Targeted alveolar regeneration with Frizzled-specific agonists.

Wnt ligands oligomerize Frizzled (Fzd) and Lrp5/6 receptors to control the specification and activity of stem cells in many species. How Wnt signaling is selectively activated in different stem cell populations, often within the same organ, is not understood. In lung alveoli, we show that distinct Wnt receptors are expressed by epithelial (Fzd5/6), endothelial (Fzd4), and stromal (Fzd1) cells. Fzd5 is uniquely required for alveolar epithelial stem cell activity, whereas fibroblasts utilize distinct Fzd receptors. Using an expanded repertoire of Fzd-Lrp agonists, we could activate canonical Wnt signaling in alveolar epithelial stem cells via either Fzd5 or, unexpectedly, non-canonical Fzd6. A Fzd5 agonist (Fzd5ag) or Fzd6ag stimulated alveolar epithelial stem cell activity and promoted survival in mice after lung injury, but only Fzd6ag promoted an alveolar fate in airway-derived progenitors. Therefore, we identify a potential strategy for promoting regeneration without exacerbating fibrosis during lung injury.

Teeth and alveolar bones as tracers of metals and radionuclides in inhabitants of a uranium region.

Biodosimetry can define risks in inhabitants of areas with potential contaminants, ensuring environmental protection and living conditions due to toxic and radioactive effects. This study aimed to evaluate metals and radionuclides in dental structures and alveolar bones in residents of a uranium area in Paraíba and Pernambuco, Brazil. Eighty-nine specimens were pulverized, fractionated, and chemically prepared for analysis by EDXRF, FAAS, and ICP-MS. Levels of Ca, Cu, Fe, Si, Mn, Ni, Pb, Sr, Ti, V, Zn, K, Mn, Th, and U were investigated. Higher concentrations were measured for Ca, with an average of 272,986.4 mg kg-1. Ni presented in lower concentrations, with an average of 30.4 mg kg-1. For U, concentrations ranged from 1.5 to 145.0 mg kg-1, with more than 27% of the samples above the reference value of 8.1 µg kg-1. For Th, almost 38% of the results were above the limit of 3.5 µg kg-1. In the bone spicules, the contents of U and Th ranged from 45.1 to 1451.2 µg kg-1 and from 7.5 to 78.4 µg kg-1, in this order. The levels of radionuclides were more expressive for the teeth collected in São José do Sabugi, suggesting contamination through food and water consumption. In the bone spicules, the levels of U were up to 179 times higher than the safety limit. The results indicate a possible risk of contamination with probable induced radiobiological effects.

Ozone therapy effect in medication-related osteonecrosis of the jaw as prevention or treatment: microtomographic, confocal laser microscopy and histomorphometric analysis.

OBJECTIVE: This study aimed to evaluate the efficacy of ozone therapy in the preoperative (prevention) and/or postoperative (treatment) of MRONJ. MATERIAL AND METHODS: Forty male Wistar rats were caudally treated with zoledronic acid (ZOL) and to ozone therapy before extraction (prevention, POG), after extraction (treatment, TOG), or both (prevention and treatment, TPOG), and treated with saline (SAL). The animals received intramuscular fluorochrome (calcein and alizarin), and 28 days postoperatively, they were euthanized, and the tissues were subjected to microtomographic computed tomography (microCT), LASER confocal, and histomorphometric analyses. RESULTS: Micro-CT showed a higher bone volume fraction average in all groups than that in the ZOL group (P < 0.001), the ZOL group showed high porosity (P = 0.03), and trabecular separation was greater in the TOG group than in the POG group (P < 0.05). The mineral apposition rate of the POG group was high (20.46 ± 6.31) (P < 0.001), followed by the TOG group (20.32 ± 7.4). The TOG group presented the highest mean newly formed bone area (68.322 ± 25.296) compared with the ZOL group (P < 0.05), followed by the SAL group (66.039 ± 28.379) and ZOL groups (60.856 ± 28.425). CONCLUSIONS: Ozone therapy modulated alveolar bone repair in animals treated with ZOL, mainly after surgery trauma, leading to bone formation as healing tissue. CLINICAL RELEVANCE: Osteonecrosis has been a challenge in dentistry, and owing to the lack of a consensus regarding therapy, studies presenting new therapies are important, and ozone has been one of the therapies explored empirically.

Evaluation of maxillary arch symmetry in cleft patients undergoing orthodontic treatment: a comparative study.

OBJECTIVE: Patients with a cleft require structured procedures to achieve feasible treatment results. Since many treatment protocols coexist without being superior to one another, this study investigated the Saarland University Hospital treatment concept for patients with unilateral and bilateral clefts to evaluate its effects upon dental arch dimensions until the early mixed dentition. MATERIAL AND METHODS: Digitized plaster models were used for data collection. Records of 83 patients (Cleft n = 41 [UCLP n = 28, BCLP n = 13], Non-Cleft Control n = 42) comprised 249 casts. The evaluation included established procedures for measurements of edentulous and dentate jaws. Statistics included Shapiro-Wilk, Friedmann, Wilcoxon and Mann-Whitney-U-Tests for the casts. The level of significance was set at p < 0.05. RESULTS: The cast analysis showed an approximation of arch dimensions towards those of age-matched patients without a cleft until early mixed dentition. The mean values of patients with and without cleft lip and palate were almost indistinguishable when compared in primary and/or early mixed dentition. CONCLUSIONS: The evaluated treatment concept leads to feasible outcomes regarding dental arches in patients with unilateral and bilateral clefts compared to an age-matched non-cleft control. CLINICAL RELEVANCE: The evaluated treatment concept leads to favorable outcomes until early mixed dentition.

Intelligence among ear deformities and cleft lip and/or alveolus and/or cleft palate patients during 50 years in Israel.

PURPOSE: We evaluated hearing loss and general intelligence among persons with auricle anomalies and cleft lip and/or alveolus and/or cleft palate (CLAP). METHODS: A nationwide cross-sectional study of data recorded during 1966-2019, as mandatory pre-military recruitment of individuals. RESULTS: Of 3 182 892 adolescents, 548 were diagnosed with auricle anomalies and 2072 with CLAP. For the latter, the adjusted odds ratios for the low, low to medium and medium general intelligence categories compared to the highest category were 1.4 [95% CI 1.5-1.2], 1.2 [95% CI 1.4-1.1] and 1.1 [95% CI 1.2-0.9] respectively. The corresponding values for the auricle anomalies were not significant. CONCLUSIONS: General intelligence was impaired among individuals with CLAP, but no significant correlation was found among individuals suffering from auricle anomalies.

Cone-beam computed tomography assessment of maxillary anterior alveolar bone remodelling in extraction and non-extraction orthodontic cases using stable extra-alveolar reference.

OBJECTIVE: To explore alveolar cortical positional change in response to tooth movement in extraction and non-extraction orthodontic cases, using cone-beam computed tomography (CBCT) and stable extra-alveolar references. MATERIALS AND METHODS: The pre-treatment (T1) and post-treatment (T2) CBCT scans of 25 extraction (EXT) and matched 25 non-extraction (Non-EXT) orthodontic cases were imported into Dolphin Imaging 3D, and oriented uniformly. Sagittal and axial CBCT cross-sections were traced using customized software-generated guides. The displacement of teeth and alveolar bone cortices were automatically measured using the palatal plane (PP) and the line perpendicular to PP and passing Sella as reference. Intra- and inter-group differences between T1 and T2 were analysed. Subjects were also superimposed three-dimensionally using Geomagic Control X for qualitative analysis of cortical remodelling. RESULTS: The EXT group showed incisor retraction, while the Non-EXT group exhibited statistically significant incisor anterior tipping (P < .05). In EXT, both the labial and palatal cortices are resorbed. Non-EXT showed labial cortex anterior modelling, and statistically significant palatal cortex resorption (P < .05). In both groups, statistically significant decrease in total and palatal alveolar widths, increase in labial widths, and palatal dehiscence were observed. Comparatively, EXT showed significantly more incisal total and palatal width decrease and palatal vertical bone loss. CONCLUSION: Labial cortical remodelling was shown to follow anterior tooth movement, but the palatal cortical response to incisor retraction and labial cortical remodelling in general remained inconclusive. Narrowing of the alveolar housing and palatal dehiscence were observed regardless of extraction following orthodontic treatment.

Adverse Effects of High Temperature On Mammary Alveolar Development In Vitro.

In the mammary glands during pregnancy, the alveolar buds are first branched from the mammary ducts after which they form the alveolar luminal structure for milk production postparturition. Body temperature could increase for several reasons, such as infectious disease and heat stress. We have previously reported that high temperature adversely effects on the lactation capacity of mouse mammary epithelial cells (MECs). However, it remains unclear how high temperature influences mammary morophogenesis during pregnancy. In this study, we investigated the effects of high temperature on this mammary alveolar development process using two types of culture models including embedded organoids of MECs in Matrigel; these models reproduced mammary alveolar bud induction and alveolar luminal formation. Results showed that a culture temperature of 41 °C repressed alveolar bud induction and inhibited alveolar luminal formation. In addition, the treatment at 41 °C decreased the number of proliferating mammary epithelial cells but did not affect cell migration. Levels of phosphorylated Akt, -ERK1/2, -HSP90, and -HSP27 were increased in organoids cultured at 41 °C. The specific inhibitors of HSP90 and HSP27 exacerbated the disruption of organoids at 41 °C but not at 37 °C. Furthermore, the organoids precultured at 37 and 41 °C in the alveolar luminal formation model showed differences in the expression levels of caseins and tight junction proteins, which express in MECs in lactating mammary glands, after induction of MEC differentiation by prolactin and dexamethasone treatment in vitro. These results suggest that elevated temperature directly hinders mammary alveolar development; however, heat shock proteins may mitigate the adverse effects of high temperatures.

Predictive factors for secondary alveolar bone graft failure in patients with cleft alveolus.

OBJECTIVE: This single-centre retrospective cohort study aimed to evaluate secondary alveolar bone grafting (SABG) and identify the factors associated with failure. METHODS: Individuals born with alveolar cleft with or without cleft palate who had SABG consecutively between 2004-2006 and 2011-2013 were enrolled in this study. After the exclusion of 20 cases due to poor quality radiographs, 115 patients (50 girls and 65 boys) who had undergone 131 SABG procedures were included. According to a modification of the Bergland Scale (mBS), the alveolar bone level was assessed using occlusal films obtained 3 months after SABG. Data on factors plausible for SABG failure were collected from patient records, photographs, cast models, and presurgical occlusal radiographs. The Mantel Haenszel Chi-Square test was used to test the possible impact of these factors on the mBS scores. RESULTS: A total failure (mBS score of 4) was observed in 9% of the cases. The alveolar bone level correlated with cleft laterality (P = 0.039), alveolar cleft extension (P = 0.033), age at SABG (P = 0.007), root developmental stage (P = 0.021), and oral hygiene (P = 0.007). CONCLUSION: Secondary alveolar bone grafting failure was correlated with a bilateral alveolar cleft, absence of an initial partial alveolar bridge, higher age, increased root developmental stage, and poor oral hygiene. Efforts to achieve optimal oral hygiene are recommended to improve outcomes, particularly when SABG is performed in individuals with a bilateral cleft, increased alveolar cleft extension, or at higher ages.

Regenerative therapy based on miRNA-302 mimics for enhancing host recovery from pneumonia caused by Streptococcus pneumoniae.

Bacterial pneumonia remains a leading cause of morbidity and mortality worldwide. A defining feature of pneumonia is lung injury, leading to protracted suffering and vulnerability long after bacterial clearance. Little is known about which cells are damaged during bacterial pneumonia and if the regenerative process can be harnessed to promote tissue repair and host recovery. Here, we show that infection of mice with Streptococcus pneumoniae (Sp) caused substantial damage to alveolar epithelial cells (AEC), followed by a slow process of regeneration. Concurrent with AEC regeneration, the expression of miRNA-302 is elevated in AEC. Treatment of Sp-infected mice with miRNA-302 mimics improved lung functions, host recovery, and survival. miRNA-302 mediated its therapeutic effects, not by inhibiting apoptosis and preventing damage, but by promoting proliferation of local epithelial progenitor cells to regenerate AEC. These results demonstrate the ability of microRNA-based therapy to promote AEC regeneration and enhance host recovery from bacterial pneumonia.

Low-level laser therapy (LLLT) improves alveolar bone healing in rats.

The main objective of the present study was to evaluate the effect of low-level laser therapy (LLLT) in enhancing bone healing in irradiated alveolus post-tooth extraction. Sixty male Wistar rats (180 ± 10 g) were used in the present study. The left maxillary first molars were extracted, and the alveolar region was irradiated by diode laser device (GaAlAs) immediately after extraction and for more 3-day daily applications. The animals were randomly assigned into two groups: control group (n = 30, with left maxillary molar extraction-CG) and experimental group (n = 30, with tooth extraction and low-level laser therapy applied to the dental alveolus for 42 s-EG). These groups were divided into subgroups (five rats per subgroup) according to the observation time point-1, 2, 3, 5, 7, and 10 days-post-tooth extraction. The maxillary bone was separated, and the specimens were stained with hematoxylin and eosin, Masson's trichrome, and picrosirius red and immunohistochemistry for RUNX-2. Parametric and nonparametric tests were used with a significance level of 5%. LLLT accelerated bone healing with mature collagen fiber bundles and early new bone formation. Histomorphometric analysis revealed an increase of osteoblast (RUNX-2) and osteoclast (TRAP) activity and in the area percentage of cancellous bone in the lased alveolus compared to the control group. This increase was statistically significant (p < 0.05). Application of LLLT with a GaAlAs diode laser device enhanced bone healing and mineralization on alveolar region.

3D Lung Tissue Models for Studies on SARS-CoV-2 Pathophysiology and Therapeutics.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), has provoked more than six million deaths worldwide and continues to pose a major threat to global health. Enormous efforts have been made by researchers around the world to elucidate COVID-19 pathophysiology, design efficacious therapy and develop new vaccines to control the pandemic. To this end, experimental models are essential. While animal models and conventional cell cultures have been widely utilized during these research endeavors, they often do not adequately reflect the human responses to SARS-CoV-2 infection. Therefore, models that emulate with high fidelity the SARS-CoV-2 infection in human organs are needed for discovering new antiviral drugs and vaccines against COVID-19. Three-dimensional (3D) cell cultures, such as lung organoids and bioengineered organs-on-chips, are emerging as crucial tools for research on respiratory diseases. The lung airway, small airway and alveolus organ chips have been successfully used for studies on lung response to infection by various pathogens, including corona and influenza A viruses. In this review, we provide an overview of these new tools and their use in studies on COVID-19 pathogenesis and drug testing. We also discuss the limitations of the existing models and indicate some improvements for their use in research against COVID-19 as well as future emerging epidemics.

Insufficient development of vessels and alveoli in lungs of infants with trisomy 18-Features of pulmonary histopathological findings from lung biopsy.

The aim of this study was to evaluate the features of pulmonary histopathological changes in cases of trisomy 18 complicated with congenital heart disease and pulmonary arterial hypertension. Twenty-eight patients with trisomy 18 underwent open lung biopsy at the time of primary operation in our hospital between 2008 and 2019. We compared these histopathological findings with those from previously described groups without trisomy 18. Mean age at primary cardiac surgery was 37 days (range, 9-69 days). According to the Heath-Edwards (HE) classification, 1, 8, 12, and 5 patients were graded as 0, 1, 2, and 3, respectively, whereas 2 patients were not classifiable due to medial defects in the small pulmonary arteries (MD). Four (14.3%) and 13 (46.4%) patients presented with MD and hypoplasia of the small pulmonary arteries (HS). Fifteen (53.6%) and 21 (75.0%) patients presented with alveolar hypoplasia (AH) and alveolar wall thickening (AT). MD, HS, and AH in trisomy 18 were present frequently, differing significantly from previous reports. These findings might be associated with congenital inadequate development of vessels and alveoli in the lung, contributing to a high risk of PAH in trisomy 18.

Alveolar cortical plate changes associated with incisor retraction and its influence on the limits of orthodontic tooth movement.

OBJECTIVE: The extent to which the modelling behaviour of the anterior alveolus limits tooth movement remains unclear. Will the labial and lingual cortical plates model as incisors retract, or will they remain unchanged, therefore limiting the extent of possible tooth movement? SETTING AND SAMPLE POPULATION: Pre- and post-treatment lateral cephalometric radiographs of 29 bimaxillary protrusive patients of South Korean descent were examined. Treatment consisted of two premolar extractions in one or both arches with en masse retraction of the incisors using miniscrew anchorage. MATERIALS AND METHODS: Pre- and post-treatment measurements of both tooth and cortical plate position were made at various increments along the length of the root and then compared using paired t tests. RESULTS: Despite the use of miniscrew anchorage, the incisors were retracted by controlled tipping. The labial cortical plates in both arches modelled to follow tooth movement. Following retraction of the incisors in the maxilla, the incisor root approached the lingual cortical plate, which remained unchanged. In the mandible, the lingual cortical plate position was unchanged except at the level closest to the cementoenamel junction. CONCLUSIONS: The maxillary and mandibular lingual cortical plates did not model to follow the incisor movement while the labial cortical plates did. These findings suggest that lingual cortical plates may act as limitations to planned orthodontic tooth movement.

Relationship Between Crown to Root Ratio and Alveolar Bone Support in Patients With Unilateral Cleft Lip and Alveolus.

OBJECTIVES: To evaluate the tooth lengths, crown to root ratios (CRRs), and alveolar bone support (ABS) around cleft-adjacent maxillary central incisors (U1s) in patients with unilateral cleft lip and alveolus (UCLA) and to investigate the relationships between CRR and ABS. DESIGN: This is a retrospective study. SETTING: Cleft Lip and Palate Care Center of Shanghai Ninth People's Hospital, Shanghai, China. PATIENTS: Fifty-eight Chinese patients with UCLA. MAIN OUTCOME MEASURE: Cone beam computed tomography data from 58 nonsyndromic patients with UCLA (36 males, 22 females; mean age = 12.65 ± 3.64 years) were evaluated. Crown length and root length, alveolar bone thickness (ABT), and the distances between the cementoenamel junction and alveolar bone crest on 4 surfaces of cleft-adjacent U1 were measured and compared with those of noncleft side in the same patients. Crown to root ratio and frequency of dehiscence were calculated and comparisons were also made between cleft and noncleft sides. Regression analysis was performed to explore the association between CRR and ABS. RESULTS: The CRR of cleft-adjacent U1 and alveolar bone crest heights (ACHs) on the 4 surfaces were significantly greater than those of noncleft side (P < .01). A 3 mm labial, all lingual, and apico-distal ABTs decreased on the cleft side (P < .01). A positive correlation was found between lingual ACH and CRR (R = 0.316, P < .05), between the 3 mm (R = 0.417, P < .05) and 6 mm labial (R = 0.448, P < .05) ABT and CRR. A negative correlation was found between the 3 mm and 6 mm labial ABTs and the root length. CONCLUSIONS: It can be suggested that the CRR is related to ACH and ABT. The lingual ACH, the 3 mm, and 6 mm labial ABTs tend to increase with the increasing CRR.

Morphologic analysis of alveolar bone in maxillary and mandibular incisors on sagittal views.

PURPOSE: The aim of this study was to analyze the morphologic features of alveolus in relatively healthy maxillary and mandibular incisors using cone-beam-computed tomography (CBCT). METHODS: CBCT images of 318 patients were retrospectively acquired. Alveolar bone in incisive area was divided into: type 1 (thick), type 2 (relatively thick with mono-plate concavity), type 3 (thin with double-plate concavities), and type 4 (vulnerably thin). Alveolus prevalence and widths were analyzed statistically relative to age, gender, and molar relationship. RESULTS: Prevalence of type 1 alveolus was 78.9% in maxillary central incisors, 15.1% in maxillary lateral incisors, 24.1% in mandibular central incisors, and 5.0% in mandibular lateral incisors. Type 2 alveolus was commonly observed in the maxillary lateral incisors (82.2%), mandibular central incisors (66.2%), and mandibular lateral incisors (87.9%). Prevalence of type 3 and 4 alveoli ranged from 0.0 to 9.4%. As for maxillary central incisors, type 1 was the widest both at the alveolar crest (7.77 ± 0.58 mm) and apical area (9.05 ± 1.86 mm), while type 3 had the lowest width at the apical region (4.08 ± 0.51 mm). Among maxillary central incisors, prevalence of type 1 tended to decrease with age. At all maxillary and mandibular incisor sites, alveolus widths were significantly thicker in males than in females. At maxillary lateral incisor and mandibular incisor sites, prevalence of alveolus type was significantly different among three molar relationships. CONCLUSION: A 4-type classification system was suggested for alveolus morphology in incisive region. Identification of alveolus type might aid in the corresponding treatment.

Alveolar mimics with periodic strain and its effect on the cell layer formation.

We report on the development of a new model of alveolar air-tissue interface on a chip. The model consists of an array of suspended hexagonal monolayers of gelatin nanofibers supported by microframes and a microfluidic device for the patch integration. The suspended monolayers are deformed to a central displacement of 40-80 µm at the air-liquid interface by application of air pressure in the range of 200-1,000 Pa. With respect to the diameter of the monolayers, that is, 500 µm, this displacement corresponds to a linear strain of 2-10% in agreement with the physiological strain range in the lung alveoli. The culture of A549 cells on the monolayers for an incubation time of 1-3 days showed viability in the model. We exerted a periodic strain of 5% at a frequency of 0.2 Hz for 1 hr to the cells. We found that the cells were strongly coupled to the nanofibers, but the strain reduced the coupling and induced remodeling of the actin cytoskeleton, which led to a better tissue formation. Our model can serve as a versatile tool in lung investigations such as in inhalation toxicology and therapy.

P2 Purinergic Signaling in the Distal Lung in Health and Disease.

The distal lung provides an intricate structure for gas exchange in mammalian lungs. Efficient gas exchange depends on the functional integrity of lung alveoli. The cells in the alveolar tissue serve various functions to maintain alveolar structure, integrity and homeostasis. Alveolar epithelial cells secrete pulmonary surfactant, regulate the alveolar surface liquid (ASL) volume and, together with resident and infiltrating immune cells, provide a powerful host-defense system against a multitude of particles, microbes and toxicants. It is well established that all of these cells express purinergic P2 receptors and that purinergic signaling plays important roles in maintaining alveolar homeostasis. Therefore, it is not surprising that purinergic signaling also contributes to development and progression of severe pathological conditions like pulmonary inflammation, acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and pulmonary fibrosis. Within this review we focus on the role of P2 purinergic signaling in the distal lung in health and disease. We recapitulate the expression of P2 receptors within the cells in the alveoli, the possible sources of ATP (adenosine triphosphate) within alveoli and the contribution of purinergic signaling to regulation of surfactant secretion, ASL volume and composition, as well as immune homeostasis. Finally, we summarize current knowledge of the role for P2 signaling in infectious pneumonia, ALI/ARDS and idiopathic pulmonary fibrosis (IPF).

The Three-Dimensional Ultrastructure of the Human Alveolar Epithelium Revealed by Focused Ion Beam Electron Microscopy.

Thin type 1 alveolar epithelial (AE1) and surfactant producing type 2 alveolar epithelial (AE2) cells line the alveoli in the lung and are essential for normal lung function. Function is intimately interrelated to structure, so that detailed knowledge of the epithelial ultrastructure can significantly enhance our understanding of its function. The basolateral surface of the cells or the epithelial contact sites are of special interest, because they play an important role in intercellular communication or stabilizing the epithelium. The latter is in particular important for the lung with its variable volume. The aim of the present study was to investigate the three-dimensional (3D) ultrastructure of the human alveolar epithelium focusing on contact sites and the basolateral cell membrane of AE2 cells using focused ion beam electron microscopy and subsequent 3D reconstructions. The study provides detailed surface reconstructions of two AE1 cell domains and two AE2 cells, showing AE1/AE1, AE1/AE2 and AE2/AE2 contact sites, basolateral microvilli pits at AE2 cells and small AE1 processes beneath AE2 cells. Furthermore, we show reconstructions of a surfactant secretion pore, enlargements of the apical AE1 cell surface and long folds bordering grooves on the basal AE1 cell surface. The functional implications of our findings are discussed. These findings may lay the structural basis for further molecular investigations.

New Classification System for Cleft Alveolus: A Computed Tomography-based Appraisal.

AIM: The present study proposed a new classification system based on computed tomography (CT) scan appraisal; this enables the surgeon to identify the extent of the defect and helps to execute the proper treatment plan. BACKGROUND: Various terminologies and classifications were proposed to understand developmental defects. But none of the existing classifications/nomenclatures used the preoperative radiographic evaluation (i.e., computed tomography scan-CT scan) in the management and prognosis. Various treatments were advocated and practiced successfully for the surgical correction of lip and palate. MATERIALS AND METHODS: The available CT scans from archives of the Department of Radiology and Oral and Dental Surgery were evaluated (retrospectively) for cleft alveolus and its morphology as per the proposal. The English language literature was searched in the MEDLINE database without date restriction to revise existing literature on numerous classification systems/nomenclatures using MeSH keywords related to cleft lip, palate, alveolus, developmental disturbance, facial clefts, and classification. Existing classification systems were revisited with a note on the drawbacks. After careful examination of morphological patterns of all clefts, the new CT scan-based alveolar cleft classification is proposed depending on the extent of cleft. RESULTS: The literature revealed a total of twenty-nine classifications of cleft lip and palate starting from the year 1922 to the year 2015, but none exclusively classified the cleft alveolus based on CT scan observations. The observation of three thousand CT scans showed five types of cleft alveolus, depending on the extent of involvement. CONCLUSION: The CT scan-based classification is essential to the surgeon for successful surgical planning of cleft alveolus. The proposed classification is clinically relevant in this digital era for relating surgical outcomes. The three-dimensional viewing of a defect is essential for the surgeon for virtual planning. This paper provides a CT scan-based classification for universal acceptance in this era of digital technology, and CT scan aids in achieving these goals. CLINICAL SIGNIFICANCE: The new proposal is based on preoperative evaluation of cleft using a CT scan. CT scan imaging provides a clear picture of the cleft in three dimensions for the operating surgeon. Advanced technology-enhanced surgical management modalities like CAD/CAM guided templates to support graft for successful management. The classification system will help the medical and surgical fraternity in various aspects. The three-dimensional modeling of defect and printing of a defect model using additive manufacturing technology helps the surgeon for presurgical visualization and virtual planning in a better way. This strategy of defect classification using a CT scan will help obtain better clinical outcomes and patient satisfaction.

Natural course of diffuse large B cell lymphoma-a manifestation in buccal mucosa.

BACKGROUND: Transformation and progression of lymphoma after treatment is well known; however, since the advent of chemotherapy and radiotherapy, progression in untreated lymphoma is seldom seen. We present a case which was misdiagnosed and treated as abdominal tuberculosis later presented with progression and involvement of oral cavity. CASE PRESENTATION: A 41-year-old male who presented with urinary symptoms and abdominal pain was diagnosed as abdominal tuberculosis and treated. Two years later, he presented with B symptoms and oral cavity lesion that was diagnosed as diffuse large B cell lymphoma. The patient was treated with R-CHOP chemotherapy with complete regression of the lesion. CONCLUSION: Involvement of extranodal sites in predominantly nodal disease does occur; however, involvement of oral cavity is rare. Though primary extranodal lymphoma is reported to occur in oral cavity and oropharynx, natural progression in untreated disease is seldom documented.