. What is the hypothesis? This must be clarified.
The Table 1 was modified, but is different from a scientific format. Figure 4 was modified, but this configuration should be linear in horizontal design (3 figures a- b and c) in a horizontal design.

The Conclusion was ameliorated. Only in this section was  possible to understand the  involvement between neuroinflammatory markers observed in drug-exposed patients and the Alzheimer disease patients. This context should be presented throughout the manuscript.

In my vision, following a complete revision in the format (Introduction and discussion sections), the manuscript should be sent to another Reviewer, in search of a new opinion.

Author Response

Dear reviewer,

Thank you for giving me the opportunity to submit a revised draft of my manuscript titled

 [“Increased inflammatory markers at AMPH-addicts are related to neurodegenerative conditions: Alzheimer 's disease”] to [Applied Sciences]. I appreciate the time and effort that you have dedicated to providing your valuable feedback on my manuscript. I am grateful to the reviewers for their insightful comments on my paper. I have been able to incorporate changes to reflect most of the suggestions provided by the reviewers. I have highlighted the changes within the manuscript.

Here is a point-by-point response to the reviewers’ comments.

Author Response File: Author Response.docx