A Multicenter Training and Interrater Reliability Study of the BASED Score for Infantile Epileptic Spasms Syndrome.

PURPOSE: The best possible outcomes in infantile epileptic spasms syndrome require electroclinical remission; however, determining electrographic remission is not straightforward. Although the determination of hypsarrhythmia has inadequate interrater reliability (IRR), the Burden of AmplitudeS and Epileptiform Discharges (BASED) score has shown promise for the reliable interictal assessment of infantile epileptic spasms syndrome. Our aim was to develop a BASED training program and assess the IRR among learners. We hypothesized moderate or better IRR for the final BASED score and the presence or absence of epileptic encephalopathy (+/-EE). METHODS: Using a web-based application, 31 learners assessed 12 unmarked EEGs (length 1-6 hours) from children with infantile epileptic spasms syndrome. RESULTS: For all readers, the IRR was good for the final BASED score (intraclass correlation coefficient 0.86) and +/-EE (Marginal Multirater Kappa 0.63). For all readers, the IRR was fair to good for all individual BASED score elements. CONCLUSIONS: These findings support the use of our training program to quickly learn the BASED scoring method. The BASED score may be a valuable clinical and research tool. Given that the IRR for the determination of epileptic encephalopathy is not perfect, clinical acumen remains paramount. Additional experience with the BASED scoring technique among learners and advances in collaborative EEG evaluation platforms may improve IRR.

Is Diclofenac Transbuccal Mucoadhesive Patch Superior to Oral Diclofenac for the Management of Postoperative Sequelae After Third Molar Surgery?

BACKGROUND: Pain, swelling, and trismus are the most common sequalae following the surgical removal of mandibular third molars. They pose significant challenges for clinicians, prompting the exploration of efficacious management approaches. PURPOSE: The purpose of this study was to assess the efficacy of transbuccal mucoadhesive patch of diclofenac sodium versus an oral tablet in controlling the aforesaid sequelae. STUDY DESIGN, SETTING, SAMPLE: A prospective split-mouth, single-blinded study was conducted in the Department of Oral and Maxillofacial Surgery at AMC Dental College and Hospital, Ahmedabad. The study sample included patients of either sex, aged 18 to 45 years, requiring surgical removal of bilaterally symmetrical mandibular third molars under local anesthesia. Patients who had consumed analgesics within 24 hours prior to the procedure were excluded. PREDICTOR VARIABLE: The primary predictor variable was the route of administration of nonsteroidal anti-inflammatory drug. The study group received transbuccal mucoadhesive patches containing 20 mg diclofenac sodium, whereas the control group received oral tablets of 50 mg. MAIN OUTCOME VARIABLE: Postoperative pain, measured with visual analog scale, was the primary outcome variable, whereas swelling, mouth opening, onset of analgesic effect, and adverse events were assessed as secondary outcome variables. COVARIATES: Two categories of covariates were considered. First, demographic: age and gender. Second, perioperative: pattern of impaction. ANALYSES: Intergroup comparison was made using a paired sample t-test and an independent sample t-test, while intragroup differences were assessed with a one-way ANOVA and a paired t-test. P value ≤ .05 was considered statistically significant. RESULTS: Out of 146 patients screened initially, the final study sample included 37 subjects with a mean age of 26.08 ± 5.09 years (21 (56.75%) males and 16 (43.25%) females). The study group exhibited a significantly lower postoperative pain score compared to the control group on days 0, 1, 2, and 3 postoperatively (P ≤ .05). No statistically significant difference was observed in reduction of facial swelling and improvement in mouth opening on 1st, 2nd, and 3rd days postoperatively between both the groups (P ≥ .05). The mean onset of analgesia was statistically significant in the study group (19.96 ± 5.40 minutes) compared to the control group (52.56 ± 6.33 minutes) (P < .001). CONCLUSION AND RELEVANCE: Transbuccal mucoadhesive patch of diclofenac sodium offers effective pain control with quicker analgesia and fewer side effects compared to an oral tablet.

Effective strategies in the management of anterior mandibular fractures: a comprehensive systematic review.

This review examines the prevailing modalities for fractures of the anterior mandible, which represent a significant proportion of the maxillofacial injuries commonly treated by oral and maxillofacial surgeons. The article traces the historical shift from conservative techniques to the dominant management strategies of open reduction and fixation. Encompassing a range of studies, the review, in accordance with PRISMA 2020 recommendations, meticulously examines various fixation methods, assessing their efficacy in achieving stability of fracture, early healing, and mobilisation. The comparison of these methods highlights their unique advantages and limitations, and demonstrates the need for more nuanced and precise approaches. The review emphasises evidence-based methodology in the management of anterior mandibular fractures (AMF), highlighting the benefits offered by innovative techniques such as 3D miniplates. It also acknowledges the advantages provided by older fixation devices such as lag screws. The importance of postoperative outcomes and the need for tailored treatment strategies are recognised, considering the complex nature of these fractures.

Immunization of laboratory animal workers: occupational health and safety aspects.

Occupational immunization is an integral part of institutional occupational safety and health (OSH) programs. Laboratory animal workers (LAWs) are personnel working with various small and large vertebrate animals. LAWs are at the risk of contracting a myriad of zoonotic infections as they are occupationally exposed to animals and their biological products. Immunizing employees against such zoonotic pathogens is the best way to prevent disease transmission. This review provides information on various zoonotic diseases, vaccines available to protect against such infections, and vaccination schedules. Certain sections of institutional occupational immunization programs such as risk evaluation, immunizing special categories of personnel and exemption from immunization among others are also described. Additionally, the authors have discussed various probable modes of impact through which occupational immunization of laboratory animal workers fulfills different United Nations Sustainable Development Goals.

Health and Healthcare Disparities in Pediatric Epilepsy in the United States: A Scoping Review.

OBJECTIVES: Health disparities impact epilepsy care in children. Previous efforts to summarize data in this population have been limited. This study sought to understand how this information exists in the literature and identify gaps in knowledge. METHODS: A scoping review of peer-reviewed articles and gray literature was conducted using PRISMA guidelines. Disparity populations (e.g., Sex, Race/Ethnicity, Socioeconomic Status) and disparity outcomes (e.g., Quality of Life (QOL)/Psychological, Utilization, Mortality/Sudden Unexpected Death in Epilepsy) were identified. A finding was defined as a single result from a discrete statistical analysis of a specific clinical outcome by disparity population. Data extraction identified where this information existed in the literature and how it was reported. RESULTS: A total of 307 publications revealed 769 unique disparity/equity findings. Disparity populations were unequally represented (p < 0.0001). Sex and Race/Ethnicity had the most findings while Language/Immigration had the fewest. Nearly a quarter of findings (23%) addressed QOL/Psychological outcomes. The highest percentages of disparities were found in the Utilization, Mortality/SUDEP, and Economic categories. Of the 204 publications reporting disparity findings, fewer than half actually intended to investigate disparities as one of their original objectives. Of the disparity findings identified in peer-reviewed articles, a third were not mentioned in the abstract and 20% were not addressed in the discussion. INTERPRETATION: A comprehensive scoping review of health disparities in pediatric epilepsy found that specific disparity populations like Sex and Race/Ethnicity were robustly explored, while Language/Immigration was under-represented, despite a high rate of disparities. Health-related outcome categories were also unequally investigated. Disparity findings were often difficult to access within publications. ANN NEUROL 2024;95:733-742.

Real life retrospective study of cannabidiol therapy in alternating hemiplegia of childhood.

BACKGROUND: Many alternating hemiplegia of childhood (AHC) patients have received Cannabidiol (CBD) but, to our knowledge, there are no published data available. GOALS: Test the hypothesis that CBD has favorable effects on AHC spells. METHODS: Retrospective review of available data of AHC patients who received CBD. Primary analysis: Clinical Global Impression Scale of Improvement (CGI-I) score for response of AHC spells to CBD with calculation of 95% confidence interval (CI) for rejection of the null hypothesis. Secondary analyses, performed to achieve an understanding of the effect of CBD as compared to flunarizine, were CGI-I scores of 1) epileptic seizures to CBD, 2) AHC spells to flunarizine, 3) epileptic seizures to flunarizine. Also, Mann-Whitney test was done for comparison of CGI-I scores of CBD and flunarizine to both AHC spells and seizures. RESULTS: We studied 16 AHC patients seen at Duke University and University of Lyon. CI of CGI-I scores for AHC spells in response to CBD and to flunarizine, each separately, indicated a positive response to each of these two medications: neither overlapped with the null hypothesis score, 4, indicating significant positive responses with p < 0.05 for both. These two scores also did not differ (p = 0.84) suggesting similar efficacy of both: CBD score was 2 ± 1.1 with a 95% CI of 1.5-2.6 and flunarizine score was 2.3 ± 1.3 with a 95% CI of 1.7-3.1. In patients who had seizures, CI calculations indicated a positive effect of CBD on seizure CGI scores but not of flunarizine on seizure scores. CBD was well tolerated with no patients discontinuing it due to side effects and with some reporting positive behavioral changes. CONCLUSION: Our study indicates a real-life positive effect of CBD on AHC type spells.

A Retrospective Comparison of Electrocardiographic Parameters in Ketamine and Tiletamine-Zolazepam Anesthetized Indian Rhesus Monkeys (Macaca mulatta).

Electrocardiographic evaluation is performed in rhesus monkeys to establish the cardiovascular safety of candidate molecules before progressing to clinical trials. These animals are usually immobilized chemically by ketamine (KTM) and tiletamine-zolazepam (TZ) to obtain a steady-state heart rate and to ensure adequate human safety. The present study aimed to evaluate the effect of these anesthetic regimens on different electrocardiographic parameters. Statistically significant lower HR and higher P-wave duration, RR, QRS, and QT intervals were observed in the KTM-anesthetized group in comparison to TZ-anesthetized animals. No significant changes were noticed in the PR interval and p-wave amplitude. Sex-based significance amongst these parameters was observed in male and female animals of TZ- and KTM-anesthetized groups. Regression analysis of four QTc formulas in TZ-anesthetized rhesus monkeys revealed that QTcNAK (Nakayama) better corrected the QT interval than QTcHAS (Hassimoto), QTcBZT (Bazett), and QTcFRD (Fridericia) formulas. QTcNAK exhibited the least correlation with the RR interval (slope closest to zero and r = .01) and displayed no statistical significance between male and female animals. These data will prove useful in the selection of anesthetic regimens for chemical restraint of rhesus monkeys in nonclinical safety evaluation studies.

Attached Oral Mucosal Wound Closure using Blue Glue - A Prospective Clinical Study.

Introduction: Traditionally, sutures have been widely used to close intraoral wounds. Various alternatives have been developed amongst which newer tissue adhesives such as N-butyl-2-cyanoacrylate having accepted clinical properties are gaining popularity. The primary purpose of the present study is to evaluate the efficacy of N-butyl-2-cyanoacrylate for intraoral attached mucosal wound closure following alveoloplasty. Materials and Methods: In this prospective split-mouth study, 25 patients requiring alveoloplasty in either maxillary or mandibular arch bilaterally with a total of 50 sites were divided into two equal groups, namely silk suture (Group 1) and cyanoacrylate (Group 2). Each patient was evaluated on the first, third, seventh, 14th and 21st post-operative days. Parameters evaluated were time taken to close incision and to achieve haemostasis, pain, oedema, post-operative wound healing, patient discomfort and possible complications. Results: Time taken to close incision, time taken to achieve haemostasis, post-operative pain and oedema were found to be less in Group 2. Wound healing too was found to be better in Group 2. There was one case of adhesive peel off on the first post-operative day which was managed by reapplying the tissue adhesive. The incidence of wound dehiscence and wound infection was observed more in Group 1 on the third post-operative day. Suture breakage (16%) and adhesive dislodgement (8%) were reported on the seventh post-operative day. Discussion: The use of cyanoacrylates' inherent benefits, such as improved wound seal off in attached mucosa, quick polymerisation and bacteriostatic characteristics can be beneficial when performing minor oral surgical procedures on elderly, young and mentally challenged patients.

Methodology of a Natural History Study of a Rare Neurodevelopmental Disorder: Alternating Hemiplegia of Childhood as a Prototype Disease.

Here, we describe the process of development of the methodology for an international multicenter natural history study of alternating hemiplegia of childhood as a prototype disease for rare neurodevelopmental disorders. We describe a systematic multistep approach in which we first identified the relevant questions about alternating hemiplegia of childhood natural history and expected challenges. Then, based on our experience with alternating hemiplegia of childhood and on pragmatic literature searches, we identified solutions to determine appropriate methods to address these questions. Specifically, these solutions included development and standardization of alternating hemiplegia of childhood-specific spell video-library, spell calendars, adoption of tailored methodologies for prospective measurement of nonparoxysmal and paroxysmal manifestations, unified data collection protocols, centralized data platform, adoption of specialized analysis methods including, among others, Cohen kappa, interclass correlation coefficient, linear mixed effects models, principal component, propensity score, and ambidirectional analyses. Similar approaches can, potentially, benefit in the study of other rare pediatric neurodevelopmental disorders.

The New Era of Long-Acting Antiretroviral Therapy: When and Why to Make the Switch.

PURPOSE OF REVIEW: Despite the availability of safe and effective oral combination antiretroviral therapy, barriers to maintaining viral suppression remain a challenge to ending the HIV epidemic. Long-acting injectable antiretroviral therapy was developed as an alternative to daily oral therapy. This review summarizes the current literature on the efficacy of long-acting cabotegravir plus rilpivirine for the treatment of HIV-1, reasons to switch to injectable therapy, and barriers to switching. RECENT FINDINGS: Long-acting cabotegravir plus rilpivirine is safe and effective in maintaining HIV-1 virologic suppression. Ideal candidates for switching to long-acting cabotegravir plus rilpivirine are virologically suppressed on oral regimens with good adherence and no history of virologic failure or baseline resistance. Indications to switch to injectable therapy include patient preference, the potential for improved adherence, and avoidance of adverse effects. Implementation research is needed to assess and overcome system barriers. Long-acting cabotegravir plus rilpivirine is a novel alternative to oral antiretrovirals, with the potential to improve adherence and quality of life in people with HIV.

Development and testing of methods to record and follow up spells in patients with alternating hemiplegia of childhood.

BACKGROUND: Developing methods to record Alternating Hemiplegia of Childhood (AHC) spells is essential for clinical trials and patient care. OBJECTIVES: Test the following hypotheses: 1) Video-library training improves participants' ability to correctly identify AHC spells. 2) A custom-designed event-calendar with weekly reviews results in consistent documentation of such events over time. 3) Use of an electronic diary (e-Diary) to register events is a useful tool. METHODS: 1) A video-library of AHC type spells was developed along with specific training; the effect of the training was tested in 36 caregivers. 2) An event-calendar was similarly developed and provided to 5 caregivers with weekly videoconference meetings for 8 weeks. 3) An e-Diary was developed and offered to 33 patients; time of usage and caregivers' feedback (telephone interview) were analyzed. RESULTS: 1) Video-library training: Wilcoxon test showed improvement in caregiver identification of spells (p = 0.047), Cohen's Kappa demonstrated high degree of agreement between caregivers'-experts' classifications (>0.9). 2) Event-calendar: 96.42% of entries had complete information; this did not change during follow up (p = 0.804). 3) e-Diary: whereas 52% of respondents used the e-Diary when offered (duration: 10.5 ± 8.1 months), 96.3% indicated they would use it in future studies. Those who used it for 13 months, were very likely to use it during the rest of that year. CONCLUSIONS: Video-library training improved spell identification. Calendar with weekly reviews resulted in a sustained and consistent record keeping. Caregivers' e-Diary feedback was encouraging with long-term usage in many. These approaches could be helpful for AHC and, potentially, in similar disorders.

Comparison of different QT correction methods for nonclinical safety assessment in ketamine-anesthetized Indian rhesus monkeys (Macaca mulatta).

Rhesus monkeys are a non-rodent species employed in the preclinical safety evaluation of pharmaceuticals and biologics. These nonhuman primate species have been increasingly used in biomedical research because of the similarity in their ionic mechanisms of repolarization with humans. Heart rate and QT interval are two primary endpoints in determining the pro-arrhythmic risk of drugs. As heart rate and QT interval have an inverse relationship, any change in heart rate causes a subsequent change in QT interval. This warrants for calculation of a corrected QT interval. This study aimed to identify an appropriate formula that best corrected QT for change in heart rate. We employed seven formulas based on source-species type, clinical relevance, and requirements of various international regulatory guidelines. Data showed that corrected QT interval values varied drastically for different correction formulas. Equations were compared on their slope values based on QTc versus RR plots. The rank order of the slope for different formulas was (closest to farthest from zero) QTcNAK, QTcHAS, QTcBZT, QTcFRD, QTcVDW, QTcHDG, and QTcFRM. QTcNAK emerged to be the best correcting formula in this study. It showed the least correlation with the RR interval (r = -0.01) and displayed no significant difference amongst the sexes. As there is no universally recognized formula for preclinical use, the authors recommend developing a best-case scenario model for specific study designs and individual organizations. The data from this research will be helpful in deciding an appropriate QT correction formula for the safety assessment of new pharmaceuticals and biologics.

A randomized, controlled Phase 1b trial of the Sm-TSP-2 Vaccine for intestinal schistosomiasis in healthy Brazilian adults living in an endemic area.

BACKGROUND: Recombinant Schistosoma mansoni Tetraspanin-2 formulated on Alhydrogel (Sm-TSP-2/Alhydrogel) is being developed to prevent intestinal and hepatic disease caused by S. mansoni. The tegumentary Sm-TSP-2 antigen was selected based on its unique recognition by cytophilic antibodies in putatively immune individuals living in areas of ongoing S. mansoni transmission in Brazil, and preclinical studies in which vaccination with Sm-TSP-2 protected mice following infection challenge. METHODS: A randomized, observer-blind, controlled, Phase 1b clinical trial was conducted in 60 healthy adults living in a region of Brazil with ongoing S. mansoni transmission. In each cohort of 20 participants, 16 were randomized to receive one of two formulations of Sm-TSP-2 vaccine (adjuvanted with Alhydrogel only, or with Alhydrogel plus the Toll-like receptor-4 agonist, AP 10-701), and 4 to receive Euvax B hepatitis B vaccine. Successively higher doses of antigen (10 µg, 30 µg, and 100 µg) were administered in a dose-escalation fashion, with progression to the next dose cohort being dependent upon evaluation of 7-day safety data after all participants in the preceding cohort had received their first dose of vaccine. Each participant received 3 intramuscular injections of study product at intervals of 2 months and was followed for 12 months after the third vaccination. IgG and IgG subclass antibody responses to Sm-TSP-2 were measured by qualified indirect ELISAs at pre- and post-vaccination time points through the final study visit. RESULTS: Sm-TSP-2/Alhydrogel administered with or without AP 10-701 was well-tolerated in this population. The most common solicited adverse events were mild injection site tenderness and pain, and mild headache. No vaccine-related serious adverse events or adverse events of special interest were observed. Groups administered Sm-TSP-2/Alhydrogel with AP 10-701 had higher post-vaccination levels of antigen-specific IgG antibody. A significant dose-response relationship was seen in those administered Sm-TSP-2/Alhydrogel with AP 10-701. Peak anti-Sm-TSP-2 IgG levels were observed approximately 2 weeks following the third dose, regardless of Sm-TSP-2 formulation. IgG levels fell to low levels by Day 478 in all groups except the 100 µg with AP 10-701 group, in which 57% of subjects (4 of 7) still had IgG levels that were ≥4-fold higher than baseline. IgG subclass levels mirrored those of total IgG, with IgG1 being the predominant subclass response. CONCLUSIONS: Vaccination of adults with Sm-TSP-2/Alhydrogel in an area of ongoing S. mansoni transmission was safe, minimally reactogenic, and elicited significant IgG and IgG subclass responses against the vaccine antigen. These promising results have led to initiation of a Phase 2 clinical trial of this vaccine in an endemic region of Uganda. TRIAL REGISTRATION: NCT03110757.

Is "Bite force" a reliable parameter to compare masticatory efficiency restoration following ORIF of anterior mandibular fractures?

Objectives: Mandible is an integral part of masticatory system, and it is expected that it's fracture will have a significant impact on occlusal forces, range of motion, muscle activity levels, and occlusion. The main objective of this study was to compare the efficacy of 3-dimensional (3D) miniplate and conventional miniplates for fixation of anterior mandibular fractures on the basis of bite force as a main parameter. Methods: 66 patients having isolated anterior mandibular fractures were randomized into two groups equally: Conventional miniplates and 3D miniplates. The bite force at incisor, canine, and molar regions was measured preoperatively and postoperatively at weekly intervals until the sixth week, and the mean bite force as well as changes in mean bite force were compared between two groups. Results: An increase in bite force was noted at each subsequent follow up in both the groups across all sites. Statistically significant difference was found in mean bite force values between both the groups during mid-follow up period. The difference in changes in the mean bite force too was observed to be statistically significant during the mid to late follow up period. Interpretation & conclusion: Bite force is a reliable parameter to assess restoration of masticatory efficiency following open reduction and internal fixation (ORIF). 3D miniplates when used in anterior mandibular fractures management are efficient enough to withstand masticatory forces throughout the healing process, providing better stability of fractured segments against torsional forces during immediate post-operative period.

Evaluation of Efficacy of Ultrasonography as an Additional Diagnostic Tool for Deciding Management Protocol of Odontogenic Superficial Fascial Space Infections: A Prospective Clinical Study.

Objective: To explore the efficacy of ultrasonography as an additional diagnostic tool in superficial odontogenic fascial space infections of maxillofacial region and modifying the treatment plan when needed. Materials and Methods: Forty patients with superficial fascial space infections underwent a detailed clinical, plain radiological and ultrasonographic examination. Based on the ultrasonographic findings, final diagnosis was made and compared with clinical findings. Patients diagnosed with cellulitis were given medical line of treatment, and those with abscess were subjected to incision and drainage along with standard general supportive care and removal of etiologic agent. Results: In this study, out of 40 patients (male = 22, female = 18), clinical diagnosis of cellulitis was made in 26 cases (65%) and abscess in 14 (35.0%). On USG examination, cellulitis was present in 21 cases (52.5%), while abscess in 19 (47.5%). Final diagnosis of cellulitis was made in 13 (59.1%) males and 12(66.7%) females, while abscess was confirmed in 9 (40.9%) male and 6 (33.3%) female patients. The results showed that sensitivity of the clinical examination alone was 64% with 33% specificity, and for USG, sensitivity was 84% with specificity of 100%. Conclusion: The adjuvant role of ultrasonography in the diagnosis and timely management of superficial fascial space infections is promising owing to its accessibility, relative safety, repeatability and cost-effectiveness.

Evaluation of Anatomic Features and Assessment Tools to Determine Treatment of Ankyloglossia.

Purpose: To evaluate the use of lingual frenotomy assessment tools and the anatomical features most commonly used by dentists and otolaryngologists to determine if a frenotomy was indicated.
Methods: A nine-question survey was distributed to American Academy of Pediatric Dentistry members and otolaryngologists in the American Medical Association. The survey consisted of three categories: (1) demographics; (2) use of a standardized assessment tool; and (3) assessing anatomical features for frenotomy. Three different cases of ankyloglossia were given to assess which anatomical features were used to determine if a frenotomy was needed.
Results: Subjects included 404 practitioners. The most common frenotomy assessment tool utilized was the Hazelbaker assessment tool, followed by the LATCH and Bristol tongue assessment tools. The anatomical features used by most responders in determining if a frenotomy was indicated were the appearance of the tongue when lifted, tongue protrusion, frenulum length, and frenulum type.
Conclusions: Many practitioners believe frenotomies for ankyloglossia are indicated when there is a functional impairment and an anatomical component. This study suggests that the general appearance of the tongue when lifted is the most common anatomical feature used for assessing the need for a frenotomy.

A Community-Based Management of COVID-19 in a Mobile Container Unit.

Vaccine uptake is a multifactor measure of successful immunization outcomes that includes access to healthcare and vaccine hesitancy for both healthcare workers and communities. The present coronavirus disease (COVID-19) pandemic has highlighted the need for novel strategies to expand vaccine coverage in underserved regions. Mobile clinics hold the promise of ameliorating such inequities, although there is a paucity of studies that validate environmental infection in such facilities. Here, we describe community-based management of COVID-19 through a Smart Pod mobile clinic deployed in an underserved community area in the United States (Aldine, Harris County, TX, USA). In particular, we validate infection control and biological decontamination of the Smart Pod by testing surfaces and the air-filtration system for the COVID-19 virus and bacterial pathogens. We show the Smart Pod to be efficacious in providing a safe clinical environment for vaccine delivery. Moreover, in the Smart Pod, up-to-date education of community healthcare workers was provided to reduce vaccine hesitancy and improve COVID-19 vaccine uptake. The proposed solution has the potential to augment existing hospital capacity and combat the COVID-19 pandemic locally and globally.

Peonidin-3-O-glucoside and cyanidin increase osteoblast differentiation and reduce RANKL-induced bone resorption in transgenic medaka.

Experimental and clinical studies suggest a positive impact of anthocyanins on bone health; however, the mechanisms of anthocyanins altering the differentiation and function of osteoblasts and osteoclasts are not fully understood. This work demonstrates that dietary anthocyanins and resveratrol increased proliferation of cultured human hFOB 1.19 osteoblasts. In addition, treatment of serum starvation of hFOB osteoblasts with anthocyanins and resveratrol at 1.0 µg/ml reduced apoptosis, the Bax/Bcl-2 ratio, p53, and HDAC1 expression, but increased SIRT1/3 and PGC1α mRNA expression, suggesting mitochondrial and epigenetic regulation. In Sp7/osterix:mCherry transgenic medaka, peonidin-3-O-glucoside and resveratrol increased osteoblast differentiation and increased the expression of Sp7/osterix. Cyanidin, peonidin-3-O-glucoside, and resveratrol also reduced RANKL-induced ectopic osteoclast formation and bone resorption in col10α1:nlGFP/rankl:HSE:CFP medaka in doses of 1-4 µg/ml. The results indicate that both cyanidin and peonidin-3-O-glucoside have anabolic effects on bone, increasing osteoblast proliferation and differentiation, mitochondrial biogenesis, and by altering the osteoblast epigenome. Cyanidin and peonidin-3-O-glucoside also reduced RANKL-induced bone resorption in a transgenic medaka model of bone resorption. Thus, peonidin-3-O-glucoside and cyanidin appear to both increase bone formation and reduce bone loss, suggesting that they be further investigated as potential treatments for osteoporosis and osteomalacia.