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1. Evaluation of Adjunctive Photobiomodulation (PBMT) for COVID-19 Pneumonia via Clinical Status and Pulmonary Severity Indices in a Preliminary Trial

Author

Vetrici MA, Mokmeli S, Bohm AR, Monici M, and Sigman SA

Subjects
covid-19, low level laser therapy, pneumonia, smart-cop, bcrss, rale, Pathology, RB1-214, Therapeutics. Pharmacology, RM1-950
Abstract

Mariana A Vetrici,1,* Soheila Mokmeli,2,* Andrew R Bohm,3 Monica Monici,4 Scott A Sigman5,* 1Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, Canada; 2Training Institute, Canadian Optic and Laser Center, Victoria, BC, Canada; 3Department of Orthopedics, Lenox Hill Hospital, New York, NY, USA; 4ASA Campus J.L., ASA Res. Division – Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy; 5Department of Orthopedics, Lowell General Hospital, Lowell, MA, 01863, USA*These authors contributed equally to this workCorrespondence: Scott A SigmanDepartment of Orthopedics, Lowell General Hospital, 295 Varnum Avenue, Lowell, MA, 01863, USATel +1 978 856 7676Email sasigmanmd@icloud.comPurpose: Evidence-based and effective treatments for COVID-19 are limited, and a new wave of infections and deaths calls for novel, easily implemented treatment strategies. Photobiomodulation therapy (PBMT) is a well-known adjunctive treatment for pain management, wound healing, lymphedema, and cellulitis. PBMT uses light to start a cascade of photochemical reactions that lead to local and systemic anti-inflammatory effects at multiple levels and that stimulate healing. Numerous empirical studies of PBMT for patients with pulmonary disease such as pneumonia, COPD and asthma suggest that PBMT is a safe and effective adjunctive treatment. Recent systematic reviews suggest that PBMT may be applied to target lung tissue in COVID-19 patients. In this preliminary study, we evaluated the effect of adjunctive PBMT on COVID-19 pneumonia and patient clinical status.Patients and Methods: We present a small-scale clinical trial with 10 patients randomized to standard medical care or standard medical care plus adjunctive PBMT. The PBMT group received four daily sessions of near-infrared light treatment targeting the lung tissue via a Multiwave Locked System (MLS) laser. Patient outcomes were measured via blood work, chest x-rays, pulse oximetry and validated scoring tools for pneumonia.Results: PBMT patients showed improvement on pulmonary indices such as SMART-COP, BCRSS, RALE, and CAP (Community-Acquired Pneumonia questionnaire). PBMT-treated patients showed rapid recovery, did not require ICU admission or mechanical ventilation, and reported no long-term sequelae at 5 months after treatment. In the control group, 60% of patients were admitted to the ICU for mechanical ventilation. The control group had an overall mortality of 40%. At a 5-month follow-up, 40% of the control group experienced long-term sequelae.Conclusion: PBMT is a safe and effective potential treatment for COVID-19 pneumonia and improves clinical status in COVID-19 pneumonia.Keywords: COVID-19, low-level laser therapy, pneumonia, SMART-COP, BCRSS, RALE

Published
2021

5. Physiological adaptations affecting drug pharmacokinetics in space: what do we really know? A critical review of the literature

Author

Dello Russo, Cinzia, Bandiera, T., Monici, M., Surdo, L., Yip, V. L. M., Wotring, V., Morbidelli, L., Dello Russo C. (ORCID:0000-0002-2538-3832), Dello Russo, Cinzia, Bandiera, T., Monici, M., Surdo, L., Yip, V. L. M., Wotring, V., Morbidelli, L., and Dello Russo C. (ORCID:0000-0002-2538-3832)

Abstract

As human spaceflight progresses with extended mission durations, the demand for effective and safe drugs will necessarily increase. To date, the accepted medications used during missions (for space motion sickness, sleep disturbances, allergies, pain, and sinus congestion) are administered under the assumption that they act as safely and efficaciously as on Earth. However, physiological changes have been documented in human subjects in spaceflight involving fluid shifts, muscle and bone loss, immune system dysregulation, and adjustments in the gastrointestinal tract and metabolism. These alterations may change the pharmacokinetics (PK) and pharmacodynamics of commonly used medications. Frustratingly, the information gained from bed rest studies and from in-flight observations is incomplete and also demonstrates a high variability in drug PK. Therefore, the objectives of this review are to report (i) the impact of the space environmental stressors on human physiology in relation to PK; (ii) the state-of-the-art on experimental data in space and/or in ground-based models; (iii) the validation of ground-based models for PK studies; and (iv) the identification of research gaps.

Published
2022

8. The Future of Personalized Medicine in Space: From Observations to Countermeasures

Author

Pavez Lorie, E., Baatout, S., Chouker, A., Buchheim, J. -I., Baselet, B., Dello Russo, Cinzia, Wotring, V., Monici, M., Morbidelli, L., Gagliardi, D., Stingl, J. C., Surdo, L., Yip, V. L. M., Dello Russo C. (ORCID:0000-0002-2538-3832), Pavez Lorie, E., Baatout, S., Chouker, A., Buchheim, J. -I., Baselet, B., Dello Russo, Cinzia, Wotring, V., Monici, M., Morbidelli, L., Gagliardi, D., Stingl, J. C., Surdo, L., Yip, V. L. M., and Dello Russo C. (ORCID:0000-0002-2538-3832)

Abstract

The aim of personalized medicine is to detach from a “one-size fits all approach” and improve patient health by individualization to achieve the best outcomes in disease prevention, diagnosis and treatment. Technological advances in sequencing, improved knowledge of omics, integration with bioinformatics and new in vitro testing formats, have enabled personalized medicine to become a reality. Individual variation in response to environmental factors can affect susceptibility to disease and response to treatments. Space travel exposes humans to environmental stressors that lead to physiological adaptations, from altered cell behavior to abnormal tissue responses, including immune system impairment. In the context of human space flight research, human health studies have shown a significant inter-individual variability in response to space analogue conditions. A substantial degree of variability has been noticed in response to medications (from both an efficacy and toxicity perspective) as well as in susceptibility to damage from radiation exposure and in physiological changes such as loss of bone mineral density and muscle mass in response to deconditioning. At present, personalized medicine for astronauts is limited. With the advent of longer duration missions beyond low Earth orbit, it is imperative that space agencies adopt a personalized strategy for each astronaut, starting from pre-emptive personalized pre-clinical approaches through to individualized countermeasures to minimize harmful physiological changes and find targeted treatment for disease. Advances in space medicine can also be translated to terrestrial applications, and vice versa. This review places the astronaut at the center of personalized medicine, will appraise existing evidence and future preclinical tools as well as clinical, ethical and legal considerations for future space travel.

Published
2021

15. The Artificial Gravity Platform (AGP); a Very Large Radius Centrifuge as Human Hypergravity Habitat

Author

Jack JWA van Loon, Albiol, J., Baeyens, J. P., Barakova, E., Belavy, D., Berte, J., Blanc, S., Bok, K., Bos, J., Boyle, R., Braak, L., Bravenboer, N., Carotenuto, L., Chouker, A., Clement, G., Cras, P., Cross, E., Custaud, M. A., DE ANGELIS, Marco, de Boever, P., de Haas, O., Delavaux, T., Delfos, R., Denise, P., Eekhoff, M., Eiken, O., Felsenberg, D., Fong, K., Fuller, C., Goswami, N., Grillner, S., Groen, E., Harlaar, J., Heer, M., Heglund, N., Hinghofer Szalkay, H., Hughes Fulford, M., Iwase, S., Karemaker, Jm, Langdahl, B., Linnarsson, D., Lobascio, C., Lüthen, C., Mayrhofer, M., Mekjavic, I., Monici, M., Moss, M., Mulder, E., Narici, M., Norsk, P., O’Gorman, D., Paloski, W., Poelma, C., Prisk, K., Rauterberg, M., Rutten, M., Schultz, L., Singer, P., Sommeria, J., Stegeman, D., Stephan, A., Stienen, G., Strollo, F., Stutte, G., Suedfeld, P., Tesch, P., Ullrich, O., van den Berg, R., van de Heyning, P., GJ van Heijst, Vico, L., Woodward, E., Young, L., and Wuyts, F. L.

Published
2014

16. The Artificial Gravity Platform, AGP a very Large Radius Human Centrifuge

Author

van Loon, J. J. W. A., Baeyens, Jp, Berte, J., Blanc, S., Braak, L., Bok, K., Bos, J., Boyle, R., Bravenoer, N., Eekhoff, M., Chouker, A., Clement, G., Cras, P., Cross, Cusaud, DE ANGELIS, Marco, de Dreu, C., Delavaux, T., Delfos, R., Poelma, C., Denise, P., Felsenberg, D., Fong, K., Fuller, C., Grillner, Groen, E., Harlaar, Heer, M., Neuss, Heglund, N., Hinghofer Szalkay, H., Goswami, N., Graz, Hughes Fulfordn, M., Iwase, S., Karemaker, J. M., Langdahl, B., Linnarsson, D., Lüthen, C., Manzey, Monici, M., Mulder, E., Narici, M., Norsk, P., Paloski, W., Prisk, K., Rutten, M., Singer, Stegeman, D., Stephan, A., Stienen, G., Suedfeld, P., Tesch, P., Ullrich, O., Van den Berg, R., Van de Heyning, P., Vautmans, L., Veyt, J., Vico, L., Woodward, Young, L., and Wuyts, F.

Published
2013

18. A Large Human Centrifuge for Exploration and Exploitation Research

Author

Loon, J. J. W. A., Baeyens, J. P., Berte, J., Blanc, S., Braak, L., Bok, K., Jelte Bos, Boyle, R., Bravenboer, N., Eekhoff, E. M. W., Chouker, A., Clement, G., Cras, P., Cross, E., Custaud, M. A., Angelis, M., Delavaux, T., Delfos, R., Poelma, C., Denise, P., Felsenberg, D., Fong, K., Fuller, C., Grillner, S., Groen, E., Harlaar, J., Heer, M., Heglund, N., Hinghofer-Szalkay, H., Goswami, N., Hughes-Fulford, M., Iwase, S., Karemaker, J. M., Langdahl, B. L., Linnarsson, D., Lüthen, C., Monici, M., Mulder, E., Narici, M. V., Norsk, P., Paloski, W., Prisk, K., Rutten, M., Singer, P., Stegeman, D. F., Stephan, A., Stienen, G. J. M., Suedfeld, P., Tesch, P., Ullrich, O., Den Berg, R., Heyning, P., Delahaye, A., Veyt, J., Vico, L., Woodward, E., Young, L., Wuyts, F. L., Oral and Maxillofacial Surgery / Oral Pathology, Clinical chemistry, Internal medicine, Rehabilitation medicine, Physiology, MOVE Research Institute, Kinesiology, Movement Behavior, and Research Institute MOVE

Published
2012

19. A Large Human Centrifuge for Exploration and Exploratory Research

Author

van Loon, J. J. W. A., Baeyens, Jp, Berte, J., Blanc, S., Braak, L., Bok, K., Bos, J., Boyle, R., Bravenoer, N., Eekhoff, M., Chouker, A., Clement, G., Cras, P., Cross, Cusaud, DE ANGELIS, Marco, de Dreu, C., Delavaux, T., Delfos, R., Poelma, C., Denise, P., Felsenberg, D., Fong, K., Fuller, C., Grillner, Groen, E., Harlaar, Heer, M., Neuss, Heglund, N., Hinghofer Szalkay, H., Goswami, N., Graz, Hughes Fulfordn, M., Iwase, S., Karemaker, J. M., Langdahl, B., Linnarsson, D., Lüthen, C., Manzey, Monici, M., Mulder, E., Narici, M., Norsk, P., Paloski, W., Prisk, K., Rutten, M., Singer, Stegeman, D., Stephan, A., Stienen, G., Suedfeld, P., Tesch, P., Ullrich, O., Van den Berg, R., Van de Heyning, P., Vautmans, L., Veyt, J., Vico, L., Woodward, Young, L., and Wuyts, F.

Published
2012

21. A Large Human Centrifuge for Exploration end Explotation Research

Author

van Loon, J. J. W. A., Baeyens, Jp, Berte, J., Blanc, S., Braak, L., Bok, K., Bos, J., Boyle, R., Bravenoer, N., Eekhoff, M., Chouker, A., Clement, G., Cras, P., Cross, Cusaud, DE ANGELIS, Marco, de Dreu, C., Delavaux, T., Delfos, R., Poelma, C., Denise, P., Felsenberg, D., Fong, K., Fuller, C., Grillner, Groen, E., Harlaar, Heer, M., Neuss, Heglund, N., Hinghofer Szalkay, H., Goswami, N., Graz, Hughes Fulfordn, M., Iwase, S., Karemaker, J. M., Langdahl, B., Linnarsson, D., Lüthen, C., Manzey, Monici, M., Mulder, E., Narici, M., Norsk, P., Paloski, W., Prisk, K., Rutten, M., Singer, Stegeman, D., Stephan, A., Stienen, G., Suedfeld, P., Tesch, P., Ullrich, O., Van den Berg, R., Van de Heyning, P., Vautmans, L., Veyt, J., Vico, L., Woodward, Young, L., and Wuyts, F.

Subjects
Hypergravity • Artificial gravity • Microgravity • Weightlessness • Centrifuge • Gravity continuum • Mars • Moon • Human exploration • Human Hypergravity Habitat
Published
2011

23. Cell mechanotransduction: cytoskeleton and related signalling pathways

Author

Hughes-Fulford, M., Boonstra, J., Monici, M., van Loon, J., Celbiologie, and Sub Cell Biology

Subjects
International (English)
Abstract

Mechanical stimuli regulate a variety of cell physiological functions including gene induction, protein synthesis, proliferation and/or differentiation; understanding mechanotransduction at the cellular level is key to understanding basic biology. Here on Earth, signal transduction affects a wide array of receptors and ligands that signal induction of gene expression. The most common signaling pathways include receptor tyrosine kinase (RTK), G-Protein coupled receptors (GPCR) and extracellular matrix components (integrins). The cytoskeleton functions to maintain cell shape and to move cellular components, separate chromosomes during mitosis and provides sensing networks for mechanotransduction. Mechanotransduction is the process of translating mechanical force on a cell into a biological response. Over the last few decades, mechanotransduction has been shown to occur via extracellular matrix, integrins, cytoskeleton signals, GTPases, adenylate cyclase, PLC and MAP kinases (MAPK), all of which play significant roles in early mechanical signaling. During the last decades a wide variety of space flight experiments have demonstrated that gravity has profound effects on whole organisms, organs and tissues, resulting for example in bone and muscle resorption as well as in the occurrence of cardiovascular malfunctioning, immuno-suppression and many other aspects of clinical medicine. Interestingly, the virtual absence of gravity also has profound effects on the cellular and molecular level, including changes in cell morphology, collapse of the actin cytoskeleton, modification of gene expression, changes in signal transduction cascades and even changes in the polymerization of tubulin. The effects of mechanical stress (e.g. gravity) or lack of stress (microgravity) on cell and molecular properties is discussed with an emphasis on the involvement of signal transduction cascades of RTK, integrins and FasR as well as their role in cytoskeleton perception of gravity in mammalian cells.

Published
2010

35. Dependence of Leukemic Cell Autofluorescence Patterns on the Degree of Differentiation

Author

Monici M., Agati G., Fusi F., Pratesi R., Paglierani M., Santini V., and Bernabei P. A.

Subjects
Microscopia, Spettroscopia, Fluorescenza, Diagnostica tessuti, Cellule cancerose
Abstract

The characterisation of leukemic cell autofluorescence during differentiation, induced by 12-O-tetradecanoylphorbol 13-acetate and all-trans retinoic acid, was performed by autofluorescence microspectroscopy and multispectral imaging autofluorescence microscopy. We have found that a dependence exists between the cell autofluorescence pattern and the degree of cell differentiation. When cells differentiate, their autofluorescence emission changes, following the morphological and functional rearrangement of cell structures. A decrease in emission intensity and a different distribution of endogenous fluorophores are observed. Thus, autofluorescence monitoring on living cells is a potentially useful tool for in vitro study of the differentiation processes. Furthermore, different maturation steps can be distinguished on the basis of the cell fluorescence pattern, leading the way to future application of the technique in diagnostics.

Published
2003

39. DO SARCOGLYCANS AND INTEGRINS COLOCALIZE?

Author

Anastasi, Giuseppe Pio, Magaudda, Ludovico, DI MAURO, D., Monici, M. C., Rizzo, Giuseppina, Santoro, Giuseppe, Vita, G., and Santoro, A.

Published
2000

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