Disruption of Immune Homeostasis in Human Dendritic Cells via Regulation of Autophagy and Apoptosis by ., Meghil, Mohamed M., Tawfik Omnia K., Elashiry Mahmoud, Rajendran Mythilypriya, Arce Roger M., Fulton David J., Schoenlein Patricia V., and Cutler Christopher W. , Frontiers in immunology, 2019, Volume 10, p.2286, (2019) Abstract

As fundamental processes of immune homeostasis, autophagy, and apoptosis must be maintained to mitigate risk of chronic inflammation and autoimmune diseases. Periodontitis is a chronic inflammatory disease characterized by oral microbial dysbiosis, and dysregulation of dendritic cell (DC) and T cell responses. The aim of this study was to elucidate the underlying mechanisms by which the oral microbe () manipulates dendritic cell signaling to perturb both autophagy and apoptosis. Using a combination of Western blotting, flow cytometry, qRT-PCR and immunofluorescence analysis, we show a pivotal role for the minor (Mfa1) fimbriae of in nuclear/cytoplasmic shuttling of Akt and FOXO1 in human monocyte-derived DCs. Mfa1-induced Akt nuclear localization and activation ultimately induced mTOR. Activation of the Akt/mTOR axis downregulated intracellular LC3II, also known as Atg8, required for autophagosome formation and maturation. Use of allosteric panAkt inhibitor MK2206 and mTOR inhibitor rapamycin confirmed the role of Akt/mTOR signaling in autophagy inhibition by in DCs. Interestingly, this pathway was also linked to induction of the anti-apoptotic protein Bcl2, decreased caspase-3 cleavage and decreased expression of pro-apoptotic proteins Bax and Bim, thus promoting longevity of host DCs. Addition of ABT-199 peptide to disrupt the interaction of antiapoptotic Bcl2 and its proapoptotic partners BAK/BAX restored apoptotic death to infected DC cells. In summary, we have identified the underlying mechanism by which promotes its own survival and that of its host DCs.

Systemic Antibiotic Therapy Reduces Circulating Inflammatory Dendritic Cells and Treg-Th17 Plasticity in Periodontitis., Rajendran, Mythilypriya, Looney Stephen, Singh Nagendra, Elashiry Mahmoud, Meghil Mohamed M., El-Awady Ahmed R., Tawfik Omnia, Susin Cristiano, Arce Roger M., and Cutler Christopher W. , Journal of immunology (Baltimore, Md. : 1950), 2019 May 01, Volume 202, Issue 9, p.2690-2699, (2019) Abstract

Periodontitis (PD) is a common dysbiotic inflammatory disease that leads to local bone deterioration and tooth loss. PD patients experience low-grade bacteremias with oral microbes implicated in the risk of heart disease, cancer, and kidney failure. Although Th17 effectors are vital to fighting infection, functional imbalance of Th17 effectors and regulatory T cells (Tregs) promote inflammatory diseases. In this study, we investigated, in a small pilot randomized clinical trial, whether expansion of inflammatory blood myeloid dendritic cells (DCs) and conversion of Tregs to Th17 cells could be modulated with antibiotics (AB) as part of initial therapy in PD patients. PD patients were randomly assigned to either 7 d of peroral metronidazole/amoxicillin AB treatment or no AB, along with standard care debridement and chlorhexidine mouthwash. 16s ribosomal RNA analysis of keystone pathogen and its consortium members and confirmed the presence of all three species in the reservoirs (subgingival pockets and blood DCs) of PD patients before treatment. Of the three species, was reduced in both reservoirs 4-6 wk after therapy. Further, the frequency of CD1CCCR6 myeloid DCs and IL-1R1 expression on IL-17AFOXP3CD4 T cells in PD patients were reduced to healthy control levels. The latter led to decreased IL-1β-stimulated Treg plasticity in PD patients and improvement in clinical measures of PD. Overall, we identified an important, albeit short-term, beneficial role of AB therapy in reducing inflammatory DCs and Treg-Th17 plasticity in humans with PD.

Evaluation of Oversized Drilling on Implant Survival and Stability Versus Traditional Drilling Technique: A Randomized Clinical Trial., Seleem, Azhar, Tawfik Omnia K., and El-Nahass Hani , The International journal of oral & maxillofacial implants, 2021 Jul-Aug, Volume 36, Issue 4, p.771-778, (2021) Abstract

PURPOSE: This study aimed to investigate the influence of oversized drilling on the stability of the implant and the bone response during osseointegration.

MATERIALS AND METHODS: The trial was designed as a prospective, parallel-group randomized controlled clinical trial with 20 implants placed in the posterior region of the maxilla. The sample size was divided into two groups, 10 each, with implants being placed with manufacturer-recommended implant osteotomy preparation according to the manufacturer guidelines in one group (MR group) vs oversized osteotomy preparation (3 to 5 mm) in the other group (oversized drilling [OD] group). The implant stability was monitored for 3 months by means of resonance frequency analysis, while the crestal bone levels were recorded using parallel technique periapical radiography for 6 months. Patient-reported outcomes including pain, swelling, satisfaction, and implant survival were all monitored throughout the study.

RESULTS: In the MR group, a mean decrease in implant stability quotient (ISQ) values was detected during the first 4 weeks, after which a gradual increase in values was recorded. In comparison, the OD group showed a rapid increase in ISQ value over the entire follow-up period from baseline and up to week 12. Regarding crestal bone level, follow-up showed a significant difference when comparing baseline and 6-month radiographs (P = .00) between the OD group, 0.908 mm ± 0.343, and the MR group, 1.3 ± 0.23 mm.

CONCLUSION: Within the limitations of this study, the results suggest that the oversized osteotomy technique may lead to earlier implant stability and postsurgical recovery compared with the manufacturer-recommended technique for osteotomy preparation. However, further studies are needed to confirm these findings.

Jumping gap in immediate implant placement in the esthetic zone: A virtual implant planning using cone-beam computed tomography., Naiem, Suzy Nabil, Al-Nawas Bilal, Tawfik Omnia Khaled, and El-Nahass Hani , Journal of prosthodontic research, 2024 Apr 08, Volume 68, Issue 2, p.347-353, (2024) Abstract

PURPOSE: A jumping gap (JG) refers to the implant's future buccal wall; this study aims to estimate the jumping gap dimension in relation to virtual implant placement and subsequently link the implant diameter and implant position with the anatomical site.

METHODS: This observational study was conducted to analyze the maxillary teeth in the esthetic zone from cone-beam computed tomography (CBCT) scans using OnDemand software. The horizontal jumping gap dimension of each tooth was assessed by subtracting the calculated virtual implant diameter from the socket dimensions.

RESULTS: A total of 253 anterior and premolar maxillary teeth were analyzed from 52 CBCT scans. The estimated JG dimensions were 1.23 ± 0.59 mm, 1.80 ± 0.64 mm, 3.02 ± 0.69 mm, for central incisors, lateral incisors and canines respectively, 3.70 ± 0.68 mm for the first premolars showing the highest horizontal gap and 3.19 ± 0.88 mm for second premolars. The incisors showed the smallest horizontal gap compared to the canines and premolars.

CONCLUSIONS: In terms of JG, immediate implant placement is more favorable at the canine and premolar sites. By contrast, the incisors sites should be handled with extreme caution, where the use of narrower implants is advisable when necessary.

Evaluation of advanced platelet-rich fibrin compared to subepithelial connective tissue graft in the surgical management of interdental papilla recession: a randomized controlled trial., Barakat, Sanabel O., Tawfik Omnia K., El Kholy Samar, and Nahass Hani EL , Clinical oral investigations, 2024 Jan 11, Volume 28, Issue 1, p.87, (2024) Abstract

OBJECTIVES: The current study aims to compare advanced-platelet-rich fibrin membrane (A-PRF) to connective tissue graft (CTG) using Han and Takei's approach.

MATERIALS AND METHODS: The defective papilla was randomly allocated to either the control group (CTG) or to the experimental group (A-PRF). Papilla height (PH) and percent change in the gingival black triangle (GBT) area were recorded at 1, 3, 6, 9, and 12 months.

RESULTS: Thirty-two deficient IDPs with an initial papilla presence index (PPI) of 2 or 3 were included. At 12 months, the papilla-fill significantly increased in both groups (p < 0.001) without a significant difference between the study groups (p = 0.637). A mean gain in IDP height of 2.25 mm (± 0.97) in the CTG group and 1.86 mm (± 0.7) in the A-PRF group were recorded with a nonsignificant difference. Gingival black triangle fill showed a 57.98% fill in the CTG and 54.65% fill in the A-PRF group, with no statistically significant difference between the groups (0.956). Regarding postoperative pain patients, the CTG group consumed significantly more analgesics than the A-PRF group (11.75 ± 3.51 and 8 ± 3.08, respectively, with p = 0.003).

CONCLUSION: Both CTG and A-PRF were found to be equally effective in increasing deficient IDP height with Han and Takei's surgical technique, with no significant difference. Within the current study's limitations, A-PRF seems to be a viable alternative to CTG in the treatment of GBTs.

CLINICAL RELEVANCE: Multilayered A-PRF membrane can be used as a choice in the augmentation of receded papillae, using Han and Takei's technique.

Evaluation of buccal bone resorption in immediate implant placement in thin versus thick buccal bone plates: An 18-month follow-up prospective cohort study., Nahass, Hani EL, Tawfik Omnia K., Naiem Suzy N., Zazou Nada, and Moussa Mahmoud , Clinical implant dentistry and related research, 2024 Jun, Volume 26, Issue 3, p.532-544, (2024) Abstract

OBJECTIVES: The current guidelines recommend that immediate implants be placed in patients with thick (>1 mm) buccal bone due to the inevitable tissue remodeling that follows tooth extraction. The aim of the current study was to investigate the effect of buccal bone thickness on bone resorption in immediate implant placement and compare two measuring techniques of the aforementioned resorption.

MATERIALS: The present study was designed as a prospective nonrandomized, controlled clinical trial. A total of 30 implants were split between the two study arms, thin buccal bone and thick buccal bone. The primary outcome was to assess vertical bone changes radiographically by cone beam scans preoperatively, at 2 months and 18 months after implant placement in patients with thin and thick buccal plate. Secondary outcomes included the change in the thickness of the buccal bony plate, marginal bone loss, and pink esthetic score.

RESULTS: Only 26 implants were statistically analyzed as one early failure was observed in each group. Furthermore, 2 patients of the thick group withdrew from the study. Cone beam computed tomography measurements revealed that at 2 months the vertical bone loss was 1.09 for the thin group and 0.85 for the thick group. The buccal bone plate resorption of the thin group was 0.39 mm while it was 0.52 mm for the thick group. The buccal bone plate was 1.25 mm in the thin group and 1.88 mm in the thick group. The PES did not show any significant difference with very good esthetic results.

CONCLUSION: Within the limitations of the current study, the amount of buccal bone plate resorption and the subsequent thickness obtained after implantation in both groups suggest successful long-term results. The two measuring techniques have proven to be comparable and reliable in the measurement of buccal bony plate changes. https://classic.

CLINICALTRIALS: gov/ct2/results?cond=&term=NCT04731545&cntry=EG&state=&city=&dist=.

Evaluation of minimally invasive esthetic crown lengthening using an open flap versus flapless surgical approach: A randomized controlled clinical trial., Sourour, Marie-Line, Tawfik Omnia Khaled, Hosny Manal, and El-Sayed Karim Mohamed Fawzy , Journal of esthetic and restorative dentistry : official publication of the American Academy of Esthetic Dentistry ... [et al.], 2024 Oct, Volume 36, Issue 10, p.1353-1362, (2024) Abstract

OBJECTIVES: Esthetic crown lengthening (ECL) is commonly advocated to treat patients with altered passive eruption (APE). Since the introduction of the minimally invasive surgical concept, a limited number of studies have investigated this technique in a standardized manner, with further studies required to verify the validity and predictability of the minimally invasive FL-technique. The current randomized trial compares a minimally invasive (ECL), using piezosurgery with flapless-approach (FL), versus an open-flap (OF) approach in the management of patients with APE Type 1B.

MATERIALS AND METHODS: Twenty-four patients diagnosed with APE Type 1B were randomly assigned into test (FL) with tunneling approach or control (OF) group with minimally invasive flap reflection (n = 12/group). Postoperative pain was assessed during the first 48 h. Gingival margin (GM) level relative to a custom-made stent (rGM) and patient satisfaction were assessed preoperative, immediately after surgery, at 3 and 6 months postsurgically. Postoperative swelling was reported for the first week postsurgically. Plaque index (PI), bleeding on probing (BoP), clinical attachment level (CAL), pocket depth (PD) and pink esthetic score (PES), were evaluated at baseline and 6 months. Linear regression analysis was conducted for pain.

RESULTS: OF-group reported significantly higher pain and swelling scores than FL-group during the first 48 h (p < 0.05). FL-group showed no significant differences regarding rGM between 3 and 6 months, in contrast to OF-group, where a significant decrease in rGM was notable (p < 0.05). No significant differences in PI, BoP, CAL, PD, PES, and patient satisfaction scores were evident between groups (p > 0.05). Regression analysis demonstrated that treatment and gender were significant predictors for pain (p < 0.05).

CONCLUSIONS: Within the current study's limitations, piezo-surgical ECL with FL-approach presented significantly lower postoperative pain, swelling, and early GM stability compared to OF-approach.

CLINICAL SIGNIFICANCE: Piezosurgical ECL with a FL-approach can be considered a predictable technique with advantages over the OF-approach in the management of patients with APE Type1B.

Implant stability in the posterior maxilla: clinical and radiographic comparison of osseodensification and conventional drilling: a randomized clinical trial., Abdelraouf, Sara Amr, Dahab Omnia Aboul, Mostafa Basma, Kenawy Sarah Mohammed, and Tawfik Omnia K. , Clinical oral investigations, 2025 Sep 29, Volume 29, Issue 10, p.480, (2025) Abstract

OBJECTIVES: The aim of this randomized clinical trial was to clinically and radiographically compare the effect of osseodensification (OD) and conventional drilling (CD) on implant stability in the posterior maxilla.

MATERIALS AND METHODS: Twenty patients received 20 implants after being randomly assigned for osteotomy preparation with either OD (test) (n = 10) or CD (control) (n = 10). Implant stability quotient (ISQ) and crestal bone loss were monitored closely from implant insertion through 12 months of loading. Insertion torque and implant survival were also assessed during the study.

RESULTS: In OD group, one patient was lost to follow up and all other implants were in Function after 12 months of loading (9/9), while only 8/10 implants survived in CD group. OD was associated with significantly higher mean ISQ values; post-insertion and during the 1st month of healing, compared to CD. A high relatively unchanged stability was observed throughout osseointegration with OD method, while a stability dip occurred during the 2nd and 3rd weeks of healing in CD group. There was no significant difference in crestal bone loss and insertion torque between groups.

CONCLUSIONS: Within the limitations of this study, OD seems to provide earlier implant stability in terms of ISQ values, and may improve survival rates in the posterior maxilla, compared to CD, with no negative impact on crestal bone after 12 months of implant loading.

CLINICALTRIALS: gov Identifier: NCT04442763 (registration date 15/6/2020).

CLINICAL RELEVANCE: OD may be used as an alternative to CD to achieve earlier implant stability in the posterior maxilla.

Lip repositioning with or without myotomy: A randomized clinical trial., Tawfik, Omnia K., Naiem Suzi N., Tawfik Lobna K., Yussif Nermin, Meghil Mohamed M., Cutler Christopher W., Darhous Mona, and El-Nahass Hani E. , Journal of periodontology, 2018 Jul, Volume 89, Issue 7, p.815-823, (2018) Abstract

BACKGROUND: Lip repositioning is a conservative surgical method for the correction of excess gingival display (EGD) by limiting the upward retraction of the lips. Lip repositioning presents a simple method for the treatment of gummy smile. The aim of this randomized clinical trial (RCT) was to assess lip repositioning, compared to lip repositioning with muscle severance for efficacy in treatment of EGD and resultant stability.

METHODS: A single-blinded, controlled, parallel-group RCT was performed. Twenty patients with EGD were enrolled in the study, treated with lip repositioning with and without muscle severance. Participants were assessed for EGD reduction, changes in lip length and result stability at 3, 6 and 12 months. Additionally, pain, swelling and satisfaction, were assessed.

RESULTS: Classic lip repositioning was found capable of reducing EGD by 2.73 mm (SD ± 1.281), while lip repositioning with muscle severance offered an improved reduction in EGD with a mean reduction of 3.57mm (SD ± 1.62). Lip length, swelling and pain scores were found comparable between the two techniques.

CONCLUSION: Lip repositioning is an effective method for treating EGD, however, muscle severance provides a more stable result at 12 months when compared to the classical technique. More studies are necessary to fully assess this procedure.

Lip repositioning for the treatment of excess gingival display: A systematic review., Tawfik, Omnia K., El-Nahass Hani E., Shipman Peter, Looney Stephen W., Cutler Christopher W., and Brunner Mark , Journal of esthetic and restorative dentistry : official publication of the American Academy of Esthetic Dentistry ... [et al.], 2018 Mar, Volume 30, Issue 2, p.101-112, (2018) Abstract

BACKGROUND: Lip repositioning is a conservative surgical technique used to treat excess gingival display. An array of modifications has been introduced to the technique over time and as studies show the technique and its modifications to be successful, there is little standardized information for clinicians to make informed decisions when choosing this technique for the treatment of patients with excessive gingival display (EGD).

OBJECTIVES: To review the current literature on the topic of lip repositioning for the treatment of excessive EGD, exploring outcome, and result longevity.

METHODS: A structured systematic search was carried out using the Ovid database and Web of Science to identify published studies on lip repositioning technique. Search was restricted to studies in the English language, describing a surgical intervention. Case reports were included as the number of published studies was limited.

RESULTS: The electronic search identified 93 articles, hand search identified 1 article, and reference search identified 1 article. After excluding duplicates and screening articles, a total of 22 articles met the inclusion criteria. An estimated mean improvement of 3.4 mm (95% confidence interval, 3.0-3.8 mm) was found possible with lip repositioning. Data analysis was performed using only 4 studies, amounting to a total of 33 patients. Potential risk of bias was identified in some of the studies included.

CONCLUSIONS: Despite the limited available studies on lip repositioning, an estimated mean improvement of 3.4 mm was found to be possible with surgical lip repositioning, suggesting that the technique could be used successfully to treat EGD. However, more studies are necessary to properly evaluate the treatment approach and stability of the technique.

CLINICAL SIGNIFICANCE: Recently, the demand for esthetics has significantly increased, driven by increased patient awareness and the search for an ideal smile. Creating the perfect smile is an intricate process that requires a multidisciplinary approach, with careful consideration of the lips and the gingival outline. Excess gingival display results in an unaesthetic smile, lip repositioning offers a comparatively simple solution for this problem. While the quality literature on this topic is limited statistical analysis of collected studies show that an estimated mean improvement of 3.4 mm can be achieved with surgical lip repositioning.