Caloric restriction mitigates age-associated senescence characteristics in subcutaneous adipose tissue-derived stem cells.

Adipose tissue regulates metabolic balance, but aging disrupts it, shifting fat from insulin-sensitive subcutaneous to insulin-resistant visceral depots, impacting overall metabolic health. Adipose-derived stem cells (ASCs) are crucial for tissue regeneration, but aging diminishes their stemness and regeneration potential. Our findings reveal that aging is associated with a decrease in subcutaneous adipose tissue mass and an increase in the visceral fat depots mass. Aging is associated with increase in adipose tissue fibrosis but no significant change in adipocyte size was observed with age. Long term caloric restriction failed to prevent fibrotic changes but resulted in significant decrease in adipocytes size. Aged subcutaneous ASCs displayed an increased production of ROS. Using mitochondrial membrane activity as an indicator of stem cell quiescence and senescence, we observed a significant decrease in quiescence ASCs with age exclusively in subcutaneous adipose depot. In addition, aged subcutaneous adipose tissue accumulated more senescent ASCs having defective autophagy activity. However, long-term caloric restriction leads to a reduction in mitochondrial activity in ASCs. Furthermore, caloric restriction prevents the accumulation of senescent cells and helps retain autophagy activity in aging ASCs. These results suggest that caloric restriction and caloric restriction mimetics hold promise as a potential strategy to rejuvenate the stemness of aged ASCs. Further investigations, including in vivo evaluations using controlled interventions in animals and human studies, will be necessary to validate these findings and establish the clinical potential of this well-established approach for enhancing the stemness of aged stem cells.

Reprogramming of astrocytes to neuronal-like cells in spinal cord injury: a systematic review.

STUDY DESIGN: A Systematic Review OBJECTIVES: To determine the therapeutic efficacy of in vivo reprogramming of astrocytes into neuronal-like cells in animal models of spinal cord injury (SCI). METHODS: PRISMA 2020 guidelines were utilized, and search engines Medline, Web of Science, Scopus, and Embase until June 2023 were used. Studies that examined the effects of converting astrocytes into neuron-like cells with any vector in all animal models were included, while conversion from other cells except for spinal astrocytes, chemical mechanisms to provide SCI models, brain injury population, and conversion without in-vivo experience were excluded. The risk of bias was calculated independently. RESULTS: 5302 manuscripts were initially identified and after eligibility assessment, 43 studies were included for full-text analysis. After final analysis, 13 manuscripts were included. All were graded as high-quality assessments. The transduction factors Sox2, Oct4, Klf4, fibroblast growth factor 4 (Fgf4) antibody, neurogenic differentiation 1 (Neurod1), zinc finger protein 521 (Zfp521), ginsenoside Rg1, and small molecules (LDN193189, CHIR99021, and DAPT) could effectively reprogramme astrocytes into neuron-like cells. The process was enhanced by p21-p53, or Notch signaling knockout, valproic acid, or chondroitin sulfate proteoglycan inhibitors. The type of mature neurons was both excitatory and inhibitory. CONCLUSION: Astrocyte reprogramming to neuronal-like cells in an animal model after SCI appears promising. The molecular and functional improvements after astrocyte reprogramming were demonstrated in vivo, and further investigation is required in this field.

Metformin and adipose-derived stem cell combination therapy alleviates radiation-induced skin fibrosis in mice.

BACKGROUND: Radiation therapy often leads to late radiation-induced skin fibrosis (RISF), causing movement impairment and discomfort. We conducted a comprehensive study to assess the effectiveness of metformin and adipose-derived stem cells (ASCs), whether autologous or allogeneic, individually or in combination therapy, in mitigating RISF. METHODS: Using a female C57BL/6J mouse model subjected to hind limb irradiation as a representative RISF model, we evaluated metformin, ASCs, or their combination in two contexts: prophylactic (started on day 1 post-irradiation) and therapeutic (initiated on day 14 post-irradiation, coinciding with fibrosis symptoms). We measured limb movement, examined skin histology, and analyzed gene expression to assess treatment efficacy. RESULTS: Prophylactic metformin and ASCs, whether autologous or allogeneic, effectively prevented late fibrosis, with metformin showing promising results. However, combination therapy did not provide additional benefits when used prophylactically. Autologous ASCs, alone or with metformin, proved most effective against late-stage RISF. Prophylactic intervention outperformed late therapy for mitigating radiation skin damage. Co-culture studies revealed that ASCs and metformin downregulated inflammation and fibrotic gene expression in both mouse and human fibroblasts. CONCLUSIONS: Our study suggests metformin's potential as a prophylactic measure to prevent RISF, and the combination of ASCs and metformin holds promise for late-stage RISF treatment. These findings have clinical implications for improving the quality of life for those affected by radiation-induced skin fibrosis.

A systematic review and meta-analysis of the global epidemiology of pediatric traumatic spinal cord injuries.

Despite being relatively rare, pediatric traumatic spinal cord injury (TSCI) is a debilitating event with high morbidity and long-term damage and dependency. This study aims to provide insight on the epidemiological characteristics of pediatric TSCI worldwide. The studies were included if they provided data for the pediatric population with the diagnosis of TSCI. Information sources included PubMed, Embase, Web of Science, and Scopus. All databases were searched from 1990 to April 2023. The quality of included studies was evaluated by Joanna Briggs Institute Critical Appraisal Tools. The results of the meta-analysis were presented as forest plots. PROSPERO Registration code: CRD42020189757. We identified 87 studies from 18 developed and 11 developing countries. Of the 87 studies evaluated, 52 studies were considered medium quality, 27 studies were considered high quality, and 8 studies were considered low quality. In developed countries, the proportion of TSCIs occurring in patients aged 0-15 years was 3% (95% CI: 2.2%; 3.9%), while in developing countries, it was 4.5% (95% CI: 2.8%; 6.4%). In developed countries, the pooled incidence of pediatric TSCI was 4.3/millions of children aged 0-15/year (95% CI: 3.1; 6.0/millions children aged 0-15/year) and boys comprised 67% (95% CI: 63%; 70%) of cases. The most prevalent level of injury was cervical (50% [95% CI: 41%; 58%]). The frequency of SCI Without Obvious Radiological Abnormality (SCIWORA) was 35% (95% CI: 18%; 54%) among children 0-17 years. The most common etiology in developed countries was transport injuries (50% [95% CI: 42%; 57%]), while in developing countries falls were the leading cause (31% [95% CI: 20%; 42%]). The most important limitation of our study was the heterogeneity of studies in reporting age subgroups that hindered us from age-specific analyses.   Conclusion: Our study provided accurate estimates for the epidemiology of pediatric TSCI. We observed a higher proportion of pediatric TSCI cases in developing countries compared to developed countries. Furthermore, we identified distinct epidemiological characteristics of pediatric TSCI when compared to adult cases and variations between developing and developed countries. Recognizing these unique features allows for the implementation of cost-effective preventive strategies aimed at reducing the incidence and burden of TSCI in children. What is Known: • Pediatric Traumatic Spinal Cord Injury (TSCI) can have profound physical and social consequences for affected children, their families, and society as a whole. • Epidemiological insights are vital for they provide the data and understanding needed to the identification of vulnerable populations, aiding in the development of targeted prevention strategies and effective resource allocation. What is New: • The estimated incidence of pediatric TSCI in developed countries is 4.3 cases per million children aged 0-15. The proportion of pediatric TSCI cases in relation to all-age TSCI cases is 3% in developed countries and 4.5% in developing countries. • The etiology of TSCI in pediatric cases differs between developing and developed countries. In developed countries, transport injuries are the most prevalent cause of pediatric TSCI, while falls are the least common cause. Conversely, in developing countries, falls are the leading cause of pediatric TSCI.

Human adipose ECM alleviates radiation-induced skin fibrosis via endothelial cell-mediated M2 macrophage polarization.

Radiation therapy can lead to late radiation-induced skin fibrosis (RISF), causing movement restriction, pain, and organ dysfunction. This study evaluated adipose-derived extracellular matrix (Ad-ECM) as a mitigator of RISF. Female C57BL/6J mice that were irradiated developed fibrosis, which was mitigated by a single local Ad-ECM injection, improving limb movement and reducing epithelium thickness and collagen deposition. Ad-ECM treatment resulted in decreased expression of pro-inflammatory and fibrotic genes, and upregulation of anti-inflammatory cytokines, promoting M2 macrophage polarization. Co-culture of irradiated human fibroblasts with Ad-ECM down-modulated fibrotic gene expression and enhanced bone marrow cell migration. Ad-ECM treatment also increased interleukin (IL)-4, IL-5, and IL-15 expression in endothelial cells, stimulating M2 macrophage polarization and alleviating RISF. Prophylactic use of Ad-ECM showed effectiveness in mitigation. This study suggests Ad-ECM's potential in treating chronic-stage fibrosis.

Application of Adipose-Tissue Derived Products for Burn Wound Healing.

Burn injuries are a significant global health concern, leading to high morbidity and mortality. Deep burn injuries often result in delayed healing and scar formation, necessitating effective treatment options. Regenerative medicine, particularly cell therapy using adipose-derived stem cells (ASCs), has emerged as a promising approach to improving burn wound healing and reducing scarring. Both in vitro and preclinical studies have demonstrated the efficacy of ASCs and the stromal vascular fraction (SVF) in addressing burn wounds. The application of ASCs for burn healing has been studied in various forms, including autologous or allogeneic cells delivered in suspension or within scaffolds in animal burn models. Additionally, ASC-derived non-cellular components, such as conditioned media or exosomes have shown promise. Injection of ASCs and SVF at burn sites have been demonstrated to enhance wound healing by reducing inflammation and promoting angiogenesis, epithelialization, and granulation tissue formation through their paracrine secretome. This review discusses the applications of adipose tissue derivatives in burn injury treatment, encompassing ASC transplantation, as well as the utilization of non-cellular components utilization for therapeutic benefits. The application of ASCs in burn healing in the future will require addressing donor variability, safety, and efficacy for successful clinical application.

Nicotinamide Riboside Improves Stemness of Human Adipose-Derived Stem Cells and Inhibits Terminal Adipocyte Differentiation.

Adipose tissue plays a crucial role in maintaining metabolic homeostasis by serving as a storage site for excess fat and protecting other organs from the detrimental effects of lipotoxicity. However, the aging process is accompanied by a redistribution of fat, characterized by a decrease in insulin-sensitive subcutaneous adipose depot and an increase in insulin-resistant visceral adipose depot. This age-related alteration in adipose tissue distribution has implications for metabolic health. Adipose-derived stem cells (ASCs) play a vital role in the regeneration of adipose tissue. However, aging negatively impacts the stemness and regenerative potential of ASCs. The accumulation of oxidative stress and mitochondrial dysfunction-associated cellular damage contributes to the decline in stemness observed in aged ASCs. Nicotinamide adenine dinucleotide (NAD+) is a crucial metabolite that is involved in maintaining cellular homeostasis and stemness. The dysregulation of NAD+ levels with age has been associated with metabolic disorders and the loss of stemness. In this study, we aimed to investigate the effects of nicotinamide riboside (NR), a precursor of NAD+, on the stemness of human ASCs in cell culture. Our findings reveal that adipogenesis is accompanied by an increase in mitochondrial activity and the production of reactive oxygen species (ROS). However, treatment with NR leads to a reduction in mitochondrial activity and ROS production in ASCs. Furthermore, NR administration improves the stemness-related genes expression in ASCs and mitigates their propensity for adipocyte differentiation. These results suggest that NR treatment holds promise as a potential strategy to rejuvenate the stemness of aged ASCs. Further investigations, including in vivo evaluations using animal models and human studies, will be necessary to validate these findings and establish the clinical potential of this well-established drug for enhancing the stemness of aged stem cells.

A Practical Review of the Management of Xanthelasma palpebrarum.

Xanthelasma palpebrarum is the most common type of xanthomatous lesion. Various methods for treating Xanthelasma palpebrarum have been reported. We conducted a systematic review to evaluate the efficacy and associated complications of different treatment methods, and we summarized these findings as a practical review designed to be clinically useful, accessible, and impactful. Methods: The PubMed and Embase databases were searched to identify clinical studies that reported on outcomes and complications of different methods of Xanthelasma treatment. The electronic databases were searched from January 1990 to October 2022. Data on study characteristics, lesion clearance, complications, and recurrences were collected. Results: Forty-nine articles (including 1329 patients) were reviewed. The studies reported on surgical excision, laser modalities, electrosurgical techniques, chemical peeling, cryotherapy, and intralesional injection. The majority of studies were retrospective (69%) and single-arm (84%). Surgical excision combined with blepharoplasty and skin grafts showed excellent outcomes for large Xanthelasma. CO2 and erbium yttrium aluminum garnet (Er:YAG) were the most commonly studied lasers and showed more than 75% improvement in over 90% and 80% of patients, respectively. Comparative studies reported better efficacy for CO2 laser than both Er:YAG laser and 30%-50% trichloroacetic acid. Dyspigmentation was the most encountered complication. Conclusions: Different methods for the treatment of Xanthelasma palpebrarum have been reported in the literature, with moderate to excellent efficacy and safety profiles depending on the size and location of the lesion. Surgery is more appropriate for larger and deeper lesions, whereas laser and electrosurgical techniques can be used in smaller and more superficial contexts. Only a limited number of comparative studies have been conducted, and novel clinical trials are necessary to further augment appropriate treatment selection.

Ultrasound-Guided Radiofrequency Ablation of Locally Recurrent Thyroid Carcinoma.

INTRODUCTION: We aimed to evaluate the effectiveness and safety of radiofrequency ablation (RFA) for non-surgical treatment of locally recurrent thyroid cancers, in both well-differentiated and medullary thyroid carcinomas (DTC and MTC) that are not amenable to traditional treatments. METHODS: We conducted a retrospective review of 48 patients with 103 recurrent tumors (81 DTC, 22 MTC) who underwent ultrasound-guided RFA. Patients were followed for 12-37 months to observe the outcomes and complications. RESULTS: 64 tumors (62.1%) completely disappeared at the last follow-up visit with 61 (59.2%) being resolved within 12 months. Technical success (volume reduction ratio (VRR) > 50%) was 96% (n = 99) in all tumors. The mean largest diameter of treated tumors decreased from 11.2 ± 5.3 to 2.4 ± 3.4 mm (p value < 0.001), and the mean volume decreased from 501.0 ± 807.0 to 41.6 ± 97.1 mm3 at the last follow-up (mean VRR = 91%). Our patients had a 77.1% recurrence-free survival rate (11 recurrences, 7 DTC, 4 MTC), with an overall mean recurrence-free survival time of 34.6 months (95% confidence interval, 30.0-39.1). We observed 3 cases with complications (voice changes in DTC patients) that completely resolved during follow-ups. CONCLUSION: RFA is a safe and effective alternative to repetitive surgeries in recurrent loco-regional DTCs as well as MTCs. LEVEL OF EVIDENCE: Level 3, Non-randomized controlled cohort/follow-up study.

Direct Cost of Illness for Spinal Cord Injury: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVE: Providing a comprehensive review of spinal cord injury cost of illness studies to assist health-service planning. METHODS: We conducted a systematic review of the literature published from Jan. 1990 to Nov. 2020 via Pubmed, EMBASE, and NHS Economic Evaluation Database. Our primary outcomes were overall direct health care costs of SCI during acute care, inpatient rehabilitation, within the first year post-injury, and in the ensuing years. RESULTS: Through a 2-phase screening process by independent reviewers, 30 articles out of 6177 identified citations were included. Cost of care varied widely with the mean cost of acute care ranging from $290 to $612,590; inpatient rehabilitation from $19,360 to $443,040; the first year after injury from $32,240 to $1,156,400; and the ensuing years from $4,490 to $251,450. Variations in reported costs were primarily due to neurological level of injury, study location, methodological heterogeneities, cost definitions, study populations, and timeframes. A cervical level of the injury, ASIA grade A and B, concomitant injuries, and in-hospital complications were associated with the greatest incremental effect in cost burden. CONCLUSION: The economic burden of SCI is generally high and cost figures are broadly higher for developed countries. As studies were only available in few countries, the generalizability of the cost estimates to a regional or global level is only limited to countries with similar economic status and health systems. Further investigations with standardized methodologies are required to fill the knowledge gaps in the healthcare economics of SCI.

The effect of delayed photobiomodulation on neurosensory disturbance recovery after zygomatic trauma: A parallel controlled clinical trial.

INTRODUCTION: Zygomatic fractures are usually accompanied with neural complications, which are routinely treated by surgery or medication. However, photobiomodulation has been proven as a non-invasive method with better results in nerve's regeneration and repair. Therefore, in this study, we aimed to investigate the healing effect of photobiomodulation on neurosensory defect after facial trauma. PATIENTS AND METHODS: In this parallel controlled clinical trial, 35 control cases and 36 patients with zygomaticomaxillary complex (ZMC) fractures as well as the sustained infraorbital nerve paresthesia were included. Afterward, Laser irradiation was applied using a GaAlAs diode laser (810 nm, 27 J/cm2, 200 mW) on 12 points on malar area of paresthesia during 12 sessions within six weeks. Neurosensory evaluations were performed in four sessions as follows: at baseline, the end of treatment, one month, and three months after the last session of irradiation, which were achieved through three tests including visual analogue scales (VAS) for general sensitivity, two-point discrimination, and pain discrimination. Repeated measure ANOVA, independent t-test, and Chi-square test were used for comparing time trends, each time point, and gender, respectively. P-values less than 0.05 were considered to be statistically significant. RESULTS: The patients and controls were matched in both terms of age and gender. Baseline results showed non-significant differences between the two groups based on the VAS, pain, and two-point discrimination. Moreover, for VAS scale, some significant differences were observed between the groups by passing "one month and three months from therapy". Pain and two-point discriminations showed a significant difference between the intervention and control groups in "one month after therapy" and "at the end of the therapy, one month after therapy, and three months after therapy", respectively. CONCLUSION: Photobiomodulation could be considered as an effective treatment option for post-traumatic neurosensory disturbance of facial area in terms of VAS, pain and two-point discrimination, even if not performed early after trauma.

A Novel Mutation in PEX11ß Gene.

PEX11ß ([OMIM] 614920) mutation causes an extremely rare subgroup of peroxisomal biogenesis disorders, with only six cases reported to date. In this article, we reported a patient with episodic migraine-like attacks, delirium, mood and behavior change, polyneuropathy, and history of congenital cataract. Whole exome sequencing showed novel c.743_744delTCinsA mutation in the exon 4 of the PEX11ß gene. In contrast to previously reported patients, our case presented milder features and extended the spectrum of the clinical phenotype of this mutation. This study helps to extend the phenotype of this syndrome; besides, recognizing novel mutation variants will provide a better genotype-phenotype correlation and improve clinical clues.

Trends in cardiovascular risk factors in diabetic patients in comparison to general population in Iran: findings from National Surveys 2007-2016.

To determine levels of change in risk factors for cardiovascular disease among people with and without a previous diagnosis of diabetes from 2007 to 2016 in Iran. Data were obtained from five rounds of the World Health Organization STEPwise approach to Surveillance (STEPS) cross-sectional surveys. Participants were 7665 and 93,733 adults with and without known diabetes, respectively, aged 25-65 years. We used logistic and linear regressions to assess the trends of risk factors. Individuals with known diabetes compared to those without the condition, experienced greater reductions in mean levels of systolic blood pressure (3.0 vs. 0.5 mmHg among women and 3.9 vs. 1.6 mmHg among men), diastolic blood pressure (6.4 vs. 5.11 mmHg in women and 3.3 vs. 1.8 mmHg in men), and non-HDL cholesterol (42.4 vs. 27.2 mg/dL among women and 30.3 vs. 21.0 mg/dL among men) throughout these years. Men with diabetes also showed a greater reduction in the prevalence of daily cigarette smoking compared to their non-diabetic counterparts (7.3% vs. 2.3%). Fasting plasma glucose decreased among subjects with diabetes but increased among those without diabetes. Significant increases were observed in proportions who met goals for blood pressure, triglycerides, non-HDL cholesterol and LDL cholesterol in both groups; however, almost half of diabetic subjects did not achieve risk factor goals in 2016. Secondary prevention in diabetic patients was more effective than primary prevention in the general population; however, the rate of diabetic patients who met the designated goals for each risk factor was still suboptimal.

Ghosal Hematodiaphyseal Dysplasia: A Case Report.

Ghosal hematodiaphyseal dysplasia (GHDD) is a rare autosomal recessive disorder presenting with steroid-responsive anemia and diaphyseal dysplasia of long bones. We report a 3-year-old Iranian girl with refractory anemia, splenomegaly and radiologic signs of metadiaphyseal dysplasia in long bones. The diagnosis was established by clinical presentation and X-ray bone survey. The patient was treated with oral prednisolone therapy with considerable improvement in anemia and splenomegaly.

Evaluation and comparison of the effect of honey, milk and combination of honey-milk on experimental induced second-degree burns of Rabit.

INTRODUCTION: Burn can happen in any area and causes dominant changes in the quality of normal tissues. The aim of present article is evaluation and comparison the effect of milk, natural honey, and combination of honey-milk on healing of burnt wound. METHOD AND MATERIAL: A 4-week trial study was carried out on 10 Albino New Zealand rabbits. All dry burned wound was created on the back of the scapula by a 1 * 1 cm metal block. First group received honey dressing, second group milk dressing, third group honey-milk dressing, and the fourth group 5% sulfadiazine dressing. Sampling was performed at days 1, 10, and 20. Measurement of wound size was done in days 1, 7, 14, 21, 28. The obtained data and information were analyzed by two-way ANOVA and Duncan tests using SPSS. RESULTS: Result show that combination of milk-honey dressing had most significant effect on the improvement of wound healing in the recipient rabbits after a 4-week study. The size of burn wound in four different group was: Honey milk combination 0.428 cm2, honey 0.547 cm2, milk 0.579 cm2 and sulfadiazine 0.873 cm2. CONCLUSION: All dressing can accelerate wound healing and have promotive effect on wound healing but the combination of honey-milk had the greatest effect. Honey, milk, and sulfadiazine had next grade of effectiveness.

The starting point for bisphosphonate-related osteonecrosis of the jaw: Alveolar bone or oral mucosa? A randomized, controlled experimental study.

OBJECTIVE: Although over a decade has passed since first introduction of BRONJ, the exact pathophysiology of this disease is still unclear. The present experimental study aimed to determine whether the oral mucosa or alveolar bone serves as the starting point for BRONJ development. SUBJECTS AND METHODS: Sixty male Wistar rats were randomly assigned into study and control groups (each, n = 30), and received intraperitoneal injection of 0.06 mg/kg zoledronate and saline, respectively, once a week for 12 weeks. At the end of the week 4 of the experiment, all 60 rats underwent unilateral mandibular first molar extraction. A 4 mm defect was made in the contralateral canine alveolar mucosa. At the end of the experiment, rats were sacrificed, and the three areas of interest including extraction, soft tissue defect, and the non-intervention (canine area on the same side of extraction) sites were assessed clinically for presence of bone exposure/fistula, and histologically for status of bone remodeling (only at extraction site) and osteonecrosis. RESULTS: In the study group, the frequency of bone exposure/fistula was 80%, 0%, and 0%; and the rate of histological bone necrosis was 83.3%, 20%, and 0%; at the extraction, soft tissue defect, and non-intervention sites, respectively. No clinical and histological sign of bone necrosis was found in the control group. Normal bone remodeling was observed in 0% and 100% of the extraction sockets in the study and control groups, respectively. CONCLUSION: Injury to alveolar bone was a stronger trigger for BRONJ development compared to oral mucosal damages.

Introducing a protocol to create bisphosphonate-related osteonecrosis of the jaw in rat animal model.

OBJECTIVE: Previously published animal investigations on bisphosphonate-related osteonecrosis of the jaws (BRONJ) showed a variety of methods for BRONJ induction and inconsistent findings. The aim of present study was to develop a reliable protocol for BRONJ induction in rat animal model. SUBJECTS AND METHODS: In a pilot study, 64 rats were randomly divided into 4 groups and 16 subgroups (each containing 2 experimental and 2 control rats) based on the timing of tooth extraction and euthanasia. The experimental and control rats received intraperitoneal injection of 0.06 mg/kg zoledronate and saline, respectively, once a week until sacrificed, and evaluated for presence of bone exposure clinically, and osteonecrosis and new bone formation histologically. The protocol that successfully produced BRONJ in pilot study was tested in a randomized controlled experimental investigation using 45 rats. RESULTS: In pilot investigation, the highest rate of BRONJ was obtained after four weekly zoledronate injections, at least 4 weeks after tooth extraction. The randomized controlled experimental study verified this finding with a success rate of 83%, and also showed that more prolongation of zoledronate therapy did not increase the BRONJ rate. CONCLUSION: The protocol developed in the present study could be used reliably for future BRONJ investigations on rats.

Perioperative discontinuation of intravenous bisphosphonate therapy reduces the incidence and severity of bisphosphonate-related osteonecrosis of the jaw: A randomized, controlled, prospective experimental study in rats.

OBJECTIVE: To evaluate the effects of intravenous bisphosphonate discontinuation on incidence and severity of bisphosphonate-related osteonecrosis of the jaw (BRONJ). MATERIAL AND METHODS: Seventy rats were randomly divided into 7 groups. In control and S0 groups, weekly injection of saline and 0.06 mg/kg zoledronate (respectively) for 4 weeks, tooth extraction, continuation of injections for 2 months and euthanasia were performed. In group S1, zolendronate injection for 4 weeks, tooth extraction, zolendronate discontinuation for 2 months, and euthanasia were done. For groups S2, S3, S4, and S5, zolendronate injections for 4 weeks, drug holiday for 1-4 months (respectively) before and 2 months after tooth extraction, and euthanasia were performed. Presence of bone exposure, osteonecrosis, and new bone formation were clinically and histologically evaluated. RESULTS: The rate of BRONJ in control, S0, S1, S2, S3, S4, and S5 groups was 0%, 85%, 80%, 65%, 60%, 50%, and 40%, respectively. In control group, epithelial healing, bone formation, and absence of osteonecrosis; and in S0 group, unhealed epithelium, osteonecrosis, and impaired bone formation were histologically observed. In study groups, prolongation of drug holiday caused diminished osteonecrosis, and improved bone and epithelial healing. CONCLUSION: Zolendronate discontinuation significantly decreased the incidence and severity of BRONJ in rats.

Evaluation of third molar development and its relation to chronological age: a panoramic radiographic study.

INTRODUCTION: Third molar development, in comparison to other teeth in the dentition, has the greatest variation in morphology, anatomical position, and time of development and eruption, and its reliability for chronological age estimation is controversial. The aim of the present study was to evaluate third molar development and its relation to chronological age using panoramic radiography. MATERIAL AND METHODS: A total of 2536 digital panoramic radiographs of individuals aged between 5 and 26 years were selected. The developmental status of the third molars was assessed using eight-stage developmental scoring proposed by Demirjian et al., with one modification: a stage 0 was added. The collected data were entered into a checklist and subjected to statistical analyses. RESULTS: The mean ages of the first appearance of third molar bud, complete crown formation, and root apex closure were around 9, 14, and 22 years, respectively. In both jaws, third molar development occurred symmetrically, and sexual dimorphism was observed at some developmental stages. Finally, two formulas were presented to estimate age of the juveniles and adolescents based on their gender and developmental stages of the third molars, and validated on a second sample consisting of 523 individuals aged between 8 and 22. CONCLUSION: Assessment of third molar development was found to be a reliable method for age estimation of individuals between 11 and 22 years. Because of possible ethnic and geographic differences in third molar development, population specific researches were recommended.