Epidemiology of dermatologic disease in Palau: a cross-sectional study in the national public and community health service.

BACKGROUND: Dermatologic disease is a neglected public health challenge that disproportionately affects resource-poor settings. Globally, dermatologic disease contributes the fourth highest burden of nonfatal disability with the most acute impact in the Oceanic region, including the Republic of Palau. Efforts to address the dermatologic health inequality are hindered without the necessary epidemiologic evidence to guide health policy in the resource-poor setting of Palau. METHODS: We conducted a 4-year cross-sectional study of all Dermatology Service patients in the Belau National Hospital and outreach community health centers from 2015 to 2018. No other specialized dermatology service was available. Skin disease was classified by both diagnosis and Global Burden of Disease criteria and analyzed by age, gender, region, and surrounding Oceanic nations. RESULTS: The study enrolled 494 patients comprising 179 males and 315 females between 2015 and 2018. The most prevalent diseases were eczema (48.8%), superficial fungal infection (24.5%), and pruritus (22.7%). The neglected tropical disease of scabies was detected in four patients. Males were significantly more likely to present with cellulitis, keratinocyte carcinoma, stasis dermatitis, wounds, marine-related dermatitis, viral skin disease, tinea faciei, verruca, and xerosis and females with melasma and hyperpigmentation. CONCLUSION: This study presents the first primary epidemiologic data describing the prevalence of dermatologic disease in the Palauan adult population. The significant burden of disease in Palau compared with other Oceanic nations validates ongoing dermatology services and informs public health implications for resource allocation and disease management to achieve health equality in the resource-poor nation.

Epidermal Growth Factor Receptor Expression and Resistance Patterns to Targeted Therapy in Non-Small Cell Lung Cancer: A Review.

Globally, lung cancer is the leading cause of cancer-related death. The majority of non-small cell lung cancer (NSCLC) tumours express epidermal growth factor receptor (EGFR), which allows for precise and targeted therapy in these patients. The dysregulation of EGFR in solid epithelial cancers has two distinct mechanisms: either a kinase-activating mutation in EGFR (EGFR-mutant) and/or an overexpression of wild-type EGFR (wt-EGFR). The underlying mechanism of EGFR dysregulation influences the efficacy of anti-EGFR therapy as well as the nature of resistance patterns and secondary mutations. This review will critically analyse the mechanisms of EGFR expression in NSCLC, its relevance to currently approved targeted treatment options, and the complex nature of secondary mutations and intrinsic and acquired resistance patterns in NSCLC.

Sox9 and Rbpj differentially regulate endothelial to mesenchymal transition and wound scarring in murine endovascular progenitors.

Endothelial to mesenchymal transition (EndMT) is a leading cause of fibrosis and disease, however its mechanism has yet to be elucidated. The endothelium possesses a profound regenerative capacity to adapt and reorganize that is attributed to a population of vessel-resident endovascular progenitors (EVP) governing an endothelial hierarchy. Here, using fate analysis, we show that two transcription factors SOX9 and RBPJ specifically affect the murine EVP numbers and regulate lineage specification. Conditional knock-out of Sox9 from the vasculature (Sox9fl/fl/Cdh5-CreER RosaYFP) depletes EVP while enhancing Rbpj expression and canonical Notch signalling. Additionally, skin wound analysis from Sox9 conditional knock-out mice demonstrates a significant reduction in pathological EndMT resulting in reduced scar area. The converse is observed with Rbpj conditionally knocked-out from the murine vasculature (Rbpjfl/fl/Cdh5-CreER RosaYFP) or inhibition of Notch signaling in human endothelial colony forming cells, resulting in enhanced Sox9 and EndMT related gene (Snail, Slug, Twist1, Twist2, TGF-ß) expression. Similarly, increased endothelial hedgehog signaling (Ptch1fl/fl/Cdh5-CreER RosaYFP), that upregulates the expression of Sox9 in cells undergoing pathological EndMT, also results in excess fibrosis. Endothelial cells transitioning to a mesenchymal fate express increased Sox9, reduced Rbpj and enhanced EndMT. Importantly, using topical administration of siRNA against Sox9 on skin wounds can substantially reduce scar area by blocking pathological EndMT. Overall, here we report distinct fates of EVPs according to the relative expression of Rbpj or Notch signalling and Sox9, highlighting their potential plasticity and opening exciting avenues for more effective therapies in fibrotic diseases.

Revascularization-associated Intracanal Calcification: A Case Report with an 8-year Review.

Revascularization-associated intracanal calcification (RAIC) is a common finding in immature teeth managed with regenerative endodontic treatment (RET). The aim of this report was to illustrate a case in which 2 mandibular premolar teeth developed complete canal obliteration and have been reviewed for 8 years. The 3 primary outcome goals as defined by the American Association of Endodontists after RET are resolution of signs and symptoms of pulp necrosis, further root maturation, and achievement of responses to pulp vitality testing. The teeth had been included in an earlier quantitative study in which an increase in root canal width of 72.1% and 39.6% and an increase in root length of 1.7% and 0% were reported for teeth #20 and #29, respectively. Qualitative assessments over the 8-year review period showed no pathosis and a response to electric pulp testing at the final review. A quantitative assessment at the 8-year review showed an increase of 100% for canal width because complete calcification had occurred and no substantive change in root length (-0.17% and 0.68% for teeth #20 and #29, respectively). In this report, complete RAIC occurred in both teeth over time. RAIC has the potential to complicate future endodontic or prosthodontic treatment if necessary. Therefore, it is recommended that the American Association of Endodontists clinical considerations for a regenerative endodontic procedure be updated to include the incidence of RAIC after RET.

The Effect of Long-term Dressing with Calcium Hydroxide on the Fracture Susceptibility of Teeth.

INTRODUCTION: Calcium hydroxide has been widely used to treat immature teeth to achieve periodontal healing and to promote the formation of an apical barrier. However, retrospective clinical studies have shown a high incidence of cervical root fractures with long-term calcium hydroxide dressing. The alkalinity of calcium hydroxide has been suggested to weaken the root. In vitro studies using ovine teeth show conflicting results on fracture strength of dentine, although different commercial products may have influenced the results. The purpose of this study was to investigate the effects of 2 commercial products used in prior studies (Calasept Plus and UltraCal XS), as well as a new product (Calmix) that uses a nonaqueous vehicle that allows for a higher pH, on the fracture strength of dentine over time. METHODS: A total of 330 lamb incisor teeth were collected and the canals prepared so that 3 commercial calcium hydroxide products as well as a positive control of pure calcium hydroxide slurry that filled the root canal from the open apex and a negative control of saline was tested. The teeth were loaded until fracture with a universal testing machine at time points 0, 3, 6, and 9 months and the force to fracture was calculated. The data were analyzed with Friedman analysis of variance and Mann-Whitney t tests. RESULTS: No statistical differences were observed between the different calcium hydroxide products and the negative controls. CONCLUSIONS: Thin and fragile roots could be the cause of fracture rather than the calcium hydroxide dressing.

Alkaline Material Effects on Roots of Teeth.

The aim of this review was to identify and analyse all studies related to the effects of alkaline materials used in dentistry on roots of teeth. The first part of the review focused on mechanical property alterations of root dentine due to sodium hypochlorite (SH) used as an irrigant solution based on MeSH (Medical Subject Heading) terms from a previous study by Pascon et al in 2009. The second part reviewed literature on calcium hydroxide (CH), mineral trioxide aggregate (MTA) and other alkaline materials used as root canal dressings or filling materials. Additional MeSH terms used included "compressive strength", "elastic modulus" "flexural strength", "fracture strength" and "fracture resistance". The language filter was English. Of the initial 205 articles identified, 49 were included in this review, of which 29 were on SH, 21 on CH/MTA, and 1 relating to both. Many in vitro studies indicated a strong link between reduced mechanical properties of roots of teeth or radicular dentine treated with SH, and when sealers or root fillings with CH- or MTA-based materials were placed in contact with roots or radicular dentine. Recent literature indicates that the association between reduced mechanical properties and alkaline sealers and/or root-filling materials is not as straightforward as previously assumed, and requires further investigation using more valid experimental models.