The 1064-nm Nd:YAG Photobiomodulation vs. 20% Benzocaine Topical Gel in Inducing Mucosal Anesthetic Effect: A Double-Blind Randomized Clinical Trial
, Karen Tatarian 2, Carla Zogheib 3, Stefano Benedicenti 1,*, Claudio Pasquale 1,†and Andrea Amaroli 4,†Round 1
Reviewer 1 Report
This article is well presented with excellent illustrations and of clinical interest. Remaining issues are mainly of a cosmetical nature.
1) The list of references should be edited into one common style, e.g. 7,29,30,41,53,56,59,61
2) Ref. 28 is the same as ref. 65
3) page 2, the novel handpiece…. Is described twice in a few lines
4) ”et al.” or ” and collaborators”, use one
5) diode or Diode, chose one, capital letter not justified
6) page 3/93, edit
7) Page 6/145 edit last sentence (”a”)
8) Page 12/360, this sentences seems to lack a verb
9) Page 12/364 PBM rather that ”laser therapy”, to avoid the old nomenclature problems
10) Page 13/378 ”CLIII” = Class 3? Superfluous.
11) Page 13/391. 0.3W is not low in this context and a few lines above 300 mW goes without a comment
12) Page 14/435. ”light therapy features” is a bit unclear
Author Response
Dear Reviewer 1,
First of all, thank you so much for appreciating our paper and for the precious advice that improved our work.
Please find in the journal’s template our revisions highlighted in yellow.
Point-by-point answers to your comments are listed below.
Q1: The list of references should be edited into one common style, e.g. 7,29,30,41,53,56,59,61
A1: We apologise for the numerous typos. We corrected the reference list.
Q2: Ref. 28 is the same as ref. 65
A2: We corrected the references.
Q3: page 2, the novel handpiece…. Is described twice in a few lines
A3: We corrected the sentence.
Q4: ”et al.” or ” and collaborators”, use one
A4: We changed “et al” with “and collaborators”.
Q5: diode or Diode, chose one, capital letter not justified
A5: We used only lowercase letter.
Q6: page 3/93, edit
A6: We changed the typo.
Q7: Page 6/145 edit last sentence (”a”)
A7: We changed the typo.
Q8: Page 12/360, this sentences seems to lack a verb
A8: We modified the sentence.
Q9: Page 12/364 PBM rather that ”laser therapy”, to avoid the old nomenclature problems
A9: We changed laser therapy with PBM therapy.
Q10: Page 13/378 ”CLIII” = Class 3? Superfluous.
A10: We removed the word.
Q11: Page 13/391. 0.3W is not low in this context and a few lines above 300 mW goes without a comment.
A11: We corrected the sentence.
Q12: Page 14/435. ”light therapy features” is a bit unclear
A12: We changed the sentence.
Hoping to encounter your appreciation, we send you our
Best Regards
Andrea Amaroli and co-workers
Author Response File: 
Author Response.pdf
Reviewer 2 Report
1. This article is well written and it can be published in the current version.
2. A few corrections should be made or clarified. For example, “a” in the end of line 145 should be deleted. The calculation of dosage seems not clear. According to Figure 1, the parameters shown in L group, the average energy density is 30 J/cm2. However, the real calculation results should be made as follows:
60sec(exposure time)*10pulses/second(10Hz)* 0.1ms (pulse width)*0.5W/cm2=0.03J/cm2.
If you use the peak power density 499W/cm2 in the calculation procedure, the answer is 30J/ cm2. You have mentioned that the probe used in this experiment is flat-top hand-piece, the optical shape is not so distributed equally?
The parameters in Figure 1 and from line 148-149 easily to make readers confusion. Please recheck it and make it clear.
Author Response
Dear Reviewer 2,
First of all, thank you so much for appreciating our paper and for the precious advice that improved our work.
Please find in the journal’s template our revisions highlighted in green.
Point-by-point answers to your comments are listed below.
Q1: A few corrections should be made or clarified. For example, “a” in the end of line 145 should be deleted. The calculation of dosage seems not clear.
A1: According to your advice we corrected some typos.
Q2: According to Figure 1, the parameters shown in L group, the average energy density is 30 J/cm2. However, the real calculation results should be made as follows: 60sec(exposure time)*10pulses/second(10Hz)* 0.1ms (pulse width)*0.5W/cm2=0.03J/cm2.
A2: We calculated the Energy density (J/cm2) as the power density (W/cm2) multiplied by the total time of illumination.
Energy = Power * time
Energy Density = Energy/area
= Power * time/area
= Power/area * time
= Power Density * time
= 0.5 W/cm2 * 60 seconds
= 30 J/cm2
Where 0.5 W power is the average power and 500 W is the peak power (see figure 1). Figure 1 shows also that the pulse width is 100 microseconds namely 0.0001 seconds and the frequency is 10 Hz.
Therefore, according to the calculation made by Professor Wayne Selting in our first paper on 1064 nm Nd:YAG [1], and with https://www.lasercalculator.com/ program in our condition, a power peak of 500 W generate an average power of 0.5 W and, therefore, the energy density or fluence is 30 J/cm2.
[1] Amaroli A, Benedicenti A, Ravera S, Parker S, Selting W, Panfoli I, Benedicenti S. Short-pulse neodymium:yttrium-aluminium garnet (Nd:YAG 1064nm) laser irradiation photobiomodulates mitochondria activity and cellular multiplication of Paramecium primaurelia (Protozoa). Eur J Protistol. 2017 Oct;61(Pt A):294-304. doi: 10.1016/j.ejop.2017.06.003. Epub 2017 Jun 19. PMID: 28756937.
Q3: If you use the peak power density 499W/cm2 in the calculation procedure, the answer is 30J/ cm2. You have mentioned that the probe used in this experiment is a flat-top hand-piece, the optical shape is not so distributed equally?
A3: We have used a hand-piece with a flat-top beam profile having an intensity profile which is flat over most of the covered area. This is in contrast to Gaussian beams, for example, where the intensity smoothly decays from its maximum on the beam axis to zero. A flat-top beam has a constant irradiance profile through the cross-section of the laser beam. [Amaroli A, Arany P, Pasquale C, Benedicenti S, Bosco A, Ravera S. Improving Consistency of Photobiomodulation Therapy: A Novel Flat-Top Beam Hand-Piece versus Standard Gaussian Probes on Mitochondrial Activity. Int J Mol Sci. 2021 Jul 21;22(15):7788. doi: 10.3390/ijms22157788. PMID: 34360559; PMCID: PMC8346075.]
Q4: The parameters in Figure 1 and from line 148-149 easily to make readers confusion. Please recheck it and make it clear.
A4: We changed the sentence and we referred the parameters to figure 1.
Hoping to encounter your appreciation, we send you our
Best Regards
Andrea Amaroli and co-workers
Author Response File: Author Response.pdf
