Dilemma with implant placement in patients with florid cemento-osseous dysplasia: A literature review.

METHODOLOGY: An electronic search was done in PUBMED, SCOPUS, and a hand search was done in radiology, periodontology, and oral surgery journals. The search yielded 428 results, from which only 6 articles were selected for this literature review. Both prospective and retrospective studies were included. Clinical studies with information on the pre-implant condition of the site, detailed implant procedure, and follow-up after implant placement of more than 6 months were only considered for this review. RESULTS AND CONCLUSION: Limited clinical studies, shorter follow-up periods were the shortcomings of this review. However, it can be summarized that dental implants should not be placed at the site of FCOD, however can be placed at adjacent sites. Variations in implant type or the implant length had no bearing on the survival of implants at the sites of FCOD.

Immune Inhibitory Molecule PD-1 Homolog (VISTA) Colocalizes with CD11b Myeloid Cells in Melanoma and Is Associated with Poor Outcomes.

Tumors evade immunity through the overexpression of immune inhibitory molecules in the tumor microenvironment such as PD-L1/B7-H1. An immune inhibitory molecule named PD-1 homolog (also known as V-domain Ig-containing suppressor of T cell activation [VISTA]) functions to control both T cells and myeloid cells. Current clinical trials using anti-VISTA-blocking agents for treatment of cancer are ongoing. We sought to determine the extent of VISTA expression in primary cutaneous melanomas (n = 190), identify the critical cell types expressing VISTA, and correlate its expression with PD-L1 expression using multiplexed quantitative immunofluorescence. Within the tumor subcompartments, VISTA is most highly expressed on CD11b myeloid cells, and PD-L1 is most highly expressed on CD68 myeloid cells in our melanoma cohort. There is little correlation between VISTA and PD-L1 expression intensity, suggesting that individual tumors have distinct immunosuppressive tumor microenvironments. High levels of VISTA expression on CD11b myeloid cells but not PD-L1 expression were associated with greater melanoma recurrence and greater all-cause mortality. Our findings suggest that cell-specific VISTA expression may be a negative prognostic biomarker for melanoma and a future potential therapeutic target.

An IQ Consortium Perspective on Best Practices for Bioanalytical and Immunogenicity Assessment Aspects of CAR-T and TCR-T Cellular Therapies Development.

CAR-T therapies have shown remarkable efficacy against hematological malignancies in the clinic over the last decade and new studies indicate that progress is being made to use these novel therapies to target solid tumors as well as treat autoimmune disease. Innovation in the field, including TCR-T, allogeneic or "off the shelf" CAR-T, and autoantigen/armored CAR-Ts are likely to increase the efficacy and applications of these therapies. The unique aspects of these cell-based therapeutics; patient-derived cells, intracellular expression, in vivo expansion, and phenotypic changes provide unique bioanalytical challenges to develop pharmacokinetic and immunogenicity assessments. The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) Translational and ADME Sciences Leadership Group (TALG) has brought together a group of industry experts to discuss and consider these challenges. In this white paper, we present the IQ consortium perspective on the best practices and considerations for bioanalytical and immunogenicity aspects toward the optimal development of CAR-T and TCR-T cell therapies.

Protocol for a systematic review and meta-analysis of tobacco-cessation interventions delivered perioperatively.

INTRODUCTION: Tobacco smoking is associated with a substantially increased risk of perioperative complications. The perioperative period is an opportunity to introduce tobacco-cessation strategies. A previous systematic review provided evidence that perioperative interventions increase short-term abstinence and may reduce postoperative complications. The evidence base has since expanded, with the subsequent publication of numerous randomised studies. This protocol outlines a systematic review examining the impact of perioperative tobacco-cessation interventions on successful abstinence from tobacco smoking, and on the incidence of perioperative complications. METHODS AND ANALYSIS: A systematic search of the literature will be run across EMBASE (Ovid), MEDLINE (Ovid), CINAHL (Ebsco) and PsycInfo (ProQuest), from inception to present, using text words and subject headings. Randomised controlled trials published in English, examining adults in the perioperative period and reporting the outcomes from tobacco-cessation interventions will be included.Abstract screening and data extraction will be performed by five reviewers. Each abstract will be screened by two blinded reviewers, with discrepancies resolved by group consensus. The primary outcome will be point prevalence abstinence from tobacco-use at the time of surgery. Secondary outcomes are prolonged abstinence from tobacco use at 6 months and 12 months, and postoperative complications. Any other reported outcomes will be documented in the descriptive analysis. The review will also describe details of the investigated perioperative tobacco-cessation interventions. If sufficient studies report relevant data, meta-analysis of the primary and secondary outcomes will be undertaken. Results will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. ETHICS AND DISSEMINATION: No ethical approval is required. Results will be disseminated by open-access, peer-reviewed journal publication and conference presentations. Results will underpin future work to modify perioperative tobacco-cessation interventions to enhance engagement and accessibility, and to develop trials aiming to facilitate abstinence from tobacco-use in patients presenting for surgery.

Best Practices and Considerations for Clinical Pharmacology and Pharmacometric Aspects for Optimal Development of CAR-T and TCR-T Cell Therapies: An Industry Perspective.

With the promise of a potentially "single dose curative" paradigm, CAR-T cell therapies have brought a paradigm shift in the treatment and management of hematological malignancies. Both CAR-T and TCR-T cell therapies have also made great progress toward the successful treatment of solid tumor indications. The field is rapidly evolving with recent advancements including the clinical development of "off-the-shelf" allogeneic CAR-T therapies that can overcome the long and difficult "vein-to-vein" wait time seen with autologous CAR-T therapies. There are unique clinical pharmacology, pharmacometric, bioanalytical, and immunogenicity considerations and challenges in the development of these CAR-T and TCR-T cell therapies. Hence, to help accelerate the development of these life-saving therapies for the patients with cancer, experts in this field came together under the umbrella of International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) to form a joint working group between the Clinical Pharmacology Leadership Group (CPLG) and the Translational and ADME Sciences Leadership Group (TALG). In this white paper, we present the IQ consortium perspective on the best practices and considerations for clinical pharmacology and pharmacometric aspects toward the optimal development of CAR-T and TCR-T cell therapies.

PK/PD and Bioanalytical Considerations of AAV-Based Gene Therapies: an IQ Consortium Industry Position Paper.

Interest and efforts to use recombinant adeno-associated viruses (AAV) as gene therapy delivery tools to treat disease have grown exponentially. However, gaps in understanding of the pharmacokinetics/pharmacodynamics (PK/PD) and disposition of this modality exist. This position paper comes from the Novel Modalities Working Group (WG), part of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ). The pan-industry WG effort focuses on the nonclinical PK and clinical pharmacology aspects of AAV gene therapy and related bioanalytical considerations.Traditional PK concepts are generally not applicable to AAV-based therapies due to the inherent complexity of a transgene-carrying viral vector, and the multiple steps and analytes involved in cell transduction and transgene-derived protein expression. Therefore, we explain PK concepts of biodistribution of AAV-based therapies and place key terminologies related to drug exposure and PD in the proper context. Factors affecting biodistribution are presented in detail, and guidelines are provided to design nonclinical studies to enable a stage-gated progression to Phase 1 testing. The nonclinical and clinical utility of transgene DNA, mRNA, and protein analytes are discussed with bioanalytical strategies to measure these analytes. The pros and cons of qPCR vs. ddPCR technologies for DNA/RNA measurement and qualitative vs. quantitative methods for transgene-derived protein are also presented. Last, best practices and recommendations for use of clinical and nonclinical data to project human dose and response are discussed. Together, the manuscript provides a holistic framework to discuss evolving concepts of PK/PD modeling, bioanalytical technologies, and clinical dose selection in gene therapy.

Tobacco cessation center in a dental college: An 8 year institution-based study.

Background: Oral cancer is a major health concern in the Indian subcontinent, where it ranks among the top three types of cancer in the country. Tobacco and its products have been implicated as a major etiologic factor behind cancers. It is believed that tobacco is an epidemic in itself taking the death toll to 7 million globally. In India alone, mortality because of tobacco is more than 1.3 million. Dentists are the first to notice any change in the oral cavity or come across any suspicious looking oral lesion and therefore are instrumental in primary prevention and care. Methods: The present study data are of the patients enrolled in a Tobacco Cessation Center(TCC) at a Dental College in Meerut in Meerut from May 2012 (since its inception) to March 2020. The following methods of counseling were carried out: group counseling, interactive sessions, audio-visual aids, and individual counseling sessions. Self-training for oral cavity examination was also given after every group counseling session. Behavioral counseling and pharmacological intervention were given as per Fagerström Test for Nicotine Dependence (FTND) score. At the end of 1 year, patients who quit were graded into 0, 1, and 2, with 0 for those who failed to quit, 1 for those who did completely quit, and 2 for those who reduced their habit by more than 50%. Results: The quit rate achieved was 57.6% (complete responders -43.2% and partial responders 14.4%). The relapse reported was 1.8%. Conclusion: A Tobacco cessation Center set up in a Dental College could be of great help in the primary prevention of oral cancer and can bring a drastic increase in quit rates. Proper counseling skills once nurtured in young under-graduates can boost the tobacco-free India campaign.

Evaluation of occlusal forces using T scan analysis following mandibular fracture fixation.

Introduction: Mandible receives maximum impact following maxillofacial trauma. The dentate segment in particular is of importance as it has a direct bearing on the occlusive forces. The studies that have been carried out are either based on crude clinical evaluations or make use of elaborate and labor-intensive techniques. This study made use of T-scan analysis for objective identification of occlusive forces following mandibular fracture fixation. Materials and Methods: Eighty clinic-radiologically diagnosed cases of dentate segments of the mandible were considered, after random sampling method. The occlusion analysis was done by use of a T scan to obtain Relatively Occlusal Force. The procedure was repeated at 04-, 24-, 36-, and 48-weeks intervals. The data was recorded on Excel Spreadsheet (Microsoft Inc) and analysis was done using SPSS software. Results: The cases were predominantly males with a homogenous distribution of cases of age. The age versus gender distribution was more skewed in the female subgroup with a higher kurtosis value. Both evaluative (Pearson's) and inferential (paired t) tests were applied to reason the study. It was observed that the ROF values decreased in values as compared to pre-operative/post-treatment (Difference of Mean = 2.19, SE = 2.13) compared to 4 (Difference of Mean = -0.40 SE = 0.188),24 (Difference of Mean = -1.22, SE = 0.24) and 36 (Difference of Mean = -3.24, SE = 0.30) weeks, which however surpassed the pre-operative levels at 48 weeks post-operative period. This is suggestive of impending muscular imbalance in the initial periods. The surpass of 48 weeks may be due to optimal forces that were their pre-trauma. Conclusion: Mandibular fracture fixation is the most widely used and also a time-tested modality in the management of mandibular trauma. The evaluation of occlusive forces needs an understanding of their behavior following such fixation. The present study used T-scan analysis to objectify such forces and added extra insight apart from clinical evaluations of tooth contact and parafunctional movements.

Bone marrow metastasis of testicular germ cell tumour: A rare case.

Germ cell tumour (GCT) is the most common testicular tumour that commonly presents as a painless mass. Bone marrow metastasis in cases of testicular GCT is rare; only few case reports are available till date in the literature. Here an adult male presented with an intra-abdominal mass in right iliac fossa with inguinal lymphadenopathy with a deranged kidney function test. Bone marrow (BM) aspirate smear revealed metastatic tumour cells, but BM-biopsy was unremarkable. High serum Beta - HCG (38286 mIU/L) pointed towards germ cell lesion. Lymph node biopsy along with immunomarkers confirmed metastatic foci from germ cell tumor and managed as per standard protocol. Rarely BM aspirate is seen positive for malignancy, while biopsy turns out to be negative. Secondly, BM metastasis of GCT should be considered while dealing with cases like this. Informed consent: This is certified that the informed consent has been obtained from the patient.

Neuroendocrine carcinoma of cervix and review literature.

INTRODUCTION: Neuroendocrine carcinoma of the cervix (NECC) is a rare variant of cervical cancer with poor prognosis and high mortality. Recurrence is seen with multi-organ metastasis including liver. CASE PRESENTATION: A 65 year old female presented with vaginal bleeding for the past one year. Cervical cancer screening and biopsy demonstrated poorly differentiated squamous carcinoma. Immunohistochemistry showed positive expression of chromogranin, synaptophysin, pancytokeratin, TTP1, and CEA and negative expression of p40 and estrogen receptors. An adenocarcinoma with neuroendocrine tumor was suggested. Hysterectomy with bilateral salpingo-oophrectomy was performed. This was followed by carboplatin and etoposide therapy to have clinical remission for a year. Then recurrence was observed to start same drugs again resulting in to partial improvement. It was followed by radiotherapy. The patient succumbed to death approximately after three months. CONCLUSION: A metastatic lesion in liver may be a case of Neuroendocrine tumor of cervix, a rare condition that can be easily missed on histopathological examination. More studies are required to establish a standard therapeutic protocol.

Treatment recalcitrant cases of tinea corporis/cruris caused by T. mentagrophytes - interdigitale complex with mutations in ERG11 ERG 3, ERG4, MDR1 MFS genes & SQLE and their potential implications.

BACKGROUND: Recalcitrant dermatophyte infections are being reported from various parts of the world due to varied causes including strain variation, steroid misuse, SQLE mutations, and variable quality of itraconazole pellet formulations. The oral drug preferred in endemic areas is itraconazole, to which MIC levels remain low, and clinical failures to itraconazole reported defy a sound scientific explanation. OBJECTIVES: The objective of the study was to conduct a proteomic and genomic analysis on isolates from therapeutically recalcitrant case with isolation of gene mutations and enzymatic abnormalities to explain azole failures. METHODS: Trichophyton mentagrophyte interdigitale complex strains were isolated from seven clinically non-responding tinea corporis/cruris patients, who had failed a sequential course of 6 weeks of terbinafine 250 mg QD and itraconazole 100 mg BID. After AFST 1 strain, KA01 with high MIC to most drugs was characterized using whole genome sequencing, comparative proteomic profiling, and total sterol quantification. RESULTS: Sterol quantification showed that the standard strain of Trichophyton mentagrophytes (MTCC-7687) had half the ergosterol content than the resistant KA01 strain. Genomic analysis revealed mutations in SQLE, ERG4, ERG11, MDR1, MFS genes, and a novel ERG3 mutation. Proteomic analysis established the aberrant expression of acetyl Co-A transferase in the resistant strain and upregulation of thioredoxin reductase and peroxiredoxin. CONCLUSION: Our findings demonstrate possible reasons for multidrug resistance in the prevalent strain with mutations in genes that predict terbinafine (SQLE) and azole actions (ERG4, ERG11, ERG3) apart from efflux pumps (MDR1, MFS) that can explain multidrug clinical failures.

International consortium for innovation and quality: An industry perspective on the nonclinical and early clinical development of intravitreal drugs.

The eye, which is under constant exposure to environmental pathogens, has evolved various anatomic and immunological barriers critical to the protection of tissues lacking regenerative capacity, and the maintenance of a clear optic pathway essential to vision. By bypassing the ocular barriers, intravitreal (IVT) injection has become the mainstay for the delivery of drugs to treat conditions that affect the back of the eye. Both small molecules and biotherapeutics have been successfully administered intravitreally, and several drugs have been approved for the treatment of (wet) age-related macular degeneration and diabetic macular edema. However, IVT injection is an invasive procedure, which requires sufficient technical expertise from the healthcare professional administering the drug. Potential side effects include bleeding, retinal tear, cataracts, infection, uveitis, loss of vision, and increased ocular pressure. Pharmaceutical companies often differ in their drug development plan, including drug administration techniques, collection of ocular tissues and fluids, ophthalmology monitoring, and overall conduct of nonclinical and clinical studies. The present effort, under the aegis of the Innovation & Quality Ophthalmic Working Group, aims at understanding these differences, identifying pros and cons of the various approaches, determining the gaps in knowledge, and suggesting feasible good practices for nonclinical and early clinical IVT drug development.

Evaluation of HE4 as a prognostic biomarker in uterine cervical cancer.

INTRODUCTION: Uterine cervical cancer (UCC) is the fourth most common health problem worldwide among women. Currently available biomarkers CA125, CA199, and CEA for diagnosis or prognostic evaluation of UCC have not got widespread acceptance. METHOD: Whole blood samples of 64 patients with UCC were collected along with 63 healthy females and tested for serum levels of HE4 (sHE4). A cut-off value for positive result 64.0 pmol/L was set. Statistical analysis of different clinical variables was done. RESULT: Serum level of HE4 has a significant role in the diagnosis of uterine cervical cancer. Its level increases with age, higher parity (P < 0.05), stage (P < 0.16), tumor size, and parametrial invasion. Negative result was seen with vaginal invasion, lymph node involvement & cases which had recurrence. Various histological types showed variable results. So the serum level of HE4 (sHE) level may play a role in the diagnosis & therapeutic monitoring of UCC. But the prognostic evaluation needs further studies. CONCLUSION: sHE4 is useful in the diagnosis of cervical cancer, but its prognostic significance is under the question marks. It may be associated with higher values in higher stages. Higher parity of the patient is associated with higher level of HE4 in UCC.

Plant Extracts and Phytochemicals, a Promising Strategy Against Oral Lichen Planus: A Review on Clinical Trials.

BACKGROUND: Oral lichen planus (OLP) is an autoimmune disease that distress keratinized cells of the oral epithelium. Topical corticosteroids and other potential therapies like immunosuppressives, hydroxychloroquine, azathioprine, mycophenolate, dapsone, retinoids, biologic agents are used for the management of OLP. However, their effectiveness, best dose, duration of treatment and safety remain mostly unidentified. Moreover, recurrence of disease and dose-related side effects are the other issues. OBJECTIVE: The primary objective of the review is to explore the existing clinical trials for the efficacy of phytochemicals in treating OLP in comparison to corticosteroids. A comprehensive information about their mode of action is also discussed. METHODS: We have discussed different clinical trials conducted on various phytochemicals and plant extracts/formulations like curcumin, lycopene, quercetin, glycyrrhizin, purslane, raspberry, aloe vera gel and aloe vera mouthwash for the treatment of OLP. RESULTS: The current therapy for the management of OLP has numerous adverse effects and requires a long-term treatment. Phytochemicals can be a very good alternative in overcoming these side effects and reducing the course of treatment. CONCLUSION: Herbal extracts and their formulations can be an effective alternative to the current therapy due to their proven therapeutic effects, reduced side effects, long-term applicability, prevention of recurrence as well as progression into cancer.

Therapy related complications in plasmablastic lymphoma in immunocompetent individual.

BACKGROUND: Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of diffuse large B-cell lymphoma seen in immunocompromised individuals. It has a diffuse growth pattern, with no standard therapy and a poor survival rate. Due to overlap in presenting features with lymphoma and myeloma, PBL is often a diagnostic dilemma. We present a case of PBL in a young immunocompetent female who developed treatment associated complications. CASE REPORT: A 36-year-old presented with a lesion extending from the oral cavity to the pharynx and involving the angle of the mandible. Radiology and laryngoscopy described a growth pattern that was diagnosed to be PBL on histopathology. The patient underwent chemotherapy using level II DA-EPOCH (dose-adjusted-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) and prophylactic granulocyte-colony stimulating factor along with radiotherapy and ultimately, achieved metabolic response. However, she developed several episodes of paralytic ileus, cytopenia, oral ulcers, dermatitis and long-standing hypothyroidism as therapy-related complications and has been on treatment for the same ever since. CONCLUSIONS: Thus, a high index of suspicion is necessary for early diagnosis and rapid initiation of therapy. Further, there is a need to detect and address therapy related complications early to prevent long-standing, therapy-related side effects from developing and deteriorating the patient's quality of life.

Protective Effect of Methanolic Extract of Euglena tuba Against Dalton Lymphoma Induced Oxidative Stress in BALB/c Mice.

The identification and pharmacological validation of plant-based lead compounds for the cure of different diseases including cancer have always been globally strived. In addition to possessing numerous medicinal properties, many of the phytochemicals display antioxidant potential activities. Reactive oxygen species (ROS) causeoxidative stress leading to several severe diseases such as cancer. The antioxidants are substances that fight against ROS to protect the cells from their damaging effects. In the present study, the effects of methanol extract of Euglena tuba(ETME) have been evaluated for its antioxidant and antitumor potential against Dalton's lymphoma (DL) introduced in BALB/cmice. After 24 h of intraperitoneal inoculation of DL cells in mice, ETME (300 mg kg-1 body weight) was administered intraperitoneally upto18 alternative days. On the 18th day, the mice were sacrificed; the blood and tissues (liver and brain) were collected to determine the tumor growth parameters including morphological, behavioural, haematological profile, and antioxidant indices. The results indicated that ETME exhibited significant antioxidative and antitumor properties when compared with the data from DL bearing mice. The results from the present study indicated that ETME contained remarkable antitumor efficacy, which was mediated through amelioration of oxidative stress. The data suggested that ETME could be used as a potential natural anticancer agent.

Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper.

Immunogenicity has imposed a challenge to efficacy and safety evaluation of adeno-associated virus (AAV) vector-based gene therapies. Mild to severe adverse events observed in clinical development have been implicated with host immune responses against AAV gene therapies, resulting in comprehensive evaluation of immunogenicity during nonclinical and clinical studies mandated by health authorities. Immunogenicity of AAV gene therapies is complex due to the number of risk factors associated with product components and pre-existing immunity in human subjects. Different clinical mitigation strategies have been employed to alleviate treatment-induced or -boosted immunogenicity in order to achieve desired efficacy, reduce toxicity, or treat more patients who are seropositive to AAV vectors. In this review, the immunogenicity risk assessment, manifestation of immunogenicity and its impact in nonclinical and clinical studies, and various clinical mitigation strategies are summarized. Last, we present bioanalytical strategies, methodologies, and assay validation applied to appropriately monitor immunogenicity in AAV gene therapy-treated subjects.

Unveiling the mechanisms and biosynthesis of a novel nickel-pincer enzyme.

The nickel-pincer nucleotide (NPN) coenzyme, a substituted pyridinium mononucleotide that tri-coordinates nickel, was first identified covalently attached to a lysine residue in the LarA protein of lactate racemase. Starting from nicotinic acid adenine dinucleotide, LarB carboxylates C5 of the pyridinium ring and hydrolyzes the phosphoanhydride, LarE converts the C3 and C5 carboxylates to thiocarboxylates, and LarC incorporates nickel to form a C-Ni and two S-Ni bonds, during the biosynthesis of this cofactor. LarB uses a novel carboxylation mechanism involving the transient formation of a cysteinyl-pyridinium adduct. Depending on the source of the enzyme, LarEs either catalyze a sacrificial sulfur transfer from a cysteinyl side chain resulting in the formation of dehydroalanine or they utilize a [4Fe-4S] cluster bound by three cysteine residues to accept and transfer a non-core sulfide atom. LarC is a CTP-dependent enzyme that cytidinylylates its substrate, adds nickel, then hydrolyzes the product to release NPN and CMP. Homologs of the four lar genes are widely distributed in microorganisms, with some species containing multiple copies of larA whereas others lack this gene, consistent with the cofactor serving other functions. Several LarA-like proteins were shown to catalyze racemase or epimerase activities using 2-hydroxyacid substrates other than lactic acid. Thus, lactate racemase is the founding member of a large family of NPN-containing enzymes.

Vascular Cell Adhesion Molecule 1-Mediated Targeting of Human Hematopoietic Stem Cells to Bone Marrow Is Effective in Conferring Regeneration and Survival in Lethally Irradiated Mice.

Bone marrow (BM) transplantation has been used to treat malignant and nonmalignant BM-related disorders. Although an effective strategy, the procedure is associated with numerous complications, including graft rejection and nonspecific stem cell distribution. Avoidance of immune graft rejection has downsized the quantity of available stem cells, whereas nonspecific distribution necessitates the infusion of increased stem cell doses. A dual-purpose approach is needed to reduce the stem cell dose for transplantation. This used cell encapsulation and BM targeting to increase the quantity of transplanted stem cells reaching the BM. Cells were encapsulated with different biomaterials-chitosan (CS), polyallylamine hydrochloride (PAH), polystyrene sulfonate (PSS), and liposomes-and assessed for interaction with immune system components. The biomaterials were conjugated with vascular cell adhesion molecule 1 (VCAM1), a peptide that binds to BM-specific cell surface molecule, and evaluated for a successful transplantation. Encapsulated cells showed reduced interaction with antibody and cytokine without adverse effects on viability. Constitutive expression of VCAM1 was found to be specific on human bone marrow endothelial cells and was used for targeting by conjugating VCAM1-binding peptide to encapsulated cells. Peptide-conjugated-encapsulated stem cell formulations transplanted in irradiated mice with or without treatment with radioprotectant amifostine showed an increased percentage of cells reaching bone marrow. Post-transplantation survival along with blood count of neutrophils, platelets, and leukocytes was also enhanced for VCAM1-binding peptide-conjugated formulations with 100% survival demonstrated by peptide-conjugated CS/PSS/CS encapsulation formulation in irradiated mice for 4 weeks. Encapsulated cells retained their viability with increased shielding to the immune system, ensuring that graft rejection can be avoided. Transplanted encapsulated stem cells were distributed in a higher percentage to BM when conjugated to VCAM1-binding peptide, which could enable the use of lower stem cell doses. The peptide-conjugated CS/PSS/CS encapsulation system conferred 100% survival in irradiated mice, with increased regeneration demonstrating the ability to treat radiation-exposed victims.

Comparison of the Accuracy and Efficiency of a 3-Dimensional Dynamic Navigation System for Osteotomy and Root-end Resection Performed by Novice and Experienced Endodontists.

INTRODUCTION: The aim of the study is to investigate whether the 3-dimensional dynamic navigation system (3D-DNS) can improve experienced endodontists' (EEs') and novice endodontists' (NEs') accuracy and efficiency in osteotomy and root-end resection (RER) and to verify that the 3D-DNS enables NEs to perform osteotomy and RER as accurately and efficiently as EEs. METHODS: Seventy-six roots in cadaver heads were randomly divided into 4 groups: 3D-DNS-NE, 3D-DNS-EE, freehanded (FH)-NE, and FH-EE (all, n = 19). Cone-beam computed tomography scans were taken preoperatively and postoperatively. Osteotomy and RER were planned virtually in the X-guided software (X-Nav Technologies, Lansdale). Accuracy was calculated by measuring the 2-dimensional and 3D virtual deviations and angular deflection using superimposing software (X-Nav technologies). Efficiency was determined by the time of operation and the number of mishaps. RESULTS: Accuracy deviations were significantly fewer in the 3D-DNS-EE group than those in the FH-EE group (P < .05). We found less 2-dimensional and 3D accuracy deviations comparing the 3D-DNS-NE group to the FH-NE group (P < .05). The time required for osteotomy and RER with the 3D-DNS was ∼ ½ of that required for the FH method for both EEs and NEs (P < .05). We found no difference in the number of mishaps between the 3D-DNS and FH groups for EEs and NEs (P > .05). CONCLUSIONS: The 3D-DNS improved EEs' and NEs' accuracy and efficiency in osteotomy and RER. The NEs were as efficient as the EEs using the 3D-DNS. Notably, the 3D-DNS improved the NEs' accuracy compared to the FH method, but the 3D-DNS did not enable the NEs to perform osteotomy and RER as accurately as the EEs.