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Thereby, a multitude of stimulating signals, such as messenger molecules, ECM, pulsatile blood flow and endogenous electrical fields exist in and around the vasculature [ — ]. Additionally, in blood vessels of healthy humans, the regulation of SMC proliferation and migration is normally rigidly regulated by the endothelium formed by ECs [ ].

Some important biological processes in vivo are mediated by signals that the features of the surface provide to adhering cells. For example, neuronal axons are guided by aligned Schwann cells, which at the same time are thought to be oriented by the ECM [ — ]. Recently, it has been demonstrated in mice that Schwann cells are guided by blood vessels [ ].

In wound healing, another important biological process, cells are guided by the ECM to migrate towards the affected area for regeneration and healing [ ]. To date, many studies have been carried out in vitro in order to elucidate the role of material properties in complex biological processes. It is known that micro- and nanoscale topographies of a substrate can influence cell adhesion, morphology, proliferation rate, migration velocity and directionality, gene expression, stem cell differentiation and even the epigenetic state of a cell Figure 5 [ 10 , 12 , 79 , — ].

Therefore, the in vitro investigation of cell type-specific functions and responses with vascular cells to surface topographies, either in the micrometer or in the nanometer range, provide new solutions to control the behavior of such cells and has already attained much interest [ 3 , 5 , 12 , 23 — 24 , 30 — 31 , 45 , ].

Recent research has tried to elucidate mechanisms by which the independent stimulation of endothelial ECs and smooth muscle cells SMCs may be achieved by introducing surface topographies [ 8 — 12 , — ]. One of the main interests of these studies are the micro- and nanostructuring of medical implants for the in vivo control and stimulation of vascular cells behavior [ 8 — 10 , 12 , — ]. For example, it has been demonstrated that an efficient approach to improve the functions of a medical stent is the application of a morphological texture to the stent surface topography , which controls and regulates the behavior of vascular cells [ , ].

Generally, the investigations of the cellular behavior upon culturing cells on structured surfaces have been performed with vascular cells from different species such as human, mouse, rat, and bovine and from different organs, for example, aorta, umbilical vein, bladder, and lung [ 5 , 16 , 21 , 23 — 25 , — ]. For a systematic overview of the information presented in the following sub-sections refer to Table 1.

Endothelial and smooth muscle cells on surface topographies with different sizes at the micro- and nanoscale and geometries react by changing their adhesion strength, their proliferation rate, their genetic expression, by adapting their morphology, by migrating directionally, by changing their migration speed, or by inducing stem cell differentiation or cell reprogramming. Double arrow pointing up and down means that depending on the study or experimental conditions that parameter increases or decreases.

Often, the proliferation behavior of cells is simply evaluated by counting the number of cells and comparison of the actual number with the number of initially seeded cells [ 26 , — , — ]. However, nanopits positively regulated SMC proliferation and gene expression [ 30 ]. In other studies, human SMCs from the vascular system and bladder, showed an increased proliferation rates on a poly glycolic acid PGA mesh, as well as on poly ether urethane PU and poly lactic- co -glycolic acid PLGA substrates with nanoroughness [ 41 — 42 , 44 ].

Nevertheless, the proliferation rate of ECs on colloidal silica-coated surfaces with nanoroughness was decreased compared to ECs on flat surfaces [ 43 ]. For both types of vascular cells it is not clear through which mechanism the cell proliferation is influenced by the surface topography.

Therefore, more research has still to be performed in these cell types to determine how substrate shape and feature dimensions correlate with cell proliferation. ECs: Previous studies showed a dependence of the strength of endothelial cell adhesion on the surface structure and its size. For example, ECs on nanoislands with low height 13 or 18 nm showed an increased adhesion and spreading. However, on higher nanoislands 27 nm and above , the adhesion and spreading of ECs were reduced compared to those on flat surfaces [ 38 — 40 ].

A different work demonstrated that ECs on silicon nanoposts, revealed stronger adhesion and spreading in comparison to ECs on flat silicon surfaces [ ]. Many cells show directed migration and a polarized morphology on nano- and microstructured substrates. The process by which cells orient and migrate along the longest axis of a surface feature is called contact guidance [ , ].

Many cell types on different surface topographies of various dimensions have been observed to experience contact guidance [ — ]. The most commonly used surface structure to study this phenomenon consists of arrays of ridges and grooves. It was observed that few tenths of nanometers in structure depth was already sufficient for some cell types to trigger contact guidance [ — ]. The limit of cell sensing, by filopodia, so far has been reported to be 10 nm-high nano-islands [ ].

Furthermore, cell alignment to the direction of grooves was predicted with an automatic controller model [ ]. As follows, some examples of morphological adaptation of vascular cells on substrate topographies are explained. For an extensive summary and literature review of vascular cell reactions to topography see Table 1. Rat-derived SMCs aligned stronger along the direction of microgrooves, the narrower these grooves were [ 21 ]. Moreover, cells also change other morphological parameters, such as cell area or elongation, depending on surface structure shape and size [ ].

For example, the elongation of SMCs was enhanced by the groove structure [ ]. However, a structure composed of nanopits demonstrated no significant influence on SMC morphology [ 30 ]. ECs and SMCs: A similar effect was observed for SMCs, as well as ECs, cultured on nanogrooved structures, where the cells aligned and migrated in parallel with respect to the groove axis [ 15 , 25 , , ].

Internal cell structures important for topography detection and for conferring cell shape i. Probably the influence of the topography on these internal structures provokes the morphological change of the cells [ , ]. These morphological adaptations of the cells to surface structures were shown to be cell-type dependent [ 12 ]. This observation is important to consider in the design of cell type-specific medical implants since topographical cues of an implant could specifically and differently instruct cell reaction [ 12 ].

In addition to the tendency that cells orient their body along microstructures, cells also prefer to migrate along the longest axis of the structures present on the surface Figure 6 [ — ]. In different studies, both SMCs and ECs, were observed to migrate directed along the groove direction [ 12 — 13 , , , — ]. It has been reported for some cell types that their migration velocity on microstructured surfaces increased compared to flat surfaces [ , — ]. Nevertheless, there is still no clear consensus about the effect of surface topography on SMCs and ECs migration velocity [ 32 , , — , ].

A possible explanation to the differences in migration velocity on topographies would be the dynamicity of FAs. Moreover, the FA size was correlated with migration velocity. Generally, the bigger the FAs are, the faster cells migrate [ ]. A different study found a correlation between cell stiffness and SMCs migration velocity. When cell stiffness increased, migration velocity decreased and vice versa. The increase of cell stiffness correlated with the increase in F-actin filamentous actin and vinculin a protein from FAs [ ].

Nevertheless, systematic studies correlating the topography shape and size with vascular cell migration velocity need to be performed. Additionally, the cell mechanisms enabling directed migration to surface topography and influencing on migration velocity have still to be elucidated. These factors could have a great potential for the design of, e. The exemplary images show the cell guidance reaction of the SMCs in a wound healing experiment. After 7 h 30 min the SMCs migrated preferentially along the direction of the micrometer-sized grooves.

It is necessary to understand the signal pathways that transduce external physical stimuli into internal biological responses. The transduction of ECM surface topography information requires many intracellular mechano-sensitive elements and processes that finally lead to a cellular reaction Figure 1 and Figure 2c [ , , — ]. Often the signaling of several different mechano-sensors is combined and finally summed up.

Thus, to be able to control cell adhesion and alignment in a cell-specific manner it is important to ask how a cell senses surface topography. The ECM physical signals can be transmitted through focal adhesions and the cytoskeleton system often by a signaling cascade initiated by integrin receptor activation [ , — ]. Thus, one possible and likely scenario is the detection of the surface topography by cytoskeleton elements in particular actin and focal adhesions, and the probing of the topography by protrusions and filopodia Figure 1 and Figure 2c [ , — ].

For example, the reorganization of the actin cytoskeleton has been observed in experiments where cells were placed on small ECM islands and then showed limited spreading [ ]. In another study, focal adhesions of the same cell type grown on microgrooved substrates were more mature along the grooves, hence more tension was most likely created and cells aligned parallel being thus guided by microtopography [ 15 ].

In contrast to this work, some other studies claim that focal adhesions and actin stress fibers development are not necessary for contact guidance to take place [ — ]. However, it is still not known if actin filaments are already polymerized along grooves or if their orientation is due to preferential actin contraction along grooves. Protein unfolding or conformation change at the boundaries between grooves and ridges, could facilitate FA formation and increase of its size [ ].

For this, the authors applied an array of biofunctionalized gold nanostructures. The gold nanoparticles on these surfaces have a diameter of 8 nm and had interparticle spacings of 40 nm or 90 nm and were conjugated with a RGD-peptide or a REDV peptide R: arginine; G: glycine; E: glutamic acid; D: aspartic acid; V: valine or with vascular endothelial cadherin VE-cadherin [ ].

Non-functionalized surfaces or surfaces with spacing larger than 73 nm failed to induce the formation of FAs and actin stress fibers [ , ]. The universal distance-dependence for focal contact formation and cell adhesion shown previously for other cell types e. Although both cell types adhere equally poor on VE-cadherin compared to the RGD and REDV peptides, a universally characteristic cell adhesion behavior depending on the ligand spacing was indicated [ ].

It has been observed in other studies, that the activation of many membrane proteins such as ion channels, membrane-associated G proteins coupled receptors GPCR , and receptor tyrosine kinases RTK are related to ECM physical stimuli [ — ].

Nuclei also tend to adapt their morphology directly to surface microtopography in a similar manner as cell bodies adapt [ 17 , ]. However, in some cases the orientation of nuclei differs to that of the cell body [ , — ]. The fact that the nuclear shape is influenced by microstructures leads to the assumption that some changes in the genetic material could take place. It was revealed that changes in nuclear shape, non-invasively induced by microgrooves, caused reorganization of nuclear lamina and chromosomes repositioning [ ].

Some different gene regulations were attributed to these changes in chromosomes positions [ ]. In a different work, a dramatic drop of SMC proliferation on micropillars was reported and was argued that the deformation of the nuclear lamin was responsible of this change in proliferation rate [ ]. In the future, it would be interesting to study the influence of nucleus morphology in vascular cells gene expression and the role of mechanotransduction mechanisms involving gene regulation.

Moreover, a study correlating actin-mediated cell tension, with nuclei deformation and genetic expression changes would be of interest, since it was previously found a relation between actin-mediated cell stiffness and nucleus deformation [ ]. In this review article, we have presented the state of the art of the most commonly used materials and methods to micro- and nanostructure surfaces for vascular cell investigations. Moreover, vascular cell responses to these topographical stimuli were also presented and discussed.

Although many studies, with both cell types ECs and SMCs , have shown the influence of material, geometry and size of topographical features, on cell morphology, migration, and proliferation, there is not yet a correlation between different geometries and sizes of topography and cell response. For example, there is no clear consensus between structure dimensions and migration speed for both vascular cells.

In order to better understand how these cell responses change depending on the surface topography, the main internal structures playing a role in cell mechanotransduction focal adhesions and actin cytoskeleton have been studied. FAs and actin cytoskeleton were commonly observed in many studies to orient along structures as cells do.

Although some studies correlated differences in FA size and dynamicity with cell migration speed, further research has still to be done in order to broaden the observation. Another important aspect that it should be addressed in future research is how FAs and actin cytoskeleton are influenced by the topography. To further deepen in the understanding of vascular cell behavior on topographies, studies have been performed to analyze gene and protein expression.

Changes in genetic expression attributed to a morphological change in cell nucleus have been shown. However, the relation between shape of the nucleus and gene expression levels is still not known yet. Although a lot of investigations on vascular cells reactions to surface topographies are still to be done, this research will eventually lead to a better understanding of important biological processes e.

These new medical implants will enable the in vivo control the behavior of vascular cells without using, e. This article is part of the Thematic Series "Functional nanostructures — biofunctional nanostructures and surfaces". National Center for Biotechnology Information , U. Journal List Beilstein J Nanotechnol v. Beilstein J Nanotechnol. Published online Nov 8. Christina Wege, Guest Editor. Author information Article notes Copyright and License information Disclaimer. Corresponding author.

Alexandra M Greiner: ed. Received Mar 26; Accepted Oct 4. This article has been cited by other articles in PMC. Abstract The extracellular environment of vascular cells in vivo is complex in its chemical composition, physical properties, and architecture. Keywords: fabrication methods, materials selection, nano- and micro-topography, vascular endothelial cells, vascular smooth muscle cells. Introduction Cells adhering to biomaterials are influenced by the surface topography, the surface chemistry and the mechanical properties of the substrate Figure 1.

Open in a separate window. Figure 1. Figure 2. Figure 3. Review 1. Fabrication of micro- and nanopatterned substrates for cell biology studies The development of micro- and nanofabrication techniques has permitted the manufacturing of precise surface topographies of materials surfaces.

Figure 4. Fabrication methods In order to create tailored cell culture substrates with surface topographies established methods such as photolithography, electron- and focused-ion beam lithography, stereolithography, direct laser writing, and block co-polymer micellar nanolithography are applied. Microfabrication techniques Microfabrication techniques are mainly used to generate surface structures in the micrometer range, which is the size scale of cells.

Nanofabrication techniques Nanofabrication techniques are mainly used to generate surface structures in the nanometer range. Materials selection The importance of choosing the appropriate material for cell—substrate interaction studies depends on the inherent ability of the material to be modified in its surface chemistry since biological cell adhesion via integrins or other adhesion molecules will generally not directly occur to inorganic or organic polymeric materials.

Additional examples for materials are listed in Table 1 and in some other review articles [ 4 — 5 , 46 — 47 , 71 , 86 — 87 ] Polymers from natural sources can be divided in either protein-based e. Surface bio functionalization The surface bio chemistry of a material may regulate cell adhesion, survival, proliferation and differentiation of vascular cells or progenitor cells [ 10 , 31 , , — ]. Mechanical properties of micro- and nanostructured substrates Cells can respond to changes in the mechanical properties of a substrate.

The vascular cell system and the responses of vascular cells to surface topographies in the micro- and nanometer range The vascular system is one of the key systems of the human body and sustains normal human physiology during development, human life span and response to injuries [ ]. Figure 5. Figure 6. Conclusion In this review article, we have presented the state of the art of the most commonly used materials and methods to micro- and nanostructure surfaces for vascular cell investigations.

Notes This article is part of the Thematic Series "Functional nanostructures — biofunctional nanostructures and surfaces". References 1. Bettinger C J. Macromol Biosci. Angew Chem, Int Ed. Hahn C, Schwartz M A. Nat Rev Mol Cell Biol. Dalby M J. Med Eng Phys.

Tissue Eng. Acta Biomater. Exp Cell Res. Adv Mater. Nano Lett. Soft Matter. Biophys J. Ranjan A, Webster T J. Fertil Steril. Mater Sci Eng, C. J Nanosci Nanotechnol. PLoS One. Phys Status Solidi A. J Biomed Mater Res. Hollister S J. Nat Mater. Annu Rev Biomed Eng. J Mater Res. Dehghani F, Annabi N. Curr Opin Biotechnol. Biotechnol Adv. Shin H. Opt Express. Trends Biotechnol. Langford R M. Tissue Eng, Part B. J Cell Biochem. Bhardwaj N, Kundu S C. Acc Chem Res.

Rev Sci Instrum. Ann Biomed Eng. Nat Phys. In: Haycock J W, editor. Totowa, NJ, U. Methods in Molecular Biology. Nemir S, West J L. Trends Cell Biol. J R Soc, Interface. Expert Opin Drug Delivery. Crit Rev Biotechnol. Khan F, Ahmad S R. Biomater Sci. Appl Environ Microbiol. Langer R, Tirrell D A. Microelectron Eng. Int J Artif Organs. Lab Chip. Weng S, Fu J. Biotechnol J. Baino F, Vitale-Brovarone C.

Int J Appl Ceram Technol. Moravej M, Mantovani D. Int J Mol Sci. Am J Surg. Int J Nanomed. Exp Biol Med. New Biotechnol. Curr Opin Cell Biol. Annu Rev Immunol. Wehrle-Haller B. J Cell Sci. PLoS Biol. Hynes R O. Chem Soc Rev. J Phys Chem A. Biotechnol Appl Biochem. Plasma Processes Polym. Curr Opin Chem Biol. Eur Biophys J. Barker T H. Slater J H, Frey W. Ruoslahti E. Annu Rev Cell Dev Biol. Biochim Biophys Acta, Gen Subj. Nat Nanotechnol. Adv Mater Interfaces. Currey J D. J Biomech. Adv Eng Mater.

Trends Biochem Sci. J Micromech Microeng. Ann N Y Acad Sci. Arterioscler, Thromb, Vasc Biol. Lakatta E G, Levy D. Chen C S. Dev Cell. Biomech Model Mechanobiol. Jain R K. Nat Med. Stamenovic D, Wang N. J Appl Physiol. Mech Chem Biosyst. J Biomater Sci, Polym Ed. Brunette D M, Chehroudi B. J Biomech Eng. Cell Biol Int. Arch Mal Coeur Vaiss. Curr Pharm Des.

Cell Transplant. Allow cookies Manage Settings. Allow cookies Save Settings. Changes in healthcare parameters: number of missed working days due to psoriasis; number of visits at the doctor's office; number and duration of hospitalizations, self-assessed workability. Safety and tolerability of Humira - treatment for patient groups with frequent concommitant diseases, especially diabetes type I and II, cardio-vascular and liver and kidney functional impairment and respective concommitant medication.

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Again, a huge thank you to each and every one of you. In the midst of the Coronapocalypse, Blaine sends us a huge and eagerly awaited present! Thanks, Doc! I consider adding that info a very big plus. If you want me to table out some actual confidence interval runs from the raw data, just let me know. I contributed to version 3. Thank you for the submissions! Cheers — and a huge thank you!! This is great, Blaine. Thanks to you and Jonny for your work on this. I have a question though. I envision it being a separate chart, but not quite sure yet.

This is fantastic, Blaine! Thanks for your intensive work and for making this version bigger and better than last time. And for the collaboration with Jonny Perl to bring it alive on the web. Thank you for the feedback! The transparency by giving us the distribution charts shows the issue with sample size is small.

Most are pretty smooth…. This is the most valuable tool i use in my genetic genealogy. As a medical scientist I have a few minor comments. I cannot see may be I miss it some definitions. You mention the mean and expected value. Normally I would say that the arithmetic mean is the expected value. Do You mean the median or modus? You present the standard deviation. However since most of the distributions are skewed and not normal distributed, the standard deviation is not the best parameter.

Continue with the good work, I am so thankful and so is my genealogy colleagues. Thank you for the kind words! I used confidence intervals in the previous version, but they turned out to be too confusing for people so I simplified it in this version. So you would share exactly Thank you, Blaine, for your tireless work to make tools understandable and accessible.

You are a true leader in the genetic genealogy community! Would you accept a submission in the form of a table, if it contains the information sought? I am one of six children of my parents, and we all tested on FTDNA and so have detailed segment data. Also, we have a half sister, and numerous cousins have tested, some of them sponsored by me.

If you would accept a table containing information on my family and our cousins, and a separate table for the family of my husband, I could email the table to you. Thank you. Is the full sibling relationship number correct? Might it be not ? Alec, remember Blaine has arrived at his numbers from actual values of about 60, matches that have been provided to him. For instance, the results for the matches each of my two sisters and me are: J 2, cM across 60 segments; T 2, cM across 59 segments.

While I agree that the company breakdown was infrequently used, I tried to always point people with questions about company differences to Table 3. It was the only source for such information. I was looking forward to the update using more samples, so am disappointed in the company breakdown not being included in the version. Great job Blaine! In this version the outliers were removed using the 99th percentile method just like in v3?

The v4 PDF does not mention it, I wonder if this version includes or excludes the entries over the 99th percentile. As I work 2nd through 4th cousin trees via Ancestry, your chart has been invaluable. My big disappointment is the demise of Table 3. I have referred dozens of people that had questions about differences between companies to that often overlooked reference.

I forget if company was requested on this collection and if it is just a matter of generating Table 3 from existing data, or if the testing company was not asked for. In this role she has been able to actively participate in patient care with a focus on symptom assessment and education. Additionally, she develops and presents pharmacologic education for the palliative care medical fellowship program as well as medical and pharmacy residents and students.

She has developed the role of a pharmacist on the palliative team at and continues to expand the knowledge base of her peers on pharmacist involvement in symptom management and medication selection. Geiger earned her PharmD from the University of Findlay in Following this training, she completed a PGY1 general practice residency.

Jessica has a passion for education, specifically concerning opioids. She has presented at multiple local, state, national and international conferences about pain management and palliative care. Additionally, she teaches a pain and palliative elective to pharmacy students at her alma mater.

Sooyeon Kwon is a clinical pharmacy specialist and researcher dedicated to the field of rheumatology. Her clinical service includes high risk medication management including biologic DMARDs, through direct patient care in her clinic. Sooyeon provides consulting services for rheumatology pharmacotherapy topics such as drug information, treatment options for rare rheumatologic conditions, and literature review for off-label insurance authorization.

She believes education empowers patients to take initiative in their care that she supports rheumatology patient group activities through medication education and counseling. Persico is a clinical pharmacy specialist at a community based outpatient clinic where she uses her expertise in pain management and pharmacotherapy to provide disease state management in the primary care setting.

Pham has lectured live and by Webinar on various pain-related topics to physicians, pharmacists, nurses, and students. In addition to his clinical and teaching duties, Dr. Erica Wegrzyn is a clinical pharmacy specialist in pain management at the Stratton VA Medical Center in Albany, New York, specializing in chronic noncancer pain and palliative care with collaboration in an interdisciplinary team.

Her research interests include buprenorphine and other unique opioids as an alternative to traditional opioids, opioid transition and dosing, in-home naloxone distribution, emergency response, and technology platforms to promote opioid safety. Schatman is a clinical psychologist who has spent the past 35 years working in multidisciplinary chronic pain management. Schatman is a member of the Editorial Boards of numerous journals. Dan Jochnowitz serves as our outside General Counsel.

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It looks amazing and contains an incredible amount of information right at your fingertips. Thank you Jonny! Every person that has ever submitted even a single relationship has helped create this tool for the benefit of the entire community. Again, a huge thank you to each and every one of you. In the midst of the Coronapocalypse, Blaine sends us a huge and eagerly awaited present! Thanks, Doc! I consider adding that info a very big plus.

If you want me to table out some actual confidence interval runs from the raw data, just let me know. I contributed to version 3. Thank you for the submissions! Cheers — and a huge thank you!! This is great, Blaine. Thanks to you and Jonny for your work on this. I have a question though. I envision it being a separate chart, but not quite sure yet. This is fantastic, Blaine!

Thanks for your intensive work and for making this version bigger and better than last time. And for the collaboration with Jonny Perl to bring it alive on the web. Thank you for the feedback! The transparency by giving us the distribution charts shows the issue with sample size is small. Most are pretty smooth…. This is the most valuable tool i use in my genetic genealogy. As a medical scientist I have a few minor comments.

I cannot see may be I miss it some definitions. You mention the mean and expected value. Normally I would say that the arithmetic mean is the expected value. Do You mean the median or modus? You present the standard deviation.

However since most of the distributions are skewed and not normal distributed, the standard deviation is not the best parameter. Continue with the good work, I am so thankful and so is my genealogy colleagues. Thank you for the kind words! I used confidence intervals in the previous version, but they turned out to be too confusing for people so I simplified it in this version.

So you would share exactly Thank you, Blaine, for your tireless work to make tools understandable and accessible. You are a true leader in the genetic genealogy community! Would you accept a submission in the form of a table, if it contains the information sought? I am one of six children of my parents, and we all tested on FTDNA and so have detailed segment data. Also, we have a half sister, and numerous cousins have tested, some of them sponsored by me. If you would accept a table containing information on my family and our cousins, and a separate table for the family of my husband, I could email the table to you.

Thank you. Is the full sibling relationship number correct? Might it be not ? Alec, remember Blaine has arrived at his numbers from actual values of about 60, matches that have been provided to him. For instance, the results for the matches each of my two sisters and me are: J 2, cM across 60 segments; T 2, cM across 59 segments. While I agree that the company breakdown was infrequently used, I tried to always point people with questions about company differences to Table 3.

It was the only source for such information. I was looking forward to the update using more samples, so am disappointed in the company breakdown not being included in the version. Great job Blaine! In this version the outliers were removed using the 99th percentile method just like in v3?

The v4 PDF does not mention it, I wonder if this version includes or excludes the entries over the 99th percentile. As I work 2nd through 4th cousin trees via Ancestry, your chart has been invaluable. Atkinson specializes in complex and high-risk pain medication management through direct patient care and electronic consult services.

He is also the owner of Vanguard Pain Management Consulting where he advises clients in managed care and the pharmaceutical industry His research interests include opioid equivalencies, serum level monitoring, pain management in specialty disease states, and the elderly.

Jeffrey J. Bettinger has worked for Remitigate for 3 years and has been integral in its development and expansion over that time. He oversees review of various medical documents for plaintiff or defense, including but not limited to insurance claims and litigation. Jeff Fudin in the ongoing evolution of Remitigate as the company sets to build upon its prior success and flourish in the clinical realm.

Immediately following his general practice residency, he trained with Drs. He continues to have a strong academic background publishing in peer-reviewed journals, presenting at regional and national meetings, and teaching various classes at different colleges of pharmacy. He also mentors students and residents at his clinical sites of practice and plans on continuing this mentorship as he transitions to Saratoga Hospital. She completed her post-graduate year one general pharmacy residency training with Sentara Medical System in Norfolk, VA and then completed her post-graduate year two pain and palliative care residency training at the Albany Stratton VA Medical center in Albany, NY.

She is also board certified in ambulatory care pharmacy. Cleary serves as clinical pharmacist specializing in primary care with a focus in pain management. Recent national attention to the opioid epidemic has been an increasing subject of interest for Dr. She has numerous posters, publications and has presented both locally and nationally on the topics of pain management, pharmacogenetics, naloxone, and risk mitigation strategies to reduce opioid abuse and misuse.

Jessica Geiger is clinical pharmacist at Riverside Methodist Hospital where she specializes in pain management, palliative care, and hospice. In this role she has been able to actively participate in patient care with a focus on symptom assessment and education.

Additionally, she develops and presents pharmacologic education for the palliative care medical fellowship program as well as medical and pharmacy residents and students. She has developed the role of a pharmacist on the palliative team at and continues to expand the knowledge base of her peers on pharmacist involvement in symptom management and medication selection.

Geiger earned her PharmD from the University of Findlay in Following this training, she completed a PGY1 general practice residency.