How can we pay for it all? Understanding the global challenge of financing climate change and sustainable development solutions.

Despite the heightened attention to climate change and sustainable development initiatives by governments, civil society groups, and private companies in the USA and worldwide, the international community is confronted with a question that has existed since the 1992 Earth Summit: how can we pay for it all? To better understand this climate change and sustainable development goals (SDGs) funding dilemma, there needs to be greater clarity around four climate change investment and finance-related questions that are frequently absent or inadequately addressed in the academic and policy literature. Firstly, what are or should be the boundaries of climate change investment and finance when the problem of climate change becomes impossible to separate from biodiversity, land use management, and other dilemmas related to the broader SDGs? Secondly, how we should define and what constitutes "adequate" financial resources to address the climate change and SDGs dilemmas on the global level? Thirdly, why is it important to close the gap between climate change adaptation and mitigation funding levels? Finally, what role should the private sector and business actors play in terms of climate change investment and finance issues? In addition to achieving greater clarity around these four issue areas, I argue in this article that three questions are likely to shape the future success (or failure) of the global climate change investment and finance architecture. One, what is likely path of the United Nations as a global climate change/sustainability governance institution? Two, will the emerging Green New Deal model in the USA and in other countries actually materialize? Three, what is the future outlook for "market-fixing" sustainability-driven enterprises?

Zirconia restorations: An American Dental Association Clinical Evaluators Panel survey.

BACKGROUND: Zirconia is a relatively new dental material used for indirect dental restorations. Little is known about how dental practitioners are using this material in their practice. METHODS: A survey on zirconia restorations was developed and administered electronically through e-mail communications to the American Dental Association Clinical Evaluators (ACE) Panel on August 31, 2020. Reminders were sent to nonrespondents, and the survey closed 2 weeks after the launch date. RESULTS: When using zirconia for a restoration, respondents choose it to restore natural teeth (99%) more often than implants (76%). Almost all respondents (98%) use it for posterior crowns, whereas approximately two-thirds (61%) use it for anterior crowns. Restoration removal or replacement and shade matching and translucency were the top 2 cited disadvantages of zirconia, whereas most of the respondents (57%) cited flexural strength or fracture resistance as the biggest advantage. Fine diamonds and ceramic polishers are used most often to polish and adjust zirconia restorations, whereas coarse diamond rotary instruments and those made specifically for zirconia are most frequently used for removing these restorations. Compared with metal ceramic restorations, more than 50% of respondents experience debonding more often with zirconia restorations. CONCLUSIONS: Dentists recognize the favorable fracture resistance and flexural strength properties of zirconia, and most use similar techniques when adjusting and removing this material. Removing these restorations and shade matching are a struggle for many. PRACTICAL IMPLICATIONS: Dentists may benefit from tips on the best methods to remove, shade match, and adhesively bond zirconia restorations.

Bonding crowns and bridges with resin cement: An American Dental Association Clinical Evaluators Panel survey.

BACKGROUND: Bonding crowns and bridges with resin cement can improve retention and reinforcement of the restoration. However, there is variation in the steps taken by different practitioners to achieve this goal. METHODS: The authors developed a survey on bonding dental crowns and bridges with resin cement and distributed it electronically to the American Dental Association Clinical Evaluators (ACE) Panel on May 22, 2020. The survey remained open for 2 weeks. Descriptive data analysis was conducted using SAS Version 9.4. RESULTS: A total of 326 panelists responded to the survey, and 86% of respondents who place crowns or bridges use resin cements for bonding. When placing a lithium disilicate restoration, an almost equal proportion of respondents etch it with hydrofluoric acid in their office or asked the laboratory to do it for them, and more than two-thirds use a silane primer before bonding. For zirconia restorations, 70% reported their restorations are sandblasted in the laboratory, and 39% use a primer containing 10-methacryloyloxydecyl dihydrogen phosphate. One-half of respondents clean their lithium disilicate or zirconia restorations with a cleaning solution. Resin cements used with a primer in the etch-and-rinse mode are the most widely used. The technique used to cure and clean excess resin cement varies among respondents. CONCLUSIONS: The types of resin cements used, tooth preparation, crown or bridge preparation, and bonding technique vary among this sample. PRACTICAL IMPLICATIONS: Although many dentists bond crowns and bridges on the basis of best practices, improvement in the process may be achieved by dentists communicating with their laboratory to confirm the steps performed there, ensuring an effective cleaning technique is used after try-in and verifying that the correct primer is used with their chosen restorative material.

Dental light-curing units: An American Dental Association Clinical Evaluators Panel survey.

BACKGROUND: The ability to polymerize light-activated dental materials with dental light-curing units (DLCUs) has revolutionized dentistry. However, proper DLCU use is essential for ensuring the effectiveness and performance of these materials. METHODS: The authors developed an electronic cross-sectional survey in the American Dental Association Qualtrics Research Core platform. The survey included questions about DLCU use, unit type and selection, training, maintenance, technique, and safety measures. The authors deployed the survey to 809 American Dental Association Clinical Evaluators (ACE) panelists on October 9, 2019, and sent reminder links to nonrespondents 1 week later. They conducted exploratory and descriptive analyses using SAS software Version 9.4. RESULTS: Of the 353 ACE panelists who completed the survey, most used a DLCU in their practices (99%), and light-emitting diode multiwave units were the most common type of DLCU units (55%). Dentists use DLCUs for over one-half of their appointments each day (mean [standard deviation], 59% [22%]). Regarding technique, respondents reported that they modify their curing technique on the basis of material thickness (79%) and material type or light tip-to-target distances (59%). Maintenance practices varied, with two-thirds of respondents reporting that they periodically check their DLCUs' light output. CONCLUSIONS: DLCUs are an integral part of a general dentist's daily practice, but maintenance, ocular safety, and technique varied widely among this sample. PRACTICAL IMPLICATIONS: Because clinical effectiveness requires delivery of an adequate amount of light energy at the appropriate wavelength, variation in DLCU maintenance, safety, and techniques suggest that dentists could benefit from additional guidance and training on DLCU operation.

An American Dental Association Clinical Evaluators Panel survey.

BACKGROUND: Human papillomavirus (HPV) is a sexually transmitted oncovirus associated with several malignancies, including oropharyngeal squamous cell carcinoma. The 9-valent HPV vaccine can help protect against the high-risk HPV strains most commonly associated with HPV-related cancers. METHODS: The authors used an electronic survey to assess the roles of dentists and their team members in discussing the HPV vaccine, as well as administering the vaccine in a dental setting. On December 6, 2019, the authors e-mailed a survey link to the American Dental Association Clinical Evaluators (ACE) Panel (n = 813), a sample of American Dental Association member dentists. After 1 e-mail reminder, the survey closed on December 19, 2019, and the authors conducted exploratory and descriptive data analyses using SAS Version 9.4 (SAS). RESULTS: A total of 329 dentists responded to the survey, and 83 (25%) of them reported that they or their team members discuss the implications of the HPV vaccine with age-eligible patients or their parents or guardians. Dentists lead two-thirds (n = 218) of the discussions, and the clinical examination is the most frequent moment during the patient visit in which HPV-related topics are discussed. Some of the top reasons respondents mentioned for not discussing the vaccine in their practice were the perception that these discussions are best left to other health care professionals and not knowing how to address the topic with patients. If the scope of dental practice is expanded to include administering the vaccine, 125 (38%) of respondents would feel uncomfortable administering the vaccine. The most common potential barriers to administering the vaccine in a dental setting include obtaining reimbursement and vaccine management and preservation. CONCLUSIONS: The survey results suggest that dentists' comfort levels and perceived roles in discussing and administering the HPV vaccine vary. PRACTICAL IMPLICATIONS: There is a need to further define the role of dentists and their team members in the promotion and administration of the HPV vaccine. Resources for dentists and dental team members may be helpful to support professional education and communication about the HPV vaccine.

Characterization of niphatenones that inhibit androgen receptor N-terminal domain.

Androgen ablation therapy causes a temporary reduction in tumor burden in patients with advanced prostate cancer. Unfortunately the malignancy will return to form lethal castration-recurrent prostate cancer (CRPC). The androgen receptor (AR) remains transcriptionally active in CRPC in spite of castrate levels of androgens in the blood. AR transcriptional activity resides in its N-terminal domain (NTD). Possible mechanisms of continued AR transcriptional activity may include, at least in part, expression of constitutively active splice variants of AR that lack the C-terminal ligand-binding domain (LBD). Current therapies that target the AR LBD, would not be effective against these AR variants. Currently no drugs are clinically available that target the AR NTD which should be effective against these AR variants as well as full-length AR. Niphatenones were originally isolated and identified in active extracts from Niphates digitalis marine sponge. Here we begin to characterize the mechanism of niphatenones in blocking AR transcriptional activity. Both enantiomers had similar IC50 values of 6 µM for inhibiting the full-length AR in a functional transcriptional assay. However, (S)-niphatenone had significantly better activity against the AR NTD compared to (R)-niphatenone. Consistent with niphatenones binding to and inhibiting transactivation of AR NTD, niphatenones inhibited AR splice variant. Niphatenone did not affect the transcriptional activity of the related progesterone receptor, but slightly decreased glucocorticoid receptor (GR) activity and covalently bound to GR activation function-1 (AF-1) region. Niphatenone blocked N/C interactions of AR without altering either AR protein levels or its intracellular localization in response to androgen. Alkylation with glutathione suggests that niphatenones are not a feasible scaffold for further drug development.

Niphatenones, glycerol ethers from the sponge Niphates digitalis block androgen receptor transcriptional activity in prostate cancer cells: structure elucidation, synthesis, and biological activity.

Extracts of the marine sponge Niphates digitalis collected in Dominica showed strong activity in a cell-based assay designed to detect antagonists of the androgen receptor (AR) that could act as lead compounds for the development of a new class of drugs to treat castration recurrent prostate cancer (CRPC). Assay-guided fractionation showed that niphatenones A (3) and B (4), two new glycerol ether lipids, were the active components of the extracts. The structures of 3 and 4 were elucidated by analysis of NMR and MS data and confimed via total synthesis. Biological evaluation of synthetic analogues of the niphatenones has shown that the enantiomers 7 and 8 are more potent than the natural products in the screening assay and defined preliminary SAR for the new AR antagonist pharmacophore, including the finding that the Michael acceptor enone functionality is not required for activity. Niphatenone B (4) and its enantiomer 8 blocked androgen-induced proliferation of LNCaP prostate cancer cells but had no effect on the proliferation of PC3 prostate cancer cells that do not express functional AR, consistent with activity as AR antagonists. Use of the propargyl ether 44 and Click chemistry showed that niphatenone B binds covalently to the activation function-1 (AF1) region of the AR N-terminus domain (NTD).