Basic Science Review Research Articles

Tendon Healing: A Review of Basic Science and Current Progress

Tendon Healing: A Review of Basic Science and Current Progress

Basic science review of birth tissue uses in ophthalmology.

The birth tissue is predominantly comprised of amniotic membrane (AM) and umbilical cord (UC), which share the same cell origin as the fetus. These versatile biological tissues have been used to treat a wide range of conjunctival and corneal conditions since 1940. The therapeutic benefits of the birth tissue stem from its anti-inflammatory and anti-scarring properties that orchestrate regenerative healing. Although the birth tissue also contains many cytokines, growth factors, and proteins, the heavy chain 1–hyaluronic acid/pentraxin 3 (HC–HA/PTX3) matrix has been identified to be a major active tissue component responsible for AM/UC's multifactorial therapeutic actions. HC–HA/PTX3 complex is abundantly present in fresh and cryopreserved AM/UC, but not in dehydrated tissue. In this review, we discuss the tissue anatomy, the molecular mechanism of action based on HC–HA/ PTX3 to explain their therapeutic potentials, and the various forms available in ophthalmology.

Understanding Enterovirus D68-Induced Neurologic Disease: A Basic Science Review.

In 2014, the United States (US) experienced an unprecedented epidemic of enterovirus D68 (EV-D68)-induced respiratory disease that was temporally associated with the emergence of acute flaccid myelitis (AFM), a paralytic disease occurring predominantly in children, that has a striking resemblance to poliomyelitis. Although a definitive causal link between EV-D68 infection and AFM has not been unequivocally established, rapidly accumulating clinical, immunological, and epidemiological evidence points to EV-D68 as the major causative agent of recent seasonal childhood AFM outbreaks in the US. This review summarizes evidence, gained from in vivo and in vitro models of EV-D68-induced disease, which demonstrates that contemporary EV-D68 strains isolated during and since the 2014 outbreak differ from historical EV-D68 in several factors influencing neurovirulence, including their genomic sequence, their receptor utilization, their ability to infect neurons, and their neuropathogenicity in mice. These findings provide biological plausibility that EV-D68 is a causal agent of AFM and provide important experimental models for studies of pathogenesis and treatment that are likely to be difficult or impossible in humans.

Landmarks in Facial Rejuvenation Surgery: The Top 50 Most Cited Articles.

Facial rejuvenation procedures are common in plastic surgery. The aim of this study was to report the 50 most cited articles in the field of aesthetic facial rejuvenation surgery and provide a simple educational resource for plastic surgeons. The authors utilized the Web of Science Citation Index to identify the 50 most cited articles related to surgery for facial rejuvenation published from 1950 to 2019. Articles were classified according to their level of evidence, type of study, country of publication, and topic of interest: facelift, blepharoplasty, brow lift, neck lift, or combined areas. The mean number of citations per article was 137, and the majority of articles (n = 19) were published between 1990 and 1999. The most prevalent topic was facelift surgery (n = 24), followed by articles discussing combined procedures (n = 13), blepharoplasty (n = 6), brow lift (n = 4), and neck lift (n = 3). Most of the articles were classified as clinical (n = 26), followed by basic science studies (n = 12) and review articles (n = 12). Among the articles amenable to grading level of evidence (n = 26), most (n = 24) presented their findings utilizing level IV evidence. The nation of origin for most of the articles (n = 41) was the United States. Articles addressing facelift surgery represented the largest proportion of peer-reviewed landmark publications in aesthetic facial surgery research. A simple educational resource is presented to encourage the appreciation of the research in this field.

Game Day: A Board Game to Integrate Anatomy with Other Basic and Clinical Sciences for the Classroom

IntroductionMany medical and allied health institutions are moving away from the traditional lecture‐based approaches. Instead, students are educated through other models including case‐based collaborative learning and team‐based learning where students can apply and integrate their newly acquired basic and clinical science through small group activities. Substantial challenges for educators using these learning approaches include: delivering new and engaging activities, effective integration of content from basic and clinical disciplines, efficient use of class time, and scaling the activity to the level of the learner. Here we designed an exciting and innovative game activity to integrate clinically‐focused anatomy with other disciplines and to mitigate student disengagement.AimTo deliver a challenging and engaging classroom activity that integrates different basic and clinical science disciplines, allowing students to apply and assess their knowledge of a body system or region.MethodsIn this IRB approved study, first year medical students participated in a board game (Fig. 1) consisting of 30 challenges related to the gastrointestinal system. The board game activity was developed by experts from microbiology/immunology, anatomy, surgery, pathology, pharmacology, pathophysiology, and physiology. It was one of eleven case‐based basic science sessions that were included in a 6 week long course focused on the gastrointestinal system. The goal was to create single or integrated discipline challenges that took on a variety of formats. Using a game board and points system, student teams completed 30 challenges (Table 1) by applying high yield content while accumulating points as they progressed through the gastrointestinal tract. Students then evaluated the success of the session through a survey.Results100% of students (n=133) who participated in the board game activity completed the survey. Overall, 84.3% of students endorsed that the learning objectives for this module were met (27.6% strongly agree) and 81.5% endorsed that the overall quality of this session was excellent (33.3% strongly agree). On average, the overall quality rating of the session was 4.66(+/− 0.8) out of a 6 point Likert scale, a score that was higher than all 11 sessions in this course, and well above the mean satisfaction rating of 3.77 +/− 0.7 for all 11 sessions in this course.117 of 133 students left a narrative evaluation of the self‐study materials, activity, or their experience with their classroom facilitator. Of the 75 comments directly related to the activity, 34 stated the activity was “awesome”, “good”, or “best of the year so far”, 12 remarked that the activity was highly engaging and/or interactive, and 11 stated the activity was fun. The most commonly received negative comment was that the activity too long.DiscussionThis game‐format activity provides an engaging review of basic science and clinical disciplines that can be scaled to the ability of the learner and adapted to accommodate different disciplines. It can be easily developed by content experts and deployed with minimal faculty training, contributing to the collection of in‐class activities for health science curricula.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Estrogens and prostate cancer

Hormonal influences such as androgens and estrogens are known contributors in the development and progression of prostate cancer (CaP). While much of the research to the hormonal nature of CaP has focused on androgens, estrogens also have critical roles in CaP development, physiology as well as a potential therapeutic intervention. In this review, we provide a critical literature review of the current basic science and clinical evidence for the interaction between estrogens and CaP. Estrogenic influences in CaP include synthetic, endogenous, fungi and plant-derived compounds, and represent a family of sex hormones, which cross hydrophobic cell membranes and bind to membrane-associated receptors and estrogen receptors that localize to the nucleus triggering changes in gene expression in various organ systems. Estrogens represent a under-recognized contributor in CaP development and progression. Further research in this topic may provide opportunities for identification of environmental influencers as well as providing novel therapeutic targets in the treatment of CaP.

Pharmacokinetic/pharmacodynamic drug evaluation of enzalutamide for treating prostate cancer

ABSTRACT Introduction: Enzalutamide is the first approved second-generation androgen receptor (AR) antagonist in the treatment of metastatic castration-resistant prostate cancer (mCRPC) with or without docetaxel-based chemotherapy. Over the past 5 years, a number of attempts were made to determine the efficacy of enzalutamide in the different clinical settings. Areas covered: A literature search was performed at the PubMed, Embase, and Web of Science database to collect the most relevant and impactful studies, including basic science investigations, clinical trials, and reviews. This article focuses on the pharmacology, efficacy, tolerability, and future perspective of enzalutamide. Expert opinion: The treatment paradigm of CRPC has been dramatically challenged of late. Enzalutamide are in wide use because of its favorable efficacy and safety, but primary or acquired resistance to the drug will eventually develop. Further studies are thus necessary to identify appropriate patients who can achieve apparent benefits from enzalutamide alone or in combination with other drugs.

Ozone Therapy: Overview of its Potential Utility in Male Reproduction

Ozone (O3), a highly water-soluble inorganic molecule, is a gas made of three atoms of oxygen (O) with a cyclic structure. Ozone can be produced by medical generators from pure oxygen after passing through a high voltage gradient. Ozone therapy (OT) can be given in medical practice via several routes that include transdermal, intramuscular, rectal, nasal, oral, vaginal, intravenous, intra-arterial, intraperitoneal, intra-pleural, topical, dental, intra-discal and by auto-hemotherapy. Because ozone, a highly reactive molecule, is a potent oxidant and anti-inflammatory agent, it has strong bactericidal, antiviral, anti-fungal and anti-protozoal actions as well as therapeutic effects on the immune system. With its multifaceted route of administration, OThas been used to treat several pathologies that involve the immune system such as cancers, sepsis, abscesses and chronic wounds, skin problems (such as eczema and psoriasis), HIV infection, asthma, arthritis, urologic problems, osteomyelitis and many others. The purpose of this review article is to evaluate the role of OT in the male reproductive system. We performed a review of all available basic science, experimental animal studies and clinical peer-reviewed articles published in PubMed and Google Scholar until November 2018. The literature so far retrieved shows that most studies pertaining to the effect of OT on male reproduction were performed in animals. Results to date show that OT, via improving the immune system, significantly protects testicular function in the setting of testicular torsion/ischemia, protects against the effect of gonadotoxic agents and treats bacterial infections in the semen. This article calls for a need for at least pilot studies in humans using OT in its safest route of administration, which is probably the transdermal one. This would be significant especially considering that male factor infertility constitutes up to one third of couple infertility and it is very common that poor semen parameters are irreversible with medical or surgical treatment, such as varicocele repair or vasectomy reversal.

Anterior Cruciate Ligament Mechanoreceptors and their Potential Importance in Remnant-Preserving Reconstruction: A Review of Basic Science and Clinical Findings.

Mechanoreceptors, within the anterior cruciate ligament (ACL), are believed to have importance in proprioception, contributing to dynamic knee stability. The potential for reinnervation of the ACL graft is one of the proposed advantages of remnant-preserving reconstruction. The aim of this review is to summarize advances in the basic science underpinning this function, alongside recent clinical studies, to define the current role for remnant-preservation.A comprehensive systematic review was performed using PubMed and Medline searches. Studies were analyzed with particular focus placed on the methodology used to either identify mechanoreceptors or test proprioception.Contemporary work, using immunohistological staining, has shown mechanoreceptors primarily within proximity to the bony attachments of the ACL (peripherally in the subsynovial layer). The number of these receptors has been shown to decrease rapidly, following rupture, with adhesion to the posterior cruciate ligament slowing this decline. Recent studies have shown proprioceptive deficits, in both the injured and contralateral knees, with the clinical relevance of findings limited by testing methodology and the small differences found. The advantages of remnant-preservation, seen primarily in animal studies, have not been shown in systematic reviews or meta-analysis of clinical studies.The potential for reinnervation of the graft is likely time-dependent and reliant on continued loading of the remnant. Therefore, current clinical use and future research should focus on preserving remnants within 6 months of injury that remain loaded by adherence to the posterior cruciate ligament. Subsequent testing should account for central neurological changes and focus on clinically relevant outcomes.

Sperm DNA fragmentation testing: proceed with care.

The authors should be commended for their thorough review of DNA fragmentation and the clinical indications for testing. The basic science review of DNA fragmentation, oxidative stress, and its association with male infertility is detailed yet concise. The authors also present clinical scenarios to better illustrate the current role of evaluating sperm DNA fragmentation (SDF) in the infertility specialist’s armamentarium, and describe very convincing theoretical arguments for the potential importance of SDF. However, the clinical role of SDF in the evaluation of men with male factor infertility remains unclear, and several recommendations made in this article do not yet have sufficient clinical data to support its routine use

Application of adipose-derived stromal cells in fat grafting: Basic science and literature review

Autologous fat is considered the ideal material for soft-tissue augmentation in plastic and reconstructive surgery. The primary drawback of autologous fat grafting is the high resorption rate. The isolation of mesenchymal stem cells from adipose tissue inevitably led to research focusing on the study of combined transplantation of autologous fat and adipose derived stem cells (ADSCs) and introduced the theory of ‘cell-assisted lipotransfer’. Transplantation of ADSCs is a promising strategy, due to the high proliferative capacity of stem cells, their potential to induce paracrine signalling and ability to differentiate into adipocytes and vascular cells. The current study examined the literature for clinical and experimental studies on cell-assisted lipotransfer to assess the efficacy of this novel technique when compared with traditional fat grafting. A total of 30 studies were included in the present review. The current study demonstrates that cell-assisted lipotransfer has improved efficacy compared with conventional fat grafting. Despite relatively positive outcomes, further investigation is required to establish a consensus in cell-assisted lipotransfer.

A Team-based Assignment to Integrate Basic Science and Pharmacotherapeutic Principles for Anticancer Agents

Objective. To implement and evaluate an active-learning, team-based assignment centered on anticancer agents for the integration of basic science and pharmacotherapeutic principles. Methods. Student teams were assigned a specific anticancer agent and were expected to answer a series of questions on the written section of the assignment, followed by a presentation to the class. Each assignment was assessed using a grading rubric that was mapped to the 2013 CAPE educational outcomes. Student perceptions of the assignment were assessed using a short survey. Results. Student cohort performance on the assignment was in the B range (83%) with a mean of 33.2 out of 40. Using the grading rubric, the 12 student cohorts performed particularly well under professionalism (Domain 4.4) that focuses on personal and professional development from CAPE 2013 with means >4 on a 1-5 scale. Student impressions of the assignment suggested that students believed the assignment had a positive effect on their learning and should be continued. Conclusion. The assignment provided a focused review of basic science and pharmacotherapeutic principles and enabled integration of concepts relating to the therapeutic application of anticancer agents, and management of anticancer agent mediated adverse effects. The assignment could contribute toward preparing students for the evolving role of the pharmacist in the management of cancer.

Improved knowledge gain and retention for third-year medical students during surgical journal club using basic science review: A pilot study

BackgroundAs they enter the clinical years, medical students face large adjustments in the acquisition of medical knowledge. We hypothesized that basic science review related to the topic of journal club papers would increase the educational benefit for third-year medical students. MethodsStudents were randomized either to participation in a review session about basic science related to the journal club paper, or to no review. After one day, and after three months, students were given a 10-question quiz encompassing the basic science and the clinical implications of the paper. ResultsTwenty-six of 50 students were randomized to basic science review. These students scored better on both sections of the quiz one day after journal club, but only on basic science questions after three months. ConclusionsStudents who participated in basic science review had better knowledge gain and retention. Educational activities building upon foundational knowledge improves learning on clinical rotations.

Early Operative Versus Delayed or Nonoperative Treatment of Anterior Cruciate Ligament Injuries in Pediatric Patients.

Reference: Ramski DE, Kanj WW, Franklin CC, Baldwin KD, Ganley TJ. Anterior cruciate ligament tears in children and adolescents: a meta-analysis of nonoperative versus operative treatment. Am J Sports Med. 2014;42(11):2769-2776. Clinical Questions: In pediatric patients, does early operative treatment of an anterior cruciate ligament (ACL) injury result in decreased knee instability compared with delayed or nonoperative treatment? This review focused on the PubMed/MEDLINE and EMBASE databases. The following query searches were used: ACL or anterior cruciate ligament and young or child or children or pediatric or immature. Dates searched were not specified. A separate search was also conducted of abstracts published between 2009 and 2011 from the American Academy of Orthopaedic Surgeons; American Orthopaedic Society for Sports Medicine; International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine; European Society of Sports Traumatology, Knee Surgery, and Arthroscopy; American Orthopaedic Association; Arthroscopy Association of North America; Pediatric Orthopaedic Society of North America; and American Academy of Pediatrics conferences. Available studies were included only if they were written in English; were of level 1, 2, or 3 evidence (grading taxonomy not stated); were cohort designs that compared nonoperative and operative treatments; involved an early versus delayed ACL reconstruction that could be prospective or retrospective; and reported primary outcome interest measures. Animal studies, basic science studies, case series, reviews, commentaries, and editorials were excluded from the review. A systematic assessment tool, Guide to Community Preventive Services: Systematic Reviews and Evidence-Based Recommendations, was used by 2 of the authors to independently grade the quality of each study that met the inclusion criteria. The tool focused on 6 areas: intervention and study description, sampling, measurement, analysis, interpretation of results, and other execution factors. This tool helped to ensure consistency, reduce bias, and improve the validity and reliability of preventive health care studies. Eleven studies met the inclusion criteria. Six studies compared nonoperative with operative treatment, and 5 studies compared early reconstruction (open physes) with delayed reconstruction (closed physes). Studies in this meta-analysis consisted of the following: four level-3 prospective studies, four level-3 retrospective studies, one level-2 retrospective study, one level-3 case-control study, and one level-3 study with both prospective and retrospective data collection. All of the studies included data related to patient demographics, treatment interventions, follow-up duration, presence of any meniscal symptoms, time to return to sport participation, patient-reported outcomes (International Knee Documentation Committee [IKDC], Lysholm, or Tegner scores), the need for a second surgical procedure, and any posttreatment problems. Of those who chose the nonoperative route, 75% reported instability, whereas only 13.6% of those who had surgery reported instability. These data also showed that nonoperative or delayed-operative patients were 33.7 times more likely to report instability than the early operative group. Those who chose the nonoperative route had a 12 times greater risk (odds ratio = 12.2, 95% confidence interval = 1.55, 96.3) of developing a meniscal tear after the initial injury. Three studies included in the meta-analysis reported return to sport status, but only 2 studies provided adequate data for both operative and nonoperative patients. In 1 study, 92% of operative patients were able to return to sport, but only 43.75% of nonoperative patients were able to do so. The second study reported that all operative and nonoperative patients were able to return to the same level of sport after injury. Of those in the early operative group, 6% required a repeat surgical intervention for either an ACL rerupture or a meniscal tear, and 19% of those who initially chose nonoperative treatment eventually needed surgery to repair the ACL or meniscus. Findings favor the early operative group over the delayed operative and nonoperative groups based on IKDC scores. One study reported a significant difference in operative patients, with an IKDC mean score of 95 compared with 87 in the nonoperative group. Similarly, a different study reported a mean score of 94.6 in the early operative group compared with 82.4 in the delayed operative group and was stated to have met the minimal clinically important difference (MCID). The MCID was not met for the Lysholm and Tegner scores between operative and nonoperative patients. The results of this meta-analysis favor early operative treatment for pediatric patients with ACL tears over delayed or nonoperative treatment. Early operative treatment is initiated shortly after the injury, while the patient is still skeletally immature and the growth plates are open. Current evidence suggests that early ACL reconstruction will result in less knee instability and a more likely return to the preinjury activity level without affecting the growth plates or causing growth disturbances.

The Effect of Rosmarinic Acid on Immunological and Neurological Systems: A Basic Science and Clinical Review

Rosmarinic acid (RosA) is an ester of caffeic acid and 3,4-dihydroxyphenylactic acid. RosA has a number of beneficial biological activities, including antiviral, antibacterial, anti-inflammatory, and antioxidant properties. Oxidative stress is recognized as a common factor in many neurodegenerative diseases and is a proposed mechanism for age-related degenerative processes as a whole. RosA has shown antioxidative action, acting as a scavenger of free radicals. RosA protects neurons from oxidative stress, significantly attenuated hydrogen peroxide-induced reactive oxygen species generation, and apoptotic cell death and could contribute at least in part to neuroprotective effects. RosA has also been shown to suppress immunoglobulin responses and inflammatory responses of polymorphonuclear leukocytes which may explain its effectiveness at treating seasonal allergic rhinoconjuctivitis in human clinical trials. The anti-inflammatory effects of RosA along with its immunomodulatory effects may also make it a novel agent for the treatment of auto-immune disorders. This review is focused on the effect of RosA on both immunological and neurological systems and its potential as a novel therapeutic agent for the treatment of associated conditions, especially those in which oxidative stress is a factor.

Editorial October 2015

Editorial October 2015

Medical Marijuana and Chronic Pain: a Review of Basic Science and Clinical Evidence.

Cannabinoid compounds include phytocannabinoids, endocannabinoids, and synthetics. The two primary phytocannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), with CB1 receptors in the brain and peripheral tissue and CB2 receptors in the immune and hematopoietic systems. The route of delivery of cannabis is important as the bioavailability and metabolism are very different for smoking versus oral/sublingual routes. Gold standard clinical trials are limited; however, some studies have thus far shown evidence to support the use of cannabinoids for some cancer, neuropathic, spasticity, acute pain, and chronic pain conditions.

Aging and degeneration of the intervertebral disc: review of basic science

<p>Currently there is a growing interest in the study of intervertebral discs due to loss of manpower brought to society by low back and neck pains. These papers seek to delineate the difference between normal aging and disc degeneration, trying to understand what factor would be determining for the second condition. Thus, the morphology field was expanded and knowledge on the structure of intervertebral discs currently uses the research field of cell and molecular biology, and genetics. The results indicate that regardless of age or condition, the intervertebral disc undergoes long and extensive remodeling of its constituents, which are influenced by several factors: environmental, soluble, cell growth and extracellular matrix. In this literature review we describe the biological characteristics of the cervical and lumbar intervertebral disc with a focus on basic science of aging and degeneration, selecting the latest findings and discussions of the area, which influence future research and clinical thoughts.</p>

Using TENS for pain control: the state of the evidence.

Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological intervention that activates a complex neuronal network to reduce pain by activating descending inhibitory systems in the central nervous system to reduce hyperalgesia. The evidence for TENS efficacy is conflicting and requires not only description but also critique. Population-specific systemic reviews and meta-analyses are emerging, indicating both HF and LF TENS being shown to provide analgesia, specifically when applied at a strong, nonpainful intensity. The purpose of this article is to provide a critical review of the latest basic science and clinical evidence for TENS. Additional research is necessary to determine if TENS has effects specific to mechanical stimuli and/or beyond reduction of pain and will improve activity levels, function and quality of life.

Vitamin D improves inflammatory bowel disease outcomes: basic science and clinical review.

Vitamin D deficiency is commonly diagnosed among patients with inflammatory bowel disease (IBD). Patients with IBD are at risk of low bone density and increased fractures due to low vitamin D levels, long standing disease, and frequent steroid exposures; as a result, it is well established that vitamin D supplementation in this population is important. There is increasing support for the role of vitamin D in strengthening the innate immune system by acting as an immunomodulator and reducing inflammation in experimental and human IBD. The active form of vitamin D, 1,25(OH)D3, acts on T cells to promote T helper (Th)2/regulatory T responses over Th1/Th17 responses; suppresses dendritic cell inflammatory activity; induces antibacterial activity; and regulates cytokine production in favor of an anti-inflammatory response. Murine and human IBD studies support a therapeutic role of vitamin D in IBD. Risk factors for vitamin D deficiency in this population include decreased sunlight exposure, disease duration, smoking, and genetics. Vitamin D normalization is associated with reduced risk of relapse, reduced risk of IBD-related surgeries, and improvement in quality of life. Vitamin D is an inexpensive supplement which has been shown to improve IBD outcomes. However, further research is required to determine optimal serum vitamin D levels which will achieve beneficial immune effects, and stronger evidence is needed to support the role of vitamin D in inducing disease response and remission, as well as maintaining this improvement in patients' disease states.