Reducing maternal and child oral health disparities in Sub-Saharan Africa through a community-based strategy.

Oral conditions disproportionately affect mothers and children in Sub-Saharan Africa, due to biological vulnerabilities, a scarcity of oral health workers, deficient preventive strategies, and gender-based barriers to care. The World Health Organization (WHO) recommends integrating oral health into broader health delivery models, to reduce these disparities. We propose integrating preventive oral healthcare into community-based programs to bridge these gaps. We examine integrating preventive oral healthcare into Western Kenya's Chamas for Change (Chamas) community-based program which aims to reduce maternal and child health disparities. Chamas incorporates women's health and microfinance programs best practices to produce a low-cost, community-driven, sustainable, and culturally acceptable health delivery platform. Our strategy is based on the Maternal and Child Oral Health Framework and uses the WHO Basic Package of Oral Care principles. This framework prioritizes community involvement, cultural sensitivity, regular screenings, and seamless integration into general health sessions. We discuss the strengths, weaknesses, opportunities, and threats to enriching Chamas with oral health promotion activities. It is crucial to assess the effectiveness, sustainability, and acceptability of the proposed strategy through implementation and evaluation. Future studies should investigate the long-term impact of integrated oral health models on community health and oral health disparity reduction in Africa.

Granulocyte macrophage-colony stimulating factor and keratinocyte growth factor control of early stages of differentiation of oral epithelium.

Oral epithelial differentiation is known to be directed by underlying fibroblasts, but the responsible factor(s) have not been identified. We aimed here to identify fibroblast-derived factors responsible for oral epithelial differentiation. Primary normal human oral keratinocytes and fibroblasts were isolated from healthy volunteers after informed consent (n = 5) and 3D-organotypic (3D-OT) cultures were constructed. Various growth factors were added at a range of 0.1-100 ng/ml. 3D-OTs were harvested after ten days and assessed histologically, by immunohistochemistry and the TUNEL method. Epithelium developed in 3D-OT without fibroblasts showed an undifferentiated phenotype. Addition of granulocyte macrophage-colony stimulating factor (GM-CSF) induced expression of cytokeratin 13 in suprabasal cell layers. Admixture of GM-CSF and keratinocyte growth factor (KGF) induced, in addition, polarization of epidermal growth factor (EGF) receptor and ß1-integrin to basal cell layer and collagen IV deposition. Terminal differentiation with polarization of TUNEL-positive cells to superficial layers occurred only in the presence of fibroblasts in collagen gels either in direct contact or at distance from normal oral keratinocytes. Taken together, these results show that major aspects of oral epithelial differentiation are regulated by the synergic combination of GM-CSF and KGF. However, the terminal stage seems to be controlled by other yet unidentified fibroblast-derived diffusible factor(s).

Motivations for a Career in Dentistry among Dental Students and Dental Interns in Kenya.

A number of factors have been cited as determinants for choosing a career in dentistry around the globe. The purpose of this study was to determine motivations for a career in dentistry among dental students and dental interns in Kenya. This was a cross-sectional study where 293 individuals participated by filling and returning self-administered questionnaires. The mean age of all respondents was 22.3 years. Overall, 59.5% of the respondents had selected dentistry as their preferred career at the end of high school. Majority (76.1%) of the respondents agreed that personal interest in dentistry was an important motivating factor for them. This was followed closely by a desire to help or serve people (74%), a desire for a flexible work schedule (63%), and an aspiration to be self-employed (61.8%). There was no difference between males and females regarding these as motivating factors. On the other hand, among factors that the respondents felt had the lowest influence on their choice of dentistry was parental influence, where only 22% of the respondents indicated that this was a motivating factor for them. Other potential motivating factors such as influence by friends and siblings (30.3%) as well as career talk and guidance (41.3%) were also ranked low. In general, the respondents indicated that they were motivated much more by personal and humanitarian factors, when compared to financial and societal factors.

Oral Lesions Induced by Chronic Khat Use Consist Essentially of Thickened Hyperkeratinized Epithelium.

Objectives. The habit of khat chewing is prevalent in many Middle Eastern and African cultures and has been associated with various adverse conditions in humans. This study aimed to describe histological changes induced by chronic khat chewing on the buccal mucosa. Methods. Biopsies of the buccal mucosa from 14 chronic khat chewers, 20 chronic khat chewers who also smoked tobacco, and 8 nonchewers were compared for epithelial thickness, degree and type of keratinization, and connective tissue changes. Results. Tissues from khat chewers depicted abnormal keratinization of the superficial cell layer and showed increased epithelial thickness affecting all layers. Epithelial thickness in control samples was 205 ± 26 µm whereas thickness in khat chewers and khat chewers who smoked tobacco was significantly higher measuring 330 ± 35 µm and 335 ± 19 µm, respectively. Tissues from khat chewers also showed increased intracellular edema, increased melanin pigment deposits, and increased number of rete pegs most of which were thin and deep. Conclusions. These results show that oral lesions induced by chronic chewing of khat in the buccal mucosa present with white and brown discoloration due to increased epithelial thickness, increased keratinization, and melanin deposition.

Primary intraosseous squamous cell carcinoma arising from keratocystic odontogenic tumor.

Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare lesion that almost exclusively occurs in the jaws. Most PIOSCCs originate from epithelial lining of odontogenic cysts, especially from radicular, residual, and dentigerous cysts. A few cases have been shown to arise from keratocystic odontogenic tumors (KCOTs). This is a report of a case of PIOSCC that arose from an untreated keratocystic odontogenic tumor within a period of less than 2 years of first diagnosis. Upon malignant transformation, the tumor changed from a cystic to a solid pattern and acquired an infiltrative growth pattern, invading and destroying all surrounding bone. This case underscores the importance of early diagnosis and treatment of KCOTs and raises the question whether some of the PIOSCCs classified as "solid type" could, in fact, be late-presenting PIOSCCs arising from KCOTs and other cystic pathologic entities within the jaws.

Adverse effects of Sudanese toombak vs. Swedish snuff on human oral cells.

BACKGROUND: The high incidence of oral cancer in Sudan has been associated with the use of toombak, the local type of smokeless tobacco. However, its specific effects on human oral cells are not known. We aimed to investigate the effects of toombak on primary normal human oral keratinocytes, fibroblasts, and a dysplastic oral keratinocytic cell line, and to compare them with the effects induced by Swedish snuff. METHOD: Aqueous extracts were prepared from moist toombak and Swedish snuff and added in serial dilutions on in vitro monolayer cultured cells. Cell viability, morphology and growth, DNA double-strand breaks (gammaH2AX staining), expression of phosphatidylserine (Annexin V staining), and cell cycle were assessed after various exposure time periods. RESULTS: Significant decrease in cell number, occurrence of DNA double-strain breaks, morphological and biochemical signs of programmed cell death were detected in all oral cell types exposed to clinically relevant dilutions of toombak extract, although to a lesser extent in normal oral fibroblasts and dysplastic keratinocytes. G2/M-block was also detected in normal oral keratinocytes and fibroblasts exposed to clinically relevant dilutions of toombak extract. Swedish snuff extract had less adverse effects on oral cells, mainly at non-clinically relevant dilutions. CONCLUSION: This study indicates a potential for toombak, higher than for Swedish snuff, to damage human oral epithelium. Dysplastic oral keratinocytes were less sensitive than their normal counterparts, suggesting that they might have acquired a partially resistant phenotype to toombak-induced cytotoxic effects while still being prone to DNA damage that could lead to further malignant progression.

Cancer progression is associated with increased expression of basement membrane proteins in three-dimensional in vitro models of human oral cancer.

BACKGROUND: Although basement membrane was traditionally considered an inert barrier that tumour cells had to cross before invasion into the surrounding stroma, recent studies suggest that basement membrane components are not only degraded during tumour progression, but also newly synthesised at the invasive front. OBJECTIVE: This study aimed at evaluating (1) the expression of basement membrane proteins in human oral carcinogenesis and (2) the role that epithelial-mesenchymal interactions play on it, by using an in vitro oral cancer progression model. MATERIAL AND METHODS: In vitro three-dimensional (3D) organotypic cultures of normal, early neoplastic and neoplastic human oral mucosa were developed by growing primary normal human oral keratinocytes, dysplastic human oral keratinocytes (DOK cell line), and neoplastic human oral keratinocytes (PE/CA-PJ15 cell line) on type I collagen biomatrices, with or without primary fibroblasts isolated from normal human oral mucosa. The cultured tissues were immunohistochemically assessed for the expression of the major basement membrane proteins laminin-332, type IV collagen, and fibronectin. RESULTS: Expression of laminin-332, type IV collagen, and fibronectin was gradually more pronounced in neoplastic models when compared to normal mucosa models, and, with the exception of laminin-332, it was further enhanced by presence of fibroblasts. Deposition of type IV collagen at the epithelium-biomatrix interface occurred only in presence of fibroblasts, as well as the extracellular matrix deposition of fibronectin. CONCLUSIONS: These findings, obtained in a 3D in vitro model that closely mirrors the in vivo human oral cancer progression, show an enhanced basement membrane protein expression during human oral cancer progression that is dependent on the epithelial-mesenchymal environment, respectively the existence of fibroblasts.

Early loss of mitochondrial inner transmembrane potential in khat-induced cell death of primary normal human oral cells.

Previous studies suggest the use of khat, a psychostimulant plant used by millions of people in Middle East and Africa, as risk factor for oral cancer. We previously reported that khat is able to induce adverse affects, as cell cycle arrest and apoptosis, in normal human oral cells cultured in vitro. This study further investigates the more specific role played by mitochondria in khat-induced cell death and the kinetics of the events involved in this process. Exposure of primary normal human oral keratinocytes and fibroblasts to khat extract resulted in a swift and sustained decrease of the mitochondrial inner transmembrane potential occurring within 0.5-1h. Loss of mitochondrial membrane potential preceded all other biochemical and morphologic changes, and was associated with a significant decrease in cell survival. Subsequently, apoptosis-inducing factor was released from mitochondria into cytosol and relocated to nucleus. Cyclosporine A and bongkrekic acid delayed both the loss of mitochondrial inner transmembrane potential and the onset of cell death. This study describes a novel mechanism of khat-induced cell death in primary normal oral keratinocytes and fibroblasts involving an early pivotal effect on mitochondrial function and integrity.

Khat (Catha edulis) induces reactive oxygen species and apoptosis in normal human oral keratinocytes and fibroblasts.

Khat chewing is widely practiced in Eastern Africa and the Middle East. Khat is genotoxic to cells within the oral mucosa, and several studies have suggested an association between khat use and oral lesions like hyperkeratosis and oral cancer. This study investigated the mechanism of khat-induced cytotoxicity using primary normal human oral keratinocytes (NOK) and fibroblasts (NOF). Khat induced rounding up of cells, plasma membrane blebbing, and condensation of nuclear chromatin within 3-6 h of exposure. The cells also showed externalization of phosphatidylserine and fragmentation of DNA. Morphological and biochemical features were compatible with cell death by apoptosis. Khat also induced an increase in cytosolic reactive oxygen species (ROS) and a depletion of intracellular glutathione (GSH) within 1 h of exposure. Antioxidants reduced ROS generation, GSH depletion and delayed the onset of cytotoxicity in both cell types. Generally, NOF cells were more sensitive to khat-induced cytotoxicity than NOK cells. These effects were elicited at concentrations of khat expected to occur in the oral cavity during khat chewing. In summary, khat induced apoptotic cell death in primary normal oral keratinocytes and fibroblasts by an early effect on mechanisms that regulate oxidative stress.

Khat induces G1-phase arrest and increased expression of stress-sensitive p53 and p16 proteins in normal human oral keratinocytes and fibroblasts.

Khat is a psychostimulant plant used by over 10 million people daily, mainly in eastern Africa and the Middle East. Previous studies have suggested an association between khat use and oral lesions such as hyperkeratosis and oral cancer. This study investigated the effects of an extract of khat on primary normal human oral keratinocytes (NOK) and normal human oral fibroblasts (NOF). Low (sublethal) concentrations of khat inhibited the proliferation of both cell types in a dose-dependent and time-dependent manner. Both NOK and NOF treated with khat accumulated in the G1-phase of the cell cycle and showed increased expression of the stress-sensitive p53 protein after 24 h. Normal human oral keratinocytes showed a profound increase in p16(INK4A) (p16) after 24 h and showed morphological changes suggesting cell differentiation. Normal human oral fibroblasts showed growth inhibition and increased expression of p21(WAF1/CIP1) (p21) within 24 h. The concentrations of khat tested in this study were within the range of those found in the oral cavity of khat chewers. The results show that stress induced by khat modulates the cell cycle in oral keratinocytes and fibroblasts. It is further speculated whether khat could have similar effects in vivo, especially in keratinocytes.