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Competing Interests: Competing interests: SAS is on the BOD of the Biologic Association. KM is a Consultant for Lipogems.

Despite patient demand for stem cell therapies (SCTs) for musculoskeletal conditions, there remains limited research on why patients seek SCTs or their sources of information. We employ three questions into a consult intake form: (1) Why are you interested in stem cell treatment for your condition? (2) How did you find out about stem cell treatment for your condition? (3) Have you contacted a stem cell clinic? Responses analyzed, using a qualitative content analysis approach to identify themes reveal many patients seek SCTs to treat pain or delay surgery which may align with some current clinical evidence while other patients express motivations as expected outcomes (e.g., SCTs are better than standard of care or can regenerate tissue) which are not supported by current medical evidence. These differences suggests that patient-centered counseling may help patients by addressing misconceptions and increasing health literacy about expected outcomes of SCTs for treating musculoskeletal conditions., (© 2022. The Author(s).)

Introduction: Direct to consumer stem cell and regenerative interventions (SCRIs) for various medical conditions have increased in popularity due to unmet medical needs and the promise of SCRIs to meet those needs. These interventions may have varying levels of safety and efficacy data and many lack sufficient scientific data to be marketed. The direct to consumer SCRI industry has received significant attention due to potential physical, economic, and emotional harms to patients. Patients may seek the counsel of their primary care providers when considering stem cell therapy for their condition., Methods: Here we describe strategies primary care providers can utilize when counseling patients., Results: Although we recommend constructing these discussions around individual patients' needs, one can utilize a general approach consisting of 4 parts. First, providers should recognize what information the patient is seeking and what is their understanding of stem cell and regenerative medicine. Next, providers should convey evidence-based information at the level of patients understanding so that they are aware of the risks, benefits, and descriptions of possible procedures. Throughout the conversations, attempts should be made to guide patients to a trusted resource that can provide additional information. Finally, providers should make an effort to address misinformation in a way that is nonjudgmental and patient-centered to make the patient feel safe and comfortable., Conclusion: Effectively communicating risk information by primary care providers to patients is important given the harms reported from direct-to-consumer SCRIs. Correcting misinformation remains a priority when discussing SCRI's. Providers should strive to offer patients with additional resources such as the opportunity for consultation with a specialist or a consultation service dedicated to informing patients about regenerative medicine.

Stem cell therapies occupy a unique place in the American public's consciousness which has led to excessive enthusiasm over their potential to cure orthopedic conditions. Much has been written about direct-to-consumer marketing of cell therapies for a myriad of medical conditions. Far less has been studied on the attitudes that drive many patients to seek stem cell and orthobiologic therapies for musculoskeletal conditions. Previously published research on patient motivations for seeking stem cell therapy to treat orthopedic maladies such as osteoarthritis and chronic tendinopathies has shown that some patients were motivated by factors not supported by current medical evidence. These differing responses strongly suggest the need for patient-centered counseling to address misinformation about stem cell therapies for musculoskeletal conditions and increase health literacy about outcomes of orthobiologics.

Background: Androgenic alopecia (AGA) is a common hair loss disorder. Studies have demonstrated successful treatment with platelet-rich plasma (PRP) in men, but studies in women are few., Objective: To evaluate PRP in the treatment of AGA in women, compared with topical minoxidil., Materials and Methods: Twenty women with AGA received topical minoxidil for 12 weeks and injectable PRP for 12 weeks in a randomized crossover design with an 8-week washout between treatments. Standardized TrichoScan analysis and quality-of-life questionnaires were assessed at baseline and 12-week follow-up for each treatment., Results: After PRP, significant increases from baseline to Week 12 in TrichoScan analysis hair count (p = .002) and vellus hair density (p = .009) occurred. However, minoxidil resulted in significant increases in hair count (p < .001), vellus hair density (p = .03), terminal hair density (p = .004), and cumulative thickness (p = .004). Several quality of life responses improved from baseline to Week 12 after PRP treatment, whereas no improvements were noted after minoxidil., Conclusion: Platelet-rich plasma is an effective treatment for hair regrowth in female AGA, although not as effective as minoxidil. However, the improved quality of life responses after PRP, but not minoxidil, suggest a potential overall greater degree of satisfaction with PRP., Levels of Evidence: I., Clinical Trial Registration: NCT03488108.

Objective: Bone marrow aspiration and concentration (BMAC) is becoming a more common regenerative therapy for musculoskeletal pathology. In our current pilot study, we studied patients with mild-to-moderate bilateral knee osteoarthritis, compared pain at 12-month follow-up between BMAC-injected and saline-injected knees, and examined cartilage appearance measured by magnetic resonance imaging (MRI) T2 quantitative mapping., Design: Twenty-five patients with mild-to-moderate bilateral osteoarthritic knee pain were randomized to receive BMAC into one knee and saline placebo into the other. Bone marrow was aspirated from the iliac crests, concentrated in an automated centrifuge, combined with platelet-poor plasma for knee injection, and compared with saline injection into the contralateral knee. Primary outcome measures were T2 MRI cartilage mapping at 6-month and Visual Analog Scale and Osteoarthritis Research Society International Intermittent and Constant Osteoarthritis Pain scores and radiographs at 12-month follow-up., Results: Constant, intermittent, and overall knee pain remained significantly decreased from baseline at 12-month follow-up (all P ⩽ 0.01), with no apparent difference between BMAC- and saline-treated knees (all P ⩾ 0.54). A similar significant increase from baseline to 12-month follow-up regarding quality of life was observed for both BMAC- and saline-treated knees (all P ⩽ 0.04). T2 quantitative MRI mapping showed no significant changes as a result of treatment., Conclusions: BMAC is safe to perform and relieves pain from knee arthritis but showed no superiority to saline injection at 12-month follow-up. MRI cartilage sequences failed to show regenerative benefit with single BMAC injection. The mechanisms of action that led to pain relief remain unclear and warrant further studies.

Adipose-derived therapies have increased in popularity for treatment of painful orthopaedic conditions, such as osteoarthritis. We report the passage of fat into a Baker's cyst after injection of micro-fragmented adipose tissue in a patient with bilateral knee arthritis. Following fat grafting, the patient required drainage of fatty fluid from within the Baker's cyst on multiple occasions. Approximately 3 months postprocedure, she began to notice an improvement in her knee pain with no further recurrence of pain or swelling from her Baker's cyst., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aim: We review relevant anatomy of the iliac crest, and describe an interventional technique to maximize harvesting of desired progenitor cells with ultrasound to guide safe trochar placement., Materials & Methods: We validated the technique on both sides of the pelvis in four human cadavers., Results: Using ultrasound guidance, 32 BMA needles were placed in a safe zone along various portions of the iliac crest., Conclusion: Ultrasound guidance can improve accuracy of bone marrow aspirations form the iliac crest. Mastery of this procedure will facilitate cell harvest and aid in patient safety when procuring mesenchymal stem cells from a bone marrow source.

Oxaliplatin is one of the most commonly used drugs for patients with colorectal cancer. It has rarely been associated with disseminated intravascular coagulation (DIC) with only 3 previously reported cases. In all those instances, the patients had started receiving oxaliplatin, developed evidence of DIC during the course of planned treatment, and recovered with supportive care. We report a case of a 71-year-old man with colorectal cancer treated successfully with an oxaliplatin-based regimen who had disease relapse after 3 years. When treated again with oxaliplatin, he developed signs of an acute hypersensitivity reaction, and eventually had signs and symptoms consistent with DIC despite appropriate management. This case is unique in that a DIC reaction evolving from a hypersensitivity reaction occurred after the patient had already tolerated the drug years earlier. It suggests a possible immune-mediated etiology to this rare occurrence that should be kept in mind while utilizing this commonly employed drug., (© 2017 S. Karger AG, Basel.)

Aim: Over the last two decades, numerous experimental studies have examined the feasibility of delivering stem cells into the cochlea to restore hearing. While these studies have spawned new cell therapy companies, there is little information on what patients understand or expect from these emerging therapies. Methods: This study sought to understand the awareness and perspectives of Australian audiologists and their adult patients toward stem cell therapies for treating hearing loss. Results: An anonymous survey indicated 91% of patients and 39% of audiologists were unaware of these therapies being developed. Thirty percent of audiologists reported being asked about stem cell therapies for hearing loss, but 70% were not confident answering patient queries about this and were unsure where to gather information. Primary concerns reported by patients were cost (45%) and safety of treatment (42%). Interestingly, 58% of patients were unsure of how this therapy would improve their hearing, yet 25% of these patients expected that their hearing would return to normal. Conclusion: There was strong support for development of educational materials for both patient and clinician. The increasingly important role of audiologists in providing patient counselling was reflected in overwhelming support (from both patient and clinician) for audiologists providing such information. Plain Language Summary In recent years, scientific studies have investigated the possibility of using stem cells to improve or restore hearing. Although some companies claim to be able use stem cell therapies to treat hearing loss now, there is currently not enough evidence to show these treatments are safe or effective. This study aimed to understand the awareness and perspectives of Australian audiologists and their adult patients toward stem cell therapies for hearing restoration. The study was conducted as a survey at an audiology clinic in Melbourne, Australia. The study found 91% of patients and 39% of audiologists were not aware of stem cell therapies for hearing loss. Although 30% of audiologists said they had been asked by a patient about stem cell therapies, 70% said they would not feel confident responding to a question from a patient. Primary patient concerns about stem cell therapies for hearing loss were cost (45%) and safety (42%). Most patients (57%) were unsure what stem cell therapies would do, but 25% expected that this treatment would return their hearing to normal. This study demonstrates the increasingly important role of audiologists in providing support to patients about future potential therapies for hearing loss, as reflected in overwhelming support (from both patient and clinician) for audiologists providing such information. Article highlights Australian audiologists & their patients report a lack of awareness around current & emerging stem cell therapies for hearing loss Almost all patients surveyed in this study (92%) reported being unaware of any current or potential therapeutic use of stem cells for hearing loss, and only a third of participating audiologists noted awareness of the use of stem cells in otology. Patients show a willingness to receive stem cell therapies for hearing loss Of patients who had self-perceived hearing loss, 75% indicated that they were open to the use of stem cells for the treatment of their hearing loss, should such treatments become available in the future. Audiologists have a key role in providing accurate & relevant information to patients All audiologists within this study agreed that they should have a role in educating patients in stem cell therapies for hearing loss, but few were comfortable in replying to patient enquiries. Audiology as a profession has shifted from a biomedical perspective, where clinicians primarily focus on managing the hearing loss with available treatment options, to a more patient-centered model of practice, which emphasizes joint decision-making and consideration of the biological, psychological and social needs of the patient. Consultation with a healthcare professional & reliable online platforms were identified as preferred ways to receive new information on stem cell therapies For most patients surveyed (91.1%), consultation with a health professional was the most preferable choice. Unsurprisingly, a strong preference for online materials was noted given the ease with which this material can be accessed. Notably, unverified information online can be dangerous for patients as it can be biased toward public opinion over empirical data and exaggerate positive aspects of experimental stem cell therapies without fully disclosing the burdens that come with such treatment. Opportunities for improved patient care through open discussion & informed, evidence-based decision making The findings of this study highlight the opportunity for discussion among audiologists, patients, researchers, audiology governing bodies, stem cell peak bodies and other important stakeholders on the role of audiologists in educating patients about potential future stem cell therapies for hearing loss. This dialogue could facilitate the establishment and integration of educational material and professional guidelines that could assist audiologists with their knowledge and confidence in advising patients, as well as managing their expectations in matters relating to stem cell therapies. In turn, this could enhance patient-centered care as patients are equipped with accurate information relating to the risks, benefits and limitations of stem cell therapies. With this information, patients could be better positioned to make informed decisions about their hearing health. [ABSTRACT FROM AUTHOR]

Androgenetic alopecia (AGA) is the most prevalent type of hair loss. Its morbility is mainly psychological although an increased incidence in melanoma has also been observed in affected subjects. Current drug based therapies and physical treatments are either unsuccessful in the long term or have relevant side effects that limit their application. Therefore, a new therapeutic approach is needed to promote regenerative enhancement alternatives. These treatment options, focused on the cellular niche restoration, could be the solution to the impact of dihydrotestosterone in the hair follicle microenvironment. In this context emerging regenerative therapies such as Platelet-rich plasma or Platelet-rich fibrine as well as hair follicle stem cells and mesenchymal stem cell based therapies and their derivatives (conditioned medium CM or exoxomes) are highlighting in the evolving landscape of hair restoration. Nanotechnology is also leading the way in AGA treatment through the design of bioinks and nanobiomaterials whose structures are being configuring in a huge range of cases by means of 3D bioprinting. Due to the increasing number and the rapid creation of new advanced therapies alternatives in the AGA field, an extended review of the current state of art is needed. In addition this review provides a general insight in current and emerging AGA therapies which is intented to be a guidance for researchers highlighting the cutting edge treatments which are recently gaining ground. [ABSTRACT FROM AUTHOR]

Aims and objectives: The aim of this study is to systematically review randomized controlled clinical trials (RCTs) studying various types of regenerative medicine methods (such as platelet-rich plasma, stromal vascular fraction, cell therapy, conditioned media, etc.) in treating specific dermatologic diseases. Rejuvenation, scarring, wound healing, and other secondary conditions of skin damage were not investigated in this study. Method: Major databases, including PubMed, Scopus, and Web of Science, were meticulously searched for RCTs up to January 2024, focusing on regenerative medicine interventions for specific dermatologic disorders (such as androgenetic alopecia, vitiligo, alopecia areata, etc.). Key data extracted encompassed participant characteristics and sample sizes, types of regenerative therapy, treatment efficacy, and adverse events. Results: In this systematic review, 64 studies involving a total of 2888 patients were examined. Women constituted 44.8% of the study population, while men made up 55.2% of the participants, with an average age of 27.64 years. The most frequently studied skin diseases were androgenetic alopecia (AGA) (45.3%) and vitiligo (31.2%). The most common regenerative methods investigated for these diseases were PRP and the transplantation of autologous epidermal melanocyte/keratinocyte cells, respectively. Studies reported up to 68.4% improvement in AGA and up to 71% improvement in vitiligo. Other diseases included in the review were alopecia areata, melasma, lichen sclerosus et atrophicus (LSA), inflammatory acne vulgaris, chronic telogen effluvium, erosive oral lichen planus, and dystrophic epidermolysis bullosa. Regenerative medicine was found to be an effective treatment option in all of these studies, along with other methods. The regenerative medicine techniques investigated in this study comprised the transplantation of autologous epidermal melanocyte/keratinocyte cells, isolated melanocyte transplantation, cell transplantation from hair follicle origins, melanocyte–keratinocyte suspension in PRP, conditioned media injection, a combination of PRP and basic fibroblast growth factor, intravenous injection of mesenchymal stem cells, concentrated growth factor, stromal vascular fraction (SVF), a combination of PRP and SVF, and preserving hair grafts in PRP. Conclusion: Regenerative medicine holds promise as a treatment for specific dermatologic disorders. To validate our findings, it is recommended to conduct numerous clinical trials focusing on various skin conditions. In our study, we did not explore secondary skin lesions like scars or ulcers. Therefore, assessing the effectiveness of this treatment method for addressing these conditions would necessitate a separate study. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review presents evidence for advanced non-operative interventions, including extracorporeal shockwave therapy (ESWT), prolotherapy, platelet-rich plasma (PRP), adipose tissue-derived cells, bone marrow aspirate concentrate, various additional non-corticosteroid injectates, and needle-based interventions for common causes of anterior knee pain in the adult population. These etiologies include osteoarthritis of the knee, patellofemoral pain syndrome, chondromalacia patella, Hoffa fat pad impingement syndrome, patellar/quadriceps tendinopathy, and prepatellar bursitis. This review discusses patient care options using a case-based understanding of interventions by condition while recognizing strength of evidence., Recent Findings: ESWT and PRP are the most robustly studied and have greatest evidence for treating tibiofemoral osteoarthritis and for long-term benefit in treating patellar tendinopathy. PRP may have evidence for treatment of chondromalacia and prolotherapy for management of tibiofemoral arthritis; both have limited evidence. Botulinum neurotoxin type A has strong evidence to support use in treating patellofemoral pain syndrome. There is limited evidence to support the use of viscosupplementation, percutaneous needle tenotomy, and medicinal signaling cell-based therapies beyond platelet-rich plasma for anterior knee pain. There is limited research on the management of quadriceps tendinopathy, prepatellar bursitis, patellofemoral osteoarthritis, and Hoffa's fat pad impingement syndrome. Further research and standardization of protocols are necessary to fully assess these treatments' efficacy. ESWT, cell-based, and needle-based interventions, may serve as effective treatment options for patients with anterior knee pain. Selection of each intervention requires understanding the evidence, level of risk, and appropriate application based on a patient's level of activity to enable clinicians to enhance patient outcomes and quality of life., Competing Interests: Declarations Ethics Statement A.S.T. serves as Senior editor for PM&R Journal. He gives professional talks, such as grand rounds and medical conference plenary lectures, and receives honoraria from conference organizers. He has participated in research funded by the Arnold P. Gold Foundation (physician and patient care disparities), the Football Player Health Study at Harvard (health in American-Style Football players), the American Medical Society for Sports Medicine (bone density research), the Uniform Health Service and Enovis (Achilles tendinopathy). He is also receiving funding support from NFLPA and Department of Defense for studies evaluating shockwave for management of orthopedic injuries. He is a paid consultant for State Farm Insurance and Strava. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors. Conflict of Interest Nicole B. Katz, Nicholas Tsitsilianos, Andrew S. Nowak, Stephanie R. Douglas, and Joanne Borg-Stein declare that they have nothing to disclose., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Over the last decade, bioengineering has seen a sustained growth in scientific publications, patents, and clinical trials. As the field attempts to bridge the gap between discovery and clinical application, a broader societal dialogue is needed to build public trust and address potential ethical, societal, and regulatory challenges. In this essay, we discuss societal aspects linked to the clinical use of biomedical engineering approaches and technologies, with a specific focus on molecular systems engineering. Drawing on data from interviews with 24 scientists, we identified four key aspects for fostering societal support for translational efforts in this domain: (1) effective science communication and internal awareness; (2) open societal dialogue; (3) fair and equitable access to new technologies; and (4) adequate science and technology policies. We conclude that molecular systems engineering would benefit from anticipating future challenges with the view of building a robust bond of trust with lay publics, regulators, and society at large. [ABSTRACT FROM AUTHOR]

There are limited data on the use of mesenchymal stem cell injections for hip osteoarthritis. The goal of this study was to evaluate the literature by analyzing outcomes and comparing methodologies. Online search of PubMed, SportsDiscus and Case Reports Keywords was completed using the keywords 'stem cells' and 'hip' and 'osteoarthritis'. Six studies met the inclusion and exclusion criteria. Five out the six studies had statistically significant improvement in patient reported outcomes after mesenchymal stem cell injections. Only two studies provided information on radiological changes and findings were positive. None of the studies reported major complications. Small series of non-randomized controlled trials completed to date in the use of mesenchymal stem cells for the treatment of hip osteoarthritis reported the procedures to be safe and provide a positive clinical response. Randomized controlled trials must be performed to further confirm mesenchymal stem cells as a treatment option for hip osteoarthritis. [ABSTRACT FROM AUTHOR]

Background: Stem cell-based therapy for bone regeneration has received attention in medical settings but has not yet been used in clinical practice for treating alveolar bone defects. The objectives of this study were to explore whether periodontists had heard about this approach, and if so how, how interested they were to learn about it, which attitudes and behavioral intentions they had related to using stem cell-based grafting, and what they would like to know before using this approach., Methods: Anonymous survey data were collected from 481 members of the American Academy of Periodontology (response rate: 19.41%)., Results: Responses showed 35.3% had heard about stem cell-based therapy, mostly from publications (9.6%) and meetings (8.3%); 76.1% wanted to learn about it through in-person continuing education (CE) courses, 68.6% in online CE courses, and 57.1% from manuals; 73% considered this approach promising; and 54.9% preferred it to traditional approaches. It was important to them that it would result in more bone volume (93%), better bone quality (90.4%), and accelerated healing (83.2%). Also, 60.1% considered it likely/very likely that they would adopt this approach, 54% that patients would prefer it, and 62.1% that it would benefit their practice. When asked what they would like to know about this approach, information about short- and long-term outcomes, cost, and logistical considerations were most frequently named., Conclusions: These findings provide the basis to develop educational interventions for periodontists about this novel approach and inform future research activities aimed to translate this approach to clinical practice., (© 2024 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)

Osteoarthritis affects a significant portion of U.S. adults, and knee osteoarthritis contributes to 80% of disease burden. Previous data have shown that non-White patient populations often report worse symptoms and less favorable outcomes following arthroplasty, a definitive treatment for knee osteoarthritis. There is a lack of demographics data on race/ethnicity, as well as socioeconomic status (SES) and social determinants of health (SDOH), in knee osteoarthritis treatment guidelines and knee arthroplasty research. In addition, there is underrepresentation of non-White patient populations in the existing treatment guidelines for knee osteoarthritis. Over the past decade, orthobiologics have emerged as an alternative to surgical intervention. Our hypothesis is that there would be a similar lack of reporting of demographics data and underrepresentation of non-White populations in studies pertaining to orthobiologics, including evaluating differences in outcomes. This study reviewed U.S.-based research in orthobiologics as a treatment option for knee osteoarthritis. We identified a lack of demographics reporting in terms of race/ethnicity, and none of the studies reported SES or SDOH. Non-White populations were underrepresented; White patients contributed to 80% or more of all study populations that reported race/ethnicity. None studied the correlation between symptoms and outcome measures, and the race/ethnicity, SES, and SDOH of the patients. Based on a review of existing literature, we strongly advocate for ongoing research encompassing patients of all races/ethnicities, SES, and SDOH, and an exploration into potential variations in symptoms and outcomes among distinct population subgroups. Furthermore, SES barriers may influence health care delivery on orthobiologics for disadvantaged populations., (© 2024 The Authors. PM&R published by Wiley Periodicals LLC on behalf of American Academy of Physical Medicine and Rehabilitation.)

Purpose: Aim of this systematic review was to determine if bone marrow-derived cell-based injectable therapies induce disease-modifying effects in joints affected by osteoarthritis (OA) in animal models. Methods: A systematic review was performed on three electronic databases (PubMed, Web of Science, Embase) according to PRISMA guidelines. A synthesis of the results was performed investigating disease-modifying effects in preclinical animal studies comparing injectable bone marrow-derived products with OA controls or other products, different formulations or injection intervals, and the combination with other products. The risk of bias was assessed according to the SYRCLE's tool. Results: Fifty-three studies were included (1819 animals) with an increasing publication trend over time. Expanded cells were used in 48 studies, point-of-care products in 3 studies, and both approaches were investigated in 2 studies. Among the 47 studies presenting results on the disease-modifying effects, 40 studies (85%) reported better results with bone marrow-derived products compared to OA controls, with positive findings evident in 14 out of 20 studies (70%) in macroscopic assessment, in 30 out of 41 studies (73%) in histological assessment, and in 10 out of 13 studies (77%) in immunohistochemical evaluations. Clinical evaluations showed positive results in 7 studies out of 9 (78%), positive imaging results in 11 studies out of 17 (65%), and positive biomarker results in 5 studies out of 10 (50%). While 36 out of 46 studies (78%) reported positive results at the cartilage level, only 3 out of 10 studies (30%) could detect positive changes at the synovial level. The risk of bias was low in 42% of items, unclear in 50%, and high in 8%. Conclusion: This systematic review of preclinical studies demonstrated that intra-articular injections of bone marrow-derived products can induce disease-modifying effects in the treatment of OA, slowing down the progression of cartilage damage with benefits at macroscopic, histological, and immunohistochemical levels. Positive results have been also observed in terms of clinical and imaging findings, as well as in the modulation of inflammatory and cartilage biomarkers, while poor effects have been described on the synovial membrane. These findings are important to understand the potential of bone marrow-derived products and to guide further research to optimise their use in the clinical practice. Level of evidence: II. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the clinical and imaging findings up to 24 months of follow-up in patients treated with combined subchondral and intra-articular bone marrow aspirate concentrate (BMAC) injections for the treatment of knee osteoarthritis (OA). Methods: Thirty consecutive patients (19 males, 11 females) aged between 40 and 75 years (mean age 56.4 ± 8.1 years) with unilateral symptomatic knee OA (Kellgren–Lawrence 2–3) were included in the study. Patients were treated with combined intra-articular and subchondral bone BMAC injections (total 9 ml) under fluoroscopic control. IKDC subjective score, VAS for pain, KOOS, and EQ-VAS were prospectively evaluated up to 24 months. Radiographs were performed at baseline and at 24 months after the procedure. MRI was evaluated with the WORMS score at baseline, 6–12 months, and 24 months of follow-up. The statistical analysis was performed using SPSS v.19.0 and for all tests p < 0.05 was considered significant. Results: No major complications and a 13% failure rate were reported. The IKDC subjective score remained stable from 62.6 ± 19.4 at 12 months to 63.4 ± 17.1 at 24 months (both p < 0.0005 compared to baseline, 40.5 ± 12.5). Similar improvements were reported for all KOOS subscales, while EQ-VAS did not report any significant improvement. VAS pain worsened from 3.0 ± 1.9 at 12 months to 4.4 ± 1.8 at the final follow-up (p = 0.0001), although remaining lower compared to the baseline value of 6.3 ± 1.8 (p = 0.002). The radiographic evaluation did not reveal signs of improvement or deterioration of the OA grade. The MRI findings showed a worsening in marginal osteophytes and synovitis, but a significant reduction of bone marrow edema at 24 months (p < 0.0005). Conclusion: Combined intra-articular and subchondral BMAC injections provided clinical and imaging benefits up to 24 months for the treatment of symptomatic knee OA, with durable clinical results, a low failure rate, and a significant reduction of bone marrow edema. [ABSTRACT FROM AUTHOR]

Three‐dimensional fast spin echo imaging with long echo trains combines high resolution with reasonable acquisition times and reduced specific absorption rate due to low refocusing flip angles. Typically, an entire volume is encoded (nonselective excitation) or localization can be performed with slab select excitation, which uses a long 90° pulse for precise localization, followed by a preliminary nonselective 180° pulse bounded by spoiler gradients to destroy signal outside of the volume of interest. Subsequent flip angles in the train are nonselective and identical between the two methods. The inclusion of the initial selective pulse and spoiler gradients results in a signal‐to‐noise ratio (SNR) penalty for slab selection, beyond the slice‐averaging dependence, arising from a loss of stimulated echoes. SNR differences are explored using Bloch equation simulations of a T2‐weighted 96 echo train sequence with varying parameters including T2, T1, and B1+ and compared with phantom and in vivo brain, neck, and knee experiments. In vivo SNR measurements in the three regions showed a maximum decrease of selective SNR by 29% (gastrocnemius muscle), 25% (pons), and 22% (globus pallidus), despite similar experimental parameters to nonselective experiments. Decreased SNR was compounded by B1+ variation affecting prescribed flip angles with further smaller reductions with T2 and T1 times. In conclusion, the elimination of coherences via the preliminary nominal 180° pulse and spoiler gradients in addition to the extended echo timing from the long excitation pulse resulted in a reduction in SNR compared with the nonselective case. Consideration of the required SNR and chosen anatomy as well as sequence restrictions should be weighed before choosing slab‐selective excitation. [ABSTRACT FROM AUTHOR]

Purpose: Caizhixuan hair tonic (CZX) is a topical traditional Chinese medicine (TCM) preparation for the treatment of androgenetic alopecia (AGA). However, its active compounds and underlying mechanism for treating AGA are still unclear. The purpose of this study was to observe the effects of CZX on hair growth promotion in AGA mice and to explore the active components and mechanism. Methods: Testosterone propionate was administered subcutaneously to mice to establish an AGA mouse model. The therapeutic effects of CZX on AGA were evaluated by observing skin colour changes, hair growth time, and average hair length; calculating the hair growth score; and performing skin histopathological analysis. Following that, CZX chemical components were analysed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC–Q–TOF/MS). Network pharmacology was used to predict the major effects and possible mechanisms of CZX for the treatment of AGA. Furthermore, RT-qPCR and Western blotting were performed to assess the expression of key genes and proteins involved in PI3K/Akt and apoptosis pathways in order to validate CZX's predicted mechanism in AGA. Results: CZX promoted hair growth and improved the pathological morphology of hair follicles in the skin. In UPLC–Q–TOF/MS analysis, 69 components from CZX were isolated. Based on network pharmacology, CZX alleviated AGA by regulating PI3K/Akt and apoptosis pathways. According to RT-qPCR and Western blotting, CZX upregulated the expressions of PI3K, Akt, and Bcl-2, while downregulating that of Bax and caspase-3. Conclusions: CZX promotes hair growth to treat AGA by regulating the PI3K/Akt and apoptosis pathways. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this double-blind randomized controlled trial (RCT) was to compare clinical improvement and radiographic findings up to 2 years of follow-up of a single intra-articular injection of bone marrow aspirate concentrate (BMAC) versus hyaluronic acid (HA) for the treatment of knee osteoarthritis (OA). The hypothesis was that BMAC injection could lead to better clinical and radiographic results compared to viscosupplementation. Methods: Patients with bilateral knee OA were randomized to one intra-articular injection of tibial-derived BMAC in one knee and one HA injection in the contralateral knee. Sixty patients were enrolled, and 56 were studied up to the final follow-up (35 men, 21 women, mean age 57.8 ± 8.9 years), for a total of 112 knees. Patients were evaluated before the injection and at 1, 3, 6, 12, and 24 months with the IKDC subjective score, VAS for pain, and the KOOS score. Minimal clinically important difference (MCID), patient treatment judgement, and adverse events were documented, as well as bilateral X-Rays (Rosenberg view) before and after treatment. Results: No severe adverse events nor differences were reported in terms of mild adverse events (7.1% vs 5.4%, p = ns) and treatment failures (10.7% vs 12.5%, p = ns) in BMAC and HA groups, respectively. The IKDC subjective score improved from baseline to all follow-ups for BMAC (p < 0.0005), while it improved up to 12 months (p < 0.0005) and then decreased at 24 months (p = 0.030) for HA. Compared to HA, BMAC showed a higher improvement for VAS pain at 12 (2.2 ± 2.6 vs 1.7 ± 2.5, p = 0.041) and 24 months (2.2 ± 2.6 vs 1.4 ± 2.8, p = 0.002). The analysis based on OA severity confirmed this difference only in Kellgren–Lawrence 1–2 knees, while comparable results were observed in moderate/severe OA. Radiographic evaluation did not show knee OA deterioration for both treatment groups, without intergroup differences. Conclusion: BMAC did not demonstrate a clinically significant superiority at short-term compared to viscosupplementation, reporting overall comparable results in terms of clinical scores, failures, adverse events, radiographic evaluation, MCID achievement, and patient treatment judgment. However, while HA results decreased over time, BMAC presented more durable results in mild OA knees. Level of evidence: Level I. [ABSTRACT FROM AUTHOR]

Background: Bone marrow aspirate concentrate (BMAC) has emerged as a therapeutic option for symptomatic knee osteoarthritis (OA). Purpose: To systematically review the literature to evaluate the efficacy of isolated BMAC injection in the treatment of OA of the knee joint. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review was performed by searching the PubMed, Embase, and Cochrane Library databases up to July 2020 to identify human studies that assessed the clinical outcomes of isolated BMAC injection for the treatment of knee OA. The electronic search strategy used was "bone marrow aspirate concentrate knee osteoarthritis." Results: Eight studies met the inclusion criteria, including a total of 299 knees with a mean follow-up of 12.9 months (range, 6-30 months). Of all patient-reported outcomes assessed across studies, 34 of 36 (94.4%) demonstrated significant improvement from baseline to latest follow-up (P <.05). Five studies evaluating numerical pain scores (visual analog scale and Numeric Rating Scale) reported significant improvements in pain level at final follow-up (P <.01). However, 3 comparative studies evaluating BMAC in relation to other therapeutic injections failed to demonstrate the clinical superiority of BMAC. Conclusion: The BMAC injection is effective in improving pain and patient-reported outcomes in patients with knee OA at short- to midterm follow-up. Nevertheless, BMAC has not demonstrated clinical superiority in relation to other biologic therapies commonly used in the treatment of OA, including platelet-rich plasma and microfragmented adipose tissue, or in relation to placebo. The high cost of the BMAC injection in comparison with other biologic and nonoperative treatment modalities may limit its utility despite demonstrable clinical benefit. [ABSTRACT FROM AUTHOR]

The author talks about the potential of direct-to-consumer marketing to provide information on medications and novel treatments. Topics include a negative consequence of direct-to-consumer marketing, direct-to-consumer marketing by physicians, and the change in the Food and Drug Administration (FDA) regulations in 1997 that heralded a dramatic change in medical marketing in the U.S.

Purpose of Review: To present a synthesis of recent literature regarding the treatment of patellofemoral arthritis Recent Findings: Risk factors of PFJ OA include patella malalignment or maltracking, injury to supportive structures including the MPFL, dysfunction of hamstring and quadriceps coordination, lower limb alignment, trochlear dysplasia, patellar trauma, or ACL surgery. Special physical exam maneuvers include patellar grind test, apprehension test, and lateral patellar tilt angle. Radiographs that should be obtained first-line include weight bearing bilateral AP, lateral, and Merchant views. CT and MRI are used to assess trochlear dysplasia, excessive patellar height, and TT-TG distance. Non-operative management options discussed include non-pharmacologic treatment (patient education, self-management, physical therapy, weight loss), ESWT, cold therapy, taping, bracing, and orthotics. Pharmacologic management options discussed include NSAIDs, acetaminophen, oral narcotics, and duloxetine. Injection therapies include glucocorticoids, hyaluronic acid, PRP, and other regenerative therapies (BMAC, adipose, or mesenchymal stem cells). Other treatment options include radiofrequency ablation and botulinum toxin. The algorithm for the surgical treatment of PFJ OA can begin with arthroscopic assessment of the PF articular cartilage to address mechanical symptoms and to evaluate/treat lateral soft tissue with or without overhanging lateral osteophytes. If patients fail to have symptomatic improvement, a TTO can be considered in those patients less than 50 years of age or active patients >50 years old. In patients with severe PFJ OA, refractory to the above treatments, PFA should be considered. While early PFA design and technique were less than encouraging, more recent implant design and surgical technique have demonstrated robust results in the literature. Summary: Patellofemoral osteoarthritis is a challenging orthopedic problem to treat, in that it can often affect younger patients, with otherwise well-functioning knees. It is a unique entity compared to TF OA with distinct epidemiology, biomechanics and risk factors and treatment options. [ABSTRACT FROM AUTHOR]

Background: Autologous platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMC) are being used clinically as therapeutic agents for the treatment of knee osteoarthritis. Purpose/Hypothesis: The purpose of this study was to compare the efficacy of BMC and PRP on pain and function in patients with knee osteoarthritis up to 24 months after injection. It was hypothesized that patients receiving BMC would have better sustained outcomes than those receiving PRP. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: A total of 90 participants aged between 18 and 80 years with symptomatic knee osteoarthritis (Kellgren-Lawrence grades 1-3) were randomized into 2 study groups: PRP and BMC. Both groups completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and subjective International Knee Documentation Committee (IKDC) questionnaire before and 1, 3, 6, 9, 12, 18, and 24 months after a single intra-articular injection of leukocyte-rich PRP or BMC. A linear mixed-effects model was performed to quantify the effects over time and the difference between the groups. This model has the random effect for time to assess the extent in which the change over time differs from one person to another. Results: An overall 84 patients completed questionnaires from baseline to 12 months; however, 17 patients (n = 9; PRP group) were lost to follow-up at 18 months and 25 (n = 13; PRP group) at 24 months. There were no statistically significant differences in IKDC (P =.909; 95% CI, −6.26 to 7.03) or WOMAC (P =.789; 95% CI, −6.26 to 4.77) scores over time between the groups. Both groups had significantly improved IKDC (P <.001; 95% CI, 0.275-0.596) and WOMAC (P =.001; 95% CI, −0.41 to −0.13) scores from baseline to 24 months after the injection. These improvements plateaued at 3 months and were sustained for 24 months after the injection, with no difference between PRP and BMC at any time point. Conclusions: For the treatment of osteoarthritis, PRP and BMC performed similarly out to 24 months. BMC was not superior to PRP. Registration: NCT03289416 (ClincalTrials.gov identifier). [ABSTRACT FROM AUTHOR]

The two-bucket problem of unproven stem cell interventions (SCIs) continues to bifurcate good (ethical) from bad (unethical) practices in the translation of stem cell medicine in ways that divert attention from other salient and challenging questions. It causes scholars to focus narrowly on reprimanding bad actors through legal and regulatory approaches and distracts from other important considerations such as how best to balance evidence with unmet patient needs and address misinformation about unproven stem cell interventions potentially changing patient behavior. The stem cell science community needs to consider a range of ethical practices and aim to address important questions that have yet not received sufficient consideration. Stem cell advocates need to move from classifying stem cell therapies and the providers offering them as only good or bad, which diverts attention from other concerns. [ABSTRACT FROM AUTHOR]

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Objective: Stem cell therapy is increasingly used for knee osteoarthritis (KOA). We aimed to review the evidence of autologous mesenchymal stem cell therapy on pain, function and severity on imaging in KOA.Design: Systematic review of randomised controlled trials (RCTs).Eligibility Criteria: RCTs evaluating autologous mesenchymal stem cell (MSC) therapy on patient-reported outcome measures and disease severity.Data Sources: Seven databases were searched until 31 December 2020.Risk Of Bias and Data Synthesis: Risk of bias was assessed using the ROB V.2. We used Grading of Recommendations Assessment, Development and Evaluation to appraise the certainty of the evidence. Data were synthesised descriptively.Results: Fourteen RCTs were included. A total of 408 patients with KOA received MSC therapy derived from bone marrow, adipose tissue or activated peripheral blood. After 1 year, 19 of 26 (73%) clinical outcome measures improved with MSCs compared with control. In the MSC group, patients improved by 1.8-4.4 points on the Visual Analogue Scale (0-10) and 18-32 points of the Knee Osteoarthritis Outcome Score (0-100). Four studies showed better disease severity on imaging after MSC compared with control at 1 year. Ten of 14 (71%) RCTs were at high risk of bias on all outcomes. No serious adverse events were reported after MSC therapy during a maximum of 4 years follow-up.Conclusion: We found a positive effect of autologous MSC therapy compared with control treatments on patient-reported outcome measures, and disease severity. The certainty of this evidence was low to very low.Prospero Registration Number: CRD42019120506. [ABSTRACT FROM AUTHOR]

Copyright of Progress in Modern Biomedicine is the property of Publishing House of Progress in Modern Biomedicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Progress in Modern Biomedicine is the property of Publishing House of Progress in Modern Biomedicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Progress in Modern Biomedicine is the property of Publishing House of Progress in Modern Biomedicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Regenerative medicine, poised to transform 21st century healthcare, has aspired to enrich care options by bringing cures to patients in need. Science-driven responsible and regulated translation of innovative technology has enabled the launch of previously unimaginable care pathways adopted prudently for select serious diseases and disabilities. The collective resolve to advance the design, manufacture and validity of affordable regenerative solutions aims to democratize such health benefits for all. The objective of this Review is to outline the framework and prerequisites that underpin clinical readiness of regenerative care. Integrated research and development, specialized workforce education and accessible evidence-based practice implementation are at the core of realizing an equitable regenerative medicine vision. [ABSTRACT FROM AUTHOR]

The biology of regenerative medicine has steadily matured, providing the foundation for randomized clinical trials and translation into validated applications. Today, the growing regenerative armamentarium is poised to impact disease management, yet a gap in training next-generation healthcare providers, equipped to adopt and deliver regenerative options, has been exposed. This special report highlights a multiyear experience in developing and deploying a comprehensive regenerative curriculum for medical trainees. For academicians and institutions invested in establishing a formalized regenerative medicine syllabus, the Regenerative Medicine and Surgery course provides a patient-focused prototype for next-generation learners, offering a dedicated educational experience that encompasses discovery, development and delivery of regenerative solutions. Built with the vision of an evolving regenerative care model, this transdisciplinary endeavor could serve as an adoptable education portal to advance the readiness of the emergent regenerative healthcare workforce globally. [ABSTRACT FROM AUTHOR]

Sports injuries and secondary joint problems, mainly of the knee, are common, especially in sports associated with high impact activities and/or torsional loading. The consequences can be career ending in elite athletes and reduce exercise activities in recreational people. Various cell products can be injected intra-articularly. First, fresh cellular mixtures can be prepared and injected in the same day, such as stromal vascular fraction of adipose tissue (SVF) and bone marrow concentrates (BMCs). Second, autologous mesenchymal stromal cells (MSCs) can be isolated from BMCs or SVF and, after several weeks of laboratory expansion, several millions of MSCs can be obtained for intra-articular injection. Finally, allogeneic MSCs from the bone marrow, adipose tissue or perinatal tissues of selected donors constitute an 'off-the-shelf' experimental treatment for injection delivery in patients with osteoarthritis of the knee. The perceived efficacy of all these products is based on the hypothesis of a paracrine mechanism of action: when living cells are delivered within the joint, they establish a molecular cross-talk with immune cells and local cell phenotypes, thereby modulating inflammation with subsequent modifications in the catabolic/degenerative milieu. Current clinical research examines whether injection delivery of MSCs translates into actual clinical benefits. Overall, clinical studies lack the quality needed to answer major research questions, including clinical and structural efficacy, optimal cell dose, and number of injections and specific protocol for cell delivery. Poor experimental designs are exacerbated by the diversity of patient phenotypes that hinder comparisons between treatments. Further understanding of disease pathology is paramount to develop potent function assays and understand whether the host tissue, the cell product or both should be primed before MSCs are injected intra-articularly. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the available literature on the use of bone marrow aspirate concentrate (BMAC) and summarize the current evidence supporting its potential for the injective treatment of joints affected by osteoarthritis (OA). Methods: A systematic literature search was conducted on three electronic databases (PubMed, Embase, and Cochrane Library) in April 2020, using the following string: "((bone marrow concentrate) OR (BMC) OR (bone marrow aspirate concentrate) OR (BMAC)) AND (osteoarthritis)", and inclusion criteria: clinical and preclinical (animal) studies of any level of evidence, written in English language, and evaluating the intra-articular or subchondral use of BMAC for the injective treatment of OA joints. Results: The publication trend remarkably increased over time. A total of 22 studies were included in the qualitative data synthesis: four preclinical studies and 18 clinical studies, for a total number of 4626 patients. Safety was documented by all studies, with a low number of adverse events. An overall improvement in pain and function was documented in most of the studies, but the clinical studies present significant heterogeneity, few patients, short-term follow-up, and overall poor methodology. Conclusion: There is a growing interest in the field of BMAC injections for the treatment of OA, with promising results in preclinical and clinical studies in terms of safety and effectiveness. Nevertheless, the current knowledge is still preliminary. Preclinical research is still needed to optimize BMAC use, as well as high-level large controlled trials to better understand the real potential of BMAC injections for the treatment of patients affected by OA. [ABSTRACT FROM AUTHOR]

It has been over half a century since cellular senescence was first noted and characterized, and yet no consensus senescent marker has been reliably established. This challenge is compounded by the complexity and heterogenic phenotypes of senescent cells. This necessitates the use of multiple biomarkers to confidently characterise senescent cells. Despite cytochemical staining of senescence associated-beta-galactosidase being a single marker approach, as well as being time and labour-intensive, it remains the most popular detection method. We have developed an alternative flow cytometry-based method that simultaneously quantifies multiple senescence markers at a single-cell resolution. In this study, we applied this assay to the quantification of both replicative and induced senescent primary cells. Using this assay, we were able to quantify the activity level of SA β-galactosidase, the expression level of p16INK4a and γH2AX in these cell populations. Our results show this flow cytometric approach to be sensitive, robust, and consistent in discriminating senescent cells in different cell senescence models. A strong positive correlation between these commonly- used senescence markers was demonstrated. The method described in this paper can easily be scaled up to accommodate high-throughput screening of senescent cells in applications such as therapeutic cell preparation, and in therapy-induced senescence following cancer treatment. [ABSTRACT FROM AUTHOR]

Purpose: Osteoarthritis (OA) of the knee is a debilitating, expensive, and prevalent disease, and interest in the non-surgical management of knee OA has grown recently. Our objective was to systematically assess the level of heterogeneity among all clinical trials and published studies regarding injections for knee osteoarthritis, in terms of treatment of interest, outcomes evaluated, and time points of outcome assessment. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized to review all published studies and publically available clinical trials from 1 January 2013 to 3 May 2019evaluating intra-articular injections to treat knee OA. Their treatment group and specifics of methodology were scrutinized and compared. Results: 84 published studies and 114 clinical trials were included. Within the 84 published studies, the most common injection treatment studied was hyaluronic acid [N = 22; 26.2%]. In total, 29 different injection treatment groups were utilized. The most common time point for patient evaluation post-injection was 6 months (N = 33 studies; 50.0%), and ranged from 1 week (N = 9 studies; 13.6%) to 7 years (N = 1 study; 1.5%). The most common patient-reported outcome (PRO) measure assessed in the included studies was Western Ontario and McMaster's University Osteoarthritis Index (WOMAC) [N = 44 studies; 66.7%]. For the 114 clinical trials identified, the most common injection treatment studied is platelet-rich plasma in isolation (N = 19; 16.7%). Forty-two different injection treatment types/groups are utilized. The most common PRO measure assessed was WOMAC (N = 77 trials; 67.5%). Overall there were 34 different patient-reported outcome measures used. Conclusions: Research efforts to find the most effective injection therapy for knee OA continue with a tremendous number of injection therapies still being evaluated. Substantial heterogeneity exists in these completed and ongoing trials in terms of patient demographics, OA grades, outcome scores and relatively short-term timing of assessments, with no clear standardization of testing protocol despite proposing to answer the same clinical question. We recommend that studies of this genre going forward be standardized in terms of outcome measures and longer-term follow-up time points, and should incorporate functional assessment evaluations and imaging studies. [ABSTRACT FROM AUTHOR]

Aim: To address the unmet needs of patients interested in regenerative medicine, Mayo Clinic created a Regenerative Medicine Consult Service (RMCS). We describe the service and patient satisfaction. Materials & methods: We analyzed RMCS databases through retrospective chart analysis and performed qualitative interviews with patients. Results: The average patient was older to elderly and seeking information about regenerative options for their condition. Patients reported various conditions with osteoarthritis being most common. Over a third of consults included discussions about unproven interventions. About a third of patients received a clinical or research referral. Patients reported the RMCS as useful and the consultant as knowledgeable. Conclusion: An institutional RMCS can meet patients' informational needs and support the responsible translation of regenerative medicine. [ABSTRACT FROM AUTHOR]

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